Dosing and uses of Accolate (zafirlukast)
Adult dosage forms and strengths
tablets
- 10mg
- 20mg
Asthma
Indicated for chronic asthma treatment and prophylaxis
20 mg PO twice daily
Administration
Take at least 1 hour before or 2 hours after meals
Take at regular intervals
Hepatic Impairment
Contraindicated
Renal Impairment
Dose adjustment not necessary
Pediatric dosage forms and strengths
tablets
- 10mg
- 20mg
Asthma
<5 years: Safety and efficacy not established
5-12 years: 10 mg PO twice daily
>12 years: 20 mg PO twice daily
Administration
Take at least 1 hour before or 2 hours after meals
Take at regular intervals
Hepatic Impairment
Contraindicated
Renal Impairment
Dose adjustment not necessary
Geriatric dosage forms and strengths
Clearance reduced in patients aged 65 yr or older (Cmax and AUC 2- to 3-fold higher than in younger patients)
Potential for increased incidence of adverse effects; use caution
Accolate (zafirlukast) adverse (side) effects
>10%
headache (12.9% in age >12 yr)
1-10%
Abdominal pain (1.8%)
Infection (3.5%)
Nausea (3.1%)
Diarrhea (2.8%)
Generalized pain (1.8%)
Vomiting (1.5%)
Dyspepsia/gastritits (1.3%)
Increased ALT (1.5%)
Infection (4%)
Back pain (2%)
Weakness (2%)
Myalgia (2%)
Frequency not defined
Eosinophilia
Eosinophilic pneumonia
Vasculitis
Malaise
Bleeding
Bruising
Warnings
Contraindications
Hypersensitivity
Status asthmaticus
Hepatic impairment, including cirrhosis; Cmax and AUC ~50-60% greater than those of normal adults
Cautions
Not immediately effective and not for acute bronchospasm
Increased risk of infection if age >55 yr
Discontinue if hepatic dysfunction suspected, do not resume if confirmed
May cause eosinophilia, eosinophilic pneumonia, or vasculitis consistent with emergence of Churg-Strauss syndrome
Behavioral changes reported with therapy
Concomitant use with warfarin can result in clinical significant increase in INr
Not for use in the treatment of acute asthma attacks, including status asthmaticus
Pregnancy and lactation
Pregnancy category: B
Lactation: Excreted in breast milk; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Accolate (zafirlukast)
Mechanism of action
Inhibits bronchoconstriction as competitive receptor antagonist of leukotrienes D4 & E4; receptor occupation and cysteinyl leukotriene production has been associated with the pathophysiology of ashtma
Pharmacokinetics
Half-Life: 8-16 hr
Onset: 3-14 days
Peak plasma concentration: 326 ng/mL (healthy subjects); 568 ng/mL (asthmatics)
Peak plasm time: 3 hr (healthy subjects); 3.5 hr (asthmatics)
Clearance: 20 L/hr; significantly decreased in cirrhosis and age 65 yr
Protein bound: 99%
Vd: 70 L
Bioavailability: Reduced 40% with food
Metabolism: Hepatic CYP2C9
Excretion: Feces (90%); urine (10%)
Enzymes inhibited: Hepatic CYP2C9, CYP3A4
