Lenacapavir and Mitapivat: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Lenacapavir
Mitapivat
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.
What happens
Reduced lenacapavir exposure which may result in the loss of therapeutic effect and development of resistance to lenacapavir, increased mitapivat exposure, and an increased risk of mitapivat-mediated adverse reactions
Interaction Deep Dive
Avoid coadministration of mitapivat and lenacapavir (moderate CYP3A inhibitor) as it may increase mitapivat exposure1. If coadministration is required, do not titrate beyond 20 mg twice daily, and monitor Hb and for adverse reactions 2. Concomitant use reduces lenacapavir (SUNLENCA®) exposure which may result in the loss of therapeutic effect and development of resistance to lenacapavir 3. For individuals receiving YEZTUGO® and initiating therapy with mitapivat, continue to maintain scheduled injection dosing (YEZTUGO® 927 mg SUBQ once every 6 months) plus administer the following supplemental YEZTUGO® doses: administer 463.5 mg SUBQ on the day of mitapivat initiation. Dosing recommendations are not available for the initiation of YEZTUGO® in individuals already receiving moderate CYP3A inducers, nor in individuals receiving the weekly oral dosage. If mitapivat is coadministered for longer than 6 months, continue to administer supplemental doses of YEZTUGO® every 6 months (26 weeks +/- 2 weeks) from CYP3A inducer initiation. After stopping mitapivat, continue the once every 6 months scheduled injection dosing of YEZTUGO® 4.
Why it happens (mechanism)
Induction of CYP3A-mediated metabolism of lenacapavir; inhibition of CYP3A-mediated metabolism of mitapivat
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 34.
b) Coadministration of mitapivat with fluconazole, a moderate CYP3A inhibitor, increased mitapivat AUC(0 to 12) and Cmax by 2.6-fold and 1.6-fold, respectively, following administration of mitapivat 5, 20 or 50 mg twice daily 21.
Common questions
Can I take Lenacapavir and Mitapivat together?
Reduced lenacapavir exposure which may result in the loss of therapeutic effect and development of resistance to lenacapavir, increased mitapivat exposure, and an increased risk of mitapivat-mediated adverse reactions Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lenacapavir and Mitapivat 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 Lenacapavir or Mitapivat 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 (4)
- Product Information: AQVESME™ oral tablets, mitapivat oral tablets. Agios Pharmaceuticals Inc (per FDA), Cambridge, MA, 2025. DailyMed
- Product Information: PYRUKYND(R) oral tablets, mitapivat oral tablets. Agios Pharmaceuticals Inc (per FDA), Cambridge, MA, 2025. DailyMed
- Product Information: SUNLENCA(R) oral tablets, subcutaneous injection, lenacapavir oral tablets, subcutaneous injection. Gilead Sciences Inc (per FDA), Foster City, CA, 2024. DailyMed
- Product Information: YEZTUGO(R) oral tablets, subcutaneous injection, lenacapavir oral tablets, subcutaneous injection. Gilead Sciences Inc (per manufacturer), Foster City, CA, 2025. DailyMed
Keep reading about Lenacapavir
Keep reading about Mitapivat
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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