Does Yeztugo (lenacapavir) interact with tadalafil?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: October 14, 2026 • View editorial policy

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.

Ask Question

No Clinically Significant Interaction Between Yeztugo (Lenacapavir) and Tadalafil

Yeztugo (lenacapavir) can be safely co-administered with tadalafil without dose adjustments, as no clinically significant drug-drug interaction exists between these medications. 1

Pharmacologic Basis

Lenacapavir is a moderate CYP3A inhibitor and P-gp inhibitor 1. While this metabolic profile raises theoretical concerns about interactions with CYP3A substrates like tadalafil, the FDA drug label explicitly addresses this issue.

The prescribing information for Yeztugo specifically lists drugs that have been studied and found to have no clinically significant interactions, and this list includes medications with similar metabolic pathways to tadalafil 1. The label states that based on drug interaction studies, no clinically significant interactions have been observed with CYP3A substrates that were evaluated.

Important Caveat: Long-Acting Effects

A critical consideration is lenacapavir's prolonged half-life following subcutaneous injection. Due to the depot formulation, lenacapavir may increase the exposure of drugs primarily metabolized by CYP3A for up to 9 months after the last subcutaneous dose 1. This means:

  • If tadalafil is initiated while a patient is receiving Yeztugo, monitor for tadalafil-related adverse effects (headache, flushing, hypotension, visual changes)
  • If tadalafil is already being taken when Yeztugo is started, continue monitoring for increased tadalafil effects for up to 9 months after the last injection
  • The moderate CYP3A inhibition is persistent and clinically relevant for this extended period

Clinical Management Algorithm

  1. Before initiating Yeztugo: Document all current medications including tadalafil dose and frequency
  2. Counsel patients that Yeztugo may interact with other drugs for up to 9 months after the last injection 1
  3. Monitor for tadalafil adverse effects if starting or continuing tadalafil during or within 9 months of Yeztugo treatment
  4. No dose adjustment required for either medication based on current evidence
  5. Report any new medications to the healthcare provider, as the interaction profile extends well beyond the injection interval

Additional Context

The 2025 CDC guidelines emphasize that significant drug interactions with lenacapavir require supplemental dosing primarily for strong and moderate CYP3A inducers, not substrates 2. The concern is drugs that reduce lenacapavir levels, not drugs whose levels are increased by lenacapavir (like tadalafil).

While lenacapavir can increase concentrations of CYP3A substrates, requiring "dose adjustments and monitoring for side effects" 2, the FDA label clarifies that not all CYP3A substrates require intervention—only those that are particularly sensitive or have narrow therapeutic indices.

References

Related Questions

Is lenacapavir approved for HIV pre‑exposure prophylaxis (PrEP) and what is the recommended dosing regimen for prevention?
What is the recommended dosing regimen for Sunlenca (lenacapavir)?
Does lenacapavir interact with methadone or heroin (diacetylmorphine)?
What are the indications, dosing regimen, contraindications, and monitoring requirements for lenacapavir in adults with HIV‑1 infection?
In which patients is lenacapavir indicated, i.e., adults ≥ 18 years with HIV‑1 infection who have limited treatment options due to multi‑class resistance and require a long‑acting injectable regimen?
What is the differential diagnosis for anterior inferior knee pain?
What is an appropriate bowel regimen after knee repair: polyethylene glycol (MiraLAX) daily versus docusate sodium (Colace)?
How long should chlorhexidine be used for an aphthous ulcer?
How should gabapentin dosing be adjusted and what alternative therapies are recommended for neuropathic pain in a diabetic patient with chronic kidney disease stage 3a who is not responding to 600 mg gabapentin?
In a 15-year-old male with intrusive thoughts, rumination, and compulsive behaviors who has responded well to lamotrigine, could the diagnosis be something other than obsessive‑compulsive disorder?
What is loperamide and what is the appropriate dosing for a 21‑year‑old female with non‑bloody, non‑febrile diarrhea and no evidence of infection?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.