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Pronunciation |
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(za
FIR loo
kast) |
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U.S. Brand
Names |
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Accolate® |
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Generic
Available |
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No |
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Synonyms |
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ICI 204, 219 |
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Pharmacological Index |
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Leukotriene Receptor Antagonist |
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Use |
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Prophylaxis and chronic treatment of asthma in adults and children greater
than or equal to 7 years of age |
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Pregnancy Risk
Factor |
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B |
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Pregnancy/Breast-Feeding
Implications |
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Clinical effects on the fetus: At 2,000 mg/kg/day in rats, maternal toxicity
and deaths were seen with increased incidence of early fetal resorption.
Spontaneous abortions occurred in cynomolgus monkeys at a maternally toxic dose
of 2,000 mg/kg/day orally. There are no adequate and well controlled trials in
pregnant women.
Breast-feeding/lactation: Zafirlukast is excreted in breast milk; do not
administer to nursing women |
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Contraindications |
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Hypersensitivity to zafirlukast or any of its inactive
ingredients |
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Warnings/Precautions |
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The clearance of zafirlukast is reduced in patients with stable alcoholic
cirrhosis such that the Cmax and AUC are approximately 50% to 60%
greater than those of normal adults.
An increased proportion of zafirlukast patients >55 years old reported
infections as compared to placebo-treated patients. these infections were mostly
mild or moderate in intensity and predominantly affected the respiratory tract.
Infections occurred equally in both sexes, were dose-proportional to total
milligrams of zafirlukast exposure and were associated with coadministration of
inhaled corticosteroids.
Although the frequency of hepatic transaminase elevations was comparable
between zafirlukast and placebo-treated patients, a single case of symptomatic
hepatitis and hyperbilirubinemia, without other attributable cause, occurred in
patient who had received 40 mg/day of zafirlukast for 100 days. In this patient,
the liver enzymes returned to normal within 3 months of stopping zafirlukast.
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Adverse
Reactions |
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>10%: Central nervous system: Headache (12.9%)
1% to 10%:
Central nervous system: Dizziness, pain, fever
Gastrointestinal: Nausea, diarrhea, abdominal pain, vomiting, dyspepsia
Neuromuscular & skeletal: Myalgia, weakness |
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Overdosage/Toxicology |
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There is no experience to date with zafirlukast overdose in humans
Use supportive treatment measures |
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Drug
Interactions |
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CYP2C9 enzyme substrate; CYP2C9 and 3A3/4 enzyme inhibitor
Erythromycin: Coadministration of a single dose of zafirlukast with
erythromycin to steady state results in decreased mean plasma levels of
zafirlukast by 40% due to a decrease in zafirlukast bioavailability.
Terfenadine: Coadministration of zafirlukast with terfenadine to steady state
results in a decrease in the mean Cmax (66%) and AUC (54%) of
zafirlukast. No effect of zafirlukast on terfenadine plasma concentrations or
EKG parameters was seen.
Theophylline: Coadministration of zafirlukast at steady state with a single
dose of liquid theophylline preparations results in decreased mean plasma levels
of zafirlukast by 30%, but no effects on plasma theophylline levels were
observed.
Increased effect: Aspirin: Coadministration of zafirlukast with aspirin
results in mean increased plasma levels of zafirlukast by 45%
Increased toxicity: Warfarin: Coadministration of zafirlukast with warfarin
results in a clinically significant increase in prothrombin time (PT). Closely
monitor prothrombin times of patients on oral warfarin anticoagulant therapy and
zafirlukast, and adjust anticoagulant dose accordingly. |
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Stability |
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Store tablets at controlled room temperature (20°C to
25°C; 68°F to
77°F); protect from light and moisture; dispense in
original airtight container |
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Mechanism of
Action |
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Zafirlukast is a selectively and competitive leukotriene-receptor antagonist
(LTRA) of leukotriene D4 and E4 (LTD4 and LTE4), components of slow-reacting
substance of anaphylaxis (SRSA). Cysteinyl leukotriene production and receptor
occupation have been correlated with the pathophysiology of asthma, including
airway edema, smooth muscle constriction and altered cellular activity
associated with the inflammatory process, which contribute to the signs and
symptoms of asthma. |
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Pharmacodynamics/Kinetics |
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Absorption: Food reduces bioavailability by 40%
Protein binding: >99%, predominantly albumin
Metabolism: extensively metabolized by liver via cytochrome P-450 2C9 enzyme
pathway.
Half-life: 10 hours
Time to peak serum concentration: 3 hours
Elimination: Urinary excretion (10%) and feces |
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Usual Dosage |
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Oral:
Children 7-11 years: 10 mg twice daily
Adults: 20 mg twice daily
Elderly: The mean dose (mg/kg) normalized AUC and Cmax increase
and plasma clearance decreases with increasing age. In patients >65 years of
age, there is an 2-3 fold greater Cmax and AUC compared to younger
adults.
Dosing adjustment in renal impairment: There are no apparent
differences in the pharmacokinetics between renally impaired patients and normal
subjects.
Dosing adjustment in hepatic impairment: In patients with hepatic
impairment (ie, biopsy-proven cirrhosis), there is a 50% to 60% greater
Cmax and AUC compared to normal subjects. |
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Mental Health: Effects
on Mental Status |
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May cause dizziness |
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Mental Health:
Effects on Psychiatric
Treatment |
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None reported |
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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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No information available to require special precautions |
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Dental Health:
Effects on Dental Treatment |
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No effects or complications reported |
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Patient
Information |
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Do not use during acute bronchospasm. Take regularly as prescribed, even
during symptom-free periods. Do not take more than recommended or discontinue
use without consulting prescriber. Do not stop taking other antiasthmatic
medications unless instructed by prescriber. Avoid aspirin or aspirin-containing
medications unless approved by prescriber. You may experience headache,
drowsiness, dizziness, or blurred vision (use caution when driving or engaging
in tasks requiring alertness until response to drug is known); gastric upset,
nausea, or vomiting (small frequent meals, frequent mouth care, chewing gum, or
sucking lozenges may help). Report persistent CNS or GI symptoms; muscle or back
pain; weakness, fever, chills; yellowing of skin or eyes; dark urine, or pale
stool; skin rash; or worsening of condition. Breast-feeding precautions:
Do not breast-feed. |
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Dosage Forms |
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Tablet: 10 mg, 20 mg |
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