Drug interactions
Amitriptyline + Modafinil
Severity: Moderate
Amitriptyline and Modafinil: moderate interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Modafinil can inhibit CYP2C19 and may increase exposure to amitriptyline and its active metabolites, although effects are variable. Modafinil's wake-promoting effect also opposes amitriptyline sedation, and tricyclic toxicity such as tachycardia or anticholinergic effects may occur.
What this interaction means in plain words
Amitriptyline and Modafinil can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Amitriptyline belongs to Central Nervous System; Modafinil belongs to Central Nervous System.
Why it happens
CYP2C19 inhibition by modafinil reducing amitriptyline clearance, with opposing pharmacodynamic effects on alertness.
What to do
Monitor for tricyclic adverse effects and clinical response after starting or stopping modafinil. Adjust the amitriptyline dose or measure plasma levels if toxicity is suspected.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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Other interactions of Amitriptyline
- Amitriptyline + Isocarboxazid Contraindicated
- Amitriptyline + Methylene blue Contraindicated
- Amitriptyline + Phenelzine Contraindicated
- Amitriptyline + Pimozide Contraindicated
- Amitriptyline + Procarbazine Contraindicated
- Amitriptyline + Safinamide Contraindicated
Other interactions of Modafinil
Frequently asked questions
Can I take Amitriptyline with Modafinil?
MediHelp rates the interaction as moderate. Amitriptyline and Modafinil can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Modafinil can inhibit CYP2C19 and may increase exposure to amitriptyline and its active metabolites, although effects are variable. Modafinil's wake-promoting effect also opposes amitriptyline sedation, and tricyclic toxicity such as tachycardia or anticholinergic effects may occur.
How serious is the interaction between Amitriptyline and Modafinil?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor for tricyclic adverse effects and clinical response after starting or stopping modafinil. Adjust the amitriptyline dose or measure plasma levels if toxicity is suspected.
What other medicines interact with Amitriptyline?
MediHelp also lists interactions of Amitriptyline with, for example, Isocarboxazid, Methylene blue, Phenelzine. The full list is on the Amitriptyline page.
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