ACCOLATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ACCOLATE (ACCOLATE).
Selective leukotriene receptor antagonist (LTRA) that inhibits the cysteinyl leukotriene (CysLT1) receptor, preventing bronchoconstriction, inflammation, and airway edema.
| Metabolism | Extensively metabolized in the liver primarily via CYP2C9, with minor contributions from CYP3A4. |
| Excretion | Primarily hepatic metabolism via CYP2C9; 87% excreted in feces, 10% in urine as metabolites. Less than 1% excreted unchanged. |
| Half-life | Terminal elimination half-life is 10–20 hours (mean ~15 hours) in healthy adults; prolonged in hepatic impairment. |
| Protein binding | 99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 1.0–1.5 L/kg (about 70–105 L for a 70 kg adult), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is ~60–70% (range 40–75%); food reduces bioavailability by 40%. |
| Onset of Action | Oral: 3–7 days for FEV1 improvement; peak effect may take 3–4 weeks. |
| Duration of Action | Dosing twice daily maintains therapeutic levels; effect is sustained with regular use, not for acute symptom relief. |
20 mg orally twice daily, 1 hour before or 2 hours after meals.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for renal impairment. |
| Liver impairment | Contraindicated in patients with hepatic impairment, including Child-Pugh Class A, B, or C. |
| Pediatric use | Not recommended for use in pediatric patients under 18 years of age. |
| Geriatric use | No specific dosage adjustment; use caution due to potential age-related renal or hepatic function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ACCOLATE (ACCOLATE).
| Breastfeeding | It is not known whether zafirlukast is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ACCOLATE is administered to a nursing woman. The M/P ratio is unknown. |
| Teratogenic Risk | Pregnancy Category B. Animal studies at doses up to 160 mg/kg/day (approximately 160 times the maximum recommended human daily oral dose) revealed no evidence of teratogenicity. However, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, use during pregnancy only if clearly needed. Avoid use during first trimester due to potential risk. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to zafirlukast or any component","Hepatic impairment (Child-Pugh score >5) due to increased systemic exposure"]
| Precautions | ["Neuropsychiatric events (e.g., agitation, aggression, depression, suicidal behavior)","Not for acute asthma attacks or status asthmaticus","May cause eosinophilic conditions or Churg-Strauss syndrome","Hepatic impairment: dose adjustment not required but use with caution"] |
| Food/Dietary | Food reduces the bioavailability of zafirlukast by up to 40%. Take on an empty stomach. No other specific food interactions are clinically significant. |
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| Fetal Monitoring | Monitor liver function tests (especially ALT) periodically during therapy, as zafirlukast has been associated with hepatic dysfunction, including hepatic failure. In pregnant patients, monitor fetal growth and well-being via ultrasound if clinically indicated. Assess for signs of hepatic injury (nausea, fatigue, pruritus, jaundice) and discontinue if symptoms develop. |
| Fertility Effects | No specific human studies on fertility. In animal studies, zafirlukast did not impair fertility in rats at doses up to 200 mg/kg/day (approximately 200 times the MRHD). No adverse effects on mating or reproductive performance observed. |
| Clinical Pearls |
| ACCOLATE (zafirlukast) is a leukotriene receptor antagonist used for asthma prophylaxis. It should not be used for acute bronchospasm. Monitor hepatic function; cases of hepatitis and liver failure reported. May increase INR with warfarin. Take on an empty stomach (1 hour before or 2 hours after meals). |
| Patient Advice | Take this medication regularly to prevent asthma attacks, not for sudden breathing problems. · Take on an empty stomach: at least 1 hour before or 2 hours after meals. · Report any signs of liver problems: abdominal pain, dark urine, jaundice, or flu-like symptoms. · Inform your doctor if you are taking warfarin, as dose adjustment may be needed. · Do not stop or change dose without consulting your doctor. |