4. Drug-Drug Interactions
Patient profiles will be assessed to identify those drug regimens which may result in clinically significant drug-drug interactions.
No dosage adjustments are necessary when montelukast is co-administered with theophylline, prednisone, prednisolone, oral contraceptives, digoxin, warfarin, thyroid hormones, sedative hypnotics, nonsteroidal anti-inflammatory agents, benzodiazepines, decongestants, and cytochrome P450 enzyme inducers. Continuous monitoring for montelukast efficacy is recommended when concurrently taking cytochrome P450 enzyme inducers.
Drug-drug interactions considered clinically relevant for zafirlukast are summarized in Table 3. Only those drug-drug interactions identified as severe or those considered life-threatening which have not yet been classified will be reviewed.
| Target Drug | Interacting Drug | Interaction | Recommendation | Clinical Significance Level # |
|---|---|---|---|---|
| zafirlukast | erythromycin, clarithromycin | decreased zafirlukast concentrations; mechanism unknown | monitor patient for lack of response to zafirlukast therapy; may consider azithromycin or montelukast as alternatives | moderate (CP) |
| zafirlukast | drugs metabolized by CYP2C9 (e.g., warfarin, phenytoin) | increased concentrations of drugs metabolized by CYP2C9 due to zafirlukast enzyme inhibition; prothrombin time increased by 35% with warfarin-zafirlukast combination | monitor for increased adverse events (e.g., regularly assess PT or INR with warfarin-zafirlukast combination, phenytoin levels) | major (CP) |
| zafirlukast | other drugs metabolized by CYP3A4 (e.g., dofetilide, ergot alkaloids, aripiprazole, cilostazol) | increased concentration of drugs metabolized by CYP3A4 due to CYP3A4 inhibition by zafirlukast | carefully monitor patient therapy for potentially enhanced pharmacologic effects and toxicity | major (CP) |
| zafirlukast | pimozide | increased pimozide concentrations resulting in QTc prolongation and ventricular arrhythmias due to CYP3A4 inhibition by zafirlukast | contraindicated | severe (CP) |
| zafirlukast | saquinavir (boosted with ritonavir) | saquinavir and zafirlukast are CYP3A4 inhibitors; combined use may increase saquinavir serum levels and potentially result in life-threatening arrhythmias (including torsades de pointes) | contraindicated | severe (CP) |
| zafirlukast | theophylline | increased theophylline concentration due to CYP 1A2 inhibition by zafirlukast and/or decreased zafirlukast serum levels | monitor for theophylline toxicity and/or reduced zafirlukast efficacy | moderate (CP) |
Legend:
- *CP = Clinical Pharmacology