Download A. Severe Sepsis or Septic Shock Where Site Of Infection Is Not

CRITICAL CARE
PHARMACY
HANDBOOK
2010
CLINICAL PHARMACY WORKING COMMITTEE
(CRITICAL CARE SUBSPECIALTY)
PHARMACEUTICAL SERVICES DIVISION, MINISTRY OF
HEALTH
LIST OF CONTENTS
Page
CHAPTER 1 : THE ROLE OF PHARMACIST IN CRITICAL CARE Datin Fadilah
CHAPTER 2 :
PROTOCOLS
2.1
Dilution Protocols Masrahayu, Rahela, Maznuraini
2.2
DVT Prophylaxis  Thong
2.3
Stress Ulcer Prophylaxis  Ros Sakinah
2.4
Antibiotic Guidelines for Infections in Intensive Care Unit
2.5
Neuromuscular Blocking Agents in Critically Ill Patients Martina
2.6
Sedative Agents in Critically Ill Patients Azrina
2.7
Fluid Management in Critically Ill Patients Pn Rohana
2.8
Medication Administration through Enteral Feeding TubesNgua
2.9
Prokinetic Agents  Ngua : Pls get the doc from Pn. Siti Hir and add into this file
CHAPTER 3 :
DOSING
3.1
Renal Dosing Pn Nik Mah, Pn Nurdita
3.2
Liver Dosing Shafie
3.3
Special Dosing in Obese Patients Siti Hir
CHAPTER 4 :
4.2
NUTRITION
Parenteral Nutrition in Critically Ill Patients Mazni
CHAPTER 5 :
OTHERS
5.1
Drug Causing Haematological Disorder Irma
5.2
Poisoning Hasni
APPENDICES:
Appendix 1: Drugs that may unmask/exacerbate Myasthenia Gravis- Ain
Appendix 2: Categories of Safe & Unsafe Drugs in the Acute Porphyrias- Ain
Appendix 3: Drugs and Chemicals in Glucose-6-Phosphate Dehydrogenase Deficiency
Appendix 4 : Drug-Disease Interactions Pn Yam (Appendix 3 & 4)
2
CHAPTER 1
THE ROLE OF PHARMACIST IN CRITICAL CARE
3
CHAPTER 2
PROTOCOLS
2.1
Dilution Protocols
2.1.1
Antiarrhythmic Agents
DRUG
a. Digoxin
b. Adenosine
STRENGTH/UNIT
500mcg/2ml ( Lanoxin )
STORAGE
Below 25˚C, Protect from light
RECONSTITUITION
Already in solution
Below 25ºC ( Do not refrigerate
)
Already in solution.
STABILITY AFTER
RECONSTITUITION
Immediate use is recommended
NA
6mg/2ml ( Adenocor )
D5%
DILUENTS FOR
INFUSION
NS
For direct IV injection can be administered
undiluted or diluted with a 4 fold or greater
volume of diluents. The use of less than a 4 fold
volume of diluents could lead to precipitation of
digoxin.
NA
( eg. 2ml ampoule with 500mcg in 500ml of
diluents for infusion)
METHOD OF
ADMINISTRATION
REMARKS
IV infusion (over 10-20 mins or longer-Product
Information Lanoxin Injection). ( To be given at
least 2 hours - BNF)
IV bolus (2 seconds )
Intramuscular route are not recommended. The
IM route is painful and associate with muscle
necrosis.
IV bolus into central or large
peripheral vein.
Rapid injection is not recommended; it may
cause systemic and coronary arteriolar
constriction.
If given into an IV line, it should
be injected as proximally as
possible, and followed by a
rapid saline flush (5ml of NS ).
Mixing digoxin with other drugs in the same
container or simultaneous administration in the
same intravenous line is not recommended.
Administer with cardiac
monitoring.
REFERENCES:
1. Product information ( Lanoxin Injection).
2. Micromedex Healthcare series.
3. Pocket Guide to Injectable Drugs. Companion
to the handbook on Injectable Drugs.13 th
edition. Lawrence A. Trissel. 2005.
4. British National Formulary (BNF). 55 edition.
March 2008.
1. Product information
Adenocor.
2. Micromedex Healthcare
series.
3. Lexi-Comp's Drug
Information Handbook, 13th
Edition, Charles F, Lacy, et
al.2005
4. BNF 50, September 2005.
4
DRUG
c.
Amiodarone
d. Isoproterenol Hydrochloride
STRENGTH/UNIT
150mg/3ml ( Cordarone )
1mg/5ml ( Isuprel )
STORAGE
Below 25ºC.
20ºC - 25ºC. Protect from light.
RECONSTITUITION
Already in solution.
Already in solution.
STABILITY AFTER
RECONSTITUITION
NA
NA
DILUENTS FOR
INFUSION
D5%
NS ( for IV bolus only )
D5% ( for IV bolus and IV infusion )
IV bolus : dilute 0.2mg ( 1ml ) to 10 ml
NS or D5%.
IV ( Central line )
METHOD OF
ADMINISTRATION
Loading Dose : Dilute 300mg in 50 mL
D5%, run over 1 hour.
IV infusion : dilute 2mg ( 10ml ) in 500
ml D5%.
IM : use undiluted ( 0.2mg )
Maintenance Dose : Dilute 600mg in
500mL D5% run over 23 hours.
SC : use undiluted ( 0.2mg )
Intracardiac : use undiluted ( 0.02mg )
Do not use concentrations of less than 2
ampoules ( 300mg) in 500 ml.
Incompatible with NS.
Do not add any other products to the
infusion solution.
REMARKS
Must be administered via the central
venous route.
Concentration up to 10 times greater
have been used when limitation of
volume is essential
Rate over 30mcg/min have been used
in advanced stages of shock.
If heart rate exceed 110 beats
/min,decrease or temporarily
discontinue the infusion.
Do not use if is pinkish or darker than
slightly yellow or contain precipitate.
REFERENCES:
1. Product information Cordarone.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information
Handbook, 13th Edition,
Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
1. Product information Isuprel.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information
Handbook, 13th Edition, Charles F,
Lacy, et al.2005
4. BNF 50, September 2005.
5
DRUG
e. Streptokinase
STRENGTH/UNIT
1 500 000 IU ( Streptase )
STORAGE
2ºC - 25ºC.
RECONSTITUITION
5ml NS.
STABILITY AFTER
RECONSTITUITION
24 hours at 2ºC - 8ºC.
DILUENTS FOR
INFUSION
NS
D5%
METHOD OF
ADMINISTRATION
IV infusion : dilute up to 20 - 250mL NS or D5% over
60 mins.
REMARKS
Avoid IM use.
REFERENCES:
1. Product information Streptase.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th
Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
6
2.1.2
Antibiotics
DRUG
STRENGTH/UNIT
a. Amikacin
250mg/2ml
b. Ampicilin
c.
Azithromycin
500mg
500mg (Zithromax)
500mg/2ml
STORAGE
Below 25˚C, Protect from light,
Do not freeze
Below 25˚C
15ºC - 30ºC
RECONSTITUITION
Already in solution
5ml Water for Injection
STABILITY AFTER
RECONSTITUITION
NA
4.8ml Water for
Injection
24 hours at room
temperature
DILUENTS FOR
INFUSION
METHOD OF
ADMINISTRATION
REMARKS
REFERENCES
D5%
NS
D5% 1/2 NS
D5% 1/4 NS
Lactated Ringer's Injection
IV infusion : Adults and paed
over 30 to 60 minutes. Infant over
1 to 2 hours.
use within 1 hour
NS
Infusion concentration
should not exceed
30mg/ml.
IV Bolus : 3 - 5 min
1 week in refrigerator
NS
1/2NS
D5%
Lactated Ringer's
Injection
Infusion
concentration: 1mg/ml
- 2mg/ml
IV infusion 1mg/ml
over 3 hours
IV Infusion : 30 - 60 min
IV infusion 2mg/ml
over 1 hour
IM injection in large muscle
mass.
IM (Dissolve 500mg in
1.8ml Water for
Injection)
Amikacin should not be mixed
with other antibiotics in the same
solution and must be
administered separately.
Rapid infusion may
cause seizures.
Should not be given
as IV bolus or IM
1. Product
information
Pamecil.
2. Micromedex
Healthcare
series.
3. BNF 50,
September
2005.
1. Product
information
Zithromax.
2. Micromedex
Healthcare series.
3. Lexi-Comp's Drug
Information
Handbook, 13th
Edition, Charles F,
Lacy, et al.2005
4. BNF 50,
September 2005.
1. Product information Amikozit.
2. Micromedex Healthcare
series.
3. Lexi-Comp's Drug Information
Handbook, 13th Edition,
Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
7
DRUG
STRENGTH/UNIT
d. Cefepime
e. Cefotaxime
f.
Ceftazidime
1gm (Maxipime)
1gm
1gm , 2gm ( Fortum )
STORAGE
15ºC - 30ºC
15ºC - 30ºC , Protect
from light
Below 25ºC, Protect
from light
10ml Water for Injection, D5%,
NS
10ml Water for Injection
RECONSTITUITION
Not to be stored above
25ºC
10ml Water for
Injection ( both 1gm
and 2gm)
18 hours at below
25ºC
Not longer than 24 hours
1 week in refrigerator
NS
NS
NS
D5%
D5%
D5%
IV bolus over 3-5
minutes.
IV bolus over 3-5
minutes.
IV infusion: 100ml over
50 - 60 minutes.
IV infusion: diluent up
to 50ml over 30
minutes.
24 hours at room temperature
STABILITY AFTER
RECONSTITUITION
DILUENTS FOR
INFUSION
1 week in refrigerator
Infusion concentration:
1mg/ml - 40mg/ml
IV infusion over 30 minutes
METHOD OF
ADMINISTRATION
IM ( Dissolve 1gm in 3ml
Water for Injection, D5%, 1%
Lidocaine )
IM ( Dissolve 1gm in 4ml
Water for Injection )
IV preferable for dose
exceed 1gm
REMARKS
REFERENCES
IV preferable for patient with
severe or life-threatening
infection.
1. Product information
Maxipime.
2. Micromedex
Healthcare series.
3. Lexi-Comp's Drug
Information Handbook,
13th Edition, Charles
F, Lacy, et al.2005
4. BNF 50, September
2005.
IM ( Dissolve 1gm in
3ml Water for Injection
)
IV preferable for dose
exceeds1gm.
May be used in
peritoneal dialysis and
CAPD.
1. Product information
Rekaxime.
2. Micromedex
Healthcare series.
3. Lexi-Comp's Drug
Information
Handbook, 13th
Edition, Charles F,
Lacy, et al.2005
4. BNF 50, September
2005.
Concentration : 125 250mg for 2L of
dialysis fluid
1. Product information
Fortum.
2. Micromedex
Healthcare series.
3. Lexi-Comp's Drug
Information
Handbook, 13th
Edition, Charles F,
Lacy, et al.2005
4. BNF 50, September
2005.
8
g. Ceftriaxone
h. Cefuroxime
i.
Ciprofloxacin
DRUG
STRENGTH/UNIT
500mg ( Rocephin )
STORAGE
Below 30ºC
750mg, 1.5gm (Zinacef )
100mg/50ml, 200mg/
100ml ( Ciprobay )
25ºC
Below 25ºC, Do not
freeze
Already in solution
6ml Water for Injection
for 750mg
RECONSTITUITION
STABILITY AFTER
RECONSTITUITION
5ml of solvent
6 hours at room
temperature
24 hours in refrigerator
15ml Water for Injection
for 1.5gm
5 hours at room
temperature
NA
48 hours in refrigerator
NS
NS
0.45%NS
D5%
D5%
Ringer lactate
IV bolus over 3-5
minutes.
IV Infusion over 60
minutes
NS
DILUENTS FOR
INFUSION
D5%
IV bolus over 2-4 minutes.
METHOD OF
ADMINISTRATION
IV infusion: 50 to 100ml
over at least 30
minutes.
IM ( Dissolve 500mg in
2ml 1% Lidocaine )
IV infusion : 50 to 100ml
over 30 minutes.
IM ( Dissolve 750mg in
3ml Water for
Injection )
Slow infusion into a
large vein minimize
local IV site
reactions
Neonates : IV infusion
should at least 60
minutes.
REMARKS
Dose exceed 1gm not be
given by IM.
Only use Calcium-free
infusion solutions.
REFERENCES
1. Product information
Rocephin.
2. Micromedex Healthcare
series.
3. Lexi-Comp's Drug
Information Handbook,
13th Edition, Charles F,
Lacy, et al.2005
4. BNF 50, September 2005.
1. Product information
Zinacef.
2. Micromedex
Healthcare series.
3. Lexi-Comp's Drug
Information
Handbook, 13th
Edition, Charles F,
Lacy, et al.2005
4. BNF 50, September
2005.
Ciprofloxacin solution
can be infused
directly or mixing
with compatible
infusion diluents.
1. Product
information
Ciprobay
2. Micromedex
Healthcare series.
3. Lexi-Comp's Drug
Information
Handbook, 13th
Edition, Charles F,
Lacy, et al.2005
4. BNF 50,
September 2005.
9
DRUG
STRENGTH/UNIT
j.
Amoxicillin and
Clavulanate Potassium
1.2gm
STORAGE
Below 25ºC.
RECONSTITUITION
WFI
STABILITY AFTER
RECONSTITUITION
Solution should be made
up to full infusion volume,
immediately after
reconstitution.
DILUENTS FOR
INFUSION
METHOD OF
ADMINISTRATION
k.
Cloxacillin
l.
Sulfamethoxazole
and Trimethoprim
500mg
480mg/5ml
Below 25ºC.
Below 30ºC, Do not
refrigerate. Protect from
light.
Already in solution
10ml Water for
Injection.
30 minutes after
reconstitution.
NA
NS
NS
D5%
D5%
IV Infusion: 50-100ml over
30-40 minutes
IV bolus over 3-5
minutes.
IV Infusion over 60-90
minutes
IV Infusion complete within
4 hours of reconstitution.
IV Infusion over 2030 minutes
WFI
NS
IM ( Dissolve 500mg
in 2.5ml Water for
Injection )
1 amp(5ml) to 125ml,
2amp(10ml) to 250ml,
3amp(15ml) to 500ml
diluent.
REMARKS
Fluid restriction required,
1amp(5ml) to 75ml diluent.
Less stable in infusions
containing glucose, dextran
or bicarbonate.
Infusion commenced within
30 minutes after
preparation.
Duration of infusion not
exceed 1.5 hours.
REFERENCES
1. Product information
Moxied-CLV
2. 2. BNF 50, September
2005.
1. Product
information
Monoclox
1. Product information DBL
2. Micromedex Healthcare
series.
3. Lexi-Comp's Drug
Information Handbook,
13th Edition, Charles F,
Lacy, et al.2005
4. BNF 50, September
2005.
10
m. Fusidic Acid
DRUG
n.
Gentamicin
o.
Imipenem with cilastatin
500mg ( Fucidin)
80mg/2ml
500mg
STORAGE
15 - 20ºC
Below 25ºC
15 - 30ºC
RECONSTITUITION
10ml of buffer solution
provided.
Already in solution.
10ml of diluent for infusion
NA
4 hours at room temperature
STRENGTH/UNIT
STABILITY AFTER
RECONSTITUITION
NA
24 hours in refrigerator
NS
NS
NS
D5% **
D5%
D5%
DILUENTS FOR
INFUSION
D10%
D5%NS
Mannitol 5% and 10%
METHOD OF
ADMINISTRATION
IV Infusion: 250 -500ml over
2-4 hours
Give through central venous
line to minimize venospams
and thrombophlebitis.
If superficial vein used,
infusion over 6 hours.
Never be injected undiluted.
REMARKS
IV infusion : 100-200ml over
30 minutes.
IV infusion : 500mg in 100m
diluent for infusion. Rate depend
on dose.
For extended-interval doses,
an infusion period of 60
minutes recommended.
Dose ≤ 500mg over 20 - 30
minutes , ≥ 500mg over 40 -60
minutes.
Must use the same diluent for
reconstitution and as infusion
solution.
Administer other
antibiotic at least 1 hour
before or after gentamycin.
Must not be given
intramuscularly or
subcutaneously.
** Precipitation may occur in
infusion solution pH below 7.4
( more acidic samples of
dextrose 5% )
1.
2.
3.
REFERENCES
Product information
Fucidin.
Micromedex
Healthcare series.
BNF 50, September
2005.
1.
2.
3.
4.
Product information
Garasent.
Micromedex
Healthcare series.
Lexi-Comp's Drug
Information
Handbook, 13th
Edition, Charles F,
Lacy, et al.2005
BNF 50, September
2005.
Reconstitution of Tienam : add ≈
10 ml of appropriate infusion
solution to vial. Shake well and
transfer the suspension to
infusion solution container.
Repeat with additional 10ml
infusion solution to ensure
complete transfer of vial contents
to infusion solution. Resulting
mixture should be agitated until
clear.
1.
2.
3.
4.
Product information
Tienam.
2. Micromedex
Healthcare series.
Lexi-Comp's Drug
Information Handbook,
13th Edition, Charles F,
Lacy, et al.2005
BNF 50, September
2005.
11
DRUG
STRENGTH/UNIT
p.
Meropenem
q.
500mg , 1gm ( Meronem )
Metronidazole
r.
Linezolid
500mg/100ml
600mg/300ml ( Zyvox)
15 - 30ºC. Protect from light
STORAGE
Below 30ºC
RECONSTITUITION
500mg - 10ml , 1gm - 20ml of
NS or D5%
Already in solution
15 - 30ºC. Protect from
light.Keep in overwrap until
ready to use.
Already in solution
NS : 2 hours at RT, 18 hours
in refrigerator.
NA
NA
NA
NA
IV infusion : 100ml over 20 30 minutes.
IV infusion : 30 -120 minutes.
Avoid contact
between drug and aluminium
in infusion set.
Do not mix or infuse with other
medications.
STABILITY AFTER
RECONSTITUITION
D5% : 1 hours at RT, 8 hours
in refrigerator.
NS
DILUENTS FOR
INFUSION
D5%
IV bolus : 10ml of WFI per
500mg over 5 minutes.
METHOD OF
ADMINISTRATION
REMARKS
REFERENCES
IV infusion : 50-200ml over 15
- 30 minutes.
Recommended to use freshly
prepared solution of
Meropenem.
1. Product information
Meronem.
2. Micromedex Healthcare
series.
3. Lexi-Comp's Drug
Information Handbook,
13th Edition, Charles F,
Lacy, et al.2005
4. BNF 50, September
2005.
1.
2.
3.
Product information .
Micromedex
Healthcare series.
Lexi-Comp's Drug
Information
Handbook, 13th
Edition, Charles F,
Lacy, et al.2005
Yellow color of the injection may
intensify over time without
affecting potency.
1. Micromedex Healthcare
series.
2. Lexi-Comp's Drug
Information Handbook,
13th Edition, Charles F,
Lacy, et al.2005
12
s.
Polymixin B
t. Sulbactam
Sodium/Ampicilin
Sodium
1.5gm
DRUG
STRENGTH/UNIT
500,000 units
u. Sulbactam
Sodium/Cefoperazone
Sodium
1gm ( Sulperazon)
STORAGE
15 - 30ºC
Below 25ºC
Below 25ºC
RECONSTITUITION
500mg - 10ml , 1gm - 20ml of
NS or D5%
3.2ml Water for Injection
3.4ml Water for Injection, NS,
D5%
Stability at 25ºC and 4ºC
depends on concentration of
solution prepared. For IM
administration, used within 1
hour of reconstitution.
Water for Injection
Stability at 25ºC and 4ºC
depends on concentration of
solution prepared. For IM
administration, used within 1
hour of reconstitution.
STABILITY AFTER
RECONSTITUITION
72 hours in refrigerator.
D5%
Water for Injection
NS
D5%
NS
D5%
DILUENTS FOR
INFUSION
METHOD OF
ADMINISTRATION
Lactated ringer
IV infusion : 300-500ml over
60 - 90 minutes.
IV bolus : slowly over 10 -15
minutes
IV bolus : over minimum 3
minutes
IM : 2ml Water for Injection,
NS, 1% procaine solution.
IV infusion : 50-100ml over
15 - 30 minutes.
IV infusion : 20ml over 15 - 60
minutes.
IM : 3.2ml Water for Injection
or 2% Lidocaine
IM : 3.2ml Water for Injection,
and further diluted with 2%
Lidocaine.
IV infusion : dilute using
diluents (NS,Water for
Injection, Lactated ringer) to a
maximum concentration of
45mg/ml.
Must use the same diluent for
reconstitution and as infusion
solution.
Intrathecal : 10ml
physiological solution
Intrathecal is for meningeal
infection.
REMARKS
REFERENCES
May cause extravasation.
Monitor the IV site, rotate
infusion site frequently.
1. Micromedex Healthcare
series.
2. Lexi-Comp's Drug
Information Handbook,
13th Edition, Charles F,
Lacy, et al.2005
IV infusion : dilute using D5%
to a maximum concentration
of 30mg/ml. Administer within
2 hours.
1.
2.
3.
Product information
Easyn.
Micromedex Healthcare
series.
Lexi-Comp's Drug
Information Handbook,
13th Edition, Charles F,
Lacy, et al.2005
1.
2.
Product information Easyn.
Micromedex Healthcare
series
13
DRUG
v.
Piperacillin / Tazobactom
w.
Vancomycin
4.5gm ( Tazocin )
500mg
STORAGE
Below 25ºC
Below 25ºC. Protect from light.
RECONSTITUITION
20ml of Water for Injection, NS
STRENGTH/UNIT
STABILITY AFTER
RECONSTITUITION
DILUENTS FOR
INFUSION
Freshly prepared prior to use.
24 hours at room temperature
48 hours in refrigerator
Water for Injection
NS
NS
D5%
D5%
Slow Iv injection : 3 - 5 mins
METHOD OF
ADMINISTRATION
10ml Water for Injection.
IV Infusion : dilute with infusion fluid up
to 5mg/ml over 1 hour.
IV Infusion :- 50 ml - 150ml for 20 - 30
mins.
IM : 2.25g with 4ml WFI
IV infusion concentration can
increased to 10mg/ml in fluid
restriction, but increased risk of
infusion-related effects.
IV infusion : maximum infusion volume with
WFI is 50ml.
REMARKS
During IV infusion, discontinue primary
infusion solution.
Rate of administration not
exceed 10mg/min for doses over
500mg.
Use continuous infusion if
intermittent not feasible.
If Red-man syndrome
appears, slow infusion rate to 1½ - 2
hours and increase dilution volume.
REFERENCES
1. Product information Tazocin.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information
Handbook, 13th Edition, Charles F,
Lacy, et al.2005
4. BNF 50, September 2005.
1.
2.
3.
4.
Product information Vancotex.
Micromedex Healthcare series.
Lexi-Comp's Drug Information
Handbook, 13th Edition, Charles
F, Lacy, et al.2005
BNF 50, September 2005
14
2.1.3
Antifungal
DRUG
STRENGTH/UNIT
STORAGE
RECONSTITUITION
STABILITY AFTER
RECONSTITUITION
a.
Amphotericin B
b.
c.
Voriconazole
500mg ( Fungizone)
100mg/50ml ( Diflucan )
200mg ( Vfend)
Stored in refrigerator
Below 30ºC, Do not
refrigerate.
15-30ºC
Already in solution
19ml Water for Injection.
NA
24 hours at 2- 8ºC
NS
NS
Ringer's Solution
D5%
Hartmann's solution
Compound Sodium Lactate
Protected against exposure to
light
10ml Water for Injection
24 hours at room temperature
1 week in refrigerator
D5%
DILUENTS FOR
INFUSION
Fluconazole
Infusion concentration is
0.1mg/ml
D20%
Slow Intravenous infusion : 2 - 6
hours
IV Infusion over 1-2 hours
IV infusion: dilute to
concentration of 0.5-5mg/ml
over 1 -2 hours.
Test dose : 1mg in 20ml D5% ,
administer over 20-30 minutes
Infusion rate do not exceed
200mg/hr
Maximum rate :3mg/kg/hour.
Do not reconstitute with NS
Fluconazole is
formulated in 0.9% sodium
chloride solution, each
100mg containing 7.5mmol
of sodium.
METHOD OF
ADMINISTRATION
Begin infusion immediately after
dilution and protect from light.
REMARKS
Patient requiring
sodium or fluid restriction,
consideration given to rate
of fluid administration.
REFERENCES
1. Product information
Fungizone.
2. Micromedex Healthcare
series.
3. Lexi-Comp's Drug
Information Handbook, 13th
Edition, Charles F, Lacy, et
al.2005
4. BNF 50, September 2005.
1.
2.
3.
4.
Product information
Diflucan.
Micromedex Healthcare
series.
Lexi-Comp's Drug
Information Handbook,
13th Edition, Charles F,
Lacy, et al.2005
BNF 50, September
2005.
1.
2.
3.
4.
Product information
Vfend.
2. Micromedex
Healthcare series.
Lexi-Comp's Drug
Information
Handbook, 13th
Edition, Charles F,
Lacy, et al.2005
BNF 50, September
2005.
15
2.1.4 Antiviral
DRUG
STRENGTH/UNIT
Acyclovir
250mg
STORAGE
Below 25˚C, Protect from light
RECONSTITUITION
10ml Water for Injection
12 hours at room temperature
STABILITY AFTER RECONSTITUITION
Do not refrigerate
D5%
NS
DILUENTS FOR INFUSION
Infusion concentration should be approximately 7mg/ml
or less.
IV infusion (over 1 hour)
METHOD OF ADMINISTRATION
Should not be given intramuscularly, subcutaneously, locally
or intra-ocularly.
REMARKS
REFERENCES
Rapid infusion is not recommended to avoid possible renal
tubular damage.
1. Product information Klovireks-L.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition,
Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
16
2.1.5
Anticoagulants
Heparin
DRUG
STRENGTH/UNIT
1000 IU/ml , 5000 IU/ml.
Fondaparinux ( Arixtra )
2.5mg/0.5ml
Enoxaparin Sodium (
Clexane )
40mg/0.4ml ,
60mg/0.6ml
Below 25ºC. Do not freeze.
Below 25ºC.
Already in solution.
Already in solution.
STORAGE
15ºC - 30 ºC. Protect from
light.
RECONSTITUITION
Already in solution.
STABILITY AFTER
RECONSTITUITION
NA
NA
NS
NA
NA
Subcutaneous.
Subcutaneous.
Must not be administered
by IM.
Do not administer by IM
route.
Do not mix with other
injections or infusions.
Pre-filled syringes are
ready-to-use.
NA
D5%
DILUENTS FOR INFUSION
IV infusion : minimum volume
250ml D5%.
METHOD OF
ADMINISTRATION
Subcutaneous.
Should be avoided in children
below 2 years old and not
used in neonates.
REMARKS
Do not administer IM due to
pain, irritation and hematoma
formation.
1.
2.
Product information
Heparinol.
Micromedex
Healthcare series.
3.
Lexi-Comp's Drug
Information
Handbook, 13th
Edition, Charles F,
Lacy, et al.2005
4.
BNF 50, September
2005.
REFERENCES
Prefilled syringe is
designed with an automatic
needle protection system to
prevent needle stick
injuries.
1. Product
information
Arixtra.
2. Micromedex
Healthcare series.
3. Lexi-Comp's Drug
Information
Handbook, 13th
Edition, Charles F,
Lacy, et al.2005
4. BNF 50,
September 2005.
1.
2.
3.
4.
Product
information
Clexane.
Micromedex
Healthcare
series.
Lexi-Comp's
Drug
Information
Handbook,
13th Edition,
Charles F,
Lacy, et
al.2005
BNF 50,
September
2005.
17
2.1.6
Antiepileptics
DRUG
a.
Phenytoin
b.
Phenobarbitone
c.
Sodium Valproate
250mg/ Dilantin
200mg/ml
400mg (Epilim)
Between 15°C to 30°C (Do not
freeze)
Protect from light
Below 25°C
STORAGE
RECONSTITUITION
Already in solution
Already in solution
Reconstitute with solvent
provided
STRENGTH/UNIT
STABILITY AFTER
RECONSTITUITION
DILUENTS FOR INFUSION
24 hours at 2°C to 8°C
NA
NA
NS
NS
NS
Dilute with 50-100ml NS to
make a 1mg/ml solution. Max
concentration is 10mg/ml.
D5%
D5%
IV infusion: Dilute with at
least an equal volume of
fluid.
Dilute with at least 50ml of
NS or D5%
IV: Over 3 to 5 minutes.
Not to exceed 60mg/min.
IV infusion: Administer as
60 minutes infusion. Not to
exceed 20mg/min
IV: Rate not exceeding
50mg/minute. Sensitive patient
eg. Elderly with cardiovascular
condition should receive more
slowly (eg. 20mg/minute)
METHOD OF
ADMINISTRATION
Recommended to give through
a 0.22-0.5 micron in-line filter
due to high potential of
precipitation.
Finish infusion within 1 hour
after mixing the solution.
IM administration is approved
but not recommended due to
erratic absorption
IV infusion: eg. Emergency
in status epilepticus
IM
IV: (Loading dose) single
doses up to 15mg/kg has
been administered as rapid
infusion over 5-10 minutes.
S/C
Avoid intra-arterial injection
Divide total daily dose if
exceeds 250 mg/day
1. Product information
(Phenobarbital Sodium
Injection).
2. Micromedex
Healthcare series.
3. Lexi-Comp's Drug
Information Handbook,
13th Edition, Charles F,
Lacy, et al.2005
1. Product information
(Epilim Injection).
2. Micromedex
Healthcare series.
3. Lexi-Comp's Drug
Information Handbook,
13th Edition, Charles
F, Lacy, et al.2005
REMARKS
The solution is vesicant. Avoid
extravasation.
REFERENCES
1. Product information
(Dilantin Injection).
2. Micromedex Healthcare
series.
3. Britisn National Formulary
56
4.
4. Lexi-Comp's Drug
5.
Information Handbook, 13th
Edition, Charles F, Lacy, 6.
et
al.2005
18
d.
DRUG
Diazepam
10mg/2ml (Valium)
STRENGTH/UNIT
e.
Thiopentone (Thiopental)
500 mg (Pentotex)
Below 25°C
STORAGE
Room temperature
RECONSTITUITION
Already in solution
STABILITY AFTER
RECONSTITUITION
NA
Use immediately. Discard any
unused portion after 24 hours.
WFI
DILUENTS FOR INFUSION
Recommended to give alone
NS
But stable in NS, D5%. Use immediately
after mixing.
D5%
Dilute 10 mg with 200-250ml NS or D5%
IM
METHOD OF ADMINISTRATION
IV injection: Rate not exceeding 5mg/min
IV infusion: Rate not exceeding 5mg/min
Infusion rate exceeding 5mg/ min may
cause apnea, venous thrombosis,
REMARKS
IV infusion: as 0.2-0.4% solution.
Thiopental sodium preparation may
be given rectally as solution or
suspension
thrombophlebitis and hypotension. Avoid
extravasation.
1.
REFERENCES
IV slow: Over 20 to 40 seconds of
2.5% solution. (occasionally as 0.5%
solution)
2.
3.
4.
Product information
( Diazepam Injection).
Micromedex Healthcare series.
Britisn National Formulary 56
Lexi-Comp's Drug Information
Handbook, 13th Edition, Charles
F, Lacy, et al.2005
1. Product information
( Pentotex Injection).
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information
Handbook, 13th Edition, Charles
F, Lacy, et al.2005
19
2.1.7
Antihypertensive
a.
DRUG
Frusemide
b.
Isosorbide Dinitrate
20mg/2ml
10mg/10ml
Below 30˚C.
STORAGE
Below 25˚C. Protect from light. Do not use
if solutions yellow in colour. Refrigeration
may result in precipitation. However,
resolubilization at room temperature or
warming may be performed without
affecting the stability of frusemide.
RECONSTITUITION
Already in solution
STABILITY AFTER
RECONSTITUITION
24 hours. Protect from light.
STRENGTH/UNIT
NS
Lactated Ringer's
D5%
NS
D5%
Recommended concentration:
0.1mg/ml ( 10mg/amp in 100 ml
diluents for infusion) OR 0.2 mg/ml (
10mg/amp in 50 ml diluents for
infusion).
IM
Continuous IV infusion.
Direct IV injection (slowly over 1-2 mins)for doses<120mg
It should always be administered as
an intravenous admixture and should
never be injected directly.
IV infusion or continuous IV infusion: rate of
infusion should not exceed 4mg/min.
Unstable in acidic media but very stable in
basic media.
REMARKS
1.
2.
REFERENCES
24 hours.
.
DILUENTS FOR INFUSION
METHOD OF ADMINISTRATION
Already in solution
3.
4.
5.
Micromedex Healthcare series.
Pocket Guide to Injectable Drugs.
Companion to the handbook on
Injectable Drugs.
British National Formulary (BNF). 55
edition. March 2008.
Drug Information Handbook. 13th
edition. 2005-2006. Lexi-comps.
Product information Frusemide
Injection - AKOSET®. (Duopharma).
1-10mg/hr
Isosorbide dinitrate adsorbed to some
extent by PVC infusion containers.
Preferably use glass or polyethylene
container.
1. Micromedex Healthcare series.
2. British National Formulary (BNF).
55 edition. March 2008.
3. Product information Isosorbide
Injection - Isoket®. (Schwardz
Pharma).
20
DRUG
STRENGTH/UNIT
c.
Labetalol
25mg/5ml
STORAGE
Below 30˚C. Protected from light.
RECONSTITUITION
Already in solution
STABILITY AFTER
RECONSTITUITION
Within 24 hours.
D5%
Below 30˚C. Protected from light.
Dissolve with 1ml water for injection
Slow IV Injection: 10ml NS
IV Infusion: 500ml NS or
Ringer's solution
Recommended concentration: 1mg/ml.
Suggested volume: 200ml (200mg/40ml
labetalol injection into 160ml of compatible
diluent )
IV bolus injection - slowly over 2 minutes.
May repeat 40-80mg at 10 min intervals, up
to 300mg total dose.
METHOD OF ADMINISTRATION
20mg
Within 24 hours.
NS
DILUENTS FOR INFUSION
d. Hydralazine
Continuous IV infusion - initial rate of
2mg/min, titrate to response up to 300mg
total dose.
Incompatible with Sodium Bicarbonate and
alkaline solution. Precipitation may occur.
IM, Slow IV Injection over 1 min. 1020mg 4-6 hours as needed.
IV Infusion: Initially 200mcg300mcg/min; maintenance 50150mcg/min
D5% decrease stability of
Hydralazine
REMARKS
REFERENCES
1. Micromedex Healthcare series.
2. Pocket Guide to Injectable Drugs.
Companion to the handbook on
Injectable Drugs.
3. British National Formulary (BNF). 55
edition. March 2008.
4. Product information Labetalol Injection
(Trandate®).
5. Drug Information Handbook. 13th
edition. 2005-2006. Lexi-comps.
1. Micromedex Healthcare series.
2. British National Formulary (BNF).
55 edition. March 2008.
3. Product information Hydralazine
Injection (Apresoline®).
4. Drug Information Handbook. 13th
edition. 2005-2006. Lexi-comps.
21
2.1.8
Gastrointestinal
DRUG
a.
Ranitidine
Esomeprazole
50mg/2ml
STRENGTH/UNIT
STORAGE
Below 30˚C, Protect from light. Solution is a clear,
colorless to yellow solution; slight darkening does not
affect potency.
RECONSTITUITION
Already in solution
STABILITY AFTER
RECONSTITUITION
Within 48 hours at room temperature.
-
DILUENTS FOR
INFUSION
-
METHOD OF
ADMINISTRATION
b.
-
-
D5%
NS
Intermittent bolus injection: dilute to maximum
of 2.5mg/ml
- Intermittent infusion: dilute to maximum of
0.5mg/ml
IM: Injection is administered undiluted.
IV: must be diluted. May be administered IVP or
IVPB or continuous IV infusion.
Direct IV injection/IVP: 50mg diluted to a total of 20
ml with compatible infusion solution and given over
at least 5 mins. (Administration not greater than
4ml/min.)
Intermittent infusion/ IV PB : 50mg added to 100ml
of compatible solution and administer over 15-20
mins. (Administration not greater than 5-7ml/min).
Continuous IV infusion: 150mg diluted in 250ml of
compatible IV solution and infused at 6.25mg/hr for
24hrs
REMARKS
1.
2.
3.
REFERENCES
4.
5.
Product information Gastril Injection. (Duopharma).
Micromedex Healthcare series
Pocket Guide to Injectable Drugs. Companion to
the handbook on Injectable Drugs. 13 th edition.
Lawrence A. Trissel. 2005.
Drug Information Handbook. 13th edition. 20052006. Lexi-comps
British National Formulary (BNF). 55 edition. March
2008.
Below 30˚C. Protect from light. However,
can be stored exposed to normal in door
light outside the box for up to 24 hours.
5ml of NS (The degradation of
reconstituted solution is highly pH
dependent. It must only be reconstituted
in the specified volume of NS).
Reconstituted solution for injection: With
5ml of NS and store within 12 hours at
room temperature. Refrigeration is not
required.
Reconstitution solution for infusion: With
5ml of NS, Lactate Ringer's, D5% then
further dilute to final volume of 50ml
solution. Storage for 6hours (D5%) and 12
hours (NS and Lactate Ringer's) in room
temperature. Refrigeration is not required.
NS
Lactate Ringer's
D5%
IV injection: over a period of at least 3
mins.
IV infusion: over a period of 10-30 mins.
The stability of esomeprazole in aqueous
solution is strongly dependent upon pH.
The rate of degradation increase in
response of decreasing pH.
1. Product information Nexium Injection.
(AstraZeneca).
2. Micromedex Healthcare series.
3. British National Formulary (BNF). 55
edition. March 2008.
22
2.1.9 Inotropes
a.
DRUG
Adrenaline
1.8mg/1ml
STRENGTH/UNIT
STORAGE
15˚C - 30˚C. Protect from light.
RECONSTITUITION
Already in solution
STABILITY AFTER
RECONSTITUITION
Within 24hrs at room temperature and refrigerate.
Oxidation turns drug pink, then a brown color; solution
should not be used if they are discoloured or contain a
precipitate.
b.
Dobutamine
250mg/20ml
Below 25˚C, Protect from light
Already in solution
IV: NS
IV:D5%
Recommended: IV infusion: 1mg in 250ml of
NS
Intratracheal: dilute in NS or WFI. Absorption
is greater with distilled water, but causes
more adverse effects on PaO2.
DILUENTS FOR
INFUSION
Within 24 hours. A pink discoloration may
form due to slight oxidation of the drug but
no significant drug loss within
recommended times. If refrigerated,
solution can be stored up to 48 hours.
D5%
NS
Must be diluted to a concentration of not
more than 5mg/ml before use.
If higher
concentration is used eg 500mg
dobutamine in 50 cc diluents of infusion. It
should be protected from light.
Recommended: ( eg. 250mg-500mg of
dobutamine in 500 cc diluents of infusion)
SC, IM, slow IV injection, IV infusion, intracardiac
injection, intratracheal injection.
IM injection into the buttocks should be avoided.
METHOD OF
ADMINISTRATION
IV infusion (mcg/kg/min)
IV infusion (mcg/min): 1-10mcg/min
REMARKS
1.
2.
3.
REFERENCES
4.
5.
Central line administration if IV infusion. Avoid
extravasation.
Do not add to 5% sodium bicarbonate or
other strongly alkaline solution.
Incompatible with bicarbonate solution and other
alkaline solutions.
Should not be used in conjunction with
other agents or diluent containing sodium
bisulphites and ethanol.
Product information Adrenaline Injection BP.
(Duopharma)
Micromedex Healthcare series.
Pocket Guide to Injectable Drugs. Companion to
the handbook on Injectable Drugs. 13 th edition.
Lawrence A. Trissel. 2005.
Drug Information Handbook. 13th edition. 20052006. Lexi-comps
British National Formulary (BNF). 55 edition.
March 2008.
1. Product information Mobitil Injection.
(Duopharma)
2. Micromedex Healthcare series.
3. Pocket Guide to Injectable Drugs.
Companion to the handbook on
Injectable Drugs. 13 th edition.
Lawrence A. Trissel. 2005.
4. Drug Information Handbook. 13th
edition. 2005-2006. Lexi-comps
5. British National Formulary (BNF). 55
edition. March 2008.
23
c.
DRUG
Dopamine
200mg/5ml
STRENGTH/UNIT
STORAGE
Below 25˚C. Protected from light
RECONSTITUITION
Already in solution
STABILITY AFTER
RECONSTITUITION
Within 24 hours. Do not use the injection if it is
darker than slightly yellow or discoloured in any
other way.
d.
Noradrenaline
4mg/4ml
Below 25˚C, Protect from light
Already in solution
DILUENTS FOR
INFUSION
D5%
Within 24 hours with protection from light.
Solution gradually darkens with exposure to
light or air. Do not use if it is discoloured or
contains a precipitate.
D5%
NS
D5%in NS
Injection should be diluted before
administration.
NS alone is not recommended.(Product
Information Levophed Injection). (Lack of
oxidation protection).
Recommended: 200mg or 400mg of dopamine in
250ml or 500ml diluents for infusion. (Micromedex,
Handbook of Injectable Drugs). Max concentration:
3.2mg/ml (BNF)
IV infusion (mcg/kg/min)
METHOD OF
ADMINISTRATION
Must be diluted before infusion.
Recommended:
a. 4-8mg in 250-1000ml of diluents for
infusion. ( Micromedex). (Handbook of
Injectable drugs).
b. 4mg in 50ml of diluents for infusion. (BNF)
IV infusion (mcg/kg/min)
Do not add dopamine in any alkaline solution. It is
inactivated in alkaline solution. Incompatible with
bicarbonate
It is also sensitive to oxidizing agent and iron salts.
IV infusion must be given into a large vein.
Avoid extravasation.
Avoid extravasation. Administer into the large vein.
Avoid contact with iron salts, alkalis, or
oxidizing agents.(Product Information
Levophed).
REMARKS
1.
2.
3.
REFERENCES
4.
5.
Product information Loxin Injection
(Duopharma)
Micromedex Healthcare series.
Pocket Guide to Injectable Drugs. Companion
to the handbook on Injectable Drugs. 13 th
edition. Lawrence A. Trissel. 2005.
Drug Information Handbook. 13th edition. 20052006. Lexi-comps
British National Formulary (BNF). 55 edition.
March 2008.
Incompatible with bicarbonate solution.
1. Product information Loxin Injection
(Duopharma)
2. Micromedex Healthcare series.
3. Pocket Guide to Injectable Drugs.
Companion to the handbook on
Injectable Drugs. 13 th edition. Lawrence
A. Trissel. 2005.
4. Drug Information Handbook. 13th edition.
2005-2006. Lexi-comps
5. British National Formulary (BNF). 55
edition. March 2008.
24
2.1.10 Miscellaneous
DRUG
STRENGTH/UNIT
STORAGE
RECONSTITUITION
STABILITY AFTER
RECONSTITUITION
DILUENTS FOR INFUSION
a.
Parentrovite
5ml x 2 ampoules (1 pair)
(P-Trovite)
b.
Potassium chloride
c.
Pralidoxime
10% W/V, 10ml
500mg/20ml (Pampara)
Protect from light
Below 25˚C
Below 28˚C, Protect
from light,
Already in solution
Already in solution
Already in solution
N/A
NA
NA
NS (for the treatment of
hypokalemia)
For IV intermittent: as
5% to 10% solution (the
product is 2.5% in
strenght, so can be
readily administered)
Compatible with
commonly used
intravenous solutions
Maximum concentration
recommended for peripheral
line is 6g/L. (can dilute up to 3
gm KCL in 500ml NS).
For IV infusion: Dilute in
100ml NS
For fluid restricted patient
with central line, maximum
concentration recommended
is 11g/L.
The content of each
ampoule (No 1 and No 2)
should be mixed prior to
injection.
METHOD OF ADMINISTRATION
Although compatible with
commonly used
intravenous solutions, it is
recommended
parentrovite is given by
slow injection
REMARKS
Product information
(P-trovitel).
REFERENCES
For fluid restricted patient
with central line, maximum
concentration recommended
is 11g/L.
IV intermittent : over 5
to 10 minutes.
IIV infusion: over 15 to
30 minutes
S/C
IM
Use with caution in patients
with cardiac disease
Maximum
recommended daily
dose is 12 gm
1. Product information
(Potassium chloride 10%
W/v 10ml).
2. Micromedex Healthcare
series.
3. British National
Formulary 56.
4. Lexi-Comp's Drug
Information Handbook,
12th Edition, Charles F,
Lacy, et al.2003
1. Product information
(Pampara
injection).
2. Micromedex
Healthcare series.
3. British National
Formulary 56.
4. Lexi-Comp's Drug
Information
Handbook, 12th
Edition, Charles F,
25
Lacy, et al.2003
DRUG
d.
N-Acetylcysteine
2gm/10ml
STRENGTH/UNIT
STORAGE
RECONSTITUITION
STABILITY AFTER
RECONSTITUITION
DILUENTS FOR INFUSION
METHOD OF ADMINISTRATION
e.
Piracetam
f.
Desmopressin
1gm/5ml
4mcg/ml (Minirin)
Below 25˚C,
15°C to 25°C
2°C to 8°C
Already in solution
Already in solution
Already in solution
NA
NA
NA
5gm/25ml
D5% (Preferable)
NS
NS
IV infusion: Dilute in 50ml
NS
PCM poisoning: 150mg/kg in
200ml, then 50mg/kg in
500ml followed by 100mg/kg
in 1000ml.
PCM poisoning: IV infusion
of 150mg/kg over 15 to 60
minutes, then IV infusion of
50mg/kg over 4 hours
followed by IV infusion of
100mg/kg over 16 hours.
S/C
IM
IV infusion over 15 to 30
minutes
Prevention of radiocontrastinduced renal dysfunction
(unlabeled use): IV infusion
REMARKS
REFERENCES
For PCM poisoning patient
less than 40kg and those
requiring fluid restriction, the
volume of diluent could be
adjusted as needed to avoid
fluid overload.
1. Product information
(Hidonac NAcetylcysteine).
2. Micromedex Healthcare
series.
3. Britisn National
Formulary 56
NA
1. Product information
(Nootropil Injection).
2. Micromedex
Healthcare series.
1.
Product information
( Minirin injection).
2.
Britisn National
Formulary 56
Micromedex
Healthcare series
3.
26
4. Lexi-Comp's Drug
Information Handbook,
12th Edition, Charles F,
Lacy, et al.2003
DRUG
STRENGTH/UNIT
STORAGE
g.
Haloperidol
4.
h.
Calcium gluconate
Lexi-Comp's Drug
Information
Handbook, 13th
Edition, Charles F,
Lacy, et al.2005
i.
Dantrolene
5mg/ml
10ml
20 mg (Dantrium)
Below 25°C. Protect from
light.
Below 30°C.
Below 30 °C. Do not
refrigerate. Protect from
light.
60ml WFI (shake until
solution is clear)
RECONSTITUITION
STABILITY AFTER
RECONSTITUITION
Already in solution
Already in solution
NA
NA
Use within 6 hours at
room temperature.
D5%
NOT to be mixed with
other intravenous
infusions.
D5%
DILUENTS FOR INFUSION
If necessary transfer
individual vials into a
larger volume sterile IV
plastic bag. Do not
transfer into glass
bottle. Precipitation may
occur.
IV infusion : Dose of 0.5mg100mg in 50ml-100ml D5%
NS
IV infusion: Dilute to a
maximum concentration of
50mg/ml (eg. 1gm in 20ml)
IV slow bolus: Maximum
rate of 50mg/minute
IV push: In malignant
hyperthemia crisis
IV infusion: The diluted
solution of 50mg/ml to be
infused over 1 hour
IV infusion: Over 1 hour
in prevention of
malignant hyperthemia
Decanoate form should
never be administered IV
(IM only)
Has rarely been given by
IM and S/C, but not
recommended because the
risk of tissue necrosis.
Solution is high pH and
there is possibility for
tissue necrosis, avoid
extravasation.
1. Product information
(Manace injection 5mg)
2. Britisn National
Formulary 56
3. Micromedex Healthcare
series.
4. Lexi-Comp's Drug
1. Product information
(Calcium gluconate
injection)
2. Britisn National
Formulary 56
3. Micromedex Healthcare
series.
1. Product information
(Dantrium
Intravenous)
2. Micromedex
Healthcare series.
3. Lexi-Comp's Drug
Information
IM
METHOD OF ADMINISTRATION
IV bolus
IV infusion of 50ml-100ml
diluted solution with the rate
of 3-25mg/hour
REMARKS
REFERENCES
27
Information Handbook,
12th Edition, Charles F,
Lacy, et al.2003
DRUG
STRENGTH/UNIT
STORAGE
RECONSTITUITION
STABILITY AFTER
RECONSTITUITION
j.
Mannitol
20% (100gm/500ml)
4. Lexi-Comp's Drug
Information Handbook,
12th Edition, Charles F,
Lacy, et al.2003
k.
Potassium dihydrogen
phosphate
10mmol/10ml (1.361g)
Handbook,
l.
Human Normal
Immunoglobulin
Intragam 3g (50ml)
Between 15°C to 30°C. Do
not freeze.
Below 25°C.
Already in solution.
Already in solution
2°C to 8°C. Do not freeze.
Once removed from
refrigeration, store below
25°C and use within 3 months
Already in solution
NA
NA
NA
D5%
Can be administered
undiluted
NS
Must be diluted before use
DILUENTS FOR
INFUSION
METHOD OF
ADMINISTRATION
NA
IV doses should be
incorporated into patient's
maintenance IV fluid.
Intermittent IV infusion should
be reserved for severe
depletion patient under ECG
monitoring.
Test dose (to assess
adequate renal function): IV
over 3-5 minutes
IV infusion, slow: administer
over 6 to 12 hours. Minimum
infusion time is 4 hours.
IV infusion (eg. Cerebral
edema or increased
intraocular pressure): over
more than 30 minutes
Use a filter when infuse
mannitol solution of
concentration of 20% or
more.
REMARKS
Incompatible with calcium or
magnesium containing
solutions.
Or can be diluted with up to 2
parts of NS or D5%
IV infusion: can be given
undiluted. Start infusion at the
rate of 1ml/minute. After 15
minutes, the rate can be
gradually increased to a
maximum of 3 to 4ml/minute.
Reducing the rate in elderly
and in patients with preexisting renal disease should
be considered.
Infusion which is too rapid
may cause flushing and
changes in heart rate and
blood pressure. Prolonged
administration (over 6 hours)
using larger dose (greater
than 0.4g/kg) may result in
thrombophlebitis at the
infusion site.
28
1.
2.
REFERENCES
DRUG
Micromedex Healthcare
series.
Lexi-Comp's Drug
Information Handbook,
12th Edition, Charles F,
Lacy, et al.2003
m. Hydrocortisone
1. Product information
(Potassium Dihydrogen
Phosphate injection)
2. Lexi-Comp's Drug
Information Handbook, 12th
Edition, Charles F, Lacy, et
al.2003
n.
Methylprednisolone
Product information
(Intragam).
o.
Dexamethasone sodium
phosphate
8mg/2ml
100mg
1gm (Solu-Medrol)
Below 25˚C
Below 25°C
Below 25˚C, Protect from light.
RECONSTITUITI
ON
2ml WFI
Reconstitute with the diluent (15.6ml
WFI+ Benzyl alcohol) provided
Already in solution
STABILITY
AFTER RECONSTITUITION
Use immediately after
reconstitute
48 hours at temperature below 25°C
NA
D5%
D5%
D5%
NS
NS
NS
STRENGTH/UNI
T
STORAGE
DILUENTS FOR
INFUSION
IV infusion: Reconstituted
solution is then further
diluted to 1mg/ml
IV infusion: Dilute content of vial
with 50-100ml of diluents
Diluted solution is stable for 24
hours in room temperature or 2
days in fridge
IM
IM
IM
IV injection: Over 30
seconds to several
minutes depending on the
dose
IV bolus: The reconstitued solution
can be given undiluted. Preferred for
emergency. Only for low dose
(<125mg) - over 5 to 15 minutes and
moderate dose (below 250mg) - over
15 to 30 minutes. Maximum
concentration: 125mg/ml
IV injection: Administer as IV
bolus over 5-10 minutes or can
be administered through tubing
IV infusion: Over 20 to 30
minutes
METHOD OF
ADMINISTRATI
ON
IV infusion: Of diluted solution
IV infusion : Dilute the reconstitued
solution with D5% or NS. For high
dose (more than 250mg) - over at
least 30 minutes. Dose of more than
1 gm - over 1 hour
Special notes: For acute spinal cord
injury, start with IV bolus. After 45
minutes pause, followed by IV
infusion of 5.4mg/kg/hour for 23
hours.
29
REMARKS
REFERENCES
DRUG
STRENGTH/UNIT
none
1. Product information
1. Product information (Solumedrol)
( Stricort 100mg)
2. Lexi-Comp's Drug Information
2. Lexi-Comp's Drug
Handbook, 12th Edition, Charles
Information Handbook,
F, Lacy, et al.2003
12th Edition, Charles F,
3. Britisn National Formulary 56
Lacy, et al.2003
4. Micromedex Healthcare series.
3. British National
Formulary 56
q. Tranexamic acid
p. Vitamin K
(Phytomenadione)
10mg/ml (Kisan)
1g/10ml
STORAGE
RECONSTITUITION
STABILITY AFTER
RECONSTITUITION
DILUENTS FOR
INFUSION
1. Product information
(Penatone Injection).
2. British National Formulary 56
3. Micromedex Healthcare series.
4. Lexi-Comp's Drug Information
Handbook, 13th Edition, Charles
F, Lacy, et al.2005
r.
Sodium bicarbonate
8.4% (10mmol/10ml)
Below 25˚C. Protect from light.
Between 15˚C to 30˚C. Protect
from light.
Aiready in solution
Aiready in solution
NA
NA
NA
NS
WFI
D5%
NS
Below 25˚C. Protect from
light.
Aiready in solution
NS
D5%
D5%
S/C: Dilute to isotonicity
(1.5%) by adding 1ml of 8.4%
solution into 4.6ml WFI or NS
or D5%
IM
METHOD OF
ADMINISTRATION
Rapid IV bolus injection is
associated with high incidence of
perianal discomfort
Slow IV: Reserved for
potentially fatal haemorrhage.
Maximum per dose-20 mg and
maximum total doses - 40mg.
IV injection at rate not
exceeding 1mg/minute.
Slow IV: Do not inject more rapidly
than 1ml/min
IV continous infusion: eg. Local
fibrinolysis - 25 to 50mg/kg over
24 hours or post operation on
heart -1mg/kg/hour for 5 to 6
hours.
IV: of undiluted solution. Rate
not exceeding 10mEq/minute
(equivalent to 10ml/minute)
IV: of diluted solution
S/C: Of diluted to 1.5%
solution.
IV infusion
S/C
REMARKS
Injectable solution may be
given orally, undiluted.
Sodium bicarbonate solution
8.4% contains 1 mEq/ml
bicarbonate (and sodium)
30
REFERENCES
1. Product information ( Kisan
10mg/ml)
2. British National Formulary
56
3. Lexi-Comp's Drug
Information Handbook, 12th
Edition, Charles F, Lacy, et
al.2003
4. Micromedex Healthcare
series
DRUG
STRENGTH/UNIT
STORAGE
RECONSTITUITION
STABILITY AFTER
RECONSTITUITION
s.
1. Product information ( Tren
Injection)
2. British National Formulary 56
3. Lexi-Comp's Drug Information
Handbook, 12th Edition,
Charles F, Lacy, et al.2003
4. Micromedex Healthcare series
5. Martindale 32nd Edition
Magnesium Sulphate
1. Product information ( Sodium
Bicarbonate 8.4% injection)
2. Lexi-Comp's Drug
Information Handbook, 12th
Edition, Charles F, Lacy, et
al.2003
3. Micromedex Healthcare
series
t.
Nimodipine
2.465 g/ 5ml
10mg/50ml (Nimotop)
Below 25˚C.
Below 30˚C.
Aiready in solution
Already in solution
NA
N/A
NS
Solution is for direct infusion. See Method Of
Administration
D5%
Lactated Ringer
DILUENTS FOR INFUSION
IV: 1 ampoule (5ml) diluted with at least
7.5ml of compatible solution
IM: dilution is not required but each
ampoule (5ml) can be diluted with 5ml of
compatible solution.
IM: of undiluted or diluted solution.
IV bolus: of diluted solution at rate not
exceeding 150mg/minute
METHOD OF
ADMINISTRATION
REMARKS
IV infusion: administer as continous IV infusion
via CENTRAL catheter using infusion pump. It
should be given via three-way stopcock
together with 40ml/hr of either NS or D5% or
Lactated Ringer.
IV infusion: rate not exceeding 2g/hour
Solution must not be added to an infusion bag
or bottle.
500mg MgSO4 = 4.06 mEq Mg = 49.3
mg elemental Magnesium
Nimodipine is absorbed by PVC so the PE
tube provided must be used.
Mannitol, human albumin or blood are suitable
for co-infusion
31
1.
REFERENCES
2.
3.
4.
5.
Product information ( Magnesium
Sulphate Concentrated Injection)
British National Formulary 56
Lexi-Comp's Drug Information
Handbook, 12th Edition, Charles
F, Lacy, et al.2003
Micromedex Healthcare series
Martindale 32nd Edition
1.
2.
Product information (Nimotop)
British National Formulary 56.
2.1.11 Muscle Relaxant
DRUG
a.
Suxamethonium
b.
Rocuronium
25mg/ 2.5 ml (Esmeron)
STRENGTH/UNIT
RECONSTITUITION
STABILITY AFTER
RECONSTITUITION
50mg/ 5ml
Between 2°C to 8°C. Protect
from light.
Between 2°C to 8°C.
Multiple-dose vial solution are
stable at room temperature for 14
days
Already in solution.
Already in solution
Already in solution
NA
NA
N/A
NS
NS
D5%
D5%
NS
D5%
DILUENTS FOR INFUSION
Normally prepared as 1-2mg/ ml
solution
IM: Total dose not exceeding
150mg
METHOD OF
ADMINISTRATION
4mg/ 2ml (Pavulon)
100mg/ 2ml
Between 2°C to 8°C. Protect from
light
STORAGE
c. Pancuronium
IV injection: over 10 to 30 seconds.
Without dilution
IV infusion: Ranged from 0.5 mg10mg/ minute. Normally at the rate
of 2.5-4.3mg/ minute.
WFI
Dilute to a concentration of
0.5mg/ ml or 2mg/ml. Up to
5mg/ml.
IV bolus: of indiluted
IV infusion
IV bolus: of the
undiluted solution.
Can be administered
through the line of a
running infusion.
IV infusion.
32
Suxamethonium Chloride =
Succinylcholine chloride
REMARKS
1.
2.
3.
REFERENCES
DRUG
STRENGTH/UNIT
STORAGE
4.
Product information (
Suxamethonium Chloride Fresinius Injection).
British National Formulary 56
Lexi-Comp's Drug Information
Handbook, 12th Edition,
Charles F, Lacy, et al.2003
Micromedex Healthcare
series
d.
If stored at room temperature,
rocuronium should be used
within 60 days
1.
Atracurium
Product information
(Rocuronium bromide
Injection - Esmeron).
2. British National
Formulary 56
3. Lexi-Comp's Drug
Information Handbook,
12th Edition, Charles F,
Lacy, et al.2003
4. Micromedex Healthcare
series
e.
1.
2.
3.
Product
information
(Pavulon).
Lexi-Comp's
Drug
Information
Handbook, 12th
Edition, Charles
F, Lacy, et
al.2003
Micromedex
Healthcare
series
Vecuronium
25mg/ 2.5ml
4mg (Norcuron)
50mg/ 5ml
10mg
Between 2°C to 8°C. Protect from light.
Below 25°C. Protect from light.
Norcuron 4mg: with 1ml WFI (to make
4mg/ml solution) or with 4ml WFI (to
make1mg/ml solution)
RECONSTITUITION
STABILITY AFTER
RECONSTITUITION
DILUENTS FOR
INFUSION
Already in solution
Norcuron 10mg: with 5ml WFI (to make
2mg/ml solution) or with 10ml WFI (to make
1mg/ml solution)
NA
12 hours at 15°C to 25°C. But product
leaflet recommends to discard any unused
portion.
NS
D5%
D5%
NS
Solution may be prepared in a range of
0.2mg/ml to 5mg/ml. Common as 0.2mg/ml
and 0.5mg/ml.
Dilute reconstituted vial to 0.1-0.2mg/ml.
Stability: 24 hrs in NS, 8 hrs in D5% at 30°C
33
IV bolus: of reconstituted solution
IV infusion: of diluted solution.
Concentration of 1mg/ml may be used for
IV infusion in fluid-restricted patient
IV injection: of indiluted
METHOD OF
ADMINISTRATION
IV infusion
Not for IM due to tissue irritation.
REMARKS
REFERENCES
1. Product information ( Atralex Injection).
2. British National Formulary 56
3. Lexi-Comp's Drug Information
Handbook, 12th Edition, Charles F,
Lacy, et al.2003
4. Micromedex Healthcare series
1. Product information (Norcuron).
2. British National Formulary 56
3. Lexi-Comp's Drug Information
Handbook, 12th Edition, Charles F,
Lacy, et al.2003
2.1.12 Respiratory
DRUG
a.
Potassium chloride
b.
Pralidoxime
500mg/20ml (Pampara)
STRENGTH/UNIT
STORAGE
RECONSTITUITION
STABILITY AFTER
RECONSTITUITION
DILUENTS FOR INFUSION
c.
Salbutamol
0.5mg/ml
10% W/V, 10ml
5mg/5ml
Below 25˚C
Below 28˚C, Protect from light,
Below 30˚C, Protect
form light
Already in solution
Already in solution
Already in solution
NA
NA
NA
NS
NS (for the treatment of
hypokalemia)
For IV intermittent: as 5% to
10% solution (the product is
2.5% in strenght, so can be
readily administered)
Maximum concentration
recommended for peripheral
line is 6g/L. (can dilute up to 3
gm KCL in 500ml NS).
For fluid restricted patient with
central line, maximum
concentration recommended
is 11g/L.
For IV infusion: Dilute in 100ml
NS
D5%
WFI
WFI can be used to
dilute Ventolin 0.5mg/ml
to facilitate injection
IV infusion: Dilute
5mg/5ml salbutamol in
500ml Ns or D5% to
produce 10mcg/ml
solution.
34
IV intermittent : over 5 to 10
minutes.
S/C
IM
METHOD OF
ADMINISTRATION
IV infusion (Maximum rate is 3
gm/hour)
IIV infusion: over 15 to 30
minutes
IV slow bolus
S/C
IV infusion
IM
Use with caution in patients
with cardiac disease
REMARKS
1.
2.
REFERENCES
3.
4.
DRUG
STRENGTH/UNIT
Product information
( Potassium chloride 10%
W/v 10ml).
Micromedex Healthcare
series.
British National
Formulary 56.
Lexi-Comp's Drug
Information Handbook,
12th Edition, Charles F,
Lacy, et al.2003
d.
Maximum recommended daily
dose is 12 gm
1. Product information
(Pampara injection).
2. Micromedex Healthcare
series.
3. British National Formulary
56.
4. Lexi-Comp's Drug
Information Handbook, 12th
Edition, Charles F, Lacy, et
al.2003
Terbutaline
0.5mg/ml
1. Product information
(Ventolin injection).
2. Micromedex
Healthcare series.
3. British National
Formulary 56.
e.
Aminophylline
250mg/5ml
Below 25°C
STORAGE
RECONSTITUITION
STABILITY AFTER
RECONSTITUITION
Below 25°C
Already in solution
Already in solution
N/A
NA
NS
D5%
D5%
NS
DILUENTS FOR INFUSION
METHOD OF ADMINISTRATION
For premature labour: Dilute in D5% to
a concentration 100mcg/ml and give
via syringe pump. If pump not
available, dilute to a concentration of
10mcg/ml.
Dilute with NS to a concentration of
1mg/ml. Max concentration is 25mg/ml
S/C: For bronchodilation.
IV slow injection
IV infusion: For tocolysis acute
(unlabeled used), duration of infusion is
IV infusion: LD: Over 20-30 minutes.
35
at least 12 hours.
Rate not exceeding 25mg/minute.
Dose of aminophylline = dose of
theophylline/ 0.8
REMARKS
1.
2.
REFERENCES
2.1.13
3.
4.
Product information
(Terbutaline injection- Baltic).
Micromedex Healthcare
series.
British National Formulary 56.
Lexi-Comp's Drug Information
Handbook, 12th Edition,
Charles F, Lacy, et al.2003
1. Product information (Aminophyllin IVFresenius injection).
2. Micromedex Healthcare series.
3. British National Formulary 56.
4. Lexi-Comp's Drug Information
Handbook, 12th Edition, Charles F,
Lacy, et al.2003
Sedative
DRUG
STRENGTH/UNIT
STORAGE
RECONSTITUITION
STABILITY AFTER
RECONSTITUITION
DILUENTS FOR
INFUSION
a.
Fentanyl
0.1mg/2ml
b.
Dexmedetomidine
Hydrochloride
200mg/2ml (Precedex)
c.
Propofol
200mg/20ml (Fresofol 1%
emulsion)
Below 25°C. Protect from
light.
Between 15°C to 30°C .
Below 25°C. Do not freeze.
Shake before use.
Already in solution
Already in solution
NA
After dilution, store at 2-8°C
and use within 24 hours.
NA
NS
NS
NS
D5%
Must be diluted before use for
both LD and maintenance
dose. Dilution is the same for
LD and MD: 2ml of
dexmedetomidine add into
48ml NS.
D5%
Already in solution
Minimum concentration is
2mg propofol /1ml diluent. Do
not dilute less than 2mg/ml.
Dilute in glass bottle. Shake
before use
Also compatible with
36
lidocaine 1% (not exceeding
20mg lidocaine /200mg
propofol)
IV slow over 1-2 minutes
IV infusion (using a controlled
infusion device)
IV bolus
IV infusion
METHOD OF
ADMINISTRATION
LD: 1mcg/kg over 10 minutes
followed by infusion of 0.20.7mcg/kg/hr (titrate
accordingly)
IV infusion
IM
REMARKS
REFERENCES
DRUG
STRENGTH/UNIT
Muscle rigidity may occur
with rapid IV
administration
1. Product information
(Fentanyl Citrate
Injection).
2. Britisn National
Formulary 52
3. Micromedex
Healthcare series.
4. Lexi-Comp's Drug
Information Handbook,
12th Edition, Charles
F, Lacy, et al.2003
d.
Contious infusion not to
exceed 24 hours. Safety and
effectiveness have not been
evaluated in infusions over 24
hours.
1. Product information
(Precedex)
2. Micromedex
Healthcare series.
3. Lexi-Comp's Drug
Information Handbook,
13th Edition, Charles
F, Lacy, et al.2005
Midazolam
5mg/ml , 15mg/3ml (Dormicum)
For IV infusion, both diluted
or undiluted solution can be
used.
Duration of administration
must not exceed 7 days.
1. Product information
(Fresofol 1% MCT/LCT
emulsion).
2. Britisn National Formulary
52
3. Micromedex Healthcare
series.
e.
Morphine
10mg/ml
Below 25°C. Protect from light.
STORAGE
RECONSTITUITION
STABILITY AFTER
RECONSTITUITION
Room temperature
Already in solution
Already in solution.
NA
NA
37
DILUENTS FOR INFUSION
NS
D5%
D5%
Usual concentration for IV infusion is 0.11mg/ml
Concentration of dilution: 15mg
midazolam per 100-1000ml diluent
(source: Dormicum product insert)
For IV slow, a strenght of 2.5 to 15mg
may be diluted in 4-5ml WFI
Concentration of dilution: The
5mg/ml formulation should be
diluted to a concentration 0.5mg/ml
(source: Micromedex)
IV bolus (at a rate of 1mg over 30
seconds. Elderly: dose of 2-2.5mg
over 5-10 minutes)
IV slow (over 2-5 minutes)
IV infusion
IM
IM
S/C
None
Rapid S/C administration may cause local
tissue irritation
METHOD OF ADMINISTRATION
REMARKS
REFERENCES
2.2
1.
2.
3.
4.
Product information (Dormicum).
Britisn National Formulary 52
Micromedex Healthcare series.
Lexi-Comp's Drug Information
Handbook, 12th Edition, Charles
F, Lacy, et al.2003
IV infusion
1.
2.
3.
4.
Product information (Dormicum).
Britisn National Formulary 52
Micromedex Healthcare series.
Lexi-Comp's Drug Information
Handbook, 12th Edition, Charles
F, Lacy, et al.2003
Deep Vein Thrombosis Prophylaxis
2.2.1 INTRODUCTION
The occurrence of deep vein thrombosis in hospitalised patients is
depending upon various risk factors. In orthopaedic patients undergoing
surgery, up to 76.5% incidence of DVT has been reported.1 Meanwhile
approximately 10 to 40% among medical or general surgical patients and
40 to 60% of patients having major orthopedic surgery, and was not placed
on DVT prophylaxis are confirmed as having hospital-acquired DVT.2 One
38
quarter to one third of these thrombi involve the proximal deep veins, and
these thrombi are much more likely to produce symptoms and result in
pulmonary embolism (PE). 3In a study of 51,645 hospitalized patients, the
prevalence of acute PE was 1%, and PE was believed to have caused or
contributed to death in 37% of these cases4.
To prevent the occurrence of DVT and subsequent pulmonary embolism
which can be fatal, thromboprophylaxis is recommended. The 2 methods of
prophylaxis are either pharmacological or mechanical and are described
under methods of prophylaxis.
2.2.2 DEFINITIONS
Deep vein thrombosis (DVT) is defined as a clot that occurs in the deep
veins of the extremities. Further subclassifications include symptomatic
versus asymptomatic and proximal (above the knee) versus distal (below
the knee). 5
Pulmonary embolism is defined as being a clot usually originating from a
DVT that travels to the pulmonary vasculature where it becomes an
embolism and thereby impedes gas exchange distal to embolism. 5
Venous thromboembolism (VTE) is defined as an event due to thrombosis
of a vein and includes DVT or PE. 5
Thrombophlebitis is the inflammation of a vein around which a DVT has
occurred. This condition can be painful and chronic. This term is
synonymous with postphlebitic or postthrombotic syndrome. 5
Immobilized : restricted to bed or chair with no instruction or ability to
ambulate. 5
2.2.3 INDICATIONS FOR PROPHYLAXIS
All adult inpatients will be assessed for their risk of VTE that include the
background history and acute or subacute precipitating factors which are
shown in table 1. Clinicians will need to use their own judgment in addition
to the guideline to determine the best method of reducing the risk of VTE in
each individual patient. It is the combined responsibility of the physician and
other healthcare staff including the clinical pharmacist and nursing staff to
ensure all patients at risk for VTE have received appropriate prophylaxis
when needed.1
Table 1 : Venous Thromboembolism – Risk Factors 6
39
Background Factors









Age
Marked obesity ( BMI >30 )
Immobility ( bed rest longer than 4 days. )
Pregnancy
Puerperium
High dose estrogens
Previous DVT or PE
Thrombophilia
- Deficiency of antithrombin, protein-C or protein-S
- activated protein-C resistance
- antiphospholipid antibody or
Lupus anticoagulant.













Trauma or surgery, especially of pelvis, hip, lower limb.
Malignancy , especially pelvic , abdominal , metastatic
Heart failure
Recent myocardial infarction
Paralysis of lower limb(s)
Severe infection
Inflammatory bowel disease
Nephrotic syndrome
Polycythemia
Paraproteinemia
Paroxysmal nocturnal hemoglobinurea
Bechet’s disease.
Burns
Precipitating Factors
a.
Low-risk groups 1
 patients with minor trauma or minor medical illness at any age, in
the absence of thrombophilia, previous DVT or PE.
 patients undergoing minor surgery (duration under 30 minutes) at
any age, in the absence of other risk factors.
 patients undergoing major surgery (duration over 30 minutes) who
are aged under 40 years and have no additional risk factors.
b.
Moderate risk groups 1
40
 patients undergoing major general, urological, gynaecological,
cardiothoracic, vascular, or neurological surgery who are aged > 39
years or with other risk factors.
 patients immobilised with acute medical illness.
 major trauma
 minor surgery or trauma or illness in patients with previous deep
vein thrombosis, pulmonary embolism, or thrombophilia.
c.
High-risk groups1
 fracture or major orthopaedic surgery of pelvis, hip, or lower limb.
 major pelvic or abdominal surgery for cancer.
 major surgery, trauma, or illness in patients with previous deep vein
thrombosis, pulmonary embolism, or thrombophilia.
 lower limb paralysis (for example, hemiplegic stroke, paraplegia).
 critical lower limb ischaemia or major lower limb amputation.
2.2.4
METHODS OF PROPHYLAXIS
There are two method of prophylaxis of DVT, which are 1
a.
Pharmacological methods :
-
b.
Standard heparin (usually in low dosage)
Low molecular weight heparins
Oral anticoagulant such as warfarin
Aspirin
Mechanical methods - increase venous outflow and/or reduce stasis
within the leg veins :
- Graduated compression stockings (GCS)
- Intermittent pneumatic compression (IPC) devices
- Venous foot pump (VFP)
* Below is a summary table for recommendation of method
prophylaxis regarding the type of risk and procedure.
Table 2: Recommended DVT prophylaxis for surgical procedures and medical conditions 8
Surgery/Condition
General Surgery—low-
Recommended
Prophylaxis
None
Comments
Early ambulation
41
Surgery/Condition
Recommended
Prophylaxis
Comments
risk: minor procedures,
<40 years old, no
additional risks
General Surgery—
moderate risk: minor
procedure but with risk
factor, nonmajor
surgery age 40-60 with
no risks, or major
surgery <40 years with
no risks
Heparin , LMWH ,
ES, or IPC
General Surgery—high
risk: non-major surgery
over age 60 or over
age 40 with risks.
Heparin , LMWH
Heparin 5000 – 7500 iu bd
OR
LMWH (daily dose according to manufacturer)
with IPC or ES.
* LMWH and heparin has comparable efficacy for
DVT prophylaxis.8,9 The clinical advantages of
LMWH over LDUH is its once-daily administration
and the lower risk of heparin-induced
thrombocytopenia (HIT), BUT LMWH is more
costly.10
Heparin 5000 – 7500 iu tds
OR
LMWH (daily dose according to manufacturer)
*In high-risk general surgery patients, higher doses
of LMWH provide greater protection than lower
doses.3
General Surgery—very
high risk: major
surgery over age 40
plus prior VTE, cancer
or hypercoagulable
state
LMWH combined
with ES or IPC
LMWH (daily dose according to manufacturer
Elective Hip
Replacement
LMWH or warfarin
May combine with ES or IPC; start LMWH 12 hours
before surgery, 12-24 hours after surgery, or 4-6
hours after surgery at half the dose for initial dose
for at least 10 days. Start warfarin preoperatively or
immediately after surgery, target INR 2. 0-3. 0.
Extended prophylaxis is recommended for up to 28
to 35 days after surgery. 8
Elective Knee
Replacement
LMWH or warfarin
Both LMWH and warfarin resulted in significantly
fewer proximal DVTs compared with LDUH or IPC
(p<0.006 for each comparison).11 Pooled data from
5 trials that directly compared LMWH with warfarin
*May consider post discharge LMWH or
perioperative warfarin
42
Surgery/Condition
Recommended
Prophylaxis
Comments
showed rates of proximal DVT of 3.4% and 4.8%,
respectively.8
Hip Fracture Surgery
LMWH or warfarin
Neurosurgery
IPC, LDUH or
LMWH
Start LMWH post-surgery
Trauma
LMWH with ES or
IPC
If high risk of bleeding, may use ES and/or IPC
alone.
Acute Spinal Cord
Injury
LMWH
Continue LMWH during rehabilitation or convert to
warfarin (target INR 2.5)
Ischemic Stroke
LDUH, LMWH
If contraindication to anticoagulant, use ES or IPC.
Two studies directly comparing LDUH (5000 U
three times daily) to LMWH (enoxaparin 40 mg
once daily), using venography for diagnosis, found
greater reduction in DVT with LMWH.8
A meta-analysis of studies of hospitalized patients
with conditions other than myocardial infarction or
ischemic stroke given VTE prophylaxis with
unfractionated or low molecular weight heparin
showed no significant difference was found
between LMWH and LDUH in incidence of DVT,
PE, or mortality; however, major hemorrhage was
lower with LMWH than with LDUH (RR 0.48, 95%
CI: 0.23-1.00).12
ES
: elastic stockings
LDUH: low-dose unfractionated heparin
INR
: international normalized ratio
LMWH: low molecular weight heparin
IPC
: intermittent pneumatic compression
VTE : venous thromboembolis.
* warfarin is hardly use in critical care due to
recommended as first line
administration
problem, thus it is not
43
Table 3: MEDICATIONS USED TO PREVENT DVT
Medication Class
Unfractionated
heparin
Medication
Heparin
Dosage
Low molecular weight heparin
Enoxaparin
Fondaparinux
Moderate risk
20 mg SC daily
Adult (>50 kg)
SC Heparin 5000units
twice daily
(moderate risk surgery) OR
2.5 mg SC once daily
40 mg SC daily
Initiate dose after hemostasis
has been established, 6 – 8
hours postoperatively. 16
High risk
SC Heparin 5000units
8 hourly
(can go up to 30 mg SC q12h for
high risk general surgery, major
trauma or acute spinal cord injury) 14
Morbid obese (> 150 kg): can
increase to SC 60 mg 12 hourly 13
Dose renal adjustment ( CrCL < 30
ml/min )14
Prophylaxis dose :
SC 20 mg daily
Therapeutic dose : 1 mg/kg daily
Duration
5 days OR until
hospital discharge if
this is earlier than 5
days.
Surgical case14
7 – 10 days or longer if there is a risk
of DVT and until patient ambulatory.
Medical case14
6 – 14 days
Orthopedic and abdominal
surgery15
5 – 9 days after surgery.
In patient undergoing hip
fracture surgery 9 – 24 days (
consider the risk )
Medical patients with DVT risk
Duration of 6 to 14 days .
Monitoring
Platelet count
Platelet count
Recommendation : the
platelet count is
monitored in patients
receiving heparin for
more than five days,
Risk of thrombocytopenia (happen
between 5th and the 21st day
following the beginning of
enoxaparin therapy.) If it significant
decrease (30 to 50% of initial count),
Full blood count, serum
creatinine, and occult blood
testing of stools are
recommended. PT and APTT
are insensitive measures. 16
Medication Class
Unfractionated
heparin
Medication
Heparin
Enoxaparin
and that heparin is
stopped immediately if
thrombocytopenia
occurs.
the treatment should be discontinued
and switch to other alternative.
Contraindication16
Low molecular weight heparin
- bleeding disorders
- a history of allergy either to enoxaparin, heparin or other low
molecular
Fondaparinux
- Hypersensitivity to
fondaparinux
- severe renal impairment (CLCr
< 30 mL/min)
weight heparin 1
- body weight < 50 kg
(prophylaxis)
- active major bleeding
- bacterial endocarditis
- thrombocytopenia
Precaution16
Hypersensitivity to
drug.
May cause
thrombocytopenia.
Discontinue and
consider alternative if
platelet are <
100,000/mm3 or /and
thrombosis develop.
In neonate suggest
use preservative free
as some preparation
content large amount
benzyl alcohol (> 100
mg/kg/day) that can
cause fatal toxicity
(gasping syndrome).
Recent or anticipated neuraxial
anesthesia (epidural or spinal
anesthesia) are at risk of spinal or
epidural hematoma and subsequent
paralysis. Consider risk versus
benefit.
Risk of thrombocytopenia
Caution in patient with renal failure;
dosage adjustment need for ClCr <
30 mL/min.
Same with enoxaparin
Not to be use interchangeable
(unit-for-unit) with heparin,
LMWH or heparinoids.
Use caution in patient with
moderate renal dysfunction
Patient with severe hepatic
impairment with elevation in
prothrombin time.
Not recommended prior to and
during percutaneous coronary
prevention (PCI) for reperfusion
in STEMI patients, due to
Medication Class
Unfractionated
heparin
Medication
Heparin
Low molecular weight heparin
Enoxaparin
Fondaparinux
increasesd risk for guiding
catheter thrombosis.
Avoid administration 24 hours
before and 48 hours after
coronary artery bypass graft
(CABG) surgery.
Side effect
Thrombocytopenia
occurs in about 3-4%
of patients given
prophylactic heparin.
Allergic reactions
(including skin
necrosis), raised
serum transaminase
concentrations, and
osteoporosis with long
term use (especially in
pregnancy) 1
Drug interaction
Increased
effect/toxicity if use
with anticoagulant,
thrombolytics, dextran
and drug affect
platelet function ( eg
aspirin, NSAIDs,
dipyridamole,
ticlopidine,
clopidogrel),
cephalosporins which
contain MTT chain
and parenteral
penicillins (may inhibit
platelet aggregation).
16
Decreased effect if
use with Nitroglycerin
(IV) that may occur in
1 to 10% risk16
> 10%
CNS : fever, confusion, pain
- Fever, nausea, anemia16
Dermatology : erythema, bruising,
hematoma at site of injection
1- 10%
GI : nausea, diarrhea
Hematologic : hemorrhage,
thrombocytopenia
Hepatic : ALT/ALP increase
Increased effect/toxicity if use with
anticoagulant, thrombolytics, dextran
and drug affect platelet function ( eg
aspirin, NSAIDs, dipyridamole,
ticlopidine, clopidogrel),
cephalosporins which conatain MTT
chain and parenteral penicillins (may
inhibit platelet aggregation). 16
Edema, hypotension, insomnia,
dizziness, headache, confusion,
rash, purpura, bullous eruption,
hypokalemia, constipation,
vomiting, diarrhea, dyspepsia,
moderate thrombocytopenia,
increase in liver enzyme. 16
Increased effect/toxicity if use
with anicoagulants, antiplatelet
agents, drotecogin alfa, NSAIDs,
salicylates and thrombolytic
agents. 16
Medication Class
Unfractionated
heparin
Medication
Heparin
Low molecular weight heparin
Enoxaparin
Fondaparinux
high dosages. 16
Special
instruction
There is an increased
risk of wound
haematomas, which
can be minimised by
avoiding injections
close to wounds. 1
To avoid loss of medicinal
product when using prefill
syringe do not expel the air
bubble from the syringe before
the injection. 15
IV administration (first dose in
STEMI patients only) either
directly or use small volume (2550 ml) 0.9% saline minibag and
administer through existing IV
line over 1 -2 minute. Then flush
with saline after injection to
ensure all medicinal product is
administered.15
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
College of surgeons Malaysia. 1999 . Consensus On Prophylaxis Of Venous Thromboembolism.
Academy of medicine Malaysia.
Wiig, JN, Solhaug, JH, Bilberg, T, et al 1995. Prophylaxis of venographically diagnosed deep vein
thrombosis in gastrointestinal surgery: multicentre trials 20 mg and 40 mg enoxaparin versus
dextran. Eur J Surg 161,663-668
Geerts WH, GP, Pineo Heit JA, Bergqvist D, Lassen MR, Colwell CW, & Ray JGl. 2009.
Prevention of venous thromboembolism. Chest seventh ACCP Consensus Conference on
Antithrombotic Therapy.
Stein PD, Henry JW. 1995. Prevalence of acute pulmonary embolism among patients in a
general hospital and at autopsy. Chest 108,978-981
Thambi M, Galanter B. 2006. VTE/Deep vein thrombosis prophylaxis. University of Illinios Medical
Centre.
Thromboembolic Risk Factors ( THRIFT ) Consensus Group. Risk of and prophylaxis for venous
thromboembolism in hospital patients. BMJ 1992; 305: 567 - 74.
Kleinbart J, Williams MV and Rask KR. Chapter 31. Prevention of Venous Thromboembolism
Emory University Schools of Medicine and Public Health. www.ahrg.gov.
Geerts WH, Heit JA, Clagett GP, Pineo GF, Colwell CW, Anderson FA, et al. 2001. Prevention of
venous thromboembolism. 156S-158S. Chest Sixth ACCP Consensus Conference on
Antithrombotic Therapy.
Palmer AJ, Schramm W, Kirchhof B, Bergemann R. 1997.Low molecular weight heparin and
unfractionated heparin for prevention of thrombo-embolism in general surgery: a meta-analysis of
randomised clinical trials. Haemostasis 27:65-74.
Warkentin, TE, Levine, MN, Hirsh, J, et al 1995 Heparin-induced thrombocytopenia in patients
treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 332,13301335
11.
Freedman KB, Brookenthal KR, Fitzgerald RH, Jr. , Williams S, Lonner JH. 2000. A meta-analysis
of thromboembolic prophylaxis following elective total hip arthroplasty. J Bone Joint Surg 82A:929-938.
Mismetti P, Laporte-Simitsidis S, Tardy B, Cucherat M, Buchmuller A, Juillard-Delsart D, et al.
2000. Prevention of venous thromboembolism in internal medicine with unfractionated or lowmolecular-weight heparins: a meta-analysis of randomised clinical trials. Thromb Haemost 83:1419.
Duplaga BA, Rivers CW, Nutescu E. 2001. Dosing and monitoring of low-molecular-weight
heparins in special populations. Pharmacotherapy 21:218-34.
Enoxaparin (Clexane) product leaflet, Sanofi-Aventis
Fondaparinux (Arixtra) product leaflet, GloxiSmithKline
Drug Information Handbook 17th Edition. 2008. Lexi Comp. United States
12.
13.
14.
15.
16.
Author
1.
2.
3.
4.
5.
Dr Arbayah Rais, Head of Dept Anesthetist, Selayang Hospital
Fadilah Othman, Chief Pharmacist (Senior Clinical Pharmacist), Pharmacy Dept. Selayang Hospital
Dr Haslinda Anesthetist ICU, Selayang Hospital
Norliza Mat Ariffin, Pharmacist, Pharmacy Dept. Selayang Hospital
Masrahayu Moydin, Clinical Pharmacist, Pharmacy Dept. Selayang Hospital
2.3
STRESS ULCER PROPHYLAXIS
2.3.1
INTRODUCTION
Stress-related mucosal disease (SRMD) is an acute condition which erosion of
the gastric mucosa occur secondary to a physiologic stress.1 It can be
manifestation by bleeding which can be considered equivalent to overt
gastroduodenal bleeding that result in hemodynamic instability (measured
through a drop in blood pressure or an increase in heart rate) and subsequent
need for red blood cell transfusions or surgical intervention of the gastric ulcers. 2,
(I suggest this sentence be rephrase cos it is too long and as a reader I cannot
grasp its full meaning  comment from MartinaRos Sakinah please look into
it). 2, 3
The etiology of stress-related mucosal disease (SRMD) or stress related ulcer is
multifactorial and complex. Patients with head injury or burns represent those at
highest risk of SRMD, likely due to gastric acid secretion resulting from vagal
stimulation. Other critically ill patients appear to develop SRMD as a result of
diminishes mucosal defenses and hypoperfusion. 4 The longer the gastric pH
remains below 4 the greater the risk of hemorrhage. Clinical trials have estimates
clinically important bleeding occur in 3% to 6% of intensive care unit (ICU)
patients with the most common risk factors ( ie those who are ventilated or have
coagulopathy). 5, 6 Work by Cook and colleagues ascribed the risk of overt
bleeding to be 4.4 % and clinically significant bleeding to be 1.5%. 5 There is a
strong relationship between duration of mechanical ventilation, duration of
intensive care stay and incidence of ulceration: patient without coagulopathy and
mechanical ventilation had an incidence of bleeding of 0.1%. 5
2.3.2
INDICATION OF PROPHYLAXIS
a.
High risk patient - All patients to receive prophylaxis
- mechanical ventilation > 48 hours
- coagulopathy
- History of previous GI hemorrhage
- Current outpatient PUD treatment or prophylaxis
- Central nervous system (CNS) injury ( subarachnoid hemorrhage (SAH) /
cardiovascular attack (CVA) – hemorrhagic or ischemic)
- Sepsis with or without organ dysfunction
- Vasopressor/inotropic prescription
b.
Moderate risk patient - consider prophylaxis
- Chronic non steroidal antiinflamatory drug (NSAID) or aspirin use
- High dose prolonged steroid treatment
- ICU stay > 10 days
c.
2.3.3
Low risk patient or tolerating per oral diet/Full gastric enteral feeds –
No prophylaxis or discontinue prophylaxis
NUTRITIONAL GUIDELINE AND STRESS ULCERS
The administration of gastric nutrition reduces, but does not eliminate the risk of
GI hemorrhage. Any patient predicted to be mechanically ventilated > 48 hours
and without a contraindication to gastric enteral nutrition, is encouraged to have
nasogastric nutrition initiated within 72 hours of admission when a nasoenteric
tube is in situ.
2.3.4
PROPHYLAXIS SMRD AGENT
Many agents are available for use in patients at risk for stress-related mucosal
disease. These agents include histamine type 2 receptor antagonists (H2RAs),
proton pump inhibitors (PPIs), sucralfate, antacids, and prostaglandin analogs.
Common products, usual dosage ranges, and considerations are shown in the
Table 1.
Current studies reveal that histamine type 2 receptor antagonists are the most
widely used first-line agents; however proton pump inhibitors are widely used and
their diverse routes of administration and favorable side effect profile are
desirable features.13
The largest randomized controlled trial to date involved 1200 mechanically
ventilated patients has determined that ranitidine was significantly better than
sucralfate in reducing clinically important SRMD bleeding (odds ratio [ OR]: 0.44;
95% confidence interval [CI] : 0.21-0.92). 7
Multiple studies have examined the effects of proton inhibitors (PPIs) in ICU
patients, but all have been small and many measured intermediate endpoints. 7
Some studies have been observational with PPI therapy alone, whereas others
have compared PPI therapy with placebo or histamine-2 receptor antagonist
(H2RA) therapy. Conclusions that can be gathered currently are that acid
suppression achieved with PPI therapy is, on average, superior to that achieved
with H2RAs, and that the clinical benefit of PPIs for reducing SRMD bleeding
appears to be at least similar to that achieved with H2RAs. Current trends
indicate increasing awareness and use of acid suppression in the population,
with H2RAs representing first-line agents and PPIs gaining use.
The most common complication of stress ulcer prophylaxis is pneumonia. 10 The
hypothesis is based upon the concept that higher pH relates to overgrowth of
gastric microbes and leads to upper tracheal colonization. This concept
partnered with microspiration of intubated patients lying supine may increase the
nosocomial pneumonia rate. The ability to reliably maintain a pH < 4 will
decrease the rate of pneumonia. Several studies comparing the pneumonia rate
when comparing sucralfate, antacids and H2RA show ether improvement or
insignificant trends toward decreasing rate with sucralfate. 10 However, due to the
current incidence of outpatient ulcer and reflux reduction therapy and the
complexity of administering sucralfate, overall benefit appears to be small.
Table 1: MEDICATION USED TO PREVENT SRMD 14
Medication class
Histamine Type 2
Receptor
Antagonists
Medication
Ranitidine
Dosage
Adult
Oral : 150 mg bd
IV : 50 mg Q8H
Adjust for
creatinine
clearance
Proton pump inhibitors
Esomeprazole
40 mg daily
(IV,
nasogastric
tube, PO)
Omeprazole
20-40 mg daily (PO,
nasogastric/jejunal,
duodenal tube)
Pantoprazole
40 mg daily
(IV,nasogastric
tube, PO)
Patient who develops significant GI hemorrhage receiving
prophylaxis :
IV Omeprazole / Pantoprazole / Esomeprazole
(CrCl) < 50
ml/min.
80 mg loading dose followed by 8 mg/hr for 3 days
Oral : 150 mg
every 24 hour
- consider endoscopic evaluation
- When no evidence of bleeding for 24 hours, convert to
intermittent dosing schedule.
IV : 50 mg every
18-24 hours;
adjust dose
cautiously if
needed
Hemodialysis :
Adjust dosing
schedule so that
dose coincides
with the end of
hemodialysis.
*Defined as bleeding that requires transfusion, causes
hemodynamic changes and/or decrease in Hmeoglobin (Hgb) ≥ 1
gram
The result of 16 randomized, controlled trials involving a total of >
3,800 patients (1,892 receiving PPIs and 1,911 controls) suggest
that bolus administration plus continuous infusion of PPIs is a
more effective pharmacotherapy than bolus infusion alone in
decreasing both rebleeding and the need for surgery. 11
Medication class
Histamine Type 2
Receptor
Antagonists
Medication
Ranitidine
Monitoring
Proton pump inhibitors
Esomeprazole
Omeprazole
AST, ALT, serum
creatinine, sign
and symptoms of
PUD, occult blood
with GI bleeding,
renal function
Contraindication
Pantoprazole
Hypersecretory
disorders
Hypersensitivity to the component of the formulation
Precaution
Use in caution in
patient with
hepatic
impairment and
renal impairment
Severe liver
dysfunction may
require dose
adjustment
Bioavailability may
increase in the
elderly, Asian
population, and with
hepatic dysfunction
IV preparation
contain edentate
sodium (EDTA); use
caution in patient
who are at risk for
zinc deficiency if
other EDTA
containing solution
are co-administered
Side effect
Arrythmias,
dizziness,
headache, mental
confusion, rash,
anemia,
thrombocytopenia,
leucopenia,
hepatic failure and
pneumonia
Headache,
hypertension,
pain, dizziness,
flatulence,
diarrhesa,
constipation,
urinary tract
infection, anemia,
pneumonia
Headache,
dizziness, diarrhea,
abdominal pain,
pneumonia
Headache, diarrhea,
flatulence,
abdominal pain,
abnormal liver
function test
Drug interaction
CYP450 effect
CYP450 effect
CYP450 effect
Increase the
effect :
Cyclosporine
Increase the effect : HMG-CoA
reductase inhibitor, methotrexate,
benzodiazepine, phenytoin
Increase the effect
:
Decrease effect
Decrease effect
Warfarin,
ketoconazole,
itraconazole,
cephalosporin,
ketoconazole, itraconazole,
HMG-CoA reductase
inhibitor,
Montelukast,
phenytoin, warfarin,
methotrexate
Decrease effect
ketoconazole,
Medication class
Histamine Type 2
Receptor
Antagonists
Medication
Ranitidine
Proton pump inhibitors
Esomeprazole
Omeprazole
cycanocobalamin
Special
instruction
First line in
treatment of
SRMD
Pantoprazole
itraconazole,
If patient on PPI for chronic disease (PUD treatment or
prophylaxis) requiring this medication
Stability of PPIs after reconstitution
After reconstitution with 10 ml of isotonic sodium chloride
solution, intravenous omeprazole / pantoprazole can be
administered as a rapid injection over 2 minutes or it can be
stores for up to 2 hours at room temperature.
Intravenous admixtures of pantoprazole can be prepared by
mixing with 100 ml of isotonic sodium chloride solution, 5%
dextrose in water, or lactated Ringer’s solution to achieve a final
concentration of 0.4 mg/ml. This solution can be stored for up to
24 hours at room temperature. This admixture can be
administered over 15 minutes. 12
References
1. Sesler JM. Stress-related mucosal disease in the intensive care unit: an update on prophylaxis.
AACN Adv Crit Care. 2007; 18:119-126.
2. Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill
patients. Canadian Critical Care Trials Group. N Engl J Med. 1994; 330:377-381.
3. ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. ASHP Commission on Therapeutics
and approved by the ASHP Board of Directors on November 14, 1998. Am J Health Syst Pharm.
1999; 56:347-379.
4. Cho CH, Koo MWL, Garg GP, et al. Stress-induced gastric ulceration: Its aetiology and clinical
implications, Scand J Gastroenterol. 1992;27:257-262.
5. Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill
patients. N Eng J Med. 1994;330:337-381.
6. Brown RB, Klar J, Teres D, et al. Prospective study of clinical bleeding in intensive care unit
patients. Crit Care Med. 1988;16:1171-1176.
7. Cook DJ, Guyatt G, Marshall J et al. A comparison of sucralfate and ranitidine for the prevention
of upper gastrointestinal bleeding in patients requiring mechanical ventilation.
8. Jung R, Maclaren R. Proton pump inhibitor for stress ulcer prophylaxis in critically ill patients. Ann
Pharmacother. 2002;36:1929-1937.
9. Redbuck JA, Welage LS et al. Prevention of stress ulceration: current trends in critical care. Crit
care Med. 2004;32: 2008-2013.
10. Messori A, Trippoli S, Vaiani M, Gorini M, Corrado A. Bleeding and pneumonia in intensive care
patients given ranitidine and sucralfate for prevention of stress ulcer : meta analysis of
randomized controlled trials. BMJ 2202;321(7269):1103-1106.
11. Morgan D. Crit care Med. 2002;30:S369-S372
12. Wyeth Pharmaceutical [package insert]. Philadelphia, Pa: Wyeth laboratories;2004
13. Daley RJ, Rebuck JA, Welage LS, Rogers FB. Prevention of stress ulceration: current trends in
critical care. Crit Care Med. 2004; 32:2008-2013.
14. Drug Information Handbook 17th Edition. 2008. Lexi Comp. United States
Author
6.
7.
8.
9.
10.
11.
Dr Anselm Suresh Rao, Intensivist ICU, Selayang Hospital
Wong Kok Thong, Chief Pharmacist, Pharmacy Dept. Selayang Hospital
Fadilah Othman, Clinical Pharmacist, Pharmacy Dept. Selayang Hospital
Zainon Abudin, Pharmacist, Pharmacy Dept. Selayang Hospital
Siti Hajar Abdul Jalil, Pharmacist, Pharmacy Dept. Selayang Hospital
Masrahayu Moydin, Clinical Pharmacist, Pharmacy Dept. Selayang Hospital
2.4
ANTIBIOTIC GUIDELINE FROM INFECTIONS IN INTENSIVE CARE UNITS –
Adapted from National Antibiotic Guideline 2008, MOH Malaysia
Infection/ condition & Likely
Organism
Comments
Suggested Treatment
Preferred
Alternative
A. Severe Sepsis or Septic Shock Where Site Of Infection Is Not Identified
Severe sepsis or septic shock
Cefepime 2g IV q12h;
Meropenem 1g IV q8h;
(site of infection is unknown)
OR
Piperacillin/Tazobactam 4.5g IV q8h
OR
Imipenem 500mg IV q6h
Gram-negative bacilli
Gram-positive cocci
Methicillin-resistant S.aureus
Penicillin-resistant
Current evidence suggests that
carbapenems, 4th generation
cephalosporins or Piperacillin/
Tazobactam are equally effective in
treatment of septic shock.
If melioidosis cannot be ruled out,
carbapenem should be used as the
empirical agent.
Empirical use of Vancomycin1 is only
justified in areas with high endemic
levels of MRSA or high levels of
penicillin-resistant S.pneumoniae
PLUS OPTIONAL
Vancomycin1 1g IV q12h
S. pneumoniae
Ampicillin-resistant Enterococci
Candida
PLUS OPTIONAL
Fluconazole 400 - 800mg IV q24h
PLUS OPTIONAL
Amphotericin B 0.6 -1.0mg/kg IV
q24h
Empirical antifungal agents should
not be used on a routine basis.
Reference 1,2
Infection/ condition & Likely
Organism
Comments
Suggested Treatment
Preferred
Alternative
B. Severe Community-Acquired Pneumonia Requiring Mechanical Ventilation
Severe community-acquired
pneumonia requiring mechanical
ventilation
3rd gen. Cephalosporins, e.g;
-lactam/-lactamase inhibitors, eg;
Ceftriaxone 2g IV q24h
Amoxycillin/Clavulanate 1.2g IV q8h
PLUS
Erythromycin 500mg IV q6h
PLUS
Erythromycin 500mg IV q6h
OR
Azithromycin 500mg IV q24h
OR
Azithromycin 500mg IV q24h
Reference 3,4,5
S. pneumoniae
H. influenzae
S. aureus
K. pneumoniae
M. pneumoniae
L. pneumophilia
* If risk factors present, consider
Ceftazidime (Please Refer to Page
95(LRTI))
C. pneumoniae
*B.pseudomallei
C. Severe Nosocomial Pneumonia Requiring Mechanical Ventilation (Including Ventilator-Associated Pneumonia)
Nosocomial pneumonia requiring
mechanical ventilation (including
VAP)
Low risk for infection with multidrug resistant (MDR) organisms < 5 days
3rd gen. Cephalosporins, e.g;
S. pneumoniae
H. influenzae
OR
S. aureus
E. coli
-lactam/-lactamase inhibitors, eg;
K. pneumoniae Enterobacter spp.
Proteus spp. Serratia marcescens
-lactam/-lactamase inhibitors, eg;
Ceftriaxone 2g IV q24h;
Ampicillin/Sulbactam 1.5g IV q6h
S. aureus is more common in
diabetes mellitus, head trauma.
Amoxycillin/Clavulanate 1.2g IV q8h
Monotherapy is recommended for
early onset HAP/VAP/HCAP.
Reference 6,7
Infection/ condition & Likely
Organism
Comments
Suggested Treatment
Preferred
Alternative
High risk for infection with multidrug resistant (MDR) organisms
P. aeruginosa
Piperacillin/Tazobactam 4.5g IV q6h
OR
Cefepime 2g IV q12h
Imipenem 500mg IV q6h
OR
Meropenem 1g IV q8h
PLUS
Amikacin1 15mg/kg/24h IV
OR
Ciprofloxacin 400mg IV q8h
PLUS
Amikacin1 15mg/kg/24h IV
OR
Ciprofloxacin 400mg IV q8h
Acinetobacter spp.
Cefoperazone/Sulbactam 2g IV q12h
K. pneumoniae (ESBL)
Meropenem 1g IV q8h
OR
Imipenem 500mg IV q6h
Methicillin-Resistant S. aureus
PLUS
(if MRSA is suspected)
Vancomycin1 1g IV q12h
1Refer
Use combination therapy if MDR
pathogen is suspected.
Aminoglycoside can be stopped after
5-7 days in patients on combination
therapy who are responding to
treatment.
-lactam/-lactamase inhibitors, eg;
Ampicillin/Sulbactam 1.5g IV q6h
Appendix 1 (Clinical Pharmacokinetic Guidelines: Aminoglycosides & Vancomycin)
References:
1.
2.
Crit Care Med 2003; 31:1250-1256
Crit Care Med 2004; 32(11)S495 S512
3. Am J Respir Crit Care Med 2002, 166:717-723 6. Am J Respir Crit Care Med. 2005;171:388-416
4. Clin Infect Dis 2003;37:1405-33 Curr Anaes and 7. Crit Care 2005;16:209-219
5. Curr Opin Crit Care 2004; 10:59-64
2.5
NEUROMUSCULAR BLOCKING AGENTS IN CRITICALLY ILL PATIENTS
2.5.1
INTRODUCTION
The use of neuromuscular blocking agents in the ICU remains a problematic
issue, especially since the indications for the pharmacologic paralysis of ICU
patients are unclear. The current recommendations are that muscle relaxants be
used to facilitate mechanical ventilation in patients whom sedation alone is
inadequate in providing effective mechanical ventilation. The decision to treat a
patient in the ICU with neuromuscular blocking agents is a difficult one that is
guided more commonly by individual practitioner preference than by standards
based on evidence-based medicine.1
2.5.2
NEUROMUSCULAR TRANSMISSION AND BLOCKADE2
The neuromuscular junction consists of the nerve terminal, the synaptic cleft, and
the motor endplate. Acetylcholine (ACh) is released into the synaptic cleft when
nerve impulses reach the nerve terminal and diffuses across the synaptic cleft to
the motor endplate. Attachment of Ach to the nicotinic (not muscarinic) receptors
on skeletal muscle causes a conformational change in the receptor that
increases myocyte cell membrane permeability to sodium, potassium, chloride
and calcium ions and releases calcium from the sarcoplasmic reticulum, leading
to transmission of an action potential. Depolarization terminates when Ach
unbinds from the receptor. Ach either diffuses back into the nerve terminal or is
broken down by acetylcholinesterase.
Neuromuscular blocking agents are structurally related to Ach and act by
interfering with the binding of Ach to the motor endplate. They are divided into
depolarizing or nondepolarizing agents based upon their mechanism of action.

Depolarizing NMBAs bind to cholinergic receptors on the motor endplate,
causing initial depolarization on the endplate membrane followed by
blockade of neuromuscular transmission. Because calcium is not
resequestered in the sarcoplasmic reticulum, muscles are refractory to
repeat depolarization until depolarizing NMBAs diffuse from the receptor
to the circulation and are hydrolyzed by plasma pseudocholinesterase.

Nondepolarizing NMBAs competitively inhibit the Ach receptor on the
motor endplate. Drug binding to the Ach receptor either prevents the
conformational change in the receptor or physically obstructs the ion
channels so that an endplate potential is not generated.
2.5.3
NEUROMUSCULAR BLOCKING AGENTS

Atracurium
Atracurium is an intermediate acting NMBA with minimal cardiovascular
adverse effects and is associated with histamine release at higher doses.
Atracurium has been administered to various critically ill populations,
including those with liver failure, brain injury or multiple organ dysfunction
syndrome (MODS), to facilitate mechanical ventilation. Recovery of normal
neuromuscular activity usually occurred within one to two hours after
stopping the infusions and is independent of organ function. Long term
infusions have been associated with the development of tolerance,
necessitating significant dose increases or conversion to other NMBAs.
Atracurium has been associated with persistent neuromuscular weakness as
have other NMBAs.1

Pancuronium
Pancuronium is a long acting, nondepolarizing compound which has
vagolytic effects (more than 90% of ICU patients will have an increase in
heart rate of ≥10 beats/min), which limits its use in patients who cannot
tolerate an increase in heart rate. In patients with renal failure or cirrhosis,
neuromuscular blocking effects of pancuronium are prolonged because of its
increased elimination half-life and the decreased clearance of its 3hydroxypancuronium metabolite that has one-third to one-half the activity of
pancuronium.1

Rocuronium
Rocuronium is a nondepolarizing NMBA with a monoquaternary steroidal
chemistry that has an intermediate duration of action and has a very rapid
onset of action, with maximum neuromuscular blockade within 4 minutes.
The metabolite of rocuronium which is 17-des-acetylrocuronium has only 5 10% activity compared with the parent compound1 and rocuronium is
metabolized minimally in the liver.3

Vecuronium
Vecuronium is an intermediate acting NMBA that has a structural analogue
of pancuronium and is not vagolytic. Because of up to 35% of a dose is
renally excreted, patients with renal failure will have decreased dose
requirements. Similarly, because up to 50% of an injected dose is excreted
in bile, patients with hepatic insufficiency will also have decreased drug
requirements to maintain adequate blockade. The 3-desacetylvecuronium
metabolite has 50% of the pharmacologic activity of the parent compound,
patients with organ dysfunction may have increased plasma concentrations
of both the parent compound and the active metabolite, which contributes to
the prolongation of blockade if the dose is not adjusted. Vecuronium has
been reported to be more commonly associated with prolonged blockade
once discontinued, compared with other NMBAs and therefore it is being
used with decreased frequency in ICU.3
Table 1: Neuromuscular Blocking Agents
Atracurium
Dose
1.Adjunct to general
anaesthesia (for surgery or
intubation)
Initial :
IV injection : 0.3 – 0.6
mg/kg 4,5
Maintenance :
IV injection : 0.1 – 0.2
mg/kg 4,5 OR
IV infusion : 5 – 10
mcg/kg/min (300 – 600
mcg/kg/hr) 4,5
2.Intensive care
Initial :
Rocuronium
Pancuronium
1.Surgery procedures
(Intubation)
1.Neuromuscular blockade
Initial :
Initial :
IV injection : 0.6 mg/kg
4,6
Maintenance :
IV injection : 0.15 mg/kg
(Elderly : 0.075 – 0.1
mg/kg)4,6
OR
IV infusion : 0.3 – 0.6
mg/kg/h (Elderly : 0.4
mg/kg/h) 4,6
2.Intensive care
Initial :
IV injection : 0.06 – 0.1
mg/kg or 0.05 mg/kg after
initial dose of
succinylcholine for
intubation 3
Maintenance :
IV injection 0.01 mg/kg 60 –
100 min after initial dose,
then 0.01 mg/kg every 25 –
60 min 3
2.Intensive care
IV injection : 0.05 – 0.1
mg/kg bolus followed by 0.8
– 1.7 mcg/kg/min once
recovery from bolus seen or
0.1 – 0.2 mg/kg every 1-3
hours 3
IV injection : 0.3 – 0.6
mg/kg 4,5
IV injection : 0.6 mg/kg 4,6
Maintenance :
Maintenance :
IV infusion : 4.5 – 29.5
mcg/kg/min (usual : 11 –
13 mcg/kg/min) 4,5
IV infusion : 0.3 – 0.6
mg/kg/h for first hour then
adjusted according to
response 4,6
Onset
2 – 3 min 3
1 – 2 min (within 4 min) 3
2 – 3 min 3
Duration
20 – 35 min 3
~ 30 min 3
60 – 100 min 3
Monitoring
Vital signs (heart rate,
Peripheral nerve stimulator
Heart rate, blood pressure,
Atracurium
Rocuronium
blood pressure, respiratory
rate); renal function and
liver function 3
measuring twitch response;
heart rate, blood pressure,
assisted ventilation status 3
assisted ventilation status 3
Contraindications
Hypersensitivity to
atracurium besylate or any
component of the
formulation 3
Hypersensitivity to
rocuronium or any
component of the
formulation 3
Hypersensitivity to
pancuronium or any
component of the
formulation 3
Precautions
Reduce initial dose and
inject slowly over 1 – 2 min
in patients in whom
substantial histamine
release will be potentially
hazardous (patients with
clinically important
cardiovascular disease) 3
Use with caution in patients
with valvular heart disease,
pulmonary disease, hepatic
impairment; ventilation
must be supported during
neuromuscular blockade 3
Ventilation must be
supported during
neuromuscular blockade 3
Increased sensitivity in
patients with myasthenia
gravis and Eaton-Lambert
syndrome 3
Side effects
Increased sensitivity in
patients with myasthenia
gravis and Eaton-Lambert
syndrome 3
Pancuronium
Use with caution in patients
with renal and/or hepatic
impairment (adjust dose
appropriately) 3
Increased sensitivity in
patients with myasthenia
gravis and Eaton-Lambert
syndrome 3
1 – 10% :
>1% :
Frequency not defined :
Cardiovascular :
Bradycardia, flushing,
hypotension, tachycardia3
Cardiovascular : Transient
hypertension and
hypotension 3
<1% :
<1% (Limited to important
or life-threatening):
Cardiovascular : elevation in
pulse rate, elevated blood
pressure and cardiac output,
tachycardia, edema, skin
flushing, circulatory
collapse3
Broncheal secretions,
erythema, itching,
urticaria, wheezing 3
Abnormal ECG, anaphylaxis,
arrhythmia, bronchospasm,
edema, hiccups, nausea,
rash, rhonchi, shock,
tachycardia, wheezing,
vomiting 3
Dermatologic : Rash, itching,
erythema, burning
sensation along the vein3
Gastrointestinal : excessive
salivation3
Neuromuscular & skeletal :
profound muscle weakness3
Respiratory : wheezing,
Atracurium
Rocuronium
Pancuronium
bronchospasm3
Drug interaction
Increased effect :
Aminoglycosides, beta blocker, calcium channel blocker, clindamycin, imipenem,
quinolones, tetracycline, vancomycin, macrolides, loop diuretics (frusemide), ketamine,
magnesium sulphate, procainamide, quinidine. May increase risk of myopathy when
used with high-dose corticosteroids for extended periods3
Decreased effect :
Carbamazepine (chronic use), phenytoin (chronic use), theophylline, sympathomimetics 3
References :
o
ASHP Therapeutic Guidelines for sustained neuromuscular blockade in the adult critically
ill patient. Approved by the ASHP Board of Directors on November 17, 2001. Am J Health
Syst Pharm. 2002; 59:179-195.
o
Hanson, CW. Pharmacology of neuromuscular blocking agents in the intensive care unit.
Crit Care Clin 1994; 10:779
o
Drug Information Handbook 14th International Edition. 2006 - 2007. Lexi Comp. United
States
o
British National Formularies 54th Edition. September 2007. United Kingdom
o
GlaxoSmithKline [TracriumTM package insert]. GlaxoSmithKline Manufacturing S.p.A.,
Parma, Italy ;2005
o
Organon [Esmeron ® package insert]. N.V. Organon, Oss, Holland ;2002
2.6
SEDATIVE AGENTS IN CRITICALLY ILL PATIENTS
2.6.1
INTRODUCTION
Sedatives and analgesics are often used to facilitate patient tolerance of invasive
mechanical ventilation.1 Patients undergoing mechanical ventilation experience
significant stress superimposed on their acute medical problem, ranging from
anxiety about their surroundings and condition to distress with potential pain from
necessary nursing care and procedures. 3 The goals of sedation and analgesia in
this context include decreasing pain and anxiety, reducing the stress response,
and facilitating nursing care. Recent evidence indicates that the choice of
sedating agents, frequency of administration and regular assessment of sedation
contribute to patient outcomes2 such as length of stay in the ICU, days of
mechanical ventilation, and rate of self-extubation.1 Titrating the dose of sedative
medication based on a sedation scale will help prevent over-sedation and treat
under-sedation. Under-sedated patients may become agitated and distressed
and are at risk of adverse events such as extubation4 while over-sedation can
contribute to hypotension, venous thrombosis, prolonged ventilation, an
increased risk of pneumonia and a prolonged stay in ICU.2
Improving sedation management through sedation protocols and interventions
such as daily interruption of sedation is an increasing focus of quality
improvement initiatives in critical care.4 In 2000, Kress and co-workers showed
that daily withholding of sedative agents led to reduced length of ICU stay, less
ventilator time, fewer ICU complications and fewer neurological investigations.
Subsequent studies by the same group demonstrated daily sedation withholding
to be safe in patients with ischaemic heart disease and that it reduces the
psychological sequelae of critical illness. Sedation withholding is now part of the
‘Ventilator Care Bundle’, as outlined by the UK Department of Health and
recommended by the Surviving Sepsis Campaign.2
Assessment of sedation level is carried out mainly by nurses or critical care
physicians by assessing patient responses to simple stimuli.2 Sedation-agitation
scales can be used to identify and quantify agitation, and to grade the depth of
sedation.5 Sedation scales such as the Revised Riker Sedation and Agitation
Scale, Ramsay Scale or the Richmond Agitated-Sedation Scale are widely used.2
The Malaysian Ministry of Health ICU Management Protocol suggested that
patients are to be assessed for sedation and agitation based on the revised Riker
Sedation and Agitation Scale every 4 hours and titrate the sedative infusion rate
with the aim of keeping the sedation score between -1 to +1.6
Exceptions to keeping the sedation score between -1 and +16 :

Head injured on cerebral protection : sedation score -3

Severe sepsis on high inotropic support : sedation score of at least -1

ARDS on high ventilatory support : sedation score of at least -2

Tetanus : sedation score of at least -2
Revised Riker Sedation Agitation Scale6
Score
Description
Definition
+3
Agitated and restless
When awaken or otherwise, pulling at ETT,
trying to remove catheters or requires physical
restraints
+2
Awake but mildly agitated
Anxious but mildly agitated. Attempts to sit up
but calms down with verbal instructions
+1
Awake and calm
Awake, calm and easily follows commands
0
Aroused by voice and remains Awakens easily to verbal stimuli. Remains
calm
awake, calm and easily follows command
-1
Aroused by movement
Awakens to loud verbal stimuli or gentle
shaking. Has eye contact for at least 10
seconds but drifts off to sleep
OR
Awakens to loud verbal stimuli or gentle shaking
and follows simple commands
-2
Aroused by painful stimuli
Localising or flexion to pain.
communicate or follow commands
-3
Unarousable
Extension, minimal or no response to painful
stimuli
2.6.2
Does
not
SEDATIVE AGENTS

Benzodiazepines7
Benzodiazepines binds to a specific receptor site of the GABA receptor,
and thus the degree of modulation is limited, which explains the ceiling
effect of their CNS depression. It has been suggested that a
benzodiazepine receptor occupancy of 20% provides anxiolysis, whereas
an occupancy of 30% to 50% is associated with sedation, and 60% is
required for hypnosis.
Midazolam is the most commonly used benzodiazepine for ICU sedation.
It is a short acting, water soluble benzodiazepine that undergoes
extensive oxidation in the liver to form water soluble hydroxylated
metabolites, which are excreted in urine. However, the primary
metabolite, namely 1-hydroxymethylmidazolam, has mild CNS
depressant activity and may accumulate in the critically ill patient
especially in the case of kidney failure. Medications that interfere with the
cytochrome P450 enzyme will decrease metabolization of midazolam.
During short term infusions, midazolam is generally safe and effective
sedative agent. However, during continuous infusions, accumulation of
midazolam can occur because of the large volume distribution and its
high lipophilicity. It was shown that older patients require much lower
plasma concentrations of benzodiazepine to achieve level of sedation
comparable to those in younger patients

Propofol7
Propofol is a unique sedative-hypnotic agentwith a rapid onset and offset
action. Like the benzodiazepines, propofol acts on the GABA receptor,
although the site of action on this receptor is different.
It is available for intravenous administration dissolved in fat emulsion has
extremely rapid distribution and metabolization (by hepatic conjugation)
responsible for promptly patient arousal after a single dose or interruption
of drug infusion. Its metabolites are excreted by kidneys. Its formulation
causes a transiently elevation on triglyceride level and has some allergic
properties. It has respiratory and cardiovascular depressant effects, with
minimal influence on heart rate, and is still very expensive what limits its
routine use in ICU. Hepatic and renal diseases have little impact on the
pharmacokinetics of propofol.
Propofol infusion syndrome is a rare but serious and potentially fatal
adverse effect, typically seen with infusion rates >5 mg/kg/h for more than
48 hours. This syndrome is characterized by dysrythmias, heart failure,
metabolic acidosis, hyperkalemia and rhabdomyolisis, and it carries a
mortality rate of up to 85%. In order to minimize the risk of this syndrome,
propofol dosage should be under 4 mg/kg/h for a maximum of 7 days.

Dexmedetomidine7
Dexmedetomidine is a centrally acting α2-agonist with sedative and
analgesic properties. The sedative properties are facilitated through the
locus coeruleus site in the CNS and the analgesic effects may occur via
activation of the α2 receptors by accentuating the action of opioids. It
causes no significant effect on respiratory drive, even when used with
opioids.
Most studies involving dexmedetomidine have evaluated postoperative
ICU patients and demonstrated efficacy for short-term sedation and
analgesic sparing. Although dexmedetomidine is labeled in some
countries only for sedation of less than 24 hours, the drug has not been
extensively studied as an agent for long-term administration to critically ill,
mechanically ventilated patients.
Table 1: Drug doses
Midazolam
Dose
Propofol
Dexmedetomidine
Initial dose :
0.01 - 0.05 mg/kg (~0.5
- 4 mg for a typical
adult)9
1) Monitored
anaesthesia care
sedation (healthy
adults <55 y.o)(dih &
mdx)
Maintenance dose :
Initial dose :
0.02 – 0.1 mg/kg/h or
1 – 7 mg/h9
100 – 150 mcg/kg/min
(6 – 9 mg/kg/h) IV
infusion or 0.5 mg/kg
slow IV injection for 3 –
5 min9,10
0.2 – 0.7 mcg/kg/h for a
maximum of
24
9,10
hours
Initial dose :
Maintenance dose :
25 – 75 mcg/kg/min
(1.5 – 4.5 mg/kg/h) IV
infusion or 10 – 20 mg
incremental IV bolus
doses9,10
2) Sedation for
mechanically ventilated
ICU patient
Initial dose :
5 mcg/kg/min (0.3
mg/kg/h) IV infusion for
1 mcg/kg over 10
mins9,10
Maintenance dose :
Midazolam
Propofol
Dexmedetomidine
5 min then titrate in 5 –
10 mcg/kg/min (0.3 –
0.6 mg/kg/h)
increments to achieve
desired sedation
level9,10
Maintenance dose :
5 – 50 mcg/kg/min (0.3
– 3 mg/kg/h) or
higher9,10
Onset
1- 5 min9
9-51 sec (average 30
sec)9
Rapid9
Duration
15 – 30 min9
3 – 10 min (dose and
rate dependent)9
Cardiac effects
Minimal depressant
effect9,10
Important depressant
effect9,10
Important depressant
effect9,10
Respiratory effects
Important depressant
effect9,10
Important depressant
effect9,10
Minimal depressant
effect9,10
Analgesia
None9
None 9
Yes 9
Monitoring
Respiratory and
cardiovascular status,
blood pressure9
Anaphylactic reactions,
cardiorespiratory
depression, fever,
propofol infusion
syndrome, increased
intracranial pressure or
impaired cerebral
circulation especially in
neurosurgical patients10
Level of sedation, heart
rate, respiration,
rhythm9
Contraindication
Hypersensitivity to
midazolam and its
components including
benzyl alcohol (crosssensitivity with other
benzodiazepines may
Hypersensitivity to
propofol, fospropofol or
its components9
Hypersensitivity to
dexmedetomidine and
its components9
Allergy to eggs, egg
products, soybeans or
Use outside of intensive
care setting10
Midazolam
exist)9
Propofol
Dexmedetomidine
soy products10
Narrow-angle glaucoma
and pregnancy9
Precaution
May cause severe
respiratory depression,
respiratory arrest or
apnea9
May cause hypotension
– hemodynamic events
are more common in
paediatric patients or
patients with
hemodynamic
instability9
Hypotension and/or
respiratory depression
may occur frequently in
patients who have
received narcotic
analgesics9
Side effects
Use slower rate of
induction in elderly9
Do not administer with
blood or blood products
through the same IV
catheter9
Abrupt discontinuation
can result in rapid
awakening, anxiety,
agitation and resistance
to mechanical
ventilation9
Use cautiously in elderly
patients; hypotension
and/or bradycardia may
be more pronounced10
Use caution in patients
with heart block, severe
ventricular dysfunction,
hypovolemia, diabetes
and chronic
hypertension9
COMMON10
COMMON10
COMMON10
Gastrointestinal :
Nausea & vomiting
Gastrointestinal :
Nausea & vomiting
Gastrointestinal :
Nausea, xerostomia
Neurologic : Excessive
somnolence, headache
Musculoskeletal :
Involuntary movement
SERIOUS10
10
Respiratory : Cough
SERIOUS
Other : Hiccoughs
Cardiovascular :
Bradyarrhythmia, heart
failure
SERIOUS10
Cardiovascular : Cardiac
arrest, usually in
combination with CNS
depressant drug;
Gastrointestinal :
Pancreatitis
Immunologic :
Cardiovascular : Atrial
fibrillation,
bradyarrythmia, cardiac
dysrythmia,
hypertension,
hypotension,
tachycardia
Respiratory :
Apnea, bronchospasm,
dyspnea, hypercapnia,
Midazolam
hypotensive episode
Propofol
Anaphylaxis
Endocrine metabolic :
Neurologic : Seizure
Desaturation of blood in
Respiratory : Apnea,
paediatric patients
respiratory acidosis
Neurologic : Involuntary
movement
Dexmedetomidine
hypoventilation, pleural
effusion, pulmonary
congestion, respiratory
acidosis
Psychiatric : Agitation
Respiratory : Apnea,
respiratory arrest with
CNS depressant drug,
respiratory depression,
respiratory obstruction
Drug Interaction10
Atazanavir
(contraindicated,
theoretical)
Carbamazepine
(moderate, probable)
Clarithromycin
(moderate, probable)
Codeine (major,
probable)
Dantrolene (major,
theoretical)
Diltiazem (moderate,
probable)
Efavirenz
(contraindicated,
theoretical)
Fluconazole (moderate,
established)
Theophylline
Bupivacaine (major,
probable)
Lidocaine (major,
probable)
Succinylcholine
(moderate, probable)
Tapentadol (major,
theoretical)
Midazolam
Propofol
Dexmedetomidine
(moderate, probable)
Voriconazole
(moderate, established)
References :
1. Arroliga A, Frutos-Viva F, Hall J, Esteban A, Apezteguia C, Soto L,Anzueto A.
2005. Use of sedatives and neuromuscular blockers in a cohort of patients
receiving mechanical ventilation. Chest 128:496 – 506
2. Reschreiter H, Maiden M, Kapila A. 2008. Sedation practice in the intensive care
unit: a UK national survey. Critical Care 12:R125
3. Schweickert WD, Kress JP. 2008. Strategies to optimize analgesia and sedation.
Critical Care 12(Suppl 3):S6
4. Jackson DL, Proudfoot CW, Cann KF, Walsh TS. 2009. The incidence of suboptimal sedation in the ICU: a systematic review. Critical Care 13:R204
5. Sessler CN, Grap MJ, Ramsay MAE. 2008. Evaluating and monitoring analgesia
and sedation in the intensive care unit. Critical Care 12(Suppl 3):S2
6. Management Protocols in ICU. 2006. Program Anestesia & Cawangan Kualiti
Penjagaan Kesihatan, Bahagian Perkembangan Perubatan, Kementerian
Kesihatan Malaysia.
7. Gommerz D, Bakker J. 2008. Medications for analgesia and sedation in the
intensive care unit: an overview. Critical Care 12(Suppl 3):S4
8. Sessler CN, Wilhelm W. 2008. Analgesia and sedation in the intensive care unit:
an overview of the issues. Critical Care 12(Suppl 3):S1
9. Drug Information Handbook 14th International Edition. 2006-2007. Lexi Comp.
United States
10. MICROMEDEX® Healthcare Series Vol. 143. 2010 Thomson Reuters. United
States
2.7
MANAGEMENT OF ELECTROLYTES IMBALANCE IN CRITICALLY ILL PATIENTS
2.7.1 POTASSIUM (3.5 – 4.5 mmol/L )
Potassium is one of the body's major ions. Nearly 98% of the body's potassium is
intracellular. The ratio of intracellular to extracellular potassium is important in
determining the cellular membrane potential. Small changes in the extracellular
potassium level can have profound effects on the function of the cardiovascular
and neuromuscular systems.
a. Hypokalemia
i)
Sign and Symptoms of Hypokalemia (usually present when K<2.5mmol/L)
► Malaise, fatigue
► Neuromuscular disturbances: Weakness, hyporeflexia, paraesthesias,
cramps, restlessness leg syndrome, rhabdomylysis, paralysis.
► Gastrointestinal: Constipation, ileus
► Polyuria, polydipsia, metabolic alkalosis
► ECG changes: small or inverted T waves, prominent U wave,
depressed ST segments, prolonged PR interval.
► Arrhytmias: First and second degree heart block, atrial fibrillation,
ventricular tachycardia, ventricular fibrillation.
ii) Correction of Hypokalemia
If K+ <2.5 mmol/L
or <3mmol/L if on
digoxin
or
presence of lifethreatening
symptoms
Give KCL 2G diluted to 100 mls N/S through a central line over an
hour.
If no life threatening
symptoms, K+ <3.5
mmol/L
Give KCL 1G diluted to 50mls N/S over an hour or oral/NG KCl 20-40
mmol q6h
Max. rate 0.4 mmol/kg/hour (20-30 mmol/hour)
(1G KCL= 13.3mmol K+ )
iii) Potassium Correction Formula
= (4.5 – Current K+) x 0.4 + Body Weight + 1 x Body Weight
13.4
13.4
= g KCL
b. Hyperkalemia
i)
Sign And Symptoms of Hyperkalemia (Hyperkalemia is an emergency.
The first sign of hyperkalemia may be death. Usually occur when K>6.5
mmol/L)
►
Neuromuscular manisfestations : Bradycardia, prolongation of AV
conduction, complete heart block, wide complex tachycardia,
ventricular fibrillation and asystole.
►
Urgent 12-lead ECG; possible changes are: Tall tented T waves,
small P waves, depressed ST segments, widened QRS complexes,
sine wave (biphasic waves, pre-cardiac arrest)
► ECG has limitation in predicting cardiac toxicity. Thus, patient should
be treated even in the absence of ECG changes
ii) Correction of Hyperkalemia
If K+ > 6 mmol/L
with ECG
abnormalities
Give Calcium Gluconate 10% 20 ml IV over 3 min (may be repeated in 5
min)
5-10 units Actrapid in 100 ml 50% dextrose IV over 30-60 min.
IV Frusemide 20mg to increase urine output.
Resonium 15G q8h oral/N/G or 30G q8h enema/rectal.
IV NaHCO3 50-100 mmol over 5-10 min (not to be given after calcium as
Ca2+ bind HCO3.
Lastly dialysis.
2.7.2
SODIUM ( 135 – 145 mmol/L)
Serum sodium concentration and serum osmolarity normally are maintained
under precise control by homeostatic mechanisms involving stimulation of thirst,
secretion of antidiuretic hormone (ADH), and renal handling of filtered sodium.
Clinically significant hyponatremia is relatively uncommon and is nonspecific in its
presentation; therefore, the physician must consider the diagnosis in patients
presenting with vague constitutional symptoms or with altered level of
consciousness. Irreparable harm can befall the patient when abnormal serum
sodium levels are corrected too quickly or too slowly. The physician must have a
thorough understanding of the pathophysiology of hyponatremia to initiate safe and
effective corrective therapy. The patient's fluid status must be accurately assessed
upon presentation, as it guides the approach to correction.
a. Hyponatremia
i)
Sign and Symptoms of Hyponatremia
The clinical features of acute hyponatremia are related to osmotic water shifted
that leads to increased ICF volume and brain cells swelling. Mild hyponatremia is
usually asymptomatic.
Serum Na of about 120 mmol/L may be associated with disturbed mental state,
restlessness, confusion and irritability.
As the Na approaches 110 mmol/L, seizures and coma may occur.
ii) Correction of Hyponatremia
Total Na+ deficit (mmol)
= (130 –current Na+) x 60% of body weight in kg.
Volume (ml) required to replace total Na+ deficit using 0.9% N/S
=
Total Na+ deficit (mmol)
x 1000
154 (mmol /L)
Volume (ml) required to replace total Na deficit using 3% N/S
= Total Na+ deficit (mmol)
513 (mmol /L)
x 1000
Volume (ml) required to replace total Na deficit using 20 % N/S
= Total Na+ deficit (mmol)
x 1000
3400 (mmol/L)
The volume calculated should be given within the calculated no. of hours
= (130 –current Na+)
0.5
The rate of rise in plasma Na should not exceed 0.5 mmol/L/ hour and the final
plasma Na+ concentration should not exceed 130mmol/L.
b. Hypernatremia
i)
Sign and Synptoms of Hypernatremia
► Definition Na > 145mmol/L
► Features are tremulousness, irritability, ataxia, spasticity, mental confusion
and coma
ii) Correction of Hypernatremia
Free H2O replacement
Water deficit (L) = 0.6 x BW in kg x ( measured Na - 1)
140
To be given over 48-72 hours
Use Dextrose 5%.
2.7.3
MAGNESIUM ( 0.7 – 1 mmol/L)
Magnesium plays an important role in neuromuscular function. Only 1 % is in ECF,
60% are found in bones and reminder in cells. Therefore, serum magnesium may not
reflect total body magnesium content.
a. Hypomagnesemia
i)
Sign & Symptoms of Hypomagnesemia
► Symptomatic magnesium depletion is associated with refractory
hypokalemia, hypocalcemia and metabolic alkalosis.
► Features are : - Tremors, muscle twitching.
- Positive Trousseau’s and Chvostek’s signs
- Generalized weakness, confusion, ataxia
- Vertical nystagmus
- Tetany, seizures
- ECG  Mild to moderate: prolongation of QT or QU
intervals, bifid T waves, U wave, supraventricular and
ventricular ectopics. Severe: PSVT, R-on-T phenomena,
torsades de pointes, VT
- Hypomagnesaemia facilitates development of digoxin
cardiotaxicity.
ii) Correction of Hypomagnesemia
50% MgSo4 solution has osmolarity of 4000 mOsm/L, dilute to 10-20% solution
before IV use.
1mg MgSo4 =4 mmol (8mEq) elemental Mg
1 ml 50% MgSo4 =0.5G=2 mmol (4 mEq) Mg2+
Without symptoms
IV 0.125G/kg MgSo4 x24h then 0.0625G/kg MgSo4 daily x35 days
IV Mg SO4 20mmol in 40ml NS OVER 2 hours
IV Mg SO4 10mmol in 20ml NS OVER ½ hour
If Mg2+ <0.6 mmol/L
with
cardiac
IV 0.05-0.07G/kg MgSo4 over 20 min then 0.03-0.05G/kg/h
abnormalities/
asthma/ eclampsia/
2+
tetanus/ pulmonary Keep serum Mg 2.0-3.5 mmol/L
hypertension
c. Hypermagnesemia
i)
Sign and Symptoms of Hypermagnesemia
► Magnesium levels of 2-4 mEq/L are associated with the following:
o
o
o
o
o
Nausea
Vomiting
Skin flushing
Weakness
Lightheadedness
► High magnesium levels are associated with depressed levels of
consciousness, respiratory depression, and cardiac arrest.
ii)
Correction of Hypermagnesemia
Only in patients IV Calcium Gluconate 10% 30 mls over 3 minutes
with
impaired
Diuresis if possible
renal failure
Dialysis
2.7.4
CALCIUM ( 2.1 – 2.65 mmol/L)
Calcium regulation is critical for normal cell function, neural transmission, membrane
stability, bone structure, blood coagulation, and intracellular signaling. The essential
functions of this divalent cation continue to be elucidated, particularly in head
injury/stroke and cardiopulmonary effects. Depending on the cause, unrecognized or
poorly treated hypocalcemic emergencies can lead to significant morbidity or death
a. Hypocalcemia
i)
Sign and Symptoms of Hypocalcemia
►
Paraesthesia
►
Circumoral numbness
►
Cramp
►
Tetany
► Dystonia
► Convulsion
► Psychosis
► Chvostek’s sign – gentle tapping over facial nerve cause twitching of
facial muscles.
► Trousseau’s sign – inflation of sphygmomanometer cuff above diastolic
pressure for 5 min causes carpopaedal spasm.
► Papilloedema (severe)
► Prolonged Q-T interval on ECG
► Long-standing hypocalcemia may result in dry skin, coarse hair,
alopecia, brittle nails and hypoplastic teeth.
ii)
Correction of Hypocalcemia
10 mls 10% CaCl2 (to be given through central line) contains 272 mg
elemental calcium
10 mls 10% Ca gluconate (can be given through peripheral line) contains
90 mg elemental calcium
Treatment directed at underlying cause:
If symptomatic (muscle spasm, laryngeal spasms or cardiac involvement)
If ionised Ca2+ <0.65 mmol/L or corrected Ca2+ <2.0 mmol/L
i)
IV 10-20mls 10% Ca gluconate over 10 min followed by 1-2 mg/kg/h
x6-12h i.e. 30 mls 10% Ca gluconate diluted to 100 mls N/S run at 2540ml/h x6-12h
ii) Give Mg if deficient
iii) Daily maintenance dose of Ca 2-4G orally
b. Hypercalcemia
i)
Sign and Symptoms of Hypercalcemia
► Neurology :- Depression, proximal myopathy, fatigue, confusion,
stupor and coma.
► Renal :- Hypertension, renal colic (nephrolithiasis), polyuria and
nocturia (nephrogenic diabetes insipidus), dehydration.
► Bones:- Pain, pathological fractures – osteitis fibrosa cystics in
hyperthyroidism
(subperiosteal resorption, bone cysts).
► Abdominal:- Nausea, vomiting, constipation, abdominal colic, peptic
ulcer disease, pancreatitis.
► General:- Soft tissue and corneal calcification (band keratopathy)
► ECG changes:- Shortened QT intervals.
ii)
Correction of Hypercalcemia
N/S or 1/2N/S at 250-500 ml/h to correct hypovolaemia
Frusemide 40-80 mg I/V every 2 hours to maintain urine output 100200mls/hr.
2.7.5
PHOSPHATE ( 0.8 – 1.5 mmol/L)
Phosphate is the most abundant intracellular anion and is essential for membrane
structure, energy storage, and transport in all cells. In particular, phosphate is
necessary to produce ATP, which provides energy for nearly all cell functions.
Phosphate is an essential component of DNA and RNA. Phosphate is also
necessary in red blood cells for production of 2,3-diphosphoglycerate (2,3-DPG),
which facilitates release of oxygen from hemoglobin.
Approximately 85% of the body's phosphorus is in bone as hydroxyapatite, while
most of the remainder (15%) is present in soft tissue. Only 0.1% of phosphorus is
present in extracellular fluid, and it is this fraction that is measured with a serum
phosphorus level.
a. Hypophosphatemia
i)
Sign and Symptoms of Hypophosphatemia
► Weakness is the most common symptom suggesting hypophosphatemia and may
involve any muscular system to any extent.
o
o
o
o
Diplopia
Dysarthria
Dysphagia
Weakness of trunk or extremities, particularly the large muscle groups
► Symptoms of respiratory insufficiency or myocardial depression may indicate
hypophosphatemia.
► Neurologic symptoms may vary, ranging from simple paresthesias to profound
alterations in mental status.
ii) Correction of Hypophosphatemia
Add 2 ampuoles of KH2PO4 in 1 pint IVD
OR
IV KH2PO4 20mmol/L in 100ml NS OVER 6 hours
OR
IV KH2PO4 10mmol/L in 100ml NS OVER 4 hours
2.7.6
FLUID/IV DRIP SUMMARY
Na+
Cl-
K+
Ca2+
(mmol/L)
(mmol/L)
(mmol/L)
-
-
Dextrose 5% Saline
0.9% (500ml)
154
0.9% NaCl (500ml)
pH
Others
(mmol/L)
Osmolarity
(mOsmol)
-
-
252
3.2-6.5
Dextrose 50g
170 Kcal
154
-
-
560
154
154
-
-
308
5.0
-
0.45% NaCl (500ml)
77
77
-
-
154
5.0
-
3% NaCl (500ml)
513
513
-
-
1026
5.0
-
Hartmann’s (500ml)
130
109
4
3
273
6.0-7.5
Lactate 28mEq/L
Gelafundin (500ml)
154
120
-
-
274
7.1-7.7
Gelatin 40g/L
HES 6%
154
154
-
-
310
4.0-7.0
Starch 60g/L
Voluven (100ml)
154
154
-
-
308
5.5
Venofundin (1000ml)
154
154
-
-
309
4.0-6.5
Hydroxyethyl Starch
130/0.4 6g
Poly(O-2hydroxyethyl)starch
(HES) 60g
Sterofundin (1000ml)
140
140
4
2.5
D5% (500ml)
Dextrose 50g
170 Kcal
2.8
MEDICATION ADMINISTRATION THROUGH ENTERAL FEEDING TUBES
2.8.1
Medication plan


2.8.2 .
Enteral administration of medications






2.8.3
Temporarily discontinue medications that are not immediately necessary
Consider giving medications by an alternate route such as transdermal,
rectal, inhaled, intramuscular, subcutaneous, buccal, sublingual or
intravenous whichever possible
Evaluate tube type, tube location in the GI tract, site of drug action and
absorption and effects of food on drug absorption (e.g. sucralfate is not
suitable for intestinal feeding tubes administration as it acts on the stomach)
Drug that require administration on empty stomach, feeding should be
stopped 30 minutes before and after dosing
Liquid dosage forms is preferred whenever possible
Tablets that could be crushed into fine powder and the contents of capsules
can be mixed to a slurry in water and given through large-bore feeding tubes
Feeding tubes should be flushed with at least 30 ml of water before and after
administration of medication via the tube
Medication should not be added to enteral formula to reduce the risk of
microbial contamination and to avoid drug-nutrient incompatibilities
Medications that should not be crushed
Formulation
Sustained-release

Enteric-coated

Teratogenic,
carcinogenic or cytotoxic
medication
2.8.4
Reason



Crushing destroys the sustained-release tablets and
microencapsulated drugs, resulting in erratic blood
levels
Do not crush well but break into small chunks that bond
together when moist and clogging the tube
Decreased the efficacy of the medication
Increased stomach irritation
Aerosolized particles may be harmful to the health-care
provider
Consideration with Liquid Medications

Medication dosage or frequency may need adjustment when switching from
solid to liquid preparations (e.g. extended-release phenytoin capsules may be
given once daily, however phenytoin suspension is an immediate-release
product that need to be dosed 2 to 4 times daily)


2.8.5
Osmolality
- Many commercial liquids have osmolalities over 1000 mOsm/kg, the
osmolality of GI secretions ranges from 100 to 400 mOsm/kg
-
Diarrhea, cramping, abdominal distension and vomiting may occur after
administration of hyperosmolar products through the feeding tube – the
effects may be reduced by diluting medication with 10-30 ml of sterile
water before administration
-
Osmolality of diluted mixture = (osmolality of drug / volume of drug) / total
volume of mixture
Contents of sorbitol
-
many sweeteners including mannitol, lactose, saccharin and sucrose may
cause or worsen diarrhea, the most likely excipient to cause GI problems
is sorbitol
-
sorbitol may cause gas and bloating at total daily doses of 10 gram,
cramping and diarrhea may occur a total daily dose of 20 gram
Drug interaction and incompatibility and special consideration
Interaction / Incompatibility
Recommended intervention (s)
Syrups and other acidic medication
(pH less than 4) may clump when
mixed with enteral feeding formulas

Phenytoin absorption decreases by
50% to 75% when given with
enteral feeding





Carbamezepine absorption may
decrease with enteral feeding


Warfarin effects may be decrease
in patients receiving enteral feeding
due to reduce absorption and



Stopping the enteral feeding for 1 to 2 hours
before and 2 hours after drug administration
To avoid nutritional status compromise:
- minimize the time of feeding interruption by
using once daily or twice daily dosing
regimen
Stopping the enteral feeding for 2 hours before
and after each dose
Flushing the tube before and after each
phenytoin dose
Phenytoin suspension given through feeding
tube may be diluted with 20-60 ml of water
Close monitoring of serum concentrations is
warranted
Carbamazepine suspension may be diluted
with an equal volume of sterile water or normal
saline
Close monitoring of serum concentrations is
warranted
Consider increasing the warfarin dose or using
alternative anticoagulants
Monitor prothrombin time
Consider vitamin K contents in enteral
Interaction / Incompatibility
Recommended intervention (s)
formulas – vitamin K may directly block
warfarin’s effects in doses of 140-500 mcg.day
vitamin K antagonism
Fluroquinolones antibtiotics may
have an erratically changes in its
pharmacokinetics in patients
receiving enteral feeds



Proton-pump inhibitors – these
medications are acid labile and
inactivated by gastric acid, specially
formulated to maintain the acidity
until it delivers to alkaline pH of the
duodenum for absorption






Laxatives

Fluroquinoloes should not be given within 2
hours before or 4 hours after enteral formulas
Avoid giving via enteral feeding tubes or
concomitantly with enteral formulas –
parenteral route is preferred
If to be given via entral tube – crush tablets
and mix in 20 to 60 ml sterile water
immediately before administration
Omeprazole and lansoprazole capsules
(delayed-release) through large-bore
nasogastric or gastrostomy tubes
- may be mixed with juices (apple, orange)
- mixing with water may cause clumping and
lead to occlusion
Omeprazole and lansoprazole capsules
(delayed-release) through small-bore
jejunostomy or gastrostomy tubes
- Dissolve in sodium bicarbonate 8.4%
solution
Esomeprazole granules (delayed-release)
should be mixed with water
Commercial immediate-release omperazole
with sodium bicarbonate
- Should only be mixed with water
- Continuous enteral feeding should be held
for 3 hours before and 1 hour after
medication administration
Lansoprazole disintegrating tablet (delayedrelease)
- Dissolves on tongue or may be mixed with
small amount of water in an oral syringe
and injected through the NG tube
- Should not be given through feeding tube
– increased viscosity, tube occlusion
Continuous enteral feeding should be held for
3 hours before and 1 hour after medication
administration
Bulk forming laxatives (e.g. methycellulose)
- Should not be given via feeding tubes
- Form semisolid mass that may occlude
feeding tube when mixed with less than
250 ml fluid (still potentially block feeding
tube when mixed properly)
- Consider using fiber-containing enteral
nutrition
References:
1. Silberman H. Parenteral and Enteral Nutrition. 2nd ed. Norwalk, CT: Appleton & Lange;
1989, 117–58.
2. Estoup M. Approaches and limitations of medication delivery in patients with enteral
feeding tubes. Crit Care Nurse. 1994;14:68–72,79.
3. Gora ML, et al. Considerations of drug therapy in patients receiving enteral nutrition.
Nutr Clin Pract. 1989; 4:105–10.
4. Thomson F.C., Naysmith, M.R. & Lindsay, A. Managing drug therapy in patients
receiving enteral and parenteral nutrition. Hosp Pharmacist. 2000;7:155–64.
5. Gilbar PJ. A guide to enteral drug administration in palliative care. J Pain Symptom
Manage. 1999;17:197–207.
6. Rombeau JL, Caldwell MD, eds. Clinical Nutrition: Enteral and Tube Feeding. 3rd ed.
Philadelphia, PA: WB Saunders; 1997.
7. Janson DD, Chessman KH. Enteral nutrition. In: DiPiro JT et al, eds. Pharmacotherapy:
A Pathophysiologic Approach. 5th ed. New York, NY: McGraw-Hill; 2002, 2495–517.
8. Mitchell JF. Oral dosage forms that should not be crushed or chewed. Hosp Pharm.
2002; 37:213–14.
9. Dickerson RN, Melnik G. Osmolality of oral drug solutions & suspensions. Am J Hosp
Pharm. 1988;45:832–34.
10. Jew RK, et al. Osmolality of commonly used medications and formulas in the neonatal
intensive care unit. Nutr Clin Pract. 1997;12:158–63.
11. Lutomski DM, et al. Sorbitol content of selected oral liquids. Ann Pharmacother.
1993;27:269–74.
12. Burns PE, et al. Physical compatibility of enteral formulas with various common
medications. J Am Diet Assoc. 1988;88:1094–6.
13. Cutie AJ, et al. Compatibility of enteral products with commonly employed drug
additives. JPEN J Parenter Enter Nutr. 1983;7:186–91.
14. Healy DP, et al. Ciprofloxacin absorption is impaired in patients given enteral feedings
orally and via gastrostomy and jejunostomy tubes. Antimicrob Agents Chemother.
1996;40:6–10.
15. de Marie S, et al. Bioavailability of ciprofloxacin after multiple enteral and intravenous
doses in ICU patients with severe gram-negative intra-abdominal infections. Intensive
Care Med. 1998;24:343–6.
16. Wright DH, et al. Decreased in vitro fluoroquinolone concentrations after admixture with
an enteral feeding formulation. JPEN J Parenter Enter Nutr. 2000;24:42–8.
17. Cohn SM, et al. Enteric absorption of ciprofloxacin during tube feeding in the critically ill.
J Antimicrob Chemother. 1996;38:871–6.
18. Mueller BA, et al. Effect of enteral feeding with Ensure on oral bioavailabilities of
ofloxacin and ciprofloxacin. Antimicrob Agents Chemother. 1994;38:2101–5.
19. Mimoz O, et al. Pharmacokinetics and absolute bioavailability of ciprofloxacin
administered through a nasogastric tube with continuous enteral feeding to critically ill
patients. Intensive Care Med. 1998;24:1047–51.
20. Cacek, A.T., DeVito, J.M. & Koonce, J.R. 1986. In vitro evaluation of nasogastric
administration methods for phenytoin. Am. J. Hosp. Pharm. 43: 689-692.
21. Clark-Schmidt, A.L., Garnett, W.R., Lowe, DR et al. 1990. Loss of carbamazepine
suspension through nasogastric feeding tubes. Am. J. Hosp. Pharm. 47: 2034-2037.
22. Williams, N.E. 2008. Medication administration through enteral feeding tubes. Am. J.
Hosp. Pharm. 65(24): 2347-2357.
23. Beckwith, M.C., Feddema, S.S., Barton, R.G. & Graves, C. 2004. A guide to drug
therapy in patients with enteral feeding tubes: dosage form selection and administration
method. Hospital Pharmacy. 39(3): 225-237.
CHAPTER 3: DOSING
3.1
RENAL DOSING
Acute renal failure is common in critical care situations and is associated with significant
morbidity and mortality. Rapid assessment of renal function is important in critical care
for the following reasons:




Emergency angiography (coronary or otherwise)
Emergency dosing of drugs with narrow therapeutic window
Severe CHF or volume overload condition
Severe hyperkalemia
Investigations have to be carried on in order to determine renal status or renal injury.
Measurements included:




Estimation of GFR
Assessment of Proteinuria or other urine markers of renal injury
Functional assessment of renal function (e.g. Fractional excretion of sodium)
Urine volume
Acute Renal Failure characterized by deterioration of renal function over a period of
hours to days. The mortality rate for patients in the intensive care unit (ICU) is lower in
those who have ARF, especially when ARF is severe enough to require dialysis
treatment. In addition, evidence suggests that the relative risk of death is 4.9 in patients
in the ICU who have renal failure that is not severe enough to require dialysis. The
mortality rate in postoperative renal failure is 24 - 100% and about 50 - 70% in intensive
care who require dialysis. Mortality rate has not decreased significantly over the past 50
years.
A prospective multicenter observational study (Beginning and Supportive Therapy for the
Kidney (BEST) Study) had discovered the incidence of ARF among 29,269 subjects of
critically ill ICU patients was 5.7% and 2/3 required dialysis. 30% of the total subjects
studied already had pre-existing renal dysfunction. Overall mortality associated with ARF
was 60.3%. The most common contributing factor is septic shock. This study defined
ARF as oliguria and/or BUN > 84mg/dl (>30mmol/L).JAMA 294:813;2005
Cockcroft Gault Equation is most common method being used in estimating GFR:
(140-Age)xWeight (kg) x (0.85 if female)
72xSCr
RIFLE criteria are one type of classification to determine the progression of renal
damage. A study done on 5,383 intensive care unit patients, 67% developed acute renal
injury. 12% of patient with R classification had mortality rate of 8.8%, 27% patient with I
classification had mortality rate of 11.4% and 28% patient with F classification had
mortality rate of 26.3%. More than 50% patients progressed from ‘‘R’’to ‘‘I’’or ‘‘F’’ had
worse outcomes than non-progressed. (Hosteet al. Critical Care 10:R73, 2006et 2006)
RIFLE Criteria - adopted from Bellomo et al Crit Care 8:R204; 2004
Standard guideline
Agent
Usual Dosage
Renal Dosing
AMPICILLIN
Mild to moderate infection: 500mg
to 2g ivpb q6h. Severe infection:
2g ivpb q4h (150-200mg/kg/day)
>50/ q6h || 10-50/ q6-12h || <10/ q12-24
hours || Hemodialysis: Dose after dialysis ||
PD: 250mg q12h.
AMPICILLIN (Oral)
Usual dose: 250mg to 1g po q6h
(50-100mg/kg/ day).
>50/ no changes || 10-50/ q6-12h || <10/
q12h
AMPICILLIN SULBACTAM
(UNASYN)
Usual dose: 1.5 to 3g ivpb q6h
>30/ q6-8h || 15-29/ q12h || 5-14/ q24h
AUGMENTIN (Oral)
Usual dose: 875mg po q12h or
250-500mg po q8h
>30/ no change || 10-30/ 250-500mg q12h ||
<10/ 250-500mg po q24h
AZACTAM
Mild infection (i.e. UTI): 500mg to
1g ivpb q8-12h. Usual dose: 1-2g
ivpb q8-12h. Severe or life
threatening: 2g ivpb q6-8h. Max
8g/day
>30/ no change || 10-30/ 50% of usual dose
q6-8h || <10/ 25% of usual dose q6-8h ||
HD/PD: see <10 guidelines. (HD: 500mg
AD) Give loading dose of 1-2g before
starting regimens above.
AZITHROMYCIN
(ZITHROMAX)
Usual oral dose: 500mg x 1, then
250mg po qd x 4 days. Chlamydia:
1gram po x 1. MAC prevention:
1200mg qwk or 500mg po TTW.
PID or CAP: 500mg ivpb qd x 2
days or more than 500mg po qd.
Uncomplicated gonococcal
infection: 2 grams orally x1 *(see
comments)
No adjustments required in renal failure.
Cannot be given IM. *Because of the high
incidence of gastric upset with the 2 gram
dose--this is the least preferred regimen for
treatment of uncomplicated gonococcal
infections.
BACTRIM
IV: Usual dose: 8-10mg/kg/day
divided q6h, q8h or q12h. PCP:
15-20mg/kg/day in 3 or 4 divided
doses. Oral: UTI: 1 DS tab (160mg
TMP/800mg SMX) po q12h.
>30/ no change || 15-30/ 50% of usual dose
q12h-alternatively: 8-10mg/kg/day divided
q12h x 1-2 days, then 4-6mg/kg q24h. ||
<15/ not recommended by manufacturer.
Alternatively: 8-10mg/kg/dose q48h or 4-6
mg/kg/day.
CEFAZOLIN
Usual: 500mg to 1g ivpb 8h.
Severe: 1.5g ivpb q6h. Life
threatening: 6-12g/day.
>55/q6-8h || 35-54/q8h || 11-34/ 50% usual
dose q12h || <10 ml/min/ 50% to full dose
q24-48h. || Hemodialysis: 0.5-1 gram after
dialysis
CEFEPIME
(MAXIPIME)
Mild to moderate infection: 500mg
to 2g ivpb q12h. Severe: 2g ivpb
q8h.
>60/ 0.5-2g q12h || 30-60/ 0.5g-2g q24h ||
11-29/ 0.5g-1g q24h || <10/ 250-500mg
q24h or 0.5-2g q48h. || HD: 1g AD || PD: 1-2
Agent
Usual Dosage
Renal Dosing
grams q48h
CEFOTETAN (IV)
Usual dose: 1g ivpb q12h. Severe:
2-3g ivpb q12h. (Max 6g/day)
>30/ Usual dose || 10-30/ 50% of dose q12h
|| <10/ 25% of dose q12h.|| Hemodialysis or
PD: 50% of usual dose q24h
CEFOXITIN (IV)
Mild infection: 1g ivpb q6-8h
Moderate-severe: 1g ivpb q4h or
2g ivpb q6-8h. Life-threatening: 2g
ivpb q4h or 3g ivpb q6h.
10-50/ q8-12h || <10/ q24-48h || HD: give 1g
after Dialysis: e.g. Give Cefoxitin 1g ivpb MW-F after dialysis + a supplemental dose on
Sunday.
CEFOTAXIME (IV)
Mild infection: 1-2g ivpb q12h.
Moderate: 1-2g ivpb q8h; Severe:
2g ivpb q6-8h; Life threatening: 2g
ivpb q4h (Max dose/day= 12g)
>50/ Usual dose || 10-50/ q8-12h || <10/
q24h || HD: 0.5 to 2g ivpb q24h AD. || PD: 1g
ivpb q24h.
CEFUROXIME (IV)
Usual: 750mg to 1.5g ivpb q8h.
Severe: 1.5g ivpb q6-8h.
>20/q8h || 10-20/ q12h || <10/ 750mg q24h.
|| Hemodialysis: Give single dose after
dialysis or give 750mg q12h. || PD: 750mg1.5g q24h
CEFTIN (ORAL)
Usual dose: 250-500mg po q12h
No changes req'd (usual oral doses are not
significant).
CEFTRIAXONE (IV)
Usual dose: 1-2g ivpb q24h.
Severe: 2g ivpb q12h
No dosage adjustments req'd in renal failure.
PD: 750mg ivpb q12h
CEFTAZIDIME (IV)
Usual dose: 1g ivpb q8-12h.
Severe: 2g ivpb q8-12h. (Max
dose/day= 6 grams).
Crcl 30-50/ q12h || 10-30/ q24h || <10/
q48h
CEPHALEXIN
KEFLEX/VELOSEF
Usual dose: 250-500mg po q6h;
500mg-1g q12h.
Keflex: 10-50/ q6-12h || <10/ q12-24h .
Velosef: >20/ no change || 5-20/ 250mg q6h
|| < 5/ 250mg q12h
CIPROFLOXACIN
(CIPRO)
Oral dosing: 250-750mg po q12h;
cystic fibrosis: 750mg po q8h. IV
dosing: 200-400mg ivpb q12h.
Febrile neutrapenic pt: 400mg ivpb
q8h
>50/ no change || 10-50/ 50-75% of usual
dose q12h || <10/50% of usual dose q12.
Alternatives: [200mg ivpb or 250mg po
q12h] or [400 mg ivpb or 500mg po q24h]. ||
HD/PD: 250-500mg po or 200-400mg ivpb
q24h AD or 200mg ivpb or 250mg po q12h.
CLARITHROMYCIN
(BIAXIN)
Usual dose: 250-500mg orally
q12h. Severe (Legionella): 5001000 mg po q12h. Helicobacter:
500mg po tid.
Severe renal dysfunction: decrease dose or
increase interval. [crcl < 30 ml/min: 500mg
loading dose, then 250 mg once or twice
daily.]
Agent
Usual Dosage
Renal Dosing
CLINDAMYCIN
(IV/PO)
Usual oral dose: 150-400mg po
q6h. Usual IV dose: 600mg ivpb
q6-8h or 900mg ivpb q8h.
Maximum daily dose= 4800mg
No dosage adjustments required for renal
failure
DICLOXACILLIN
(Oral)
Usual dose: 250-500mg po q6h
No changes required for renal insufficiency.
DOXYCYCLINE
(VIBRAMYCIN)
Usual dose: 100mg po bid x1 f/b
100mg qd or divided bid (if severe:
100mg po bid) or 100-200mg ivpb
qd or divided doses q12h.
No dosage adjustments required for renal
failure
ERYTHROMYCIN
Usual oral dose: 500mg to 1g po
q12h or 250mg to 1g po q6h.
Usual IV dose: 250mg to 1g q6h.
Max 4 g/day.
>10/ No change || <10/ 50-75% of usual
dose. Max 2 grams/day. || Hemo: no
supplement.
IMIPENEM
(PRIMAXIN)
Mild to moderate infection: 250500mg ivpb q6-8h. Severe
infection: 500mg to 1g ivpb q6-8h.
Max dose/day= 50mg/kg/day or
4g/day
31-70/ 500mg q6-8h || 21-30/ 500mg q8-12h
max || 0-20/ 250-500mg q12h max. || HD:
250 mg AD + q12h. || PD: max dose=
1gram/day i.e. 500mg ivpb q12h.
LEVOFLOXACIN
(LEVAQUIN)
Usual dose: 500mg po or ivpb
q24h. UTI or pyelonephritis:
250mg po/ivpb q24h.
>50/ no change || 20-49/ 500mg x 1 then
250mg q24h || <19/HD/PD: 500mg x 1 then
250mg q48h
METRONIDAZOLE
(FLAGYL)
IV: 1 gram or 15 mg/kg load IV,
then 500mg or 7.5 mg/kg q6h
(range: q6-12h --long T ½ ). Oral:
250-750mg po tid. (occasionally
bid). Max 4g/day.
> 10/ no change || <10/ 500mg ivpb q12h.
NAFCILLIN
Mild to moderate infection: 500mg
to 1g ivpb q4h or 1-2g ivpb q6h.
Severe: 1-2g ivpb q4h
No dosage changes req'd for renal failure. ||
Renal + Hepatic dysfcn: decrease dose by
50%.
OFLOXACIN
(FLOXIN)
Usual dose: 200-400mg po/IV
q12h.
>50/ no change || 10-50/ usual dose q24h ||
<10/ 100-200mg q24h
PENICILLIN G
(Aqueous)
Usual dose: 0.5 to 4 mu q4-6h.
Severe infection: Dosing interval
q2-3h (i.e. 3mu q3h). Max dose
per day: up to 30 million units
>50/ Usual dose || 10-50/ 75% of usual dose
|| <10/ 20-50% of usual dose. || Hemo/PD:
20-50% of dose usually q6h. Max dose in
ESRD: 6 mu/day.
PEN VK (Oral)
Usual dose: 250-500mg po q6h
>10/ No Changes || <10/ 250-500mg po q8h
PENICILLIN G
Group A strept URI: 1.2 mu IM x 1.
Administer by deep IM in the upper outer
Agent
Usual Dosage
Renal Dosing
BENZATHINE
Peak: 12-24hrs
Duration: 1-4 wks.
Prophylaxis of recurrent rheumatic
fever: 1.2mu q3-4wks. Early
syphilis: 2.4mu x 1 (in 2 injection
sites). Late syphilis (> 1yr): 2.4 mu
(in 2 sites) qwk x 3.
quadrant of the buttock. Not indicated as
single drug tx of neurosyphilis, but may be
given 1 time/wk x 3 weeks following IV tx.
Levels: (time to peak): 12-24hrs. Levels are
detectable for 1-4 wks. Higher doses
increase duration not peak. Use a PCNprocaine/benzathine combination (bicillin) to
achieve early peak levels in acute infections.
[Supplied: 600,000 u/ml (1ml., 2ml, 4ml)
PENICILLIN G
PROCAINE
Dosing: 0.6 to 4.8 mu/day in 1-2
dd. Uncomplicated gonorrhea: 1g
probenecid f/b 4.8mu divided into
2 inj sites 30min later.
Endocarditis (strept): 1.2 mu q6h x
2-4wks. Neurosyphilis: 2-4 mu/day
+ 500mg probenecid qid x 1014days(Note: IV Pcn is D.O.C)
Time to peak: 1-4 hrs. Duration: 15 to 24
hours. Supplied: 600,000 u/ml (1 ml, 2ml,
4ml). 300,000u/ml-10ml vial.
PIPERACILLIN
Mild infection: 3-4g ivpb q6-8h
Serious infection: 3-4g ivpb q4-6h
(200-300mg/kg/day) Max 24g/day
>40/ No change || 20-40/ 4g q8h || <20/ 4g
q12h || HD/PD: 2g q8h. || Alternatively:
>50/q4-6h || 10-50/ q6-8h || <10/ q8h
PIPERACILLINTAZOBACTAM
(ZOSYN)
Mild infection: 3.375g ivpb q6h
Moderate to severe: 3.375g ivpb
q4h
>40/ 3.375g q6h || 20-40/ 2.25g q6h || <20/
2.25g q8h || HD: Max 2.25g q8h. 0.75g AD.
|| PD: 2.25g q8h
SYNERCID
7.5 mg/kg ivpb q8-12h (usually
q8h). Dilute dose in 250ml D5W
and infuse over 1 hour.
TETRACYCLINE
Usual dose: 250-500mg po/iv q6h.
50-90/ q8-12h || 10-50/ q12-24h || <10/ q24h
(use not recommended)
TIMENTIN
Usual dose: 3.1g ivpb q4-6h
>60/ 3.1g q4-6h || 30-60/q8-12h || 10-30/
q12-24h or 2g ivpb q8h || <10/ 2g q12h or
3.1g q24-48h || <10 + hepatic dysfcn/ 2g
q24h || PD: 3.1g q12h || Hemodialysis: 2g
q12h + 3.1g after dialysis.
Peak: 1-4 hrs
Duration: 15-24
hours
ANTIFUNGALS
AMPHOTERICIN B
Test dose: (optional): 1 mg/20-50 ml D5W over 10-30 min. Monitor temp, pulse,
RR and BP q30min x 4 hours. Do not give premeds with test dose. Maintenance
dose: Initially give 0.25-0.3 mg/kg/day. Increase as tolerated by an equivalent
amountqd. Usual daily dose: 0.5-1 mg/kg/day or up to 1.5 mg/kg qod. For lifethreatening infection may give full dose the first day (usually 0.6-0.7 mg/kg IBW on
Day # 1). Premedication: Prevention of fever/chills: Tylenol 650mg PO/PR +
Agent
Usual Dosage
Renal Dosing
Benadryl 25-50mg PO/IVP 60min prior to maintenance infusion. May also add:
Hydrocortisone 25-50mg IV/IM +/- Demerol 50mg IV. Renal dosing: <10/ q24-36h.
During therapy if the BUN increases above 40 mg/dl or the serum creatinine
exceeds 2.5-3 mg/dl, Hold Ampho B until renal function improves, then restart at a
reduced dose or change to QOD dosing until Serum creatinine/BUN improve.
Bladder irrigation: Add 30-50mg Ampho B to 1000ml (or less) sterile H2O
administered intermittently or continuously for 2 to 14 days. (Note: use of D5W for
Bladder irrigations is not recommended because of the possibility of enhancing
microbial and fungal growth in the bladder).
FLUCONAZOLE
(DIFLUCAN)
Oral: Oropharyngeal candidiasis:
200mg po x 1, f/b 100mg po qd.
Esophageal candidiasis: 100-200
mg po qd (up to 400mg/day).
Cryptococcal meningitis: 400mg
po x 1, f/b 200mg po qd x 10-12
weeks (Suppression: 50-200mg
po qd). Onychomycosis: 200300mg qweek or 100-200mg po
qod (further studies needed). IV:
since oral absorbtion is rapid and
essentially complete-IV dose=oral
dose.
>50/ no change || <50 / 50% of usual dose. ||
Alternatively: 20 to 50/ give normal dose
q48h. || <20 / 50% of usual dose q48h. ||
Hemodialysis: give 100-200mg after each
dialysis. || CAPD: give 50% of usual dose at
usual interval.
FLUCYTOSINE
(ANCOBON
Dosing: 12.5 to 37.5 mg/kg po q6h
(50 to 150mg/kg/day). Doses up to
250 mg/kg/day have been used in
severe infections. Capsules
should be taken a few at a time
over 15 min to minimize N&V.
>50 / no change || 10 to 50/ q12-24 hrs ||
<10 / q24-48 hrs. || Hemodialysis: Single
doses after dialysis || CAPD: 500mg to 1
gram q24h
ITRACONAZOLE
(SPORANOX)
Systemic mycosis: 200mg po qd
with food (up to max of 400mg/day
if unsatisfactory clinical response
with lower dose). Doses >200mg
are given in 2 divided doses.
Onychomycosis: 200mg po bid for
1 week each month x 2 months
(fingernails); x 3-4 months
(toenails). Oropharyngeal
candidiasis: 200mg (20ml)-oral
solution-swish vigorously then
swallow once daily x 1-2 weeks.
Esophageal candidiasis: 100mg
(10ml) oral soln-swish and swallow
qd x 3 weeks. May increase to
200mg/day. Life-threatening
infections: Loading dose: 200mg
No adjustments necessary in renal
insufficiency.Duration of therapy: Oral
candidiasis, Tinea Corporis, and Tinea
Cruris: 15 days. Tinea Pedis: 30 days. Tinea
Capitis: 4-8 weeks.[100mg capsule; 10
mg/ml oral soln]
Agent
Usual Dosage
Renal Dosing
po tid should be given for the first
3 days of therapy, then 200400mg/day.
TERBINAFINE
(LAMISIL)
Superficial mycoses(tinea
corporus, cruris, pedis, capitis;
cutaneous candidiasis): 250 mg
po qd. Onychomycosis:
(fingernails) 250mg po qd x 6
weeks or pulse dosing: 500mg po
qd for 1st week of month x 2
months. (Toenails): 250mg po qd
x 12 weeks or pulse dosing:
500mg po qd for 1st week of
month x 4 months. Systemic
mycosis: 250-500mg po qd.
Specific guidelines are not available for renal
or hepatic insufficiency. [250mg tab]
ACYCLOVIR
(ZOVIRAX)
Mucocutaneous herpes simplex:
IV: 5 mg/kg/dose q8h x 5-10 days.
Encephalitis: 10mg/kg/dose IV
q8h. Primary HSV infection-genital
(Oral tx): 200mg q4h while awake
(5x/day) or 400mg po tid x 10
days. Recurrent genital: 400mg po
tid x 5 days. Herpes Zoster:
800mg po q4h while awake
(5x/day) x 7 days. If severe give
10-12 mg/kg IV q8h x 7-14 days.
Chronic suppression (genital
herpes): 400mg po bid. Zovirax
ointment: apply ½" q3h (6 x/day).
50 - 90/ 5 to 12.4 mg/kg q8h || 10-50 / 5-12.4
mg/kg q12-24h || <10 / 2.5 to 6 mg/kg q24h.
Alternatively: (Oral): 10-25 / dose q8h || <10
/ dose q12h. (IV): 25-50/ 5-10mg/kg q12h ||
10-25/ 5-10mg/kg q24h || <10/ 2.5 to 5mg/kg
IV q24h. || HD: dose after dialysis || CAPD:
see < 10.
FAMCICLOVIR
(FAMVIR)
Herpes Zoster: 500mg po q8h x 7
days. Recurrent herpes
simplex(genital): 125 mg po bid x
5 days. Primary Genital herpes
simplex: 250 mg po tid x 5-10
days. Genital-chronic suppression:
250 mg po bid. [125mg, 250mg,
500mg tablet]
>60/ no change || 40-59/ 500mg q12h || 1139/ 500mg q24h || <10/ 250 mg q48h || HD:
250mg after dialysis.
VALACYCLOVIR
(VALTREX)
Herpes zoster: 1000mg po tid x 7
days. Primary genital herpes:
1000mg po bid x 10 days.
Recurrent genital: 500mg po bid x
5 days. Genital-chronic
>50/ no change || 30-49/ 1 gram q12h || 1029/ 1 gram q24h || <10/ 500mg q24h. || HD:
dose after dialysis. || CAPD: 500mg q24h.
ANTIVIRALS
Agent
Usual Dosage
Renal Dosing
suppression: 500mg po qd [500mg
caplet]
AMANTADINE
(SYMMETREL
Parkinsons dx: 100mg po bid.
Influenza A viral infection:
200mg/day in 1-2 divided doses.
50-60/ 200mg alternating c 100mg po qd ||
30-50/ 100mg qd || 20-30/ 200mg twice
weekly || 10-20/ 100mg 3x/week || <10/ 200
mg alternating c 100mg q7 days. || HD/PD:
No supplemental dose req'd.
RIMANTADINE
(FLUMADINE)
Prophylaxis and treatment of
influenza A virus. Dosing: 100mg
po bid. [100mg tab; 50mg/5ml
syrup]
> 10/ no change || <10/ 100mg po qd
Cimetidine
(Tagamet)
Active ulcer: Oral: 800 mg orally at
bedtime or 300mg orally four times
daily or 400 mg orally twice daily.
IM/IV: 300mg every 6 hours or
37.5 mg/hr continuous infusion.
Active bleed: 37.5 mg/hr
continuous IV (maximum
2400mg/day). Maintanance
(duodenal ulcer prophylaxis):
400mg orally at bedtime. Gastric
hypersecretory conditions: 300600mg every 6 hours.
CRCL (> 40ml/min) / 300mg q6-8h ; (2040 ml/min) / 300 mg q8h ; (5-20ml/min)
/200-300mg q12h; (< 5ml/min) / 200mg
q12h.
Famotidine (Pepcid)
Usual dose (Acute): 40mg orally at
bedtime or 20mg orally twice daily.
Maintenance: 20 mg orally at
bedtime. Hypersecretory
conditions: 20mg orally every 6
hours. May increase up to 160mg
orally every 6 hours
CRCL > 50 ml/min: No changes (40mg
IV/PO qd or 20mg q12h.) || CRCL < 50
ml/min: Oral: 20mg qd or 40mg qod. IV:
20mg q24h.
[Since CNS adverse effects have been
reported in patients with moderate and
severe renal insufficiency, to avoid excess
accumulation of the drug in patients with
moderate or severe renal insufficiency, the
dose of PEPCID may be reduced to half the
dose or the dosing interval may be
prolonged to 36-48 hours as indicated by the
patient's clinical response.]
Nizatidine (Axid)
Usual: 300mg orally at bedtime or
150 mg orally twice daily.
Maintenance: 150mg orally at
bedtime. Supplied: [150, 300mg
capsule]
CRCL > 50 ml/min: Usual dose || CRCL
20-49 ml/min: 150mg qd. || CRCL < 20
ml/min: 150mg qod.
H2 Antagonists
Agent
Ranitidine (Zantac)
Usual Dosage
Renal Dosing
Usual dose: 150mg orally twice
daily or 300mg orally at bedtime.
Maintenance: 150mg orally at
bedtime. Gastric hypersecretory
conditions: 150mg orally 2 to 4
times daily. IVPB: 50mg every 6
to 8 hours (Maximum:
400mg/day) Continuous infusion:
(preferred in actively bleeding
patients): 6.25 mg/hr titrated to
gastric pH >4 for prophylaxis or
>7.0 for treatment.
CRCL (ml/min) >50/ no change; 10-50:
Administer at 75% of normal dose or
administer 50mg IV or 150mg orally every
18-24 hours. CRCL <10 mL/minute:
Administer at 50% of normal dose or
administer 50mg IV every 18-24 hours or
150mg orally q24h. || Hemodialysis: Slightly
dialyzable (5% to 20%). Give dose at end of
dialysis session.
References
1. American Hospital Formulary Service. Drug Information. Bethesda, MD: ASHP, 1997.
2. Bartlett JG.1998 Pocket Book of Infectious Disease Therapy., Ninth Edition. Baltimore,MD:
Williams&Wikins,1998.
3. Bennett, WM, Aronoff, GR et. al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults.
Fourth Edition, 1999.
4. Drug Information Handbook, 5th Ed. 1997, Lexi-Comp inc.
5. Gilbert DN, Moellering RC, Sande MA. The Sanford Guide to Antimicrobial Therapy 2000. 30th ed.
Hyde Park,VT: Antimicrobial Therapy, Inc.; 2000.
ANTIBIOTIC DOSING IN RENAL IMPAIRMENT
DRUG NAME
ABACAVIR
ACYCLOVIR
USUAL DOSE
(Normal renal function)
300 mg PO q12h
5 - 10 mg/kg IV q8h
CrCl
(ml/min)
no change
> 50
25-50
24-10
0-9
HD
200 mg PO q4h (5x
daily)
> 10
DOSAGE ADJUSTMENT (in renal
insufficiency)
no change
5 - 10 mg/kg IV q8h
5-10 mg/kg IV q12h
5 - 10 mg/kg IV q24h
2.5 -5 mg/kg IV q24h
2.5 - 5 mg/kg IV q24h (give dose after
dialysis on dialysis days)
no adjustment necessary
0-10
>10
200 mg PO q12h
no adjustment necessary
0-10
> 25
200 - 400 mg PO q12h
no adjustment necessary
400 mg PO q4 (5x
daily) - 12h
800 mg PO q4 (5x
DRUG NAME
USUAL DOSE
(Normal renal function)
daily) - 12h
CrCl
(ml/min)
24-10
0-9
HD
AMOXICILLIN
500 mg - 1 gm PO
q12h
> 30
24-10
<10
HD
AMOXICILLIN +
CLAVULANATE
500 - 875 mg PO q12h
>15
15-5
<5
HD
AMPHOTERICIN B
0.25 - 1.5 mg/kg/day *
not to exceed total
daily dose of 1.5
mg/kg
250 mg - 2 gm IV q46h
no dose
change
necessary
AMPICILLIN /
SULBACTAM
1.5 - 3 gms IV q6h
> 30
15-30
< 15
HD
AMPRENAVIR
AZITHROMYCIN
1200 mg PO q12h
500 mg IV/PO once
daily for 3 days
1 - 2 gms IV q8h
no change
no change
AMPICILLIN
AZTREONAM
> 30
30-10
< 10
HD
> 30
30-10
<10
HD
CEFAZOLIN
500 mg - 1 gm IV q8h
CEFEPIME
1 - 2 gm IV q12h
> 35
35-10
< 10
HD
> 60
30 - 60
29-10
< 11
DOSAGE ADJUSTMENT (in renal
insufficiency)
800 mg PO q8 - 12h
400 - 800 mg PO q12h
800 mg PO q12h (give dose after dialysis
on dialysis days)
no dose adjustment necessary
250 - 875 mg PO q12h
250 - 875 mg PO q24h
250 - 875 mg PO q24h + 250 - 500 mg
after each HD
normal dose and interval
500 - 875 mg q24h
250 - 500 mg q24h
250 - 500 mg q24h + 250 - 500mg after
each HD
no dose adjustment necessary
normal dose q6 - 8h
normal dose q8h
normal dose q8h + supplemental dose
after each HD
normal dose IV q6h
normal dose IV q12h
normal dose IV q24h
normal dose q24h + supplemental dose
after each HD
no change
no change
normal dose
load with 1-2 gm, then 500 mg - 1 gm IV
q8h
load with 1-2 gm, then 250 - 500 mg IV
q8h
dose for CrCl < 10 + supplemental dose
after HD
no dose adjustment necessary
500 mg - 1 gm q12h
500 mg - 1 gm q24h
2 gm after each HD
no dose adjustment necessary
1 - 2 gm q 24h
500 mg - 1 gm q24h
250 - 500 mg q24h
DRUG NAME
USUAL DOSE
(Normal renal function)
CrCl
(ml/min)
HD
2 gm IV q8h
(meningitis)
> 60
1 gm IV q8h
(neutropenic fever)
CEFTRIAXONE
CEFUROXIME
AXETIL
CEFOTAXIME
1 - 2 gms IV q24h
* max. dose = 4
gm/day
250 - 500 mg PO q12h
500 mg - 1 gm IV q8h
CLARITHROMYCIN
250 - 500 mg PO q12h
CLINDAMYCIN
600 mg IV q8h
OR 150 - 450 mg PO
q6h
125 - 500 mg PO q6h
> 60 kg: 200 mg PO
q12h
OR
400 mg PO q24h
(tablets)
<60kg: 125 mg PO
q12h 250 mg PO q24h
(tablets)
OR
DICLOXACILLIN
DIDANOSINE (ddI)
DOXYCYCLINE
EFAVIRENZ
100 mg IV/PO q12h
600 mg PO q24h
30-60
29-10
< 10
HD
> 60
30 - 60
29-10
< 11
HD
no change
> 10
< 10
> 35
35-10
< 10
> 30
< 30
no change
no change
 50
26 - 49
25-10
< 10
HD
no change
no change
DOSAGE ADJUSTMENT (in renal
insufficiency)
dose for CrCl < 11 + 250 - 500 mg after
each HD
no dose adjustment necessary
2 gm IV q12h
2 gm IV q24h
1 gm IV q24h
dose for CrCl < 11 + 1 gm after each HD
no dose adjustment necessary
1 gm IV q12h
1 gm IV q24h
500 mg IV q24h
dose for CrCl < 11 + 500 mg after each
HD
* adults with both renal and hepatic
failure should not receive more than 2
gm/day
normal dose
250 mg PO q24h
no dose adjustment necessary
1 gm q12h
1 gm q24h
normal dose
If normal dose is 500 mg PO q12h: give
load of 500 mg then 250 mg q12h If
normal dose is 250 mg PO q12h, give
250 mg q24h
no change
no change
> 60 kg: normal dose
< 60 kg: normal dose
> 60 kg: 100 mg PO q12h or 200 mg PO
q24h (tablets) < 60 kg: 75 mg PO q12h
or 150 mg PO q24h (tablets)
> 60 kg: 150 mg PO q24h (tablet)
< 60 kg: 100 mg PO q24h (tablet)
> 60 kg: 100 mg PO q24h (tablet)
< 60 kg: 75 mg PO q24h (tablet)
dose for CrCl < 10
no change
no change
DRUG NAME
ERYTHROMYCIN
ETHAMBUTOL
FLUCONAZOLE
FLUCYTOSINE
(5-FC)
GANCICLOVIR IV
IMIPENEM
(Refer to product
information for
complete
prescribing
information for
patients requiring
different total daily
doses)
USUAL DOSE
(Normal renal function)
250 - 500 mg PO q6 12h
OR
15 - 20 mg/kg/day IV
divided q6h
15 - 25 mg/kg/day
Loading Dose: 100 800 mg PO/IV q24h
Maintenance Dose:
50 - 800 mg PO/IV
q24h
CrCl
(ml/min)
no change
DOSAGE ADJUSTMENT (in renal
insufficiency)
no change
> 50
10-50
< 10
HD
> 50
normal dose
normal dose q24 -36h
normal dose q48h
normal dose after each HD
normal dose
< 50 (no
HD)
HD
50% normal dose q24h
load with 100 - 400 mg, then normal
dose after each HD
50 - 150 mg/kg/day
> 40
normal dose
PO divided q6h
20 - 40
12.5 - 37.5 mg/kg q12h
20-10
12.5 - 37.5 mg/kg q24h
< 10
12.5 - 37.5 mg/kg q24 - 48h
HD
If receiving HD q 48 - 72h then 20 - 50
mg/kg immediately after each HD
Induction: 5 mg/kg IV >70
5 mg/kg q12h
q12h x 14 - 21 days
50-69
2.5 mg/kg q12h
25-49
2.5 mg/kg q24h
<25
1.25 mg/kg q24h
HD
1.25 mg/kg 3x/week with doses given
after HD
Maintenance: 5 mg/kg >70
5 mg/kg q24h
IV q24h
50-69
2.5 mg/kg q24h
25-49
1.25 mg/kg q24h
<25
0.625 mg/kg q24h
HD
0.625 mg/kg 3x/week with doses given
after HD
500 mg IV q6h (2
> 71
> 70 kg: 500 mg q6h 60 - 69 kg: 500 mg
g/day) [Note that
q8h 50 - 59 kg: 250 mg q6h 40 - 49 kg:
meningitis dose is
250 mg q6h 30 - 39 kg: 250 mg q8h
higher (up to 1g q 6h, 41 - 70
> 70 kg: 500 mg q8h 60 - 69 kg: 250 mg
depending on renal
q6h 50 - 59 kg: 250 mg q6h 40 - 49 kg:
function- consult ID)]
250 mg q8h
21 - 40
> 70 kg: 250 mg q6h
**In patients undergoing hemodialysis or with a Clcr of 6-20 ml/min, the
500mg IV q 12 hour dose should be reserved for treatment of severe
infections. Patients with Clcr < 5 ml/min should not receive
imipenem/cilastatin unless dialysis is going to be instituted within 48
hours. These patients may be at an increased risk of seizures.
DRUG NAME
INDINAVIR
ISONIAZID
ITRACONAZOLE
LAMIVUDINE
LAMIVUDINE/ZIDO
VUDINE
(COMBIVIR)
LEVOFLOXACIN
USUAL DOSE
(Normal renal function)
800 mg PO q 8h
300 mg PO daily
100 - 200 mg PO
(capsule / solution)
q12h OR 200 mg IV
q12h x 4 doses, then
200 mg IV q24h ***IV
use NOT TO EXCEED
14 days***
150 mg po q 12h
METRONIDAZOLE
DOSAGE ADJUSTMENT (in renal
insufficiency)
no change
no change
PO: no change
> 50
150 mg PO q12h
30-49
150 mg PO q24h
15-29
150 mg x 1,then 100 mg PO q24h
14-May
150 mg x 1, then 50 mg PO q24h
<5
150 mg x 1, then 25 mg PO q24h
HD
150 mg x 1, then 25 - 50 mg PO q24h
normal dose
not recommended due to injectable
excipient
1 tablet PO q12h
not recommended in fixed combination for Clcr <
50 ml/min
If normal dose 250 mg
IV/PO q24h
> 20
< 20 and
HD
> 50
20 - 49
< 20 and
HD
CVVHD
> 50
20 - 49
< 20 and
HD
CVVHD
250 mg q24h
250 mg q48h
no change
>50
26-50
25-Oct
<10
HD
no change
normal dose
normal dose q12h
50% normal dose q12h
50% normal dose q24h
50% normal dose q24h + 50% normal
dose after each HD
no change
If normal dose 500 mg
IV/PO q24h
LINEZOLID
MEROPENEM
CrCl
(ml/min)
no change
no change
PO: no
change
IV: > 30
IV: < 30
If normal dose 750 mg
IV/POq24 h (note that
the 500 mg q 24h
dosage schedule
shown above should
be used if the
levofloxacin MIC is
<0.5 ug/ml)
600 mg IV/PO q12h
1 gm IV q 8h - (note
that meningitis dose
is higher, 2g q 8h,
with normal renal
function)
500 mg IV/PO q12h
no change
500 mg q24h
500 mg q48h
500 mg x 1, then 250 mg q48h
500 mg q 48h
750 mg q24h
750 mg q48h
750 mg X 1, then 500 mg q48h
750 mg q 48h
DRUG NAME
CrCl
(ml/min)
no change
DOSAGE ADJUSTMENT (in renal
insufficiency)
no change
NAFCILLIN
NELFINAVIR
NEVIRAPINE
NITROFURANTION
USUAL DOSE
(Normal renal function)
500 mg IV/PO q8h (C.
difficile diarrhea)
2 gm IV q4-6h
1250 mg PO q12h
200 mg PO q12h
50-100 mg PO q12h
no change
no change
no change
> 40
< 40
NORFLOXACIN
400 mg PO q12h
PENICILLIN G
2.0 - 4.0 million units
IV q4h
PENTAMIDINE
4 mg/kg IV or IM q24h
PIPERACILLIN/TAZ
OBACTAM
Mild to Moderate
Infections: 3.375 gm
IV q6h
> 30
< 30
> 125
60 - 124
40 - 59
20 - 39
19-Oct
< 10 & HD
< 10 &
ESLD
> 50
Oct-50
< 10
HD
>40
20-40
<20
HD
no change
no change
no change
normal dose
avoid use: therapeutic levels not attained
in the urine
normal dose
normal dose PO q24h
3.0 - 4.0 million units q4h
1.8 - 2.0 million units q4h
1.3 - 1.5 million units q4h
800,000 - 1.0 million units q4h
800,000 - 1.0 million units q6h
500,000 - 800,000 units q6h
500,000 units q8h
Severe/life
threatening
infections: 4.5 gm IV
q6h
>40
20-40
<20
HD
Pseudomonas
aeruginosa
infections*: 3.375 gm
IV q4h. *
Combination therapy
with an
aminoglycoside may
be indicated,
depending on
piperacillin MIC and
site of infection.
Treatment of
uncomplicated UTIs
can be with "mild to
moderate infection"
>40
20-40
<20
HD
normal dose
normal dose q24-36h
normal dose q48h
dose for CrCL < 10 ml/min
normal dose
2.25 gm q6h
2.25 gm q8h
2.25 gm q8h + 1.125 gm supplemental
dose after each HD
normal dose
4.5 gm q8h
4.5 gm q12h
2.25 gm q8h + 1.125 gm supplemental
dose after each HD
normal dose
3.375 gm q6h
3.375 gm q8h
2.25 gm q8h + 1.125 gm supplemental
dose after each HD
DRUG NAME
QUINUPRISTIN/DA
LFOPRISTIN
PYRAZINAMIDE
PYRIMETHAMINE
RIFABUTIN
RIFAMPIN
RITONAVIR
SAQUINAVIR
STAVUDINE
STREPTOMYCIN
USUAL DOSE
(Normal renal function)
dosages
7.5 mg/kg IV q8h
CrCl
(ml/min)
no change
no change
15-30 mg/kg/d
(maximum 2 gm/day)
> 10
<10
HD
25 - 75 mg PO q24h
300 mg PO q24h
600 mg IV/PO q12 24h
600 mg PO q12h
600 mg PO q8h
> 60kg: 40 mg PO
q12h < 60kg: 30 mg
PO q12h
no change
no change
no change
normal dose
25-30 mg/kg three times weekly
25-30 mg/kg three times weekly, postdialysis
no change
no change
no change
15 mg/kg/day IM
no change
no change
> 50
26-49
< 25 and
HD
> 80
50-80
< 15
HD
NOT ADVISED-
> 30
29-Oct
normal dose
1 g q24 hrs
<10
HD
500 mg q24 hrs
500 mg q24 hrs dosed post-dialysis
< 10
HD
VALACYCLOVIR
Urinary Tract
Infections: 5
mg/kg/day of
trimethoprim
component given in
divided doses Serious
Systemic Infections:
8-10 mg/kg/day of
trimethoprim
component given in
divided doses (q 6 12hr) Pneumocystis
carinii Pneumonia
15-20 mg/kg/day of
trimethoprim
component given q 68hr
Primary Genital
Herpes Simplex 1 gm
PO q12hrs
no change
no change
normal dose
normal dose q24h
50% normal dose q24h
normal dose
1 gram loading dose, then 7.5 mg/kg
q24h
1 gram loading dose, then 7.5 mg/kg
q24-72h
7.5 mg/kg q72-96h
give 50-75% of loading dose after each
HD
normal dose q24h
normal dose
normal dose divided q12h x 48-72h then
50% of normal daily dose given q24h
NOT ADVISED
Oct-49
TMP/SMX (Bactrim,
Septra) 1SS tablet =
80 mg TMP; 1DS
tablet =160 mg TMP;
1 ampule(5 ml) = 80
mg TMP
DOSAGE ADJUSTMENT (in renal
insufficiency)
< 10
> 30
15 - 30
DRUG NAME
VALGANCICLOVIR
USUAL DOSE
(Normal renal function)
Recurrent Herpes
Simplex (genital) 500
mg PO q12h
Herpes zoster: 1 gm
PO q8h
CrCl
(ml/min)
> 30
< 29
HD
> 50
30-49
29-Oct
<10
HD
900 mg po q12h
> 60
40 - 59
25 - 39
24-Oct
ZALCITABINE
(ddC)
0.75 mg PO Q8H
ZIDOVUDINE
200 mg PO q8h
HD
> 50
Oct-49
< 10 and
HD
> 26
< 25 and
HD
DOSAGE ADJUSTMENT (in renal
insufficiency)
normal dose
500 mg PO q24h
dose for Clcr < 29, given after HD
normal dose
1 gm PO q12h
1 gm PO q24h
500 mg PO q24h
dose for Clcr < 10, given after HD
INDUCTIO
MAINTENANCE
N
900 mg po
900 mg po q24h
q12h
450 mg po
450 mg po q24h
q12h
450 mg po
450 mg po q2days
q24h
450 mg po
450 mg po twice weekly
q2days
do not use in patients on hemodialysis
normal dose
0.75 mg q12h
0.75 mg q24h
normal dose
100 mg q8h
Ali Olyaei PharmD, 2005
REFERRENCES
Joshi MC. Dose Adjustment- An Important Issue in Critical Care. Internet Journal of Medical
Update Vol1, No1, Jan-jun 2006
Mahendra Agraharkar, MD, FACP. Acute Renal Failure
3.2
LIVER DOSING
DRUGS
DOSAGE ADJUSTMENT
Acyclovir
No adjustment
Adenosine
No adjustment
Adrenaline
No adjustment
Alprazolam
Reduce dose by 50 % to 60% or avoid in cirrhosis. May
precipitate coma in liver disease.
Amikacin
No adjustment
Aminophylline
Adjusted according to serum level measurement during
the first 12 to 24 hours. Use with caution.
Amiodarone
Dosage adjustment should be considered, drug extensively
metabolised by liver.
Amitryptylline
Increase sedative effect; avoid or use with caution in liver
disease.
Amlodipine
Required dosage adjustment; 2.5mg od for hypertension,
5 mg od for angina.
Amoxycillin-Clavulanate
No adjustment
(Augmentin)
Ampicillin + Sulbactam
No adjustment
(Unasyn)
Amphotericin B
No adjustment
Aspirin
Avoid use in severe liver disease; may increase risk of
gastrointestinal bleeding.
Atenolol
No adjustment
Atracurium
No adjustment
Atropine
No adjustment
Atorvastatin
Contraindicated in active liver disease and increase in
serum transaminase
Azithromycin
Not necessary; use with caution due to potential
hepatotoxicity (rare). Specific dosing guidelines for
hepatic impairment have not been established.
Baclofen
No adjustment
Budesonide
Reduced dose in moderate to severe case
Bupivacaine
Reduced dose in severe case; use with caution
Calcium Polystyrene Sulfonate
No adjustment as drug not absorbed systematically.
Powder (Kalimate)
Carbamazepine
Avoided if aggravated liver dysfunction or active liver
disease
Caspofungin
Mild case: no adjustment necessary
Moderate case: 35mg/day; initial 70mg loading dose
should still be administered in treatment of invasive
infections; Esophageal candidiasis: 35mg/day
Severe case: no clinical experience
Cefepime
No adjustment
Cefoperazone-Sulbactam
Reduce dose by 50 % in patient with advanced liver
(Sulperazone)
cirrhosis, maximum daily dose: 4 g.
Cefotaxime
Moderate dosage reduction is recommended in severe
liver disease.
Ceftazidime
No adjustment
Ceftriaxone
Decrease dose and monitor plasma concentration if both
hepatic and severe renal impairment.
Cefuroxime
No adjustment
Celecoxib
↓ 50% in moderate case. Avoided in severe case.
Ciprofloxacin
No adjustment
Clarithromycin
No need if renal function normal. Elderly : age related
reduction in renal function; monitor and adjust dose if
necessary.
Clindamycin
Reduced dose (adjustment recommanded in severe
hepatic diseases).
Cloxacillin
No adjustment
Clopidogrel
Caution (risk of bleeding); avoid in severe hepatic
impairment. Reduced in moderate case.
Dantrolene
Chronic therapy contraindicated in active liver disease;
has potential for hepatotoxicity
Dexamethasone
No adjustment
Dexmedetomidine
Dose reduction may need to be considered (↓ clearence)
Diazepam
Use with caution. Reduced by 50%.
Digoxin
No specific dosage adjustment is necessary
Diltiazem
↓ dose. Safe in cirrhosis up to 90mg/day.
Dobutamin
No adjustment
Dopamin
No adjustment
Doxycycline
No adjustment
Enalapril
No adjustment
Enoxaparine
Use with caution in hepatic impairment
Erythromycin
May cause idiosyncratic hepatotoxicity. Decrease dose in
moderate and severe cases.
Esmolol
No adjustment
Esomeprazole
Severe hepatic disease dose should not exceed 20mg. Mild
to moderate- no adjustment.
Felodipine
Begin at dose of 2.5mg/day. Dose above 10mg/day should
not be used as incidence and severity of adverse event
outweighs additional hypotensive effects.
Fentanyl
No adjustment.
Fondaparinux
No adjustment.
Frusemide
Hepatic disease: 20-120mg/day; used as adjunct to
spirinolactone and other measures.
Fucidic acid
Not excrete renally. Patient with hyperbilirubinemia prior
to fucidic acid therapy have experienced an elevation of
bilirubin levels during therapy which returned to
pretreatment levels with discontinuation. Drug should be
avoided in these patient. Patient with cholestasis : 500mg
intravenously.
Gemfibrozil
No adjustment
Gentamicin
No adjustment
Glycopyrrolate
No adjustment
Griseofulvin
Avoid in severe liver disease
Haloperidol
No adjustment
Heparin
No adjustment
Hydralazine
No adjustment
Hydrocortisone
Dosage adjustment may be necessary.
Imipenem-Cilastatin (Tienam)
No adjustment.
Ipratropium
No adjustment.
Isoniazid
Use with caution; monitor liver function regularly in the
first 2 months. Dose should be reduced in severe liver
disease.
Itraconazole
Use only if benefit outweighs risk; dose reduction may be
necessary.
Isoflurane
No adjustment
Ketoconazole
Specific adjusment not described. Dose reduction in
severe liver disease.
Ketorolac
Use with caution, may cause elevation of liver enzyme.
Hepatic dose may prolong elimination half life.
Labetalol
Chronic liver disease → ↓ metabolism of labetalol.
Dosage reduction is required to avoid decrease in heart
rate and supine blood pressure.
Lactulose
No adjustment.
Lamotrigine
Moderate →severe : initial escalation & maintenance
doses should ↓ by 25%.
Severe & ascites: initial escalation & maintenance should
↓ by 50%.
Lansoprazole
Dose should not > 30mg od in severe liver disease.
Levetiracetam
Mild to moderate no need adjustment;
Severe: ↓ dose by 50 %.
Levobupivacaine
Caution in liver disease.
Levofloxacin
No adjustment.
Lignocaine
↓ dose in acute hepatitis & cirrhosis by 50%.
Linezolid
Mild to moderate hepatic impairment : no dosage
adjusment neccessary. Use in severe not been adequately
evaluated.
Lorazepam
No dose adjusment needed. The administration with the
lowest , effective dose is recommended.
Losartan
↓initial dose to 25mg/day.
Lovastatin
Use with caution in patient with past history of liver
disease; active liver disease is contraindicated.
Mannitol
No adjustment.
Meloxicam
Mild to moderate: no adjustment necessary.
Severe : not been adequately studied
Meropenem
No dosage adjustment .
Metformin
Risk factor for lactic acidosis, should be avoided in
patients with hepatic insufficiency.
Methyldopa
No adjustment.
Methylprednisolone
No adjustment
Metoclopramide
Dosage adjustment necessary, 10 mg tds effective and safe
for treatment of nausea and heartburn.
Metoprolol
Dosage adjustment may be required; reduce dose slightly.
Metronidazole
Mild : no need adjusment
Severe: ↓ dose; maximum 500mg iv suggested.
Midazolam
Reduced midazolam clearance in patients with cirrhosis.
Dose reduction is necessary.
Morphine
Mild: unchange but avoid in severe.
Excessive sedation may occur in cirrhosis.
Duration of action prolonged, dosage should be adjusted.
Dosing interval suggested to be increased 1.5 to 2 times
normal dose.
Nalbuphine
Administrated with caution in reduced doses
Naproxene
Suggested that dose of naproxene↓ at least 50%.
Nifedipine
↓ dose in severe liver disease
Noradrenaline
No adjustment.
Omeprazole
Not > 20mg od in liver disease
Pantoprazole
Maximum 20mg od in severe liver disease & cirrhosis
→monitor liver function ( discontinue if deterioration)
Paracetamol
Dose related toxicity – avoid large doses
Safely administered in therapeutic dose in stable hepatic
disease, t ½ ↑ in patient with acetaminophene induced
liver disease.
Parecoxib
Mild →no adjustment
Halve dose in moderate case (max: 40mg od)
Severe hepatic impairment – no data; not recommended
Perindopril
No adjustment
Pethidine
↓ initial dose in severe hepatic impairment; use with
caution.
Phenobarbital
use with caution; initial dose should be reduced.
Phenytoin
Mild : safe in usual dose
Reduced dose in moderate to severe.
Phytomenadione (Vit K)
No adjustment
Piracetam
Cirrhosis : clearance ↓; dose adjustment necessary
Piperacillin-tazobactam
No adjustment.
(Tazocin)
Polymyxin B
No adjustment.
Prazosin
Initially 0.5mg od; increased with caution.
Prednisolone
No adjustment.
Propofol
No adjustment.
Propranolol
Marked slowing of heart rate may occur during cirrhosis
with conventional dose ; low initial dose required.
Pyrazinamide
Monitor hepatic function ; idiosyncratic hepatoxicity
more common
Specific dosage recommendation not provided.
Ranitidine
No adjustment.
Ramipril
No adjustment.
Rifampicin
Avoid or do not exceed 8mg/kg od. Discontinue treatment
if symptom such as nausea, vomiting, malaise or jaundice
develop.
Rocuronium
Routine dose adjustment not necessary.
Ropivacaine
↓ dose or avoid.
Salbutamol
No adjustment.
Sevoflurane
Use with caution in patient with underlying hepatic
condition.
Simvastatin
Contraindicated in active liver disease.
Sodium bicarbonate
In patient with fluid retention, avoid those contain large
amount of sodium.
Sodium polystyrene sulfonate
No adjustment as drug not absorbed systematically.
powder (Resonium)
Sulfamethoxazole &
trimethoprim (Bactrim)
No adjustment.
Suxamethonium
Prolonged apnoe may occur in severe liver disease due to
reduced hepatic synthesis of pseudocholinesterase. May
↓dose.
Telmisartan
20-40mg od in mild / moderate impairment, avoid in
severe.
Terbutaline
No adjustment.
Theophylline
Monitor serum level and ↓ dose.
Thiopental
No adjustment.
Tigecycline
No adjustment.
Topiramate
Use with caution in hepatic impairment;
May decrease clearance but no specific dosing.
Tramadol
Cirrhosis: 50mg bd.
Valpraote (valproic acid)
Avoid if possible, hepatotoxicity & hepatic failure may
occur (usually in first 6 month)
Valsartan
Mild to moderate ≤ 80mg/day; avoid if severe.
Vancomycin
No adjustment
Vecuronium
Not recommended; if must be used, lowest effective dose
must is recommended.
Verapamil
↓ dose by 20% to 50% of normal dose ; patient should be
monitored for abnormal prolongation of the PR interval.
Voriconazole
Mild to moderate : follow standard loading dose, ↓
maintenance dose by 50% .
Severe : used only if benefit outweighs risk.
Warfarin
Avoid in severe liver disease especially if protrombin time
already prolonged.
Respond to oral anticoagulant may be enhance in
obstuctive jaundice (due to ↓ vit K absorption), hepatitis
and cirrhosis (due to ↓ production of vit K dependent
clotting factor)
Zolpidem
↓ dose to 5mg od.
References:
1. Micromedex (R) Healthcare Series. Vol 141
2. British Formulary 56, September 2008.
3. Drug Information Handbook. 15th Edition 2003.
4. Infectious Disease Handbook; Antimicrobial Therapy & Diagnostic test/Procedure. 5th
Edition. Lexi-Comp.2003.
5. Anesthesiology & Critical Care Drug Handbook. 6th Edition.2005. Lexi-Com
6. Medical Toxicology. Richard C. Dart. .2004.pg 1914. Dantrolene.
7. www.rxlist.com/mevacor-drug.htm. Lovastatin Drug Information: Used, Side effect, Drug
Dosage.
8. Dexmedetomidine: a novel sedative-analgesic agent
Ralph Gertler, MD, 1 H. Cleighton Brown, MD,1 Donald H. Mitchell, MD,1 and Erin N.
Silvius, MD1
2001.
3.3
SPECIAL DOSING IN OBESE PATIENTS
Obesity is defined by the CDC as a BMI of >30kg/m2, and morbid obesity is defined as a
BMI of >40kg/m2.
3.3.1
Physiological changes in obesity
Can alter pharmacodynamic and pharmacokinetic of a drug which includes:





Dramatically increased adipose tissue
Slightly increased lean tissue mass
Increased cardiac output
Increased glomerular filtration rate
Fatty infiltration of liver
A higher proportion of body tissue can influence drug with lipophilic properties
whereas increased organ mass, lean body mass, and blood volume in obesity
can affect hydrophilic medications.
Failure to adjust doses in obesity may result either in sub therapeutic failure or
increased toxicity.
3.3.2
Reported dosing adjustment in obesity
Drugs
Antimicrobials
Acyclovir
Aminoglycosides
Amphotericin B
Beta-lactams
Ciprofloxacin
Erythromycin
Fluconazole
Ganciclovir
Mycobacterial antibiotics
Vancomycin
Muscle relaxant
Suxamethonium
Atracurium
Pancuronium
Sedative
Propofol
Suggested dosing weight
Additional dosing
recommendation
IBW 1
IBW + 0.4(ABW-IBW)1
ABW for conventional
preparation; IBW for lipid
preparation1
IBW + 0.3(ABW-IBW)2
IBW + 0.45(ABW-IBW)2
IBW 1
Consider higher doses in
obese patient1
ABW 3
IBW 2
ABW 2
IBW 3
IBW 3
IBW 3
ABW 5
ABW = actual body weight
IBW = ideal body weight
Calculations:IBW (Ideal body weight):
Male IBW (kg) = 50 kg + 2.3 (height in inches over 60 inches)
Female IBW (kg) = 45.5 kg + 2.3 (height in inches over 60 inches)
3.3.3
Creatinine clearance in obese patient4
Overestimation or underestimation of clearance can occur in obesity when
considering actual body weight versus ideal body weight, respectively. The
Cockcroft-Gault equation is commonly used to calculate glomerular filtration rate
(GFR) in lean patients, however its use in obesity is questionable due to the
disparity between muscle mass and body weight ratio observed in obesity.
The Salazar-Corcoran equation takes into account multiple factors to provide a
better estimation of ClCr in obesity including serum creatinine, gender, actual
weight, age, and height.
Salazar-Corcoran Equation4:
ClCr(Male) =
(137-age)x[(0.285xWt)+(12.1xHt2)]
(51xSCr)
ClCr(Female) = (146-age)x[(0.287xWt)+(9.74xHt2)]
(60xSCr)
Wt= actual body weight in kg
Ht= height in meters
SCr=serum creatinine in mg/dl
Although some drugs have established dosing adjustments for obesity, it remains
unknown for the majority of drugs if dosing adjustment is warranted.
References:
1. Optimal antibiotic dosing for obese patients a challenge for clinicians by Elizabeth Dodds Ashley,
PharmD, BCPS Infectious Disease News June 2007
2. Antimicrobial Dosing in Obesity Rebecca Wurtz, GailItokazu, and Keith Rodvold Clinical Infectious
Diseases1997;25:112C
3. Uptodate 17.1
4. Pharmacokinetics Alterations in Obesity By Jane B. Lee, PharmD; P. Shane Winstead,
PharmD;Aaron M. Cook, PharmD ORTHOPEDICS 2006; 29:984
5. MICROMEDEX(R) Healthcare Series Vol. 143
CHAPTER 4: NUTRITION
4.1
PARENTERAL NUTRITION IN CRITICALLY ILL PATIENTS
ESPEN Guidelines on Parenteral Nutrition: Intensive Care (Adapted from Singer et al.,
2009)
Recommendations
Grade
Indications



Starvation and underfeeding in ICU patients is aasociated with increased
morbidity and mortality
Parenteral Nutrition (PN) should be initiated within 24 to 48 hours in all
patients who are not expected to be on normal nutrition within 3 days when
enteral nutrition (EN) is not feasible
All patients receiving less than their targeted enteral feeding after 2 days
should be considered for supplementary PN
C
C
C
Requirements



A complete PN formulation should be given to ICU patients to cover their
needs fully
The aim in acute illness is to provide energy as close as possible to the
measured energy expenditure (to reduce negative energy balance)
ICU patients should receive 25 kcal/kg/day increasing to target over the next
2-3 days (in the absence of indirect calorimetry)
C
B
C
Carbohydrates


The minimal amount required is about 2g/kg of glucose per day
Hyperglycemia (glucose >10 mmol/L) contributes to death in critically ill
patient and should be avoided to prevent infectious complications
B
Lipids should be an integral part of PN for energy and to ensure essential fatty
acid provision in long term ICU patients
Intravenous lipid emulsions can be administered safely at a rate of 0.7 g/kg
up to 1.5 g/kg over 12 to 24 hours
The tolerance of mixed LCT/MCT lipid emulsions in standard use is sufficiently
documented
Olive oil-based PN is well tolerated in critically ill patients
EPA and DHA containing lipid emulsions had demonstrable effects on cell
membranes and inflammatory process. Fish oil-enriched lipid emulsions
probably decrease length of stay in crtitically ill patients
B
B
Lipids





B
C
B
B
Recommendations
Grade
Amino Acids

A balanced amino acid mixture should be infused at approximately 1.3-1.5
g/kg of ideal body weight per day in conjunction with an adequate energy
supply
 In critically ill patients indicated for PN, the amino acid solution should
contain 0.2-0.4 g/kg/day of L-glutamine (e.g. 0.3-0.6 g/kg/day alanylglutamine dipeptide)
Micronutrients

B
A
All PN prescriptions should include a daily dose of multivitamins and of trace
elements
C
A central venous access is required to administer the high osmolarity PN
mixture
Peripheral venous access may be considered for low osmolarity PN mixture
(<850 mOsm/L)
If peripherally administered PN does not allow full provision of the patient’s
need, then PN should be administered via the central venous access
C
PN admixtures should be administered as a complete all-in-one bag
B
Route



C
C
Mode

Reference:
Singer, P., Berger, M.M., Van den Berghe, G., Biolo, G., Calder, P., Forbes, A., Griffiths, R.,
Kreyman, G., Leverve, X. & Pichard, C. 2009. ESPEN guidelines on parenteral nutrition:
intensive care. Clinical Nutrition. (28). 387-400.
CHAPTER 5: OTHERS
5.1
DRUG CAUSING HAEMATOLOGICAL DISORDER
Drugs may produce hematologic toxicity by one of three general mechanisms:

direct drug (or a metabolite) toxicity

toxicity due to a drug effect on a genetic abnormality in the bone marrow

toxicity involving immune mechanisms.
The four major blood dyscrasias attributable to drugs are:

agranulocytosis or leukopenia (loss of the white blood cells)

aplastic anemia (loss of all the formed elements of the blood)

thrombocytopenia (loss of the platelets)

hemolytic anemia (loss of the red blood cells).
The incidence of these adverse hematologic drug reactions, the relative importance of
various etiologic chemicals, and their resultant morbidity and mortality vary.
5.1.1
Drugs Suspected of Inducing Agranulocytosis (Leukopenia)
Drug-induced agranulocytosis is classified as Type 1 (due to an immune
mechanism) and Type II (drug effect on bone marrow DNA synthesis). In Type I
reactions, blood immunoglobins are directed against drug-related antigens
located on circulating leukocytes.
Allopurinol*
Anticonvulsants
Isotretinoin
Aminopyrine
Antimalarials
L-dopa
Chloramphenicol
Aspirin
Mercurial diuretics
Chlordiazepoxide
Captopril
Methyldopa
Chloroquine
Cephalosporins
Naproxyn
Chlorpromazine
Chlorthalidone
Nitrofurantoin
Indomethacin
Cimetidine
Penicillins
Mefenamic acid
Clindamycin
Phenothiazines
Penicillamine
Diazepam
Piroxicam
Phenylbutazone
Diflunisal
Procainamide
Phenytoin
Doxycycline
Propranolol
Quinidine
Fenoprofen
Spironolactone
Rifampicin
Gentamicin
Streptomycin
Sulfonamides
Griseofulvin
Sulfonylureas
Thiazides
Hydralazine
Sulindac
Acetaminophen §
Ibuprofen
Tolmetin
Acetazolamide
Isoniazid
Vancomycin
* Underlined drugs are most significant
§ Many of these other drugs have been implicated in only one or a few case reports
5.1.2
Drugs Suspected of Inducing Aplastic Anemia
Aplastic anemia is an unexpected peripheral-blood pancytopenia with variable
bone marrow hypocellularity in the absence of underlying malignant or
myeloproliferative disease.
Severe aplastic anemia is seen with a bone marrow of less than 25% of normal
cellularity or a bone marrow of less than 50% of normal cellularity with less than
30% of the hematopoietic cells and at least two of the following peripheral blood
values:

Granulocytes fewer than 500/mm3

Platelets fewer than 20,000/mm3

Anemia with reticulocytes fewer than 1%. 15 About 65% of people with aplastic
anemia die within 4 months of diagnosis; few die after this 4-month period.'
Allopurinol*
Sulfonamides
Naproxyn
Aminopyrine
Acetaminophen §
Organic solvents
Chloramphenicol
Aspirin
Phenytoin
Chloroquine
Benzene
Piroxicam
Gold salts
Captopril
Sulfonylureas
Indomethacin
Chlordiazepoxide
Sulindac
Mefenamic acid
Chlorpromazine
Thiazides
Phenylbutazone
Fenoprofen
Thiocyanate
Propylthiouracil
Indoprofen
*Underlined drugs are most significant
§ Many of these other drugs have been implicated in only one or a few case reports
5.1.3
Drugs Suspected of Inducing Thrombocytopenia
Drug-induced immune thrombocytopenia is characterized by acute purpura,
confluent petechiae or ecchy-moses- particularly after mild trauma-and
gastrointestinal, central nervous system, or urinary tract bleeding,all associated
with a mild or severe lack of blood platelets.
Drugs may induce marrow hypoplasia, destroy platelets directly, or be
responsible for an immune reaction. Thrombocytopenia may be associated with
several disease states (acute leukemia, Gaucher's disease, systemic lupus
erythematosus, sarcoidosis); drug-induced thrombocytopenia usually remits 1 to
2 weeks after drug discontinuance.
Gold salts*
Aspirin
Isotretinoin
Indomethacin
Codeine
Para-aminosalicyclic acid
Mefenamic acid
Danazol
Phenytoin
Quinidine
Diclofenac
Piroxicam
Quinine
Digitoxin
Ranitidine
Thiazides
Fenoprofen
Sulindac
Acetaminophen §
Heparin
Tolmetin
Aminopyrine
Ibuprofen
Amiodarone
*Underlined drugs are most significant
§ Many of these other drugs have been implicated in only one or a few case reports
5.1.4
Drugs Suspected of Inducing Hemolytic Anemia
Aminopyrine*
Diclofenac
Quinine
Methyldopa
Ibuprofen
Rifampicin
Quinidine
L-dopa
Sulfonamides
Acetaminophen §
Mefenamic acid
Sulindac
Aspirin
Naproxyn
Tetracyclines
Cephalosporins
Penicillins
Thiopental
Chlorpromazine
Phenylbutazone
Volatile nitrites
Phenytoin
*Underlined drugs are most significant.
§ Many of these other drugs have been implicated in only one or a few case reports.
5.2
POISONING
Treatment Option
Dose & Duration
Dilution
Side Effects
Contraindications
Monitoring
Organophosphate Poisoning
1. Prevention of
absorption
- Activated
Charcoal
Adult : 25 – 100 gm
Dilute 30 gm in 240 ml
Impaired intestinal
motility
Absence of bowel
sounds, GI perforation,
intestinal obstruction,
recent surgery, GI
haemorrhage
Serum electrolyes,
ECG, serum amylase
Adult :
Given undiluted
2 mg q5-10 min
Hypersensivity,
Myasthenia Gravis,
paralytic ileus, pyloric
stenosis and prostatic
enlargement
Pulse rate, EKG, urine
output, GI motility
I/Tracheal : Dilute dose
in 1-2 ml of NS
Antimuscarinic effect
e.g dry skin, dilated
pupil, flushing, urinary
retention,↓bronchial
secretion, constipation,
bradycardia etc
Dilute up to 20 mg/ml
with WFI for IV inj.
given over 5-10 min
Blurred vision, diplopis,
dizziness,
drowsiness,↑BP
Hypersensitvity to any
component of the
product
Vital signs, ECG, urine
output
Inf : dilute in 100ml NS
over 15-30 min
headache,transient ↑
LFT, impaired
accommodation, N,
tachycardia,
GIVE only after patient
is adequately
atropinised
Child : 25 – 50 gm
< 1 yr : 0.5 – 1 gm/kg
Tx : Cont until pt clinical
condition improve.
2. Treatment
- Atropine
(IV) until atropinised
Child :
0.05 mg/kg (IV),
then 0.02-0.05
mg/kg q15-60 min
until atropinised
Tx : cont for 12 – 24 H
Commnet from Martina
Want to include the
infusion dose?
- Pralidoxime
Adult :
30mg/kg (bolus),
repeat at 4-6 H,
Inf : 8mg/kg/H
(Max : 12 gm/day)
Child :
20 – 50 mg/kg,
10 – 20 mg/kg/H
(Max : 2gm/dose)
Note : administer as soon as
possible after exposure,
however pt presenting late (26 days post exposure) may
Treatment Option
Dose & Duration
Dilution
Tx : until pt clinical
condition improve
Side Effects
Contraindications
Monitoring
still benefit
laryngospasm
Paraquat Poisoning
Prevention of
absorption
- Activated
Charcoal
- Fdbck from
Martina: Fuller’s
earth?
Adult : 25 – 100 gm
Dilute 30 gm in 240 ml
Impaired intestinal
motility
Absence of bowel
sounds, GI perforation,
intestinal obstruction,
recent surgery, GI
haemorrhage
Serum electrolyes,
ECG, serum amylase
Adult :
Maybe given undiluted
Hypersensitivity to
naloxone
Vital Signs
0.4 – 2 mg q 2-3 min
(bolus) (Max : 10 mg)
Infusion :
Hyperyension, N, V,
sweating, tachycardia,
elevated PTT
Child : 25 – 50 gm
< 1 yr : 0.5 – 1 gm/kg
Tx : Cont until pt clinical
condition improve
Opiods Poisoning
1. Overdosage
- Naloxone
Child :
0.01 mg/kg, then 0.1
mg/kg if no response
Tx : up to 48H
2. Reversal of Opiod
induced resp
distress
1.5 – 3 µg/kg (IV), if
4mg in 500ml in NS, D5
discrd inf after 24H
Treatment Option
- Naloxone
Dose & Duration
Dilution
Side Effects
Contraindications
Monitoring
needed increment of
0.1mg q2min, further
dose IM after 1-2H prn
Benzodiazepines Poisoning
1. Prevention of
absorption
- Activated
Charcoal
Adult : 25 – 100 gm
Dilute 30 gm in 240 ml
Impaired intestinal
motility
Absence of bowel
sounds, GI perforation,
intestinal obstruction,
recent surgery, GI
haemorrhage
Serum electrolyes,
ECG, serum amylase
Given undiluted or
further dilute with
D5,NS,½ NS
N, V, Flushing,
agitation, anxiety,
transient ↑BP, HR
Life threatening
condition controlled by
BDZ (e.g ↑ intracranial
pressure, status
epilepticus)
Airway, breathing,
circulation, vital signs,
ECG
Child : 25 – 50 gm
< 1 yr : 0.5 – 1 gm/kg
Tx : Cont until pt clinical
condition improve.
2. Treatment
- Flumazenil
Adult :
0.2 mg (15 sec), then
0.1mg q1min prn, usual
0.3-0.6mg (Slow IV),
Inf : 0.1-0.4 mg/H (Max
: 2 mg)
Child :
5µg/kg every 60
sec, max 40 µg/kg
Discard solution after
24H
Treatment Option
Dose & Duration
Dilution
Side Effects
Contraindications
Monitoring
then 2-10 µ/kg/H
Tx : until desired level of
consciousness with max
dose achieved
Heparin and Derivatives Poisoning
Severe Haemorrhage
- Protamine Sulfate
Adult :
Undiluted over 10 min
1mg /100U hep,
Maybe further dilute
with NS or D5.Rate
<5mg/min inf over 2-3H
(Max : 100 mg)
Hypotension,
bradycardia and
dyspnoea
None when use as
indicated
Airway, breathing,
circulation, vital signs,
Coagulation Profile,
FBC
Impaired intestinal
motility
Absence of bowel
sounds, GI perforation,
intestinal obstruction,
recent surgery, GI
Serum electrolyes,
ECG, serum amylase
Child :
1mg/100U hep,
0.5mg/100U hep. If >
1H (slow IVstat), subs
dose1mg/kg (Max : 50
mg)
Tx : any dose over 100mg
in 2H should be justified
by coagulation studies
Warfarin Overdosage
1. Prevention of
absorption
- Activated
Adult : 25 – 100 gm
Child : 25 – 50 gm
Dilute 30 gm in 240 ml
Treatment Option
Charcoal
Dose & Duration
Dilution
Side Effects
< 1 yr : 0.5 – 1 gm/kg
Contraindications
Monitoring
haemorrhage
Tx : Cont until pt clinical
condition improve.
2. Treatment
- Vitamin K
Adult : 10 mg
(Max : 25 – 50 mg)
Child : 1-5 mg
Dilute 10mg in 50ml D5
over 30 min or into Y
site of fast running D5
Venous irritation,
phlebitis, anaphylaxis
Hypersensitivity to
components
Airway, breathing,
circulation, vital signs,
Coagulation Profile,
FBC, INR
Impaired intestinal
motility
Absence of bowel
sounds, GI perforation,
intestinal obstruction,
recent surgery, GI
haemorrhage
Serum electrolyes,
ECG, serum amylase
Max 40mg over 24H
(Max : 0.6 mg/kg)
Tx : may repeat in 6-8H if
initial response is not
adequate
Paracetamol Poisoning
1. Prevention of
absorption
- Activated
Charcoal
Adult : 25 – 100 gm
Child : 25 – 50 gm
< 1 yr : 0.5 – 1 gm/kg
Tx : Cont until pt clinical
condition improve.
Dilute 30 gm in 240 ml
Treatment Option
Dose & Duration
Dilution
Side Effects
Contraindications
Monitoring
2. Treatment
- N-Acetylcysteine
Adult :
Adult :
150mg/kg over 15min,
then 50mg/kg over 4H,
then 100mg/kg over
16H
Initial dilute in 200ml
D5% given over 15min,
then in 500ml over 4H,
then in 1L over 16 H
Child : Same as adult
Child (<12y) :
Tx : usually total infusion
time is 21H
Dilution ½ of adult
given at the same rate
of adult dose.
Child (<20 kg) :
Initial dilute as 3ml/kg
over 15 min, then
7ml/kg over 4H, then
14/kg over 16H.
References :
Rash, anaphylaxis,
bronchospasm,
hypocalcaemia and
ECG changes
From Martina: Want to
add what to do if these
happens. Stop or not to
stop NAC?
Hypersensitivity to
acetylcysteine or any of
its component
Airway, breathing,
circulation, vital signs,
Ca2+ level, LFT, ECG
Notes : NAC therapy should
begin within 8H of ingestion if
possible. NAC efficacy
decrease progressively from
8-16H post ingestion
1.
2.
3.
4.
BNF 51, March 2006
Drug Doses, 13th Ed 2005, Frank Shann
Intravenous Medication 2008, 24th Ed, Betty LG, Adrienne RN
Micromedex (R) Healthcare Series Vol. 13
APPENDICES
APPENDIX 1: DRUGS THAT MAY UNMASK/EXACERBATE MYASTHENIA GRAVIS
Anesthetic agents
Chloroprocaine
Diazepam
Ether
Halothane
Ketamine
Lidocaine
Neuromuscular blocking agents
Propanidid
Procaine
Antibiotics
Aminoglycosides
Amikacin
Gentamicin
Kanamycin
Neomycin
Netilmicin
Paromomycin
Spectinomycin
Streptomycin
Tobramycin
Fluoroquinolones
Ciprofloxacin
Levofloxacin
Norfloxacin
Others
Ampicillin
Clarithromycin
Clindamycin
Colistin
Erythromycin
Lincomycin
Quinine
Telithromycin
Tetracyclines
Anticonvulsants
Gabapentin
Phenytoin
Trimethadione
Antipsychotics
Chlorpromazine
Lithium
Phenothiazines
Antirheumatic drugs
Chloroquine
Penicillamine
Cardiovascular drugs
Beta blockers
Bretylium
Procainamide
Propafenone
Quinidine
Verapamil and calcium channel blockers
Glucocorticoids
Corticotropin
Methylprednisolone
Prednisone
Neuromuscular blockers and muscle relaxants
Botulinum toxin
Magnesium sulfate and magnesium salts
Methocarbamol
Ophthalmologic drugs
Betaxolol
Echothiophate
Timolol
Tropicamide
Proparacaine
Other drugs
Anticholinergics
Carnitine
Cholinesterase inhibitors
Deferoxamine
Diuretics
Emetine (Ipecac syrup)
Interferon alpha
Iodinated contrast agents
Narcotics
Oral contraceptives
Oxytocin
Ritonavir and antiretroviral protease inhibitors
Statins
Thyroxine
* Drugs listed here should be used with caution in patients with myasthenia gravis. Aminoglycosides
should be used only if absolutely necessary with close monitoring. Please refer to the text for further
information.
Ref: Uptodate 17.1
APPENDIX 2: CATEGORIES OF SAFE & UNSAFE DRUGS IN THE ACUTE PORYPHYRIAS
Categories of safe drugs in the Acute Porphyrias
Drugs Which are SAFE to use:
Acetaminophen
Acetazolamide
Allopurinol
Amiloridine
Aspirin
Atropine
Bethanidine
Bromides
Bumetanide
Chloral hydrate
Cimetidine
Corticosteroids
Coumarins
Fluoxetine
Gabapentin
Gentamycin
Guanethidine
Insulin
Narcotic analgesics
Ofloxacin
Paracetamol
Penicillins
Phenothiazines
Propranalol
Streptomycin
Succinylcholine
Tetracycline
Drugs which are PROBABLY
SAFE to use:
Adrenaline
Amitriptyline
Azathioprine
Chloramphenicol
Cisapride
Colchicine
Cyclosporin
Cytarabine
Dicumarol
Chloroquine
Digoxin
Daunorubicin
Doxazosin
Estrogens (natural/endogenous)
Ibuprophen
Imipramine
Indomethacin
Labetalol
Lithium
Losartan
Drugs which are PROBABLY
SAFE to use: (cont.)
Methenamine
Methylphenidate
Naproxen
Neostigmine
Nortriptyline
Nitrous oxide
Penicillamine
Procaine
Propanidid
Propofol
Propoxyphene
Rauwolfia alkaloids
6-Thioguanine
Thiouracils
Thyroxine
Tricyclic antidepressants
Tubocurarine
Vigabatrin
Vitamin B
Vitamin C
This list is NOT comprehensive and does not reflect all information and opinions about drug
safety in the acute porphyrias. There is considerable evidence for classification of drugs in the
"Safe" category, but much less evidence, or conflicting evidence, for drugs in the "Probably
Safe" category. Additional information concerning safe and unsafe drugs can be found in the
text, including available websites. Reproduced with permission from Anderson, KE, et al.
Disorders of heme synthesis: X-linked sidero-blastic anemia and the porphyrias. In: The
metabolic and molecular bases of inherited disease (Scriver, CR, Beaudet, AL, Sly, WS, Valle,
D, eds). McGraw-Hill Medical Publishing Division, New York. p 2991. Copyright © 2000 The
McGraw-Hill Companies.
Categories of Unsafe drugs in the Acute Porphyrias
Drugs which are
UNSAFE
Drugs which are
UNSAFE (cont.)
Drugs which are
POTENTIALLY UNSAFE
ACE inhibitors
Antipyrine
Aminopyrine
(amidopyrine)
Aminoglutethamide
Barbiturates (all)
Nbutylscopolammonium
bromide
Calcium channel
blockers
Carbamazepine
Chlorpropamide
Danazol
Dapsone
Diclofenac
Enalapril
Diphenylhydantoin
Ethosuximide
Ergot preparations
Ethchlorvynol
Ethinamate
Felbamate
Glutethimide
Griseofulvin
Ketoconazole
Lamotrigine
Mephenytoin
Metoclopramide
Meprobamate
Methyprylon
Nefazadone
Nifedipine
Novobiocin
Phenazone
Phenylbutazone
Primidone
Pargyline
Progesterone
(progestins)
Rifampin
Succinimides
Sulfasalazine
Sulfonamide antibiotics
Sulfonmethane
(sulfonal)
Sulfonethylmethane
(trional)
Sulfonylureas
Trimethadione
Valproic acid
Tranylcypromine
Alfadolone acetate
Alfaxolone
Alkylating agents*
Altretamine
(hexamethylmelamine)
Benzodiazepines
Busulfan
Captopril
Cephalosporins
Chlorambucil
Chlordiazepoxide
Clonidine
Cyclophosphamide
Dacarbazine
Deferoxamine
Diazepam
Diltiazem
Colistin
Dacarbazine
Diphenhydramine
EDTA
Etomidate
Estrogens (synthetic)
Erythromycin
5-Fluorouracil
Gold compounds
Fluroxene
Drugs which are
POTENTIALLY UNSAFE
(cont.)
Heavy metals (eg, Gold)
Hydralazine
Hyoscine
Ketamine
Lisinopril
Mefenamic acid
Melphalan
Mifepristone
Methyldopa
Metyrapone
Nalidixic acid
Nikethamide
Nitrazepam
Nitrofurantoin
o,p'-DDD
Pentazocine
Phenoxybenzamine
Procarbazine
Pyrazinamide
Spironolactone
Theophylline
Tiagabine
Tramadol
Tricyclic
antidepressants
Troglitazone
This list is NOT comprehensive and does not reflect all information and opinions about drug
safety in the acute porphyrias. There is considerable evidence for classification of drugs in the
"Unsafe" category, but much less evidence, or conflicting evidence, for drugs in the "Probably
Unsafe" category. Additional information concerning safe and unsafe drugs can be found in the
text, including available websites.
* Chlorambucil and Melphalan may be safer than the other alkylating agents listed here.
Reproduced with permission from Anderson, KE, et al. Disorders of heme synthesis: X-linked
sidero-blastic anemia and the porphyrias. In: The metabolic and molecular bases of inherited
disease (Scriver, CR, Beaudet, AL, Sly, WS, Valle, D, eds). McGraw-Hill Medical Publishing
Division, New York. p 2991. Copyright © 2000 The McGraw-Hill Companies.
Ref: Uptodate 17.1
APPENDIX 3: DRUGS AND CHEMICALS IN GLUCOSE-6-PHOSPHATE DEHYDROGENASE
Unsafe for class I, II, and III variants
Acetanilid
Dapsone
Furazolidone
Methylene blue
Nalidixic acid
Naphthalene (mothballs, henna)
Niridazole
Nitrofurantoin
Phenazopyridine
Phenylhydrazine
Primaquine
Sulfacetamide
Sulfamethoxazole
Sulfanilamide
Sulfapyridine
Thiazosulfone
Toluidine blue
Trinitrotoluene
* Safety for class I variants is usually not known.
Data from Beutler, E, Blood 1994; 84:3613.
Reference: Uptodate 17.1
Safe for class II and III variants*
Acetaminophen
Aminopyrine
Ascorbic acid (except in very high doses)
Aspirin
Chloramphenicol
Chloroquine
Colchicine
Diphenhydramine
Isoniazid
L-DOPA
Menadione
Paraaminobenzoic acid
Phenacetin
Phenytoin
Probenecid
Procainamide
Pyrimethamine
Quinidine
Quinine
Streptomycin
Sulfamethoxpyridazine
Sulfisoxazole
Trimethoprim
Tripelennamine
Vitamin K
APPENDIX 4: DRUG-DISEASE INTERACTIONS
Drug
Disease
Remarks
Management
Ref
1
Aminoglycosides
Myasthenia
Gravis
Cause significant increase in weakness,
respiratory depression. Aminoglycosiderelated postoperative respiratory
depression caused the greatest frequency
of drug-induced neuromuscular blockade
Avoid or use only if
absolutely necessary with
close monitoring
www.uptodate.com
2
Androgens
(testosterone)
HF
Edema
Endocrine Society Guideline
(US) recommend not to use
in NYHA III, IV
Uptodate vs 17.1
3
Amiodarone
Thyroid
disorders
the iodine-rich amiodarone affects the
thyroid gland, causing overt
hypothyroidism or thyrotoxicosis in 14%18% of cases.
Thyroid function to be
monitored.
Complex Drug-Drug-Disease
Interactions Between
Amiodarone, Warfarin, and the
Thyroid
GlandKurnik, Daniel MD;
Loebstein, Ronen MD; Farfel, Zvi
MD; Ezra, David MD; Halkin,
Hillel MD; Olchovsky, David MD
4
Antiarrhythmic
(sotalol, ibutilide)
HF
Negative inotropic, precipitate HF,
proarrhythmic
Amiodarone is the
preferred choice in
arrhythmias in HF
Uptodate vs 17.1
5
ACE inhibitors gold
salts and interferon .
Psoriasis
Occasional triggers of a psoriatic flare
Use Cautiously
Skin Therapy Letter • Editor: Dr.
Stuart Maddin • Vol. 4 No. 3
6
Antimalarials
Psoriasis
Exacerbate
Not contraindicated.
Skin Therapy Letter • Editor: Dr.
Stuart Maddin • Vol. 4 No. 3
7
Antipsychotics
Parkinson’s
disease
Parkinsonism
Use with caution
Neurology, Vol 66, Issue
6, March 2006
8
Drug
Disease
Remarks
Management
Ref
Beta Blockers
COPD, Asthma
Non selective beta blockers prevents
bronchodilatation
-All beta blockers are
contraindicated in severe disease
Uptodate vs 17.1
-Non selective ones to be avoided in
mild to moderate disease. Selective
or combined alpha/beta to be used
cautiously at low dose
9
Beta Blockers
Diabetes
Facilitation of hypoglycaemia
Use cautiously
Uptodate vs 17.1
10
Beta Blockers
Peripheral
Vascular
Disease,
Raynaud’s
phenomenon
Non selective beta blockers implicated.
Reduction in cardiac output and blockade
of beta-2-receptor-mediated skeletal
muscle vasodilation contribute to the
vascular insufficiency [
Selective agents can be used
cautiously
Uptodate vs 17.1
11
Beta blockers
Bradycardia,
heart block
-ve Chronotropic effect.
Use cautiously
Uptodate vs 17.1
Psoriasis
May aggravate existing disease
Not contraindicated in psoriasis.
However,
Skin Therapy Letter • Editor: Dr.
Stuart Maddin • Vol. 4 No. 3
12
Beta Blockers
-maintenance of cardiac output depends
on sympathetic drive
when there is a clear
relationship between the
exacerbation of
the psoriasis and the intake of a
beta blocker, it sometimes help
to switch from a noncardioselective beta 2 blocker to
Drug
Disease
Remarks
Management
Ref
a cardioselective beta 1 blocker.
13
Beta Blockers
Myasthenia
gravis
Exacerbate
Use with caution
Uptodate vs 17.1
14
Chemotherapeutic
agents
(cyclophospha-mide,
traztuzumab,
bevacizumab,
anthracycline-like
chemo agents
HF
Cardiotoxic
Altenative administration
schedule. Baseline and
periodic monitoring of ECG
and LVEF (with either ECHO)
is recommended.
Uptodate vs 17.1
15
CNS depressants,
opioids, muscle
relaxants
Myasthenia
Gravis
Increase symptoms when used together or
at high doses
Use cautiously
Uptodate vs 17.1
16
Corticosteroids
Psoriasis
Rebound that invariably follows their
Avoid
Skin Therapy Letter • Editor: Dr.
Stuart Maddin • Vol. 4 No. 3
use. The flare-up may be even worse than
the original attack.
Drug
Disease
Remarks
Management
Ref
17
COX-2 selective
inhibitosr
HF
Exacerbation of HF
Use with caution
Uptodate vs17.1
18
Calcium Channel
Blockers
CHF
Avoid use of shorter acting
dihydropyridines
Efficacy and safety of calcium
channel blockers in heart
failure: focus on recent trials
with second-generation
dihydropyridines.
Negative Inotropic, increase
sympathetic activity by short acting
dihydropyridines. Longer acting ones
appears safe
AU de Vries RJ; van
Veldhuisen DJ; Dunselman PH
SO Am Heart J 2000
Feb;139(2 Pt 1):185-94.
19
Calcium channel
blockers (short acting
–verapamil,
diltiazem, nifedipine)
2nd-3rd degree
heart block
20
Fluoroquinolones
Myasthenia
gravis
Exacerbate
Use with caution
Uptodate vs17.1
21
Lithium
Psoriasis
Well recognised cause of exacerbation.
Lithium does not aggravate a
pre-existing
Skin Therapy Letter • Editor: Dr.
Stuart Maddin • Vol. 4 No. 3
Negative Inotropic.
It may even cause pustular or
erythrodermic psoriasis in a significant
proportion of
affected patients.
Avoid use of shorter acting
dihydropyridines
psoriasis in all cases, and
therefore is not
contraindicated
Drug
Disease
Remarks
Management
Ref
in all patients with psoriasis.
22
Lignocaine and
procaine may cause
worsening if given iv
Myasthenia
Gravis
23
Magnesium Sulfate
Myasthenia
Gravis
Relatively contraindicated since it has
inhibitory effect on acetylcholine release
Relative contraindication
Uptodate vs 17.1
24
Metformin
HF
Increased risk of lactic acidosis
Use with caution
Uptodate vs 17.1
25
NSAIDs, Aspirin
Peptic Ulcers
Gastrotoxicity
Use with caution
Uptodate vs 17.1
26
NSAIDs, Aspirin
Asthma
Acute exacerbation of airway
inflammation. Less likely with COX-2
inhibitors
Avoid in aspirin sensitive
asthma. Use with caution in
others
Uptodate vs 17.1
27
NSAIDs
HF
Exacerbation and impaired response to
ACE-I
Use with caution
Uptodate vs 17.1
28
NSAIDs
Psoriasis
Anecdotal reports suggest adversely
affecting psoriasis
Consider discontinuing a
NSAID if the patient’s
psoriasis worsened on
starting, and
Uptodate vs 17.1
Uptodate vs 17.1
improved after stopping that
drug
29
Neuromuscular
Myasthenia
Unmask or exacerbate MG
Titrate judiciously
Uptodate version 17.1
Drug
Disease
Remarks
Management
Ref
Blocking Agents
Gravis
30
High Dose
Prednisolone,
glucocorticoids in
high doses
Myasthenia
Gravis
Exacerbation during early stages of
treatment
During crisis, use only if
patient’s airway is protected
Uptodate version 17.1
31
Penicillamine
Myasthenia
Gravis
Induces autoimmune Myasthenic
syndrome. Reversible
Avoid
Uptodate version 17.1
32
Phenytoin,
Gabapentin
Myasthenia
Gravis
Rare cases of exacerbation
Use cautiously
Uptodate version 17.1
33
Procainamide,
quinidine, quinine,
Myasthenia
Gravis
Cause significant increase in weakness
Avoid
Uptodate version 17.1
List is
comprehensiveRefer Appendix 1
34
PDE-3 (Cilostazol)
HF
Increased mortality
Contraindicated
Uptodate vs 17.1
35
PDE-4 (Anagrelide)
HF
+inotropic, vasodilatory, leading to fluid
retention and heart failure
Avoid
Uptodate vs 17.1
36
PDE-5 (sildenafil,
vardenafil, tadalafil)
HF
Potentially hazardous in patients with HF
with borderline BP. Avoid in IHD
Use with caution
Lexicomp
37
Statins
Myasthenia
Gravis
Unmasking subclinical MG due to
myotoxicity, new and worsening MG
Use cautiously
Uptodate version 17.1
Drug
Disease
38
Sildenafil
CHD
39
Sulfonamide
Antibiotics, Penicillin
(but not the semi
synthetic ones)
SLE
40
Theophylline
Cardiac disease
41
Theophylline
42
43
Remarks
Management
Ref
Use with caution
Lexicomp Drugs
Avoid
Uptodate vs 17.1
Can reduce theophylline clearance by as
much as 50%
Monitor level closely
Shannon: Haddad and
Winchester's Clinical
Management of Poisoning
and Drug Overdose, 4th
ed. Ch 65
Primary
Hepatic
Disease
Can reduce theophylline clearance by as
much as 50%
Monitor level closely
Shannon: Haddad and
Winchester's Clinical
Management of Poisoning
and Drug Overdose, 4th
ed. Ch 65
Theophylline
Cystic Fibrosis,
Hyperthyroidism
Increase clearance
May need to increase dose
Shannon: Haddad and
Winchester's Clinical
Management of Poisoning
and Drug Overdose, 4th
ed. Ch 65
TNF blockers
HF
New onset or worsening pre-existing HF
Use with caution in patients
with HF or decreased left
ventricular function; worsening
and new-onset HF has been
reported." In addition,
Drug labels
Safety and efficacy has not been
studied in these patients
Exacerbate SLE
Drug
Disease
Remarks
Management
Ref
infliximab is contraindicated at
doses higher than 5 mg/kg in
patients with moderate or
severe HF (NYHA class III/IV)
44
TNF blockers
Psoriasis
45
Telithromycin
Myasthenia
Gravis
46
Warfarin
Thyroid
disorders
47
Inexhaustive list (see
Appendix 2)
Acute
Intermittent
Porphyria
48
Inexhaustive list (see
Appendix 3)
G6PD
deficiency
Possibility of emergence or worsening of
psoriasis during treatment with TNF
blockers, particularly pustular and
palmoplantar forms of psoriasis.
Black box warning on possibility of
exacerbating or unmasking MG. Should
not use.
Monitor
thyroid disorders may affect warfarin
sensitivity, with hypothyroidism and
thyrotoxicosis resulting in increased or
decreased warfarin requirements,
respectively
Thyroid function should be
tested in any patient with
otherwise unexplained
changes in warfarin dose
requirements, particularly
if concomitantly treated
with amiodarone.
Complex Drug-Drug-Disease
Interactions Between
Amiodarone, Warfarin, and the
Thyroid Gland
Kurnik, Daniel MD; Loebstein,
Ronen MD; Farfel, Zvi MD; Ezra,
David MD; Halkin, Hillel MD;
Olchovsky, David MD
Can exacerbate disease
Refer to Appendix 2
Uptodate 17.1
Can cause hemolysis
Refer to Appendix 3
Uptodate 17.1
FDA ALERT [8/4/2009]
Uptodate version 17.1