LENACAPAVIR INJ,SOLN
Clinical Criteria Summary
Document 477: MON Lenacapavir SUNLENCA YEZTUGO Monograph UPDATE Nov 2025
Indications & Patient Population
- HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant (MDR) HIV-1 infection failing current antiretroviral treatment (ART) regimen due to resistance, intolerance, or safety considerations
- 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
Dosing & Administration Requirements
- Administered as extended-release injectable suspension for subcutaneous (SQ) administration
- Maintenance dose: 927 mg (3 mL = 2 vials) SQ injection every 26 weeks (±2 weeks) from the date of the last SQ injection
- Requires oral initiation dosing prior to maintenance injections (Option #1 for HIV treatment/PrEP or Option #2 for HIV treatment only)
- Dosing series must be restarted with initiation dosing if more than 28 weeks have elapsed since the last injection
Safety, Monitoring & Contraindications
- Boxed warning: Risk of drug resistance with use of LEN for PrEP in undiagnosed HIV-1 infection
- Must test for HIV-1 infection prior to initiating LEN and with each subsequent injection using a test approved or cleared by the FDA; do not initiate unless negative infection status is confirmed
- Contraindicated with concomitant administration of strong CYP3A inducers (risk of loss of therapeutic effect and development of resistance)
- Not recommended with moderate CYP3A inducers, P-gp inhibitors, UGT1A1 inhibitors, or strong CYP3A4 inhibitors (including cobicistat and ritonavir) due to risk of increased LEN serum concentration
- LEN is a moderate CYP3A inhibitor; may increase exposure of drugs primarily metabolized by CYP3A initiated within 9 months after the last SQ dose
- Immune reconstitution syndrome possible during initial phase for HIV treatment
- If discontinued, initiate an alternative fully suppressive ART or PrEP regimen within 28 weeks after the last LEN dose; subtherapeutic serum concentrations may extend beyond 12 months after stopping LEN for PrEP
Adherence & Place in Therapy Considerations
- For HIV treatment: Reserve for patients unable to formulate a viable suppressive regimen with two fully active agents due to predicted resistance (genotypic or phenotypic), drug intolerance, DDIs, or dual-mixed/CXCR4-tropism (for maraviroc)
- Requires patient understanding and commitment to receive LEN SQ injection every 26 weeks (±2 weeks) administered by a healthcare provider
- For PrEP: Reserved for individuals with contraindications, intolerance, or inability to adhere to oral TDF/FTC; daily oral TDF/FTC remains the preferred first-line PrEP agent
Storage & Handling
- Oral tablets must be dispensed only in original blister pack and stored at 20–25 °C
- SQ injection dosing kit (2 single-dose vials) must be stored at 20–25 °C in the original carton to protect from light until preparation
- Injection should be administered as soon as possible once solutions are drawn into syringes
Document 326: HIV PrEP Clinical Recommendations for Use DEC 2025
Indications & Target Populations
- HIV preexposure prophylaxis (PrEP) for men who have sex with men (MSM), transgender women (TGW), cisgender men, and cisgender women at risk for HIV sexual acquisition.
- Patients at very high risk of transmission (e.g., frequent condom-less sexual encounters, partners with uncontrolled HIV infection).
Renal & Skeletal Considerations
- Alternative to oral PrEP for patients with renal dysfunction.
- Unlikely to impact renal function or bone mineral density.
- Appropriate alternative for patients with osteoporosis or osteopenia.
Adherence & Behavioral Factors
- Beneficial for patients unable to adhere to daily oral dosing due to unstable housing, stigma, cognitive difficulties, uncontrolled mental illness, or substance use disorders.
- Requires patient agreement to comply with a strict every-2-month injection and testing schedule.
- Long half-life may pose a risk if therapy is abruptly discontinued while continuing high-risk behaviors (subtherapeutic concentrations may persist for up to 1 year, increasing resistance risk).
Contraindications & Drug Interactions
- Should not be used in patients receiving strong CYP inducers.
- Indicated for patients with contraindications or intolerance to tenofovir or emtricitabine.
Monitoring & Testing Requirements
- HIV must be excluded at baseline and at least every 2 months while on therapy.
- Adherence counseling and support required; patients educated on side effects, particularly during the first month of therapy.
- Additional monitoring (e.g., sexually transmitted infections, serum lipids, weight) per CDC/USPSTF guidelines.
Administration & Prescribing Requirements
- Long-acting intramuscular injection formulation.
- Oral lead-in is optional but may be used to assess early tolerance prior to long-lasting injection; oral CAB must be procured from Theracom.
- Prior authorization (PA-F) on the VA National Formulary (VANF).
- Must be prescribed by Infectious Diseases, HIV, or other PrEP providers with training/experience in managing HIV PrEP patients.
Document 819: Lenacapavir YEZTUGO CFU
Criteria for Lenacapavir (YEZTUGO) Injection/Solution for HIV Pre-Exposure Prophylaxis (PrEP)
- Exclusion Criteria
- History of non-adherence with follow-up appointments or laboratory visits
- Unmanageable drug-drug interactions
- Laboratory requirements: Must have confirmed negative HIV-1 Ag/Ab laboratory test immediately prior (e.g., 7 days) of each lenacapavir injection; an HIV-1 RNA assay should be drawn prior to each injection (results should not delay administration); if an HIV RNA test is not available, obtain a repeat HIV-1 Ag/Ab test within 1 month of initiation
- Inclusion Criteria
- Care provided by a VA specialty provider or locally designated expert
- Substantial risk of HIV acquisition (e.g., sex without condoms, multiple sexual partners, recent or frequent sexually transmitted infections [STIs], sexual relationship with HIV-infected partner, injection drug use with equipment sharing)
- Additional Inclusion Criteria
- Select ONE of the following:
- Intolerance or contraindication to Truvada (FTC/TDF)
- CrCl of 15-59 mL/min or multiple risk factors for significant renal dysfunction
- Environmental-specific factors in which injectable PrEP is a more reliable route of administration (e.g., homelessness or unstable housing)
- Patient-specific factors impacting adherence to daily oral PrEP (e.g., cognitive difficulties, gastrointestinal dysfunction, fear of stigma or discovery)