LENACAPAVIR INJ,SOLN

Clinical Criteria Summary

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

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

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

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

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

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).

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).

Should not be used in patients receiving strong CYP inducers.
Indicated for patients with contraindications or intolerance to tenofovir or emtricitabine.

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.

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.

Significant noncompliance with follow-up appointments unless barriers to compliance have been significantly addressed by provider
Drug interactions that preclude administration of lenacapavir (moderate or strong CYP3A or P-gp inducers; combined P-gp, UGT1A1 and strong 3A4 inhibitors)

Lenacapavir prescribed by, or in collaboration with, a provider with experience or training in the administration of PrEP (designated facility providers)
Substantial risk of HIV acquisition (sex without condoms, multiple sexual partners, recent or frequent sexually transmitted infections, sexual relationship with HIV infected partner, injection drug use with equipment sharing)
Documentation that patient agrees to required HIV testing and dosing schedule

Intolerance or contraindication to Truvada (TDF/FTC)
CrCl of 15-59 mL/min or multiple risk factors for significant renal dysfunction
Patient specific factors impacting adherence to daily oral PrEP (e.g., cognitive difficulties, gastrointestinal dysfunction, unstable housing, stigma, or fear of discovery)

Confirmed negative HIV-1 Ag/Ab lab based test within 7 days of each administration
HIV RNA test recommended prior to initiation; results should not delay initiation; if unavailable, obtain repeat HIV-1 Ag/Ab test within 1 month of initiation

Subcutaneous administration into the abdomen (preferred) or thigh (alternative) only
Day 1: 927mg by subcutaneous injection (2 x 1.5mL injections) AND 600mg orally (2 x 300mg tablets)
Day 2: 600mg orally (2 x 300mg tablets), self-administered at home
Every 6 months (26 weeks +/- 2 weeks): 927mg by subcutaneous injection (2 x 1.5mL injections)