Drug interactions
Modafinil + Sertraline
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.
Overview
Potential increase in sertraline exposure due to modafinil’s CYP2C19 inhibition; combined with both agents’ activating profiles, patients may experience additive CNS stimulation (insomnia, anxiety, agitation). Clinical impact varies and is more likely in CYP2C19 poor metabolizers.
Mechanism of action
Pharmacokinetic: Modafinil inhibits CYP2C19 (and induces CYP3A4/2B6), while sertraline is partially metabolized by CYP2C19, potentially increasing sertraline concentrations; net effect may vary due to mixed enzyme effects. Pharmacodynamic: Additive CNS activation from both agents.
Clinical management
Monitor for increased sertraline adverse effects (e.g., nausea, tremor, agitation, insomnia) and for anxiety/restlessness; consider dose adjustment of sertraline if clinically indicated. Prefer morning dosing of modafinil and avoid late-day sertraline dosing if insomnia occurs. Monitor blood pressure/heart rate in symptomatic patients; consider checking serum sodium in older adults or those at risk.
Drug reference
References
- Provigil (modafinil) Prescribing Information – Drug Interactions (CYP2C19 inhibition; CYP3A4 induction; effect on probe substrates) — FDA Label
- Zoloft (sertraline) Prescribing Information – Clinical Pharmacology/Pharmacokinetics and Pharmacogenomics (CYP2C19 involvement) — FDA Label
- Modafinil: Drug Interactions and Adverse Effects — Lexicomp
- Sertraline: Drug Information (metabolism, adverse effects) — Lexicomp
Frequently asked questions
Can I take Modafinil with Sertraline?
The interaction is rated: Moderate. Potential increase in sertraline exposure due to modafinil’s CYP2C19 inhibition; combined with both agents’ activating profiles, patients may experience additive CNS stimulation (insomnia, anxiety, agitation). Clinical impact varies and is more likely in CYP2C19 poor metabolizers.
How serious is the interaction between Modafinil and Sertraline?
The interaction is rated: Moderate. Evidence level: Low.
How is the interaction between Modafinil and Sertraline managed?
Monitor for increased sertraline adverse effects (e.g., nausea, tremor, agitation, insomnia) and for anxiety/restlessness; consider dose adjustment of sertraline if clinically indicated. Prefer morning dosing of modafinil and avoid late-day sertraline dosing if insomnia occurs. Monitor blood pressure/heart rate in symptomatic patients; consider checking serum sodium in older adults or those at risk.
Why do Modafinil and Sertraline interact?
Pharmacokinetic: Modafinil inhibits CYP2C19 (and induces CYP3A4/2B6), while sertraline is partially metabolized by CYP2C19, potentially increasing sertraline concentrations; net effect may vary due to mixed enzyme effects. Pharmacodynamic: Additive CNS activation from both agents.
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