Drug Interaction Report

Repotrectinib and Lenacapavir Injection: Interaction Details

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

Lenacapavir Injection

Sunlenca Sunlenca® Yeztugo
+

Repotrectinib

Augtyro
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Aug 8, 2026
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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 70 documented Repotrectinib interactions, 66 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

Reduced lenacapavir exposure which may result in the loss of therapeutic effect and development of resistance to lenacapavir, increased repotrectinib exposure, and an increased risk of repotrectinib-related adverse effects

Interaction Deep Dive

Avoid concomitant use of repotrectinib with moderate CYP3A inhibitors, such as lenacapavir, as it may increase repotrectinib exposure and the incidence and severity of adverse reactions. Discontinue the CYP3A inhibitor for 3 to 5 elimination half-lives of the CYP3A inhibitor prior to initiating repotrectinib3.. Additionally, concomitant use of lenacapavir (SUNLENCA®) with a moderate CYP3A inducer, such as repotrectinib, is not recommended, as coadministration reduces lenacapavir exposure which may result in the loss of therapeutic effect and development of resistance to lenacapavir 2; however, lenacapavir (YEZTUGO®) and a moderate CYP3A inducer can be considered with dosage adjustments 1.

Why it happens (mechanism)

Induction of CYP3A-mediated metabolism of lenacapavir; inhibition of P-gp-mediated efflux transport of repotrectinib; inhibition of CYP3A metabolism of repotrectinib

Literature reports

2 reports — tap to read

a) In the interaction studies conducted in subjects without HIV-1, concomitant administration of single dose of lenacapavir 300 mg orally with efavirenz (fasted) [inducer of CYP3A (moderate) and P-gp and UGT] 600 mg once daily, the mean ratio for AUC and Cmax of lenacapavir with and without efavirenz were 0.44 (90% CI, 0.32 to 0.59) and 0.64 (90% CI, 0.45 to 0.92) respectively 21.

b) In the drug interaction studies, repotrectinib AUC (0 to inf) increased by 5.9-fold and Cmax by 1.7-fold following concomitant use with itraconazole (a strong CYP3A and P-gp inhibitor) 3.

Common questions

Can I take Repotrectinib and Lenacapavir Injection together?

Reduced lenacapavir exposure which may result in the loss of therapeutic effect and development of resistance to lenacapavir, increased repotrectinib exposure, and an increased risk of repotrectinib-related adverse effects Always confirm with your pharmacist or prescriber before making any change.

How serious is the Repotrectinib and Lenacapavir Injection 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.

Questions for your pharmacist

  • Does my dose of Repotrectinib or Lenacapavir Injection 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 (3)

  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
  3. Product Information: AUGTYRO(TM) oral capsules, repotrectinib oral capsules. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2023. DailyMed
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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.