ZAFIRLUKAST
Clinical safety rating: safe
Animal studies have demonstrated safety
Zafirlukast is a selective and competitive receptor antagonist of cysteinyl leukotrienes (LTC4, LTD4, LTE4) at the CysLT1 receptor, inhibiting bronchoconstriction, mucus secretion, and airway inflammation.
| Metabolism | Extensively metabolized in the liver primarily via CYP2C9; minor metabolism via CYP3A4. |
| Excretion | Zafirlukast is primarily eliminated by hepatic metabolism, with less than 1% excreted unchanged in urine. Fecal excretion accounts for approximately 10% of the dose, primarily as metabolites. |
| Half-life | Terminal elimination half-life is approximately 10 hours in healthy adults, allowing twice-daily dosing. Half-life may be prolonged in patients with hepatic impairment (e.g., cirrhosis) but is not significantly affected by renal impairment. |
| Protein binding | Zafirlukast is highly protein-bound (>99%), primarily to albumin. |
| Volume of Distribution | Volume of distribution is approximately 1.2 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 30-40% due to extensive first-pass metabolism. Food significantly reduces bioavailability (by about 40%); therefore, it should be taken on an empty stomach. |
| Onset of Action | Oral: Onset of bronchodilator effect occurs within 1-2 hours after a single dose, with maximal effect at 4-6 hours. Regular dosing is required for sustained benefit in asthma prophylaxis. |
| Duration of Action | Duration of action is approximately 12 hours, supporting twice-daily dosing. Clinical effect is maintained with regular use; continuous therapy is necessary for asthma control. |
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; specific GFR-based guidelines not established. |
| Liver impairment | Contraindicated in hepatic impairment including cirrhosis; not recommended due to risk of hepatotoxicity. For Child-Pugh A (mild): caution, not established; Child-Pugh B or C: not recommended. |
| Pediatric use | Children 5-11 years: 10 mg orally twice daily; Children 12 years and older: 20 mg twice daily. |
| Geriatric use | No specific adjustment recommended, but monitor for adverse effects due to potential age-related decreased hepatic function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Warfarin metabolism is inhibited increasing INR Can cause hepatic failure and Churg-Strauss syndrome.
| Breastfeeding | Zafirlukast is excreted in human breast milk in low concentrations. The milk-to-plasma ratio (M/P) is not reported in humans. Caution is advised in breastfeeding women; consider risk-benefit. No adverse effects in infants have been documented. |
| Teratogenic Risk | Zafirlukast is classified as Pregnancy Category B. Animal studies have not demonstrated fetal harm, but adequate and well-controlled studies in pregnant women are lacking. In the first trimester, risk cannot be ruled out; second and third trimester data are insufficient. However, zafirlukast crosses the placenta in animal models. Use only if clearly needed. |
■ FDA Black Box Warning
None
| Common Effects | Headache |
| Serious Effects |
Hypersensitivity to zafirlukast or any component of the formulation; concomitant use with warfarin (due to increased risk of bleeding).
| Precautions | Hepatic toxicity (elevated liver enzymes, hepatic failure), Churg-Strauss syndrome, neuropsychiatric events (agitation, depression, insomnia), increased risk in patients with pre-existing hepatic impairment. |
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| Fetal Monitoring | Monitor hepatic function (ALT, AST) during therapy due to risk of hepatic toxicity. In pregnancy, monitor FEV1, asthma symptoms, and fetal growth (ultrasound) if maternal asthma is poorly controlled. No specific fetal monitoring required for zafirlukast alone. |
| Fertility Effects | No human studies on fertility. In animal studies, no adverse effects on fertility or reproductive performance were observed. Theoretical risk is low, but data are insufficient for definitive conclusions. |