Does montelukast have any drug interactions?

Drug Interactions with Montelukast

Montelukast has clinically significant interactions with CYP2C8 inhibitors like gemfibrozil, which can increase montelukast plasma concentrations by approximately 4.3-fold, but has minimal interactions with CYP3A4 inhibitors. 1

Key Drug Interactions

Established Significant Interactions

1. CYP2C8 Inhibitors

   • Gemfibrozil significantly increases montelukast plasma concentrations (4.3-fold increase in AUC) 1
   • CYP2C8 accounts for approximately 80% of montelukast's metabolism 1
   • This interaction could potentially increase the risk of montelukast-related adverse effects

2. Enzyme Inducers

   • Phenobarbital decreases montelukast AUC by approximately 40% 2
   • Other potent cytochrome P450 enzyme inducers (e.g., rifampin) may similarly decrease montelukast concentrations 2
   • Clinical monitoring is recommended when these inducers are co-administered with montelukast

Minimal or No Significant Interactions

1. CYP3A4 Inhibitors

   • Itraconazole (a potent CYP3A4 inhibitor) has no significant effect on montelukast's pharmacokinetics 1
   • CYP3A4 only mediates the formation of minor metabolites and is not important in montelukast elimination 1

2. Other Common Medications

   • Montelukast does not significantly alter the pharmacokinetics of:
     • Theophylline (CYP1A2 substrate) 2
     • Warfarin (CYP2C9, 3A4, and 1A2 substrate) 2
     • Digoxin 2
     • Terfenadine/fexofenadine 2
     • Oral contraceptives containing norethindrone/ethinyl estradiol 2
     • Prednisone or prednisolone 2

3. Rosiglitazone and CYP2C8 substrates

   • Despite being a potent CYP2C8 inhibitor in vitro, montelukast does not inhibit CYP2C8 in vivo 2
   • No significant effect on drugs primarily metabolized by CYP2C8 (e.g., paclitaxel, rosiglitazone, repaglinide) 2

Special Considerations

Potential Neuropsychiatric Effects

• Case report suggests possible interaction between montelukast and efavirenz, leading to worsened neuropsychiatric symptoms 3
• This may be due to overlapping side effect profiles or potential interaction through CYP pathways

Hepatotoxicity Risk

• Rare case reports suggest potential hepatotoxicity risk when montelukast is combined with certain dietary supplements 4
• Montelukast itself has been associated with rare cases of reversible hepatitis and hepatic failure 5

Clinical Implications

1. Monitoring Recommendations

   • Monitor for increased adverse effects when combining montelukast with CYP2C8 inhibitors like gemfibrozil
   • Consider dose adjustment or alternative therapy when using montelukast with strong enzyme inducers like phenobarbital

2. Patient Populations Requiring Special Attention

   • Patients with hepatic impairment (montelukast elimination is slightly prolonged) 2
   • Patients taking multiple medications that might affect CYP enzyme pathways
   • HIV patients on efavirenz (potential for increased neuropsychiatric effects) 3

3. Practical Approach

   • No dosage adjustment is required for patients with mild-to-moderate hepatic insufficiency 2
   • No dosage adjustment is required for patients with renal insufficiency 2
   • Clinical monitoring is recommended when potent cytochrome P450 enzyme inducers are co-administered 2

By understanding these interactions, clinicians can optimize montelukast therapy while minimizing potential adverse effects from drug interactions.