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College of Pharmacy
UQU UNIVERSITY
Vancomycin
Vancomycin is an antibiotic with grampositive spectrum of activity that is effective
in treatment of nafcillin or Methicillin Resistant Staphy-lococcus aureus ( NRSA or
MRSA ) . it is also an alternative to penicillin
in patients , Vancomycin is bactericidal for
most gram-positive organism, except against
enterococci and it is synergistic with gentamicin against most strain of S. aureus and
enterococci it is not effective gram-negative bacteria.
Vancomycin is poorly absorbed orally and has been used to treat gastrointestinal
overgrowths of gram-positive bacteria when used to treat systemic infection , vancomycin
must be given by the IV route for those patients receiving continuous ambulatory peritoneal
dialysis the usual dose , in patients with normal renal function is 1g ( 10 to 15 mg/kg ) over
60 minutes every 8 to 12 hours .
Drug Name ( generic )
Vancomycin
Class / Therapeutic Category
Antibiotic Cell wall biosynthesis
Action
inhibition PG synthesis by binding directly
to the D-Ala - D- Ala end of the peptide ,
forms a cap over the end of the chain ,
blocks cross linking
Pharmacokinetics
● Vancomycin is poorly absorbed from
the intestinal tract
● The drug is widely distributed in the
body. Cerebrospinal fluid levels 7–
30% of serum concentrations
● Metabolism Excreted unchanged
<3%
● percent of the drug is excreted by
glomerular filtration.
● The drug has a serum elimination
half-life of about 6 hours.
Factor affecting Pharmacokinetic
● Age
● Gender
● Body Weight.
Indications
For the treatment of serious or severe
infections caused by susceptible strains of
methicillin-resistant (beta-lactam-resistant)
staphylococci.
Contraindication / precautions
● Poisoning by Antibiotic Vancomycin
● Hearing Problem
● Kidney Disease
● Clostridium difficile colitis
● systemic mastocytosis
● Decreased Neutrophils a Type of
White Blood Cell
Adverse Reaction Interactions
The most common adverse reactions (≥ 10%)
were nausea (17%), abdominal pain (15%),
and hypokalemia (13%).
Dosing Information
Based on Total Body weight and renal
function
(15 - 20 mg/kg )
Monitoring
● 10 – 15 mcg/mL: bacteremia, skin
and soft tissue infections
● 15 – 20 mcg/mL: osteomyelitis,
meningitis, pneumonia
Overdose
● Ototoxicity
● nephrotoxicity.
● “red man” or “red neck” syndrome
College of Pharmacy
UQU UNIVERSITY
Digoxin
Digoxin is an inotropic agent primarily used to treat CHF and atrial fibrillation. It is
incompletely absorbed and once absorbed a substantial fraction is cleared by kidneys . in
the acute care seting historically digoxin loading dose of = 1 mg/70 kg were administered
before the initiation of the usual maintenance dose were from an era when target levels
were 1 to 2 mcg/L and probably tody doses of approximately one half would be more
common in patients with heart failure Because it has a relatively long elimination half life in
adults , Digoxin is given once daily. Dosage adjustments can be important for patients who
are being converted from parenteral to oral therapy patients with renal impairment CHF or
thyroid abnormalities or patients who take amiodarone concurrently
Drug Name ( generic )
Digoxin
Class / Therapeutic Category
Cardiac Glycosides
Action
Digoxin inhibits the Na-K-ATPase
membrane pump, resulting in an increase in
intracellular sodium. The sodium calcium
exchanger (NCX)in turn tries to extrude the
sodium and in so doing, pumps in more
calcium. Increased intracellular
concentrations of calcium may promote
activation of contractile proteins (e.g., actin,
myosin). Digoxin also acts on the electrical
activity of the heart, increasing the slope of
phase 4 depolarization, shortening the
action potential duration, and decreasing
the maximal diastolic potential.
Pharmacokinetics
● Absorption 80 % absorbed after
oral administration of (tablets 75-80
% absorbed) after administration of
(elixir 75-80 % absorbed from liquid
filled) (capsule 80 % absorbed) IM
but not recommended
● Distribution Bound tightly to
muscles tissues Vd Correlated well
with lean body Tissues , very large
distribution volume Vd = 7.3 L/kg x
IBW
● metabolism via stepwise cleavage of
the sugar moieties and lactone ring
reduction Less than 10 % undergoes
hepatic metabolism not dependent
of the cytochrome P450 system a
● Elimination follows first-order
kinetics 50-70% is excreted almost
entirely unchanged by the kidney
Affected by some drugs interactions
& diseases conditions Half life 3648 hours and increase in case of
renal impairment Elimination
Factor affecting Pharmacokinetic
● Age
● Gender
● Body Weight.
Indications
For the treatment of congestive heart failure
and atrial fibrillation
Contraindication / precautions
● Digoxin toxicity
● Advanced A-V block without
pacemaker
● Bradycardia or sick sinus without PM
● PVC’s and VT
● Marked hypokalemia
● W-P-W with atrial fibrillation
Adverse Reaction Interactions
● Amiodarone
● Propafenone
● Quinidine
● Ritonavir
Dosing Information
Loading Dose ( 1.0 to 1.5 mg/ 70kg )
Maintenance dose ( ( 0.25 mg/kg )
Monitoring
obtain level within 24 hours of digitalization
weekly until stable, and at steady state ,
Measure every two days, or every day in
unstable renal function
Overdose
● anorexia
● nausea
● Vomiting
● visual changes and cardiac
arrhythmias
College of Pharmacy
UQU UNIVERSITY
Valproic Acid
Valproic acid is currently used to
treat various seizure disorder and
variety of psychiatric such as
anxiety , depression and other
behavioral disturbances the
mechanism of action for valproic
acid is uncertain , the usual initial
dose of valproic acid for treatment
seizure is 15mg/kg/day and the
usual starting dose of valproic acid is 25mg/kg/day , the metabolism of phenobarbital and
the major metabolite of carbamazepine appear to be inhibited by valproic acid
Drug Name ( generic )
Valproic Acid
Class / Therapeutic Category
Antiepileptic
Action
It purportedly increase the brain
concentration of gamma aminobutyric acid
(GABA) , an inhibitory neurotransmitter in
the central nervous system
Pharmacokinetics
● Rapid absorption from
gastrointestinal tract
● Distribution 11 L/1.73 m2 [total
valproate] 92 L/1.73 m2 [free
valproate]
● Valproate is metabolized almost
entirely by the liver
● Valproic acid is almost entirely
eliminated from the body through
hepatic metabolism less than 5% of
the drug is eliminated by the renal
route
Factor affecting Pharmacokinetic
● Age
● Gender
● Body Weight.
Indications
For treatment and management of seizure
disorders, mania, and prophylactic
treatment of migraine headache. In
epileptics, valproic acid is used to control
absence seizures, tonic-clonic seizures
(grand mal), complex partial seizures, and
the seizures associated with Lennox-Gastaut
syndrome.
Contraindication / precautions
● hepatic disease
● mitochondrial disorders caused by
mutations in mitochondrial DNA
polymerase
● hypersensitivity to the drug
● urea cycle disorders
Adverse Reaction Interactions
● Rifampin
● Felbamate
● Carbapenem Antibiotics
● Aspirin
Dosing Information
● Complex partial seizures: Initial
dose: 10 to 15 mg/kg Maintenance
dose: 10 to 60 mg/kg
● Simple and complex absence
seizures: Initial dose: 15 mg/kg
Monitoring
● General: Patients receiving doses
near the maximum recommended
daily dose should be monitored
more closely.
● Hematologic: Platelet counts
● Hepatic: Liver function tests
● Nervous system: Seizures
● Psychiatric: Emergence or worsening
of depression, suicidal thoughts or
behavior, and/or unusual changes in
mood or behavior
Overdose
● heart block
● deep coma
● hypernatremia
● Fatalities
College of Pharmacy
UQU UNIVERSITY
Phenobarbital
Phenobarbital is a long acting barbiturate
used in the treatment of seizure disorder ,
insomnia and anxiety. Ti is most commonly
administered orally may it administered IM ,
IV as well.
The usual adult maintenance dose of 2
mg/kg/day produced steady state
concentrations of approximately 20 mg/L. It
has half life of approximately 5 days a
loading dose of 15 mg/kg can be administered, usually in three divided doses of 5 mg/kg
given every 2 to 3 hours
Drug Name ( generic )
Phenobarbital
Class / Therapeutic Category
Anticonvulsant
Action
Pharmacokinetics
Chloride Channel opener (Gaba operated)
● ABSORPTION - Oral bioavailability:
100% - Oral Tmax: 4-12 hours.
(absorption rate depends on food
and on pharmaceutical preparation)
● DISTRIBUTION - Bound in plasma:
» 50% - Vd (70 Kg): » 40 L - Bound
and free drug concentrations in
brain are equal to those in plasma
● METABOLISM- 75% by the liver
(biotransformation rate is low)
● EXCRETION - By the kidney: 25%
(acid urine) up to 75% (in alkaline
urine) Total Clearance: » 4.5
mL/min(70 Kg) Half-life: adults: » 100
hours children: » 50 hours
Factor affecting Pharmacokinetic
● Age
● Gender
● Body Weight.
Indications
is a central nervous system depressant. In
ordinary doses, the drug acts as a sedative
and anticonvulsant. Its onset of action
occurs within 30 minutes, and the duration
of action ranges from 5 to 6 hours. It is
detoxified in the liver.
Contraindication / precautions
● Absence seizures, myoclonic seizures,
atonic seizures
● Porphyria (acute intermittent,
variegata)
● Previous history of serious allergic
reactions to barbiturates
● Serious respiratory or liver diseases
● Patients with severe pain Pregnancy
Adverse Reaction Interactions
● Griseofulvin
● Phenytoin, Valproic Acid
● Doxycycline
● Corticosteroids
● CNS Depressants
Dosing Information
The most commonly recommended dose in
dogs is 2-3 mg phenobarbital per kilogram
of body weight given every 12 hours
Monitoring
Phenobarbital serum concentrations (as
clinically indicated); CNS status; liver
enzymes (periodic); CBC with differential
(periodic); renal function (periodic); seizure
activity; signs and symptoms of suicidality
(eg, anxiety, depression, behavior changes)
IV use: Respiratory rate, heart rate, blood
pressure, IV site (stop injection if patient
complains of pain in the limb)
Overdose
The signs and symptoms of barbiturate
poisoning are referable especially to the
central nervous system and the
cardiovascular system. but late in the course
of barbiturate poisoning they may show
hypoxic paralytic dilatation. Respiration is
affected early. Breathing may be either slow
or rapid and shallow; Cheyne-Stokes rhythm
may be present.
College of Pharmacy
UQU UNIVERSITY
Lithium
Lithium is a monovalent cation that has been used ofr more than 50 years in the treatment
and prevention of various psychiatric conditions , lithium salts have been prescribed to
prevent future manic or depressive episodes , lithium is administered as the carbonate salt
formulation which contains 8.12 mEq of lithium pre 300mg tablet or capsule and it is
available as extended release the usual daily dose range from 600 to 1,500 mg
Drug Name ( generic )
Lithium
Class / Therapeutic Category
Psychotropic Drugs
Action
Preclinical studies have shown that lithium
alters sodium transport in nerve and muscle
cells and effects a shift toward intraneuronal
metabolism of catecholamines, but the
specific biochemical mechanism of lithium
action in mania is unknown.
Pharmacokinetics
The digestive absorption of lithium is complete and the
maximum plasma concentration is observed two to four
hours after an oral intake of a non sustained release
form.
The average plasma half-life of lithium is about 22
hours. Its plasma level at steady state regarded as
therapeutically effective ranges from 0.5 to 0. 8 mmol/L.
When blood sampling is performed in the morning
before the first daily intake or in the evening before the
single intake of a sustained-release formulation the
plasma level should be between 0.8 and 1.2 mmol/liter.
Its volume of distribution is close to 0.8 L/kg
corresponding to a very broad distribution,
approximately equal to that of total water. Although
lithium is not bound to plasma proteins, its transfer into
the brain and the cerebrospinal fluid is slow, and at
equilibrium, the cerebrospinal fluid contains
approximately 40% of the plasma concentration.
The elimination is more than 95% urinary and any renal
impairment delays it. Approximately 80% of lithium
filtered by the glomerulus is reabsorbed from the
proximal tubule; its clearance is approximately 20% of
that of creatinine. A decrease of sodium intake
increases lithium retention by the kidney and
conversely. Thiazide diuretics, nonsteroidal
antiinflammatory drugs, ACE inhibitors reduce its renal
elimination and increase its plasma concentratio
Factor affecting Pharmacokinetic
● Age
● Gender
● Body Weight.
Indications
Lithium carbonate is indicated in the
treatment of manic episodes of manicdepressive illness. Maintenance therapy
prevents or diminishes the intensity of
subsequent episodes in those manicdepressive patients with a history of mania.
Contraindication / precautions
● Dysfunction of the Brain
● Brugada Syndrome
● Abnormal Heart Rhythm
● Chronic Heart Failure
● Kidney Disease
● Excess Urination
● Pregnancy
Adverse Reaction Interactions
Convulsions, Cardiac arrhythmias, Cardiac
arrhythmias, Dehydration, Hypercalcemia,
Sinus bradycardia, Hyperthyroidism,
Leukocytosis, Dysarthria.
Dosing Information
The usual daily dose range from 600 to 1,500
mg because lithium possesses a relatively
narrow therapeutic range and exhibits fairly
predictable pharmacokinetic behavior , it serves
as an excellent candidate for routine
therapeutic drug monitoring
Monitoring
To insure proper AND safe administration of
phenobarbital, it is very important to
monitor the level in the blood.
Overdose
● Central Nervous System: blackout
spells, epileptiform seizures, slurred
speech, dizziness.
● Cardiovascular: cardiac arrhythmia,
hypotension, peripheral circulatory
collapse.
● Gastrointestinal: anorexia, nausea,
vomiting, glycosuria.
College of Pharmacy
UQU UNIVERSITY
Carbamazepine
Is an anticonvulsant compound that is
structurally similar to the tricyclic
antidepressant agents it is the drug of choice
for treatment of trigeminal neuralgia and
used for seizure and also for pain syndromes
, Carbamazepine is available in many dosage
forms including oral , chewable tablet , oral
tablet . it is labeled use in adults and children
. it ia in pregnancy class D , effective doses
for adults with seizure disorder are the range of 15 to 25 mg/kg/day or 800 to 1200 mg/day
at steady state and it is eliminated primairly by the metabolic route by the P450 , less than
2% of carbazepine is excreted uncahnged in the urine
Drug Name ( generic )
Carbamazepine
Class / Therapeutic Category
Anticonvulsants
decreasing nerve impulses that cause
Action
Pharmacokinetics
seizures and pain
● Absorption:
● VD: 0.7 to 2.7 L/kg
● Pb: 60-80%
● Metabolism: Primarily hepatic
● Route of Elimination : by kidney.
● Cl: 0.64 +/- 0.18 L/min
● Half-life:109 mins
Factor affecting Pharmacokinetic
age of the patients and total daily dose
Indications
For the treatment of epilepsy and pain
associated with true trigeminal neuralgia.
Contraindication / precautions
● Hypersensitivity to this drug or
tricyclic antidepressants
● History of bone marrow suppression
● MAO inhibitor use within 14 days
Use with caution
Adverse Reaction Interactions
Atracurium, Cisatracturium, Pancuronium,
Vecuronium: May decrease the effects of
nondepolarizating muscle relaxant, causing
it to be less-effective
Dosing Information
● Adults and Children Over 12 Years
of Age: Initial: 200 mg b.i.d. Increase
at weekly intervals by adding up to
200 mg/day using a t.i.d. or q.i.d.
regimen until the optimal response
is obtained. Dosage generally should
not exceed 1000 mg daily in children
12 to 15 years of age, and 1200 mg
daily in patients above 15 years of
age. Doses up to 1600 mg daily have
been used in adults in rare instances.
Maintenance: Adjust dosage to the
minimum effective level, usually 800
to 1200 mg daily.
● Children 6 to 12 Years of Age:
Initial: 100 mg b.i.d. Increase at
weekly intervals by adding up to 100
mg/day using a t.i.d. or q.i.d.
regimen until the optimal response
is obtained. Dosage generally should
not exceed 1000 mg daily.
Maintenance: Adjust dosage to the
minimum effective level, usually 400
to 800 mg daily.
Monitoring
Patients should be monitored for concrelated side effects:
● Nausea
● vomiting
● lethargy
● dizziness
Overdose
● Respiration: Irregular breathing,
respiratory depression.
● Gastrointestinal Tract: Nausea,
vomiting.
● Kidneys and Bladder: Anuria
College of Pharmacy
UQU UNIVERSITY
Lidocaine
Is local anesthetic agent with antiarrhythmic
it is used for acute treatment of severe
ventricular arrhythmias and is one of the
most common agents for the acute
treatment of ventricular arrhythmias , also
used for neonatal seizures that do not
respond to conventional anticonvulsants ,
maintain lidocaine levels at 3 to 6 mg/L for
seizure control or <9 mg/L to minimize
potential cardiac toxicity , and it is poor oral bioavailability is almost exclusively
metabolized by liver and has short action for these reasons administered initially as bolus
dose followed by continuous infusion .
Drug Name ( generic )
Lidocaine
Class / Therapeutic Category
Analgesics and Anesthetics
Action
stabilizing the neuronal membrane
Pharmacokinetics
● Absorption : completely absorbed
following parenteral administration
● Distribution (VD) : 0.7 to 2.7 L/kg
[healthy volunteers]
● Metabolism : by hepatic
● Elimination : Lidocaine and its
metabolites are excreted by the
kidneys.
Factor affecting Pharmacokinetic
Hepatic metabolism mainly by CYP3A4
Indications
For production of local or regional
anesthesia by infiltration techniques such as
percutaneous injection and intravenous
regional anesthesia by peripheral nerve
block techniques such as brachial plexus
Contraindication / precautions
● Bradycardia
● Accelerated idioventricular rhythm
● Pacemaker
● Porphyria, especially acute porphyria
(AIP);
Adverse Reaction Interactions
● arbutamine
● bupropion
● dofetilide
● GenESA (arbutamine)
Dosing Information
1-1.5 mg/kg followed by continuous
infusion 1-9 mg/min
Monitoring
there may be a desire to maintain lidocaine
levels at 3 to 6 mg/L for seizure control or
<9 mg/ L to minimise potential cardiac
toxicity .Lidocaine has poor oral
bioavailability , is almost exclusively
metabolised by the liver , and has a
relatively short duration of action . For
these reasons , lidocaine is almost always
administered initially as a bolus dose of 1
to 1.5 mg\kg, followed by a continuous
infusion of approximately 1 to 4 mg/min .
Overdose
● Hypoxia
● acidosis
● bradycardia
● Arrhythmias
● cardiac arrest
College of Pharmacy
UQU UNIVERSITY
Ethosuximide
Is an anticonvulsant used primarily for the
treatment of uncomplicated absence seizure it is
available as 250 mg capsule and as solution
containing 250 mg of ethosuximide per 5 mL
and is eliminated primarily by metabolism to an
inactive hydroxyethyl metabolite which excreted
in urine as the glucuronide approximately 20%
of unchanged . the usual dosage range 15 - 30
mg/kg/day , maintenance dose of 15 - 40 mg/kg/day , divided into two daily doses given
every 12 hours
Drug Name ( generic )
Ethosuximide
Class / Therapeutic Category
Succinimide anticonvulsants
Action
reducing low threshold Ca2+ channel
current (T-type channel) in thalamus At high
concentrations: Inhibits Na+/K+ ATPase
Depresses cerebral metabolic rate
Potentiates GABA
Pharmacokinetics
● Bioavailability :93% .
● VD :0.7 l/kg .
● metabolism: Hepatic, via CYP3A4
and CYP2E1.
● CL:17-38%.
● half-life: 53-56 hr.
Factor affecting Pharmacokinetic
● Age
● Gender
● Body Weight.
Indications
Ethosuximide is indicated for the control of
absence (petit mal) epilepsy.
Contraindication / precautions
Ethosuximide should not be used in
patients with a history of hypersensitivity to
succinimides.
Adverse Reaction Interactions
Dosing Information
Monitoring
gastrointestinal intolerance
20-30mg/kg/day, Available as syr./caps.
Seizure frequency; trough serum
concentrations, CBC, platelets, liver enzymes
(periodic), urinalysis (periodic); signs of rash;
suicidality (eg, suicidal thoughts, depression,
behavioral changes)
Overdose
● Drowsiness
● Headache
● Lethargy
● Dysequilibrium
● Unsteadiness
College of Pharmacy
UQU UNIVERSITY
Theophylline
Is a bronchial smooth muscle relaxant used
to treat bronchial asthma and other
diseases , is relegated to third line agent in
the treatment of asthma , the low dose
theophylline leading to concentrations of 5
-10 mg/L has anti inflammatory and
immunomodulatory effect is poorly soluble
in water about 1% and in the past usually
administered by IV and it is slowly
absorbed , aminophylline is the most
widely used salt of theophylline , loading
dose of 300 - 500 mg and is followed by IV infused and the usual oral maintenance dose is
200- 300 mg three to four times a day or 200 - 400 mg twice daily
Drug Name ( generic )
Theophylline
Class / Therapeutic Category
bronchodilator
Action
Theophylline relaxes smooth muscles of
respiratory tract and suppresses the
response of the airways to stimuli, may
increase tissue concentration of cyclic
adenine monophosphate (cAMP) by
inhibiting 2 isoenzymes of
phosphodiesterase (PDE III and, to a lesser
extent, PDE IV), which ultimately induces
release of epinephrine from the adrenal
medulla cells
Pharmacokinetics
● Absorption: well oral absorption.
● Vd:0.45.
● Pb: 40-50%.
● Metabolism: Hepatic via
demethylation (CYP 1A2) and
hydroxylation (CYP 2E1 and 3A4)
● Elimination: in urine
● Half-life:8h
Factor affecting Pharmacokinetic
Smoking can affect the pharmacokinetics of
the drugs by decreasing the half-life to 4 or
5 hours.
Indications
Theophylline is indicated for the treatment
of the symptoms and reversible airflow
obstruction associated with chronic asthma
and other chronic lung diseases, e.g.,
emphysema and chronic bronchitis.
Contraindication / precautions
Theophylline (Anhydrous) Extended-Release
Tablets are contraindicated in patients with
a history of hypersensitivity to Theophylline
or other components in the product.
Adverse Reaction Interactions
adding a drug that inhibits Theophylline
metabolism (e.g., cimetidine, erythromycin,
tacrine) or stopping a concurrently
administered drug that enhances
Theophylline metabolism (e.g.,
carbamazepine, rifampin).
Dosing Information
10-15 mcg/mL
Monitoring
Monitor heart rate, CNS effects (insomnia,
irritability); respiratory rate (COPD patients
often have resting controlled respiratory
rates in low 20s); arterial or capillary blood
gases (if applicable)
Overdose
Adenosine receptors are widely distributed
throughout the body. Antagonism of these
receptors has both therapeutic and toxic
effects, including: Bronchodilatation,
Tachycardia, Cardiac arrhythmias, Seizures,
Cerebral vasoconstriction.
College of Pharmacy
UQU UNIVERSITY
Warfarin
Drug Name ( generic )
Warfarin
Class / Therapeutic Category
Anticoagulants
Action
Interferes with hepatic synthesis of vitamin
K-dependent coagulation factors (II, VII, IX,
X)
Pharmacokinetics
● Absorption : Rapidly absorbed
following oral administration with
considerable interindividual
variations. Also absorbed
percutaneously.
● Distribution (VD) : 0.14 L/kg
● Metabolism : by hepatic microsomal
enzymes. S-warfarin is predominantly
metabolized by cytochrome P450
● Elimination : by metabolism. Very
little warfarin is excreted unchanged
in urine. The metabolites are
principally excreted into the urine;
and to a lesser extent into the bile.
Factor affecting Pharmacokinetic
● Age
● Gender
● Body Weight.
Indications
For the treatment of retinal vascular
occlusion, pulmonary embolism,
cardiomyopathy, atrial fibrillation and flutter,
cerebral embolism, transient cerebral
ischaemia, arterial embolism and
thrombosis.
Contraindication / precautions
● Pregnancy
● Hemorrhagic tendencies or blood
dyscrasias
● Bleeding tendencies
● Threatened abortion, eclampsia, and
preeclampsia
Adverse Reaction Interactions
Dosing Information

bivalirudin

naproxen, oxaprozin

venlafaxine, vilazodone

aspirin
The dosage and administration of Warfarin
sodium tablets must be individualized for
each patient according to the patient’s
International Normalized Ratio (INR)
response to the drug. Adjust the dose
based on the patient’s INR and the
condition being treated. Consult the latest
evidence-based clinical practice guidelines
regarding the duration and intensity of
anticoagulation for the indicated conditions.
Monitoring
Prothrombin time, hematocrit; INR
(frequency varies depending on INR
stability); may consider genotyping of
CYP2C9 and VKORC1 prior to initiation of
therapy, if available
Overdose
Bleeding (e.g., appearance of blood in
stools or urine, hematuria, excessive
menstrual bleeding, melena, petechiae,
excessive bruising or persistent oozing from
superficial injuries, unexplained fall in
hemoglobin) is a manifestation of excessive
anticoagulation.