What are the potential drug interactions with melatonin?

Melatonin Drug Interactions: Important Considerations

Melatonin has several important drug interactions that require caution, particularly with warfarin, medications metabolized by CYP enzymes, and CNS depressants. 1

Key Drug Interactions

• Warfarin: Caution is advised when prescribing melatonin to patients taking warfarin due to potential interactions reported to the World Health Organization 1

• Medications metabolized by CYP enzymes: Melatonin shows product-dependent inhibition of CYP1A2, CYP2C19, and CYP3A7, potentially affecting metabolism of drugs utilizing these pathways 2

• CNS depressants: Severe sedation has been reported when melatonin is combined with medications like citalopram, nortriptyline, and oxycodone 2

• 5-methoxypsoralen: This potent CYP1A2 inhibitor can impair melatonin metabolism at pharmacologically relevant concentrations 3

• Photosensitizing medications: Patients using these medications should only use melatonin with periodic ophthalmological and/or dermatological monitoring 1

Specific Patient Populations Requiring Extra Caution

• Epilepsy patients: Caution is advised when prescribing melatonin to patients with epilepsy based on case reports 1

• Patients with glucose metabolism disorders: Melatonin has been associated with impaired glucose tolerance in healthy women after acute administration 1

• Patients with depression: Melatonin has been associated with increased depressive symptoms in some individuals 1

Common Side Effects That May Compound With Other Medications

• Daytime sleepiness (1.66% of users) - may compound with other sedating medications 4

• Headache (0.74% of users) - potential for additive effects with other headache-inducing medications 4

• Dizziness (0.74% of users) - may worsen with other medications causing similar effects 4

• Hypotension or hypertension - reported at higher melatonin doses in healthy adults and at lower doses in those with relevant preexisting conditions 1

• Gastrointestinal upset - may compound with medications having similar side effects 1

Medication Selection and Dosing Considerations

• Start with lower doses: Lower doses (3mg) may be more effective than higher doses (10mg) which can cause receptor desensitization 5

• Timing of administration: Take 1.5-2 hours before desired bedtime for optimal effect 5

• Product selection: Choose United States Pharmacopeial Convention Verified formulations for more reliable dosing and purity 1

• Monitoring: When using melatonin with interacting medications, monitor for enhanced sedation, changes in blood pressure, and mood alterations 1

Overdose Considerations

• While melatonin generally has low toxicity potential, severe sedation can occur with overdose, especially when combined with other CNS depressants 6

• Supportive measures and vital sign monitoring are crucial in overdose treatment 6

Practical Recommendations

• Document concurrent medications: Before recommending melatonin, review all medications for potential interactions 1

• Consider alternatives: For patients on multiple medications with potential interactions, consider non-pharmacological sleep interventions first 1

• Monitor long-term use: Studies addressing long-term effects are scarce, so periodic reassessment is advisable 1

• Avoid in complex medication regimens: Exercise caution when adding melatonin to regimens containing multiple CNS-active medications 2