Drug Interaction Report

Methadone and Lenacapavir Oral: Interaction Details

A pharmacist-reviewed analysis of the Methadone and Lenacapavir Oral interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Methadone

Diskets Dolophine Methadose
+

Lenacapavir Oral

Sunlenca Sunlenca® Yeztugo
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
How we grade severity & evidence

Severity levels

  • Contraindicated: These should generally not be used together.
  • Major: Potentially serious — often needs a change or close monitoring.
  • Moderate: Can be significant — usually manageable with monitoring.
  • Minor: Usually limited clinical impact.

Evidence grades

  • Established: Well documented — supported by controlled studies or strong clinical data.
  • Probable: Good supporting evidence, though not definitively proven.
  • Suspected: Some evidence suggests this interaction, but it is not well established.
  • Possible: Limited or conflicting evidence; the interaction may occur.
  • Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.

Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.

Of 129 documented Methadone interactions, 125 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
theoretical
Severity
Major

What happens

Altered (increased or reduced) methadone exposure

Interaction Deep Dive

Coadministration of lenacapavir (a moderate CYP3A inhibitor) together with methadone (narcotic analgesic metabolized by CYP3A) may increase the exposure of methadone. Lenacapavir may increase the exposure of drugs primarily metabolized by CYP3A, initiated within 9 months after the last dose of lenacapavir, which may also increase the potential risk of adverse reactions21. Careful monitoring of therapeutic effects and adverse reactions associated with methadone including potentially fatal respiratory depression is recommended when coadministered with lenacapavir. During initiation of methadone in patients taking lenacapavir, carefully titrate the dose of methadone to the desired effect and use the lowest feasible initial or maintenance dose. During initiation of lenacapavir in patients taking methadone, a dose adjustment for methadone may be needed. Monitor clinical signs and symptoms 2.

Why it happens (mechanism)

Inhibition of CYP3A-mediated metabolism of methadone; unknown

Common questions

Can I take Methadone and Lenacapavir Oral together?

Altered (increased or reduced) methadone exposure Always confirm with your pharmacist or prescriber before making any change.

How serious is the Methadone and Lenacapavir Oral interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

The documented onset is "unspecified". The timing of this interaction is not well characterized.

How strong is the evidence for this interaction?

The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

From our Q&A

Real reader questions about these medications, each personally answered by our pharmacist:

Questions for your pharmacist

  • Does my dose of Methadone or Lenacapavir Oral need adjusting while I take them together?
  • What symptoms should prompt me to call you or my prescriber right away?
  • Does the timing of my doses matter for this combination?
  • Is there a safer alternative to one of these medications for me?

References (2)

  1. Product Information: YEZTUGO(R) oral tablets, subcutaneous injection, lenacapavir oral tablets, subcutaneous injection. Gilead Sciences Inc (per manufacturer), Foster City, CA, 2025. DailyMed
  2. Product Information: SUNLENCA(R) oral tablets, subcutaneous injection, lenacapavir oral tablets, subcutaneous injection. Gilead Sciences Inc (per FDA), Foster City, CA, 2024. DailyMed
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Methadone

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All Methadone interactions (129)
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Lenacapavir Oral

Keep reading about Lenacapavir Oral

All Lenacapavir Oral interactions (213) Lenacapavir Oral drug information
Also serious with: Encorafenib Colchicine Carbamazepine Apalutamide
Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

Methadone + 1,4-butanediol Activated Charcoal Beer Gamma-hydroxybutyrate (ghb) Grapefruit Kava L-tryptophan Lithium + 215 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.