Lenacapavir

YEZTUGO is an HIV-1 antiretroviral agent with long-acting properties [see Microbiology (12.4) ].

• YEZTUGO is indicated for pre‑exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating YEZTUGO [see Dosage and Administration (2.1) and Warnings and Precautions (5.1) ].ICD-10: B20

• YEZTUGO is contraindicated in individuals with unknown or positive HIV-1 status [see Warnings and Precautions (5.1) ]. Unknown or positive HIV-1 status.contraindicated

HIV-1 screening: Screen all individuals for HIV-1 infection prior to initiating YEZTUGO, prior to each injection of YEZTUGO, and additionally as clinically appropriate. ( 2.1 ) Dosing schedule: Initiation dosing (injection and tablets) followed by once every 6-months continuation injection dosing. Tablets may be taken without regard to food. ( 2.3 ) Initiation Day 1 927 mg by subcutaneous injection (2 x 1.5 mL injections) and 600 mg orally (2 x 300 mg tablets) Day 2 600 mg orally (2 x 300 mg tablets) Continuation 927 mg by subcutaneous injection (2 x 1.5 mL injections) every 6-months (26 weeks) from the date of the last injection +/-2 weeks. Anticipated delayed injections: If scheduled injection is anticipated to be delayed by more than 2 weeks, YEZTUGO tablets may be used on an interim basis (for up to 6 months if needed) until injections resume. Dosing schedule for delayed injection is 300 mg orally once every 7 days. ( 2.4 ) Missed injections: If more than 28 weeks have elapsed since the last injection and tablets have not been taken, restart initiation from Day 1 if clinically appropriate. ( 2.4 ) Dosage modifications (supplemental doses) of YEZTUGO are recommended when initiating strong or moderate CYP3A inducers. ( 2.5 ) YEZTUGO injection is for subcutaneous administration only. Two 1.5 mL injections are required for complete dose.

Comprehensive management to reduce the risk of HIV-1 acquisition. ( 5.1 ) Potential risk of developing resistance to lenacapavir if an individual acquires HIV-1 either before or when receiving YEZTUGO, or following discontinuation of YEZTUGO. Test before each injection and additionally as clinically appropriate to confirm HIV-1 negative status ( 5.2 ) Residual concentrations of lenacapavir may remain in systemic circulation for up to 12 months or longer. ( 5.3 ) Improper administration (intradermal injection) has been associated with serious injection site reactions. ( 5.4 ) 5.1 Comprehensive Management to Reduce the Risk of HIV-1 Infection and Other Sexually Acquired Infections Use YEZTUGO to reduce the risk of HIV-1 acquisition as part of a comprehensive prevention strategy including adherence to the administration schedule and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs). YEZTUGO is not always effective in preventing HIV-1 acquisition [see Clinical Studies (14) ]. The time from initiation of YEZTUGO for HIV-1 PrEP to maximal protection against HIV-1 infection is unknown. Risk for HIV-1 acquisition includes behavioral, biological, or epidemiologic factors including, but not limited to, condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high prevalence area or network.

The following adverse reactions are discussed in other sections of the labeling: Serious Injection Site Reactions with Improper Administration [see Warnings and Precautions (5.4) ]. Most common adverse reactions (incidence greater than or equal to 5%, all grades) are injection site reactions, headache, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The primary safety assessment of YEZTUGO is based on data from two randomized, double-blind, active-controlled trials, PURPOSE 1 and PURPOSE 2, in which a total of 8616 adult and adolescent participants received YEZTUGO (N=4323), DESCOVY (emtricitabine [FTC]/tenofovir alafenamide [TAF]; N=2135) once daily, or TRUVADA (FTC/tenofovir disoproxil fumarate [TDF]; N=2158) once daily for HIV-1 PrEP. In PURPOSE 1, the median duration of exposure to YEZTUGO, DESCOVY, and TRUVADA was 43, 42, and 41 weeks, respectively. In PURPOSE 2, the median duration of exposure to both YEZTUGO and TRUVADA was 39 weeks. The most common adverse reactions (all Grades) reported in at least 5% of participants receiving YEZTUGO in either PURPOSE 1 or PURPOSE 2 were injection site reactions, headache, and nausea.

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to YEZTUGO during pregnancy. Healthcare providers are encouraged to register individuals by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Available data from a randomized, controlled trial (PURPOSE 1) with YEZTUGO use during pregnancy have not identified a drug-associated risk for miscarriage, or adverse maternal or fetal outcomes when compared to the active control (see Data ) . The rate of major birth defects in YEZTUGO-exposed pregnancies did not exceed the background prevalence rates. The risk estimates are imprecise due to small numbers of exposed pregnancies (see Data ) . There is an increased risk of HIV-1 transmission from the mother to the child during acute HIV-1 infection (see Clinical Considerations ). In animal reproduction studies, no adverse developmental effects were observed when lenacapavir was administered to rats and rabbits at exposures (AUC) ≥7 times the exposure in humans at the recommended human dose (RHD) of YEZTUGO ( see Data ). The APR has been established to monitor for birth defects following prenatal exposure to antiretrovirals. The APR uses the Metropolitan Atlanta Congenital Defects Program (MACDP) as the U.S.

Metabolism

The pharmacokinetic (PK) properties of lenacapavir are provided in Table 8 . The population PK parameter estimates of YEZTUGO after oral and subcutaneous administration to adults are provided in Table 9 .

No data are available on overdose of YEZTUGO. If overdose occurs, monitor the individual for evidence of toxicity. Treatment of overdose with YEZTUGO consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the individual. As lenacapavir is highly bound to plasma proteins, it is unlikely to be significantly removed by dialysis.

• Dec 22, 2022NDANDA215973Gilead Sciences Inc
• Dec 22, 2022NDANDA215974Gilead Sciences Inc
• Jun 18, 2025NDANDA220018Gilead Sciences Inc
• Jun 18, 2025NDANDA220020Gilead Sciences Inc

1. 1Injection Site Discharge13533%
2. 2Injection Site Pain12430%
3. 3Injection Site Nodule10225%
4. 4Injection Site Erythema378.9%
5. 5Injection Site Mass348.2%
6. 6Injection Site Swelling225.3%
7. 7Injection Site Bruising133.1%
8. 8Nausea92.2%
9. 9Vomiting92.2%
10. 10Injection Site Discomfort81.9%
11. 11Injection Site Haemorrhage81.9%
12. 12Loss Of Consciousness81.9%
13. 13Injection Site Reaction71.7%
14. 14Pain71.7%
15. 15Product Administered At Inappropriate Site71.7%

The 10 most recently updated of 37 ClinicalTrials.gov registrations naming Lenacapavir as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study of GS-3242 in Combination With Lenacapavir Versus Biktarvy in Virologically Suppressed People With HIV-1
  Not yet recruiting · Phase 2 · Interventional · 175 enrolled · Gilead Sciences
  NCT07645287updated 2026-06-12
• Study of Bictegravir/Lenacapavir in Children and Adolescents With HIV-1
  Active not recruiting · Phase 2 · Phase 3 · Interventional · 75 enrolled · Gilead Sciences
  NCT06532656updated 2026-06-04
• Implementation Study of Lenacapavir Pre-exposure Prophylaxis for HIV Prevention
  Recruiting · Observational · 3,000 enrolled · Gilead Sciences
  NCT07473778updated 2026-05-29
• Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Standard of Care in Virologically Suppressed People With HIV-1
  Active not recruiting · Phase 3 · Interventional · 600 enrolled · Gilead Sciences
  NCT06630299updated 2026-05-29
• The TAIL-PrEP Study
  Recruiting · Interventional · 30 enrolled · Columbia University
  NCT06868641updated 2026-05-28
• Study of Lenacapavir Taken Twice a Year for HIV Pre-Exposure Prophylaxis (PrEP)
  Active not recruiting · Phase 2 · Interventional · 268 enrolled · Gilead Sciences
  NCT06513312updated 2026-05-19
• Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed People With HIV-1
  Active not recruiting · Phase 3 · Interventional · 609 enrolled · Gilead Sciences
  NCT06630286updated 2026-04-30
• A Study of Teropavimab and Zinlirvimab in Combination With Capsid Inhibitor Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection
  Active not recruiting · Phase 2 · Interventional · 83 enrolled · Gilead Sciences
  NCT05729568updated 2026-04-27
• Evaluation of Long-Acting Lenacapavir for the Treatment of HIV-1 in Treatment-experienced Adolescents and Children
  Recruiting · Phase 2 · Interventional · 12 enrolled · Gilead Sciences
  NCT06749054updated 2026-04-24
• Protecting Against Lenacapavir Misinformation With Young Women in Gauteng, South Africa ( PROTECT-L)
  Not yet recruiting · Interventional · 1,500 enrolled · University of Pennsylvania
  NCT07518914updated 2026-04-23

Frequently asked questions

How does Lenacapavir work?

YEZTUGO is an HIV-1 antiretroviral agent with long-acting properties [see Microbiology (12.4) ].

What is Lenacapavir used for?

According to FDA labeling, Lenacapavir carries indications including: YEZTUGO is indicated for pre‑exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating YEZTUGO [see Dosage and Administration (2.1) and Warnings and Precautions (5.1) ].. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Lenacapavir?

Lenacapavir is classified as Other antivirals, Human Immunodeficiency Virus 1 Capsid Inhibitor, Breast Cancer Resistance Protein Inhibitors, Cytochrome P450 3A Inducers, Cytochrome P450 3A Inhibitors, HIV Capsid Inhibitors, P-Glycoprotein Inhibitors, Viral Envelope Wrapping Protein Inhibitors.

What are the brand names for Lenacapavir?

Lenacapavir is marketed under brand names including Sunlenca, Yeztugo.

What are the contraindications for Lenacapavir?

Lenacapavir labeling lists contraindications including: YEZTUGO is contraindicated in individuals with unknown or positive HIV-1 status [see Warnings and Precautions (5.1) ]. Unknown or positive HIV-1 status.. Always consult the full prescribing information and a clinician.