Download Pharmacy Administraion News - May 1, 2001

KALEIDA Health, May 2001
COX-2 INHIBITORS: CELECOXIB
(CELEBREX®), ROFECOXIB (VIOXX®)A THERAPEUTIC REVOLUTION?
Cyclooxygenase (COX) consists of two isoforms
(COX-1COX-2) and is the key enzyme in the biosynthesis of
prostaglandins,.(1,2) The function of COX-1 is to stimulate the
synthesis of prostaglandins that regulate platelet aggregation,
homeostatic function of the vasculature, the gastrointestinal
mucosa, and the renal system. The production of COX-2 is
induced dramatically during the inflammatory process, giving
rise to pain, swelling and stiffness. (1,2)
Non-steroidal anti-inflammatory drugs (NSAIDS)
nonselectively inhibit both COX-1 and COX-2. The adverse
effects (renal insufficiency, hypertension, gastrointestinal
toxicity and inhibition of platelet function) associated with
NSAIDs are well known and thought to be due to the
inhibition of COX-1.(1,2)
The newly developed COX-2 inhibitors (celecoxib,
rofecoxib) have been approved by the US Food and Drug
Administration for the treatment of rheumatoid arthritis and
osteoarthritis but not for analgesia.(1,2) Often these agents are
used for conditions not regarded as inflammatory. Many
clinical trials evaluating the safety of the COX-2 inhibitors are
of short duration and exclude patients with comorbid illnesses
and concomitant drug therapy. Extrapolating their results to
all patients seen in general clinical practice is difficult.
Although clinical trials have shown that these agents have no
effect on platelet function,(3,4) it has also led to the dangerous
assumption that these agents have few, if any, adverse
effects.(1,2)
Most notable is the notion that COX-2 inhibitors are
“gastro-safe”. Silverstien et al evaluated the association of
celecoxib and upper gastrointestinal (GI) toxicity as compared
to ibuprofen.(5) A total of 8059 healthy (>18 years old)
patients were enrolled in a 6 month trial. The annualized
incidence of upper GI ulcer complications was reported to be
lower in the celecoxib treated patients (0.76% (11 events/1441
patient years) versus NSAIDs (1.45% (20 events/1384 patient
years) (p=0.09).(5) Converting the absolute risk reduction into
numbers needed to treat (NNT), it can be seen that 145
patients would have to be treated with celecoxib to avoid one
GI bleed. Moreover, for patients taking aspirin for
cardiovascular prophylaxis (< 325mg per day), the annualized
incidence of upper GI complications was not significantly
different in patients taking celecoxib versus NSAIDS (2.01%;
6 events/298 patient years versus 2.12%; 6/283 patient years
respectively; P=0.92).(5) This translates into a NNT of 909.
Clearly, it cannot be assumed that celecoxib is more “gastrosafe” than ibuprofen.
Other safety concerns are the effects of COX-2
inhibitors on cardiovascular and renal function. COX-2 is
expressed in the kidney, where is it inducible in response to
salt restriction and appears to be important in the control of
renin release.(2) Although two small, short-term studies
have shown conflicting results when evaluating the impact of
COX-2’s on renal function in healthy adult patients(6,7) , a
large study in a more representative elderly population has
examined the impact of COX-2’s on cardiovascular function.
In this 6 week, parallel-group, double-blind trial,
810 patients with osteoarthritis, > 65 years of age, with stable,
medication controlled hypertension were randomized to receive
celecoxib 200mg once daily (n = 411) or rofecoxib 25mg once daily
1
(n = 399). Primary endpoints were the development of peripheral
edema and changes in diastolic and systolic blood pressure(8) .
Significant edema was reported in both treatment groups (38/411,
9.5% and 20/399, 4.9%, rofecoxib and celecoxib respectively;
(P=0.014)).(8) Sixty-six patients receiving rofecoxib versus 45
patients receiving celecoxib reached the systolic blood pressure
endpoint, (P=0.032) and 9 versus 6 patients reached the diastolic
blood pressure endpoint, (P=0.44).(7) In addition, 6 patients in each
group developed clinically significant serum renal lab abnormalities
which represented only minor increases in serum creatinine, blood
urea nitrogen, or serum potassium.(8)
In summary, the clinical trials suggest that predisposed
patients, such as those with congestive heart failure, hypertension, or
concurrent aspirin use, may experience adverse events similar to
those observed with the non-selective NSAIDs. Careful monitoring is
essential to avoid what may become a severe adverse drug reaction.
In addition, the specificity of the COX-2 inhibitors limits their
therapeutic application. They will not replace aspirin’s cardiovascular
protective effect that is mediated through COX-1. Also, suggestions
that COX-1 may be induced at sites of inflammation imply that the
COX-2 inhibitors may be less effective as anti-inflammatory or
analgesic agents. (2)
References:
1.
Gossel, TA, , Wuest RJ COX-2 Inhibitors: An Introduction. Carolina Journal of
Pharmacy. May 1999;29-33.
2.
Hawkey CJ. COX-2 Inhibitors. The Lancet. 1999;353:307-314.
3.
Leese PT,Hubbard RC et al. Effects of Celecoxib, a Novel Cyclooxygenase-2
Inhibitor, on Platelet Function in Healthy Adults: A Randomized Control Trail
Journal of Clinical Pharmacology. 2000;40:124-132.
4.
Greenberg HE, Gottesdiener K et al. A New Cyclooxygenase Inhibitor, Rofecoxib
(VIOXX®), Did Not Alter the Antiplatelet Effects of Low-Dose Aspirin in Healthy
Volunteers. Journal of Clinical Pharmacology. 2000;40:1509-1515.
5.
Silverstein FE, Faich G et al. Gastrointestinal Toxicity with Celecoxib vs.
Nonsteroidal Anti-inflammatory Drugs for Osteoarthritis and Rheumatoid arthirits:
A Class Study: A Randomized Controlled trial. JAMA. 2000;284(10):1247-1255.
6.
Whelton, A, Schulman, G et al. Effects of Celecoxib and Naproxen on Renal
Function in the Elderly. Archives of Internal Medicine. 2000;160(10):1465-1470.
7.
Swan SK, Rudy DW et al. Effect of Cyclooxygenase-2 Inhibition on Renal
Function in Elderly Persons Receiving a Low-Salt Diet: A Randomized, Controlled
Trial. Annals of Internal Medicine. 2000;133(1):1-9.
8.
Whelton, A, Fort JG et al. Cyclooxygenase-2 Specific Inhibitors and Cardiorenal
Function: A Randomized, Controlled Trial of Celecoxib and Rofecoxib in Older
Hypertensive Osteoarthritis Patients. American Journal of Therapeutics/
2001;8:85-95.
Prepared by: Andrea M.C. Rubino, B.S., Pharm.D.
KALEIDA-WIDE STANDARD MEDICATION
ADMINISTRATION TIMES
Please refer to the standard medication administration times
below when ordering medications:
QD (daily) - 0800 (Exceptions: GCSF, GMCSF, warfarin and
digoxin 2000)
BID
0800, 2000 (Exception: Diuretics not in combination with
anti-hypertensives are given 0800, 1600)
TID
0800, 1600, 2200 (Adult)
TID
0800, 1400, 2000 (Pediatric)
QID
0800, 1200, 1600, 2000 (Exception: cardiac medications
Q6H; Nitrates given QID to provide nitrate-free period)
Q4H
0400, 0800, 1200, 1600, 2000, 2400
Q6H
0600, 1200, 1800, 2400
Q8H
0800, 1600, 2400
Q12H
0800, 2000
HS
2200 (Adult), 2000 (Pediatric)
STAT
As soon as possible
NOW
At the earliest convenience
K.Zammit, PharmD, BCPS editor
KALEIDA Health, May 2001
DRUG SHORTAGES
Problems in distribution, changes in production, marketing
decisions, and increasing use of obsolescent drugs can trigger a drug
shortage. Production changes can result from voluntary recalls, FDA
regulatory activities that limit manufacture or distribution, shortage of
raw materials, unpredicted events or disease outbreaks as well as shift
in product demand. Moreover, single source products where one
manufacturer has the majority of market share can also worsen the
crisis.
Below is a list of new shortages that are currently affecting
drug supplies throughout Kaleida sites. Please be advised that
shortages are subject to change on a daily basis, so please check with
your pharmacy department or the pharmacy department’s web site on
Kaleidascope for the most up-to-date information.
.Dexamethasone Long-term shortage problem. Consult
pharmacy department for equivalent doses of
inj
alternate corticosteroids.
DTP
Limited supply for patients requiring tetanus
Fentanyl
Remains in short supply. Availability may be
limited
Remains in short supply. Limited number of
0.4mg/ml syringes available
Remains in short supply. Availability may be
limited
This product is in and out of backorder. The
manufacturer is unable to keep up with the
demand. Glaxo has discontinued this product
line and the DS product is being reformulated.
All sizes are unavailable
Naloxone
(Narcan)
Metoclopramide
(Reglan)
Beclomethasone
oral inhalers
Phenobarbital Inj.
Betamethasone
Inj. (Celastone)
Due to a change in manufacturing process, this
product is available in a limited supply. No
release date has been set. Available supply
limited to premature labor patients.
Prochlorperazine
Inj
Dimehydrinate
Inj.
Prolonged shortage – therapeutic substitution
with promethazine
Prolonged shortage – therapeutic substitution
with promethazine
LOW-MOLECULAR WEIGHT HEPARIN
DOSE ADJUSTMENT
Automatic dose adjustment of enoxaparin (Lovenox®) will be
changed to adjust to the nearest 20mg increment. This policy was
approved by the Kaleida Pharmacy and Therapeutics Committee.This
will allow for dispensing of pre-packaged drug. This not only
provides convenience for nursing and pharmacy, but also may reduce
the risk of ecchymosis by administration from a pre-drawn syringe.
The chart below shows the percent increase in dose that would result
from this change in the dose adjustment policy. Given this data, we
propose the following:

Substitution will begin at doses of 70mg and above.

Only those patients with a Creatinine Clearance of > 50 ml/min
will be substituted to the nearest 20mg increment.

Patient that do not meet this criteria will continue to have an
automatic dose adjustment to the nearest 10 mg increment
2
PREVENTING MEDICATION ERRORS:
USE CAUTION- AVOID CONFUSION
Confusion and mistakes associated with drug names have been
a nationwide problem in hospitals. The Pharmacy Department
at Kaleida Health has compiled a list of the top 20 most
confused drugs. Please review the following list and use
particular caution with these medications in order to avoid
potential prescription errors. Thank you for your cooperation.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
Accupril - Accutane
Betoptic – Betagan
Buspirone – Buproprion
Celebrex – Celexa
Clonidine – Klonopin
Flomax – Fosamax
Glucotrol XL – Glucotrol
Glyburide – Glipizide
Humalog – Humulin
Hydroxyzine – Hydralazine
Imdur – K-Dur
Imuran – Tenormin
Miralax – Mirapex
Zosyn - Zofran
Oxycodone – OxyContin
Quinidine – Quinine
Symmetrel – Synthroid
Tobradex – Tobrex
Torsemide – Furosemide
Vanceril – Vancenase
2001 FORMULARY UPDATE
Additions
Argatroban (Acova) – Direct thrombin inhibitor
Dexmedetomidine (Precedex) – Sedative; Cardiac Surgery ONLY
Deletions
Lepirudin (Refludan) – Replaced with argatroban
Omeprazole Suspension (Prilosec) – Therapeutic Substitution
Therapeutic Substitutions
Lansoparzole Suspension 30mg
Lansoparzole Suspension 15mg
Promethazine Injection 12.5mg
Promethazine Injection 25mg
Omeprazole Susp 40mg
Omperazole Susp 20mg
Dimenhydrinate 25mg OR
Prochloerperazine Inj. 5mg
Dimenhydrinate Inj 50mg OR
Prochlorperazine Inj. 10mg
K.Zammit, PharmD, BCPS editor
KALEIDA Health, May 2001
LEVOFLOXACIN AUTOMATIC
SUBSTITUTION FOR CIPROFLOXACIN
March 1, 2001, all Kaleida Health sites began automatically
substituting levofloxacin for ciprofloxacin. This substitution has been
approved by both the Antibiotic Subcommittee and the P & T
Committee. The substitution will follow the scheme outlined below:
Drug Ordered
Drug Dispensed
Cipro 400mg iv bid
Levo 500mg iv daily
Cipro 200mg iv bid
Levo 250mg iv daily
Cipro 750 mg po bid
Levo 500mg po daily
Cipro 500mg po bid
Levo 500mg po daily
Cipro 250mg po bid
Levo 250mg po daily
Cipro 400mg iv q8h
Cipro 400mg iv q8h (not substituted)
Cipro 600mg iv q12h
Cipro 600mg iv q12h (not substituted)
Any Cipro D.A.W.
Cipro as per order

The substitution will follow the format of all therapeutic
substitutions at Kaleida, making use of the therapeutic equivalent
drug (TED) model.

Ciprofloxacin orders with “DAW” indicated will not be
substituted with levofloxacin, but followed by the Pharmacy
Antibiotic Management Program for suggested streamlining after
culture results are known

Ciprofloxacin 400mg iv q8h or 600mg iv q12h are assumed to
be intended for Pseudomonas therapy and will not be
substituted with levofloxacin whether or not DAW is indicated
and followed by the Antibiotic Management Program for
possible suggested streamlining after culture results are known
Rationale for the Substitution
Ciprofloxacin and levofloxacin are both quinolones with IV
and oral forms. Ciprofloxacin's microbiologic profile includes
excellent activity against Enterobacteracae, modest activity against
gram positives (staphylococcus, streptococcus), and moderate but
declining Pseudomonas activity (see tables 1 & 2 below) and no
clinically relevant anaerobic activity. Levofloxacin demonstrates
equivalent in-vitro activity against Enterobacteracae (per Kaleida
Health antibiogram 2000, and literature review – see table below)
better gram-positive activity (eg Streptococcus pneumonia), modest
Pseudomonas activity (similar percent susceptible as seen with
Ciprofloxacin - but not recommended for serious Pseudomonas
infection), and no clinically relevant anaerobic activity.
Table 1 Relative In Vitro Activity of Ciprofloxacin to Levofloxacin
Organism
MIC90
Cipro
MIC90
Levo
Cipro
AUIC
Levo
AUIC
MSSA
1.0
25
0.5
109
S. pneumo
2.0
6
1.0
55
E. coli
0.03
847
0.06
910
Klebsiella sp
0.06
423
0.25
218
Enterobacter sp
0.06
423
0.06
910
Citrobacter sp
0.06
423
0.12
455
Proteus sp
0.06
423
0.25
218
M. morganii
0.06
423
0.06
910
Salmonella sp
0.03
847
0.06
910
Shigella sp
0.03
847
0.016
3640
P. aeruginosa
2.0
13
4.0
14
S. maltophilia
8.0
3
8.0
7
H. influenza
0.015
1693
0.03
1820
M. cattarhalis
0.06
423
0.06
910
Adapted from Pickerill KE et. Al. Pharmacotherapy 2000;20;417-28
MIC = minimum inhibitory concentration,
AUIC = area under the inhibitory curve – a measure of antibiotic activity
that accounts for drug concentration and MIC value together
3
Table 2 Pseudomonas aeruginosa Susceptibility to
Ciprofloxacin at Kaleida Health
P. aeruginosa
1997
1998
1999
2000
BGH
N/A
84 %
77 %
73%
Millard
Gates
79 %
76 %
74 %
62 %
Millard
Suburban
82 %
82 %
73 %
63 %
Table 3 Pseudomonas aeruginosa Susceptibility to
Levofloxacin at Kaleida Health
P. aeruginosa
2000
BGH
71 %
Millard
Gates
66 %
Millard
Suburban
65 %
Quinolone class drug interactions/adverse effects include
binding in the gut by divalent cations (eg. Al, Fe, Mg), CNS and GI
adverse effects, potential QT prolongation. Levofloxacin overall
shows equal to less of these effects than does ciprofloxacin. Unlike
ciprofloxacin, levofloxacin also does not show any clinically
significant cytochrome P-450 enzyme inhibition and consequently no
significant drug interactions other than the divalent cation interaction.
Clinically, levofloxacin is the preferred quinolone for
Community acquired pneumonia (CID 31:347-83), while
ciprofloxacin is preferred as an alternative to aminoglycosides as part
of a combination therapy regimen for Pseudomonas infection.
However, in light of the current poor susceptibility of Pseudomonas
towards Ciprofloxacin and Levofloxacin, their use alone or in
combination for empiric therapy of suspected Pseudomonas
infection should be discouraged.
For Kaleida, levofloxacin is a more cost-effective antibiotic
than ciprofloxacin. Not only is levofloxacin dosed less frequently than
ciprofloxacin (daily vs. bid), the current total daily cost to Kaleida is
less for levofloxacin (500mg iv daily = $15.00) vs. ciprofloxacin
(400mg iv q12 = $28.00). There is no credible medical information to
justify ascertain that levofloxacin (with a T1/2 of 7 hrs) is a twice
daily antibiotic.
Questions and or concerns regarding this substitution may
be addressed to the Kaleida Health affiliated Infectious Disease
physicians or any of the clinical pharmacy coordinators.
NEW ADULT PARENTERAL NUTRITION
FORM IN USE AT ALL KALEIDA SITES
On March 12, 2001, all Kaleida sites began using the
new Adult Parenteral Nutrition Order form. Several changes
to the various forms are highlighted below:

The new form guides the user through the ordering process in a
step wise fashion. The prescriber will chose a formula, an
infusion rate, the electrolyte additives, either standard or
individually chosen, and the monitoring parameters. Suggestions
are made at each step.

Some minor changes were made to the standard formulas to
make them more uniform throughout the system. A standard
peripheral formula is no longer available.

Electrolytes made be added as a “standard” additive or
individually. Deletion of individual electrolytes is made by
customizing the electrolytes added.

Orders must be received in the pharmacy department by 1200
Please contact your site pharmacy department for any further
questions or comments.
K.Zammit, PharmD, BCPS editor
KALEIDA Health, May 2001
PROTONIX I.V. (PANTOPRAZOLE
SODIUM)
Protonix I.V. (pantoprazole sodium) was recently
approved by the FDA and becomes the first intravenous
formulation available in the class of proton pump inhibitors.
Indication:
Short-term treatment (7-10 days) of gastroesophageal
reflux disease (GERD) as an alternative to oral therapy who
are unable to continue taking oral Protonix. The safety and
efficacy of Protonix I.V. has not been established for the initial
treatment of GERD.
Recommended adult dose:
40 mg given once daily by intravenous infusion.
Dosage Conversion:
From I.V. to oral or vice versa is a 1:1 ratio.
Dosage adjustment:
No dosage adjustment is recommended in patients with renal
impairment, in patients undergoing hemodialysis, or mildmoderate hepatic impairment.
Administration:
The injection should be administered intravenously over a
period of approximately 15 minutes at a rate not greater than 3
4
mg/min (7 ml/min) through a dedicated line, using the in-line
filter that will be provided.
Availability:
Protonix I.V. is anticipated to be available in Kaleida Health
around June 15, 2001.
Kaleida Health Guidelines for appropriate use:
1.) Patient is NPO
2.) Patient has a clinical indication for acid suppression:
 Esophageal Erosion – therapy or maintenance
 Gastric Ulcer - therapy or maintenance
 Duodenal Ulcer – therapy or maintenance
 Upper GI Bleed
 Zollinger-Ellison Syndrome
 Stress Ulcer Prophylaxis in ICU patients who have patient
count less than 150,000 or greater than 50% drop
from baseline believed to be possibility related to
concomitant H2 antagonist therapy.
3.) Protonix I.V. is recommend to be discontinued when the
patient is able to resume treatment with oral Protonix.
Kaleida Health
Pharmacy Administration
BGH – 100 High Street
Buffalo, New York 14203
K.Zammit, PharmD, BCPS editor