What are the potential drug interactions with Dayvigo (lemborexant)?

Dayvigo (Lemborexant) Drug Interactions

Avoid concomitant use of Dayvigo with moderate or strong CYP3A inhibitors, and do not combine with strong CYP3A inducers, as these interactions significantly alter lemborexant exposure and can lead to excessive sedation or loss of efficacy. 1, 2

Critical Contraindicated Combinations

Strong and Moderate CYP3A Inhibitors

• Fluconazole (moderate CYP3A inhibitor) increases lemborexant Cmax and AUC by approximately 1.6-fold and 4.2-fold, respectively, substantially raising the risk of adverse reactions such as somnolence 1
• Itraconazole (strong CYP3A inhibitor) increases lemborexant exposure by 1.4- to 1.6-fold for Cmax and 3.7- to 4-fold for AUC 2
• The FDA label explicitly states to avoid concomitant use of fluconazole with lemborexant 1
• Other contraindicated CYP3A inhibitors include ketoconazole, clarithromycin, and protease inhibitors 3

Strong CYP3A Inducers

• Rifampin causes >90% decreases in lemborexant Cmax and AUC, rendering the medication ineffective 2
• Other strong inducers to avoid include carbamazepine, phenobarbital, phenytoin, and St. John's wort 3

Moderate-Risk Interactions Requiring Dose Adjustment

P-glycoprotein (P-gp) Inhibitors

• Lemborexant is a substrate for P-gp transport, making it susceptible to interactions with P-gp inhibitors 3
• Amiodarone (P-gp inhibitor) may increase lemborexant exposure by 50-60%, similar to effects seen with dabigatran 3
• Verapamil can increase exposure by 60-180% depending on formulation and timing 3
• Consider dose reduction of lemborexant when combining with P-gp inhibitors, particularly in patients with renal impairment 3

Weak CYP3A Inhibitors

• Phase 3 trial data comparing patients taking concomitant weak CYP3A inhibitors versus those not taking them substantiated modest increases in lemborexant exposure 2
• These combinations may be used with caution but monitor for increased somnolence 2

CYP2B6 Substrate Interactions

• Lemborexant induces CYP2B6, decreasing bupropion (S-bupropion) Cmax and AUC by approximately 50% and 45%, respectively 2
• This interaction may reduce the efficacy of bupropion for depression or smoking cessation 2
• Consider alternative antidepressants or monitor for reduced bupropion effectiveness 2

No Clinically Significant Interactions

CYP3A Substrates

• Midazolam exposure was not affected by lemborexant coadministration, indicating lemborexant does not inhibit or induce CYP3A enzymes 2
• This suggests no interaction with other CYP3A substrates like atorvastatin, simvastatin, or calcium channel blockers 3

CNS Depressant Combinations

• While not specifically studied with lemborexant, the general principle for orexin receptor antagonists is to exercise caution when combining with other CNS depressants 4
• Monitor for additive sedation when combining with benzodiazepines, opioids, or alcohol 5
• The 9-hour post-dose plasma concentration is only 27% of maximum concentration for the 10 mg dose, suggesting minimal next-morning residual effects 5

Anticoagulant Considerations

• No direct interaction data exists between lemborexant and anticoagulants 3
• Unlike some sleep medications, lemborexant does not affect CYP2C9 (warfarin metabolism pathway) 2
• Standard anticoagulation monitoring protocols apply without specific adjustments for lemborexant 3

Special Population Considerations

Renal Impairment

• Lemborexant pharmacokinetics may be affected by renal function, though it is not primarily renally eliminated 5
• Drug interactions are exacerbated in renal impairment, particularly with P-gp inhibitors 3
• Consider lower starting doses (5 mg) in patients with moderate to severe renal impairment taking interacting medications 5

Hepatic Impairment

• Lemborexant exposure increases 2.3-fold in moderate hepatic impairment 6
• Avoid combining with hepatotoxic medications (azole antifungals, certain antiretrovirals) in patients with liver disease 6
• Use lower doses and monitor for increased sedation in hepatic impairment 5

Elderly Patients

• No clinically relevant effects of age on lemborexant pharmacokinetics, pharmacodynamics, or safety were observed 5
• However, elderly patients may have reduced renal function requiring dose adjustment when combined with interacting medications 5

Clinical Monitoring Recommendations

• Assess for somnolence and next-day impairment when initiating lemborexant, particularly with weak CYP3A inhibitors 2, 5
• No routine laboratory monitoring is required for lemborexant drug interactions 5
• Evaluate all concomitant medications before prescribing, including over-the-counter drugs and herbal supplements 3
• Consider transitioning from other sleep medications directly to lemborexant without washout period, as demonstrated safe in clinical trials 7