Melatonin and Lisdexamfetamine Interaction
Drug interaction information between Melatonin and Lisdexamfetamine.
Melatonin and Lisdexamfetamine have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Melatonin and Lisdexamfetamine. Major interactions are generally avoided, moderate ones may need monitoring or a dose adjustment, and minor ones are usually low-risk. This page shows the documented mechanism and guidance. Label-documented interactions are not a complete safety review, so always confirm your own medications with a pharmacist or doctor. Educational information, not medical advice.
How They Interact
Lisdexamfetamine does not change how the body's enzymes break down melatonin.
What To Do
No dose adjustment is required when using these two products together.
FDA Label Information
From a pharmacokinetic perspective, no dose adjustment for drugs that are substrates of CYP1A2 (e.g., theophylline, duloxetine, melatonin), CYP2D6 (e.g., atomoxetine, desipramine, venlafaxine), CYP2C19 (e.g., omeprazole, lansoprazole, clobazam), and CYP3A4 (e.g., midazolam, pimozide, simvastatin) is necessary when VYVANSE is co-administered [see Clinical Pharmacology (12.3) ] .
Lisdexamfetamine Also Interacts With
- Omeprazole minor
- Simvastatin minor
- Duloxetine minor
- Venlafaxine minor
- Atomoxetine minor
Frequently Asked Questions
Can I take Melatonin and Lisdexamfetamine together?
This is a minor interaction. No dose adjustment is required when using these two products together.
How serious is the interaction between Melatonin and Lisdexamfetamine?
This interaction is classified as "minor" severity by the FDA. Minor interactions are unlikely to cause significant problems but should still be mentioned to your healthcare provider.
Why do Melatonin and Lisdexamfetamine interact?
Lisdexamfetamine does not change how the body's enzymes break down melatonin.
Understanding the Melatonin and Lisdexamfetamine Interaction
FDA-approved prescribing information for these two drugs flags their combination as a minor-severity interaction. Melatonin belongs to the Hormone Supplement (Sleep Aid) class and Lisdexamfetamine belongs to the CNS Stimulant class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: Lisdexamfetamine does not change how the body's enzymes break down melatonin. Severity tiers matter: major flags generally advise avoidance, moderate flags often require monitoring or dose adjustment, and minor flags may only call for awareness.
Context around a specific patient determines real-world impact. Melatonin has 2 total documented interactions on file in this dataset, and Lisdexamfetamine has 14. Each additional medication compounds the interaction surface, which is why pharmacists run full-profile checks rather than evaluating one pair at a time. FDA-derived guidance for this pair is: No dose adjustment is required when using these two products together. Timing of doses, renal and hepatic function, age, and other concurrent prescriptions all shape whether a labeled interaction matters clinically.
An interaction flag is not a verdict. A large share of labeled interactions are managed routinely in clinical practice, the fix may be as simple as spacing doses or adding a monitoring test. Others require the prescriber to choose a different medication entirely. This page surfaces FDA-sourced labeling and openFDA data for educational purposes only; it is not medical advice and cannot account for your full clinical picture. Never start, stop, or adjust either Melatonin or Lisdexamfetamine based on a web page, speak with your prescriber or pharmacist before making any change.
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. Always consult your healthcare provider about drug interactions.
Read our methodology - how this data is sourced, computed, and verified.