Introduction

Lenacapavir sodium, an antiretroviral agent, is a human immunodeficiency virus type 1 (HIV-1) capsid inhibitor.

Uses for Lenacapavir Sodium

Lenacapavir sodium has the following uses:

Lenacapavir sodium, in combination with other antiretroviral(s), is indicated for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations.

Lenacapavir Sodium Dosage and Administration

General

Lenacapavir sodium is available in the following dosage form(s) and strength(s):

Tablets: 300 mg (of lenacapavir)

Injection: 463.5 mg (of lenacapavir)/1.5 mL (309 mg/mL) in single-dose vials.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• Lenacapavir is administered orally and as subcutaneous injections.

• Recommended dosage: Initiate with one of two options followed by once every 6-months maintenance dosing. Tablets may be taken without regard to food.

• Missed dose: If more than 28 weeks have elapsed since the last injection and if clinically appropriate to continue lenacapavir treatment, restart the initiation dosage regimen from Day 1, using either Option 1 or Option 2.

• Two 1.5 mL subcutaneous injections are required for complete dose.

Contraindications

• Concomitant administration of lenacapavir sodium is contraindicated with strong CYP3A inducers.

Warnings/Precautions

Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections [such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia (PCP), or tuberculosis], which may necessitate further evaluation and treatment.

Autoimmune disorders (such as Graves' disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.

Long-acting Properties and Potential Associated Risks with Lenacapavir

Residual concentrations of lenacapavir may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer after the last subcutaneous dose). It is important to counsel patients that maintenance dosing by injection is required every 6 months, because missed doses or non-adherence to injections could lead to loss of virologic response and development of resistance.

Lenacapavir, a moderate CYP3A inhibitor, may increase the exposure to, and therefore potential risk of adverse reactions from, drugs primarily metabolized by CYP3A initiated within 9 months after the last subcutaneous dose of lenacapavir sodium.

If lenacapavir is discontinued, to minimize the potential risk of developing viral resistance, it is essential to initiate an alternative, fully suppressive antiretroviral regimen where possible no later than 28 weeks after the final injection of lenacapavir. If virologic failure occurs during treatment, switch the patient to an alternative regimen if possible.

Injection Site Reactions

Subcutaneous administration of lenacapavir may result in local injection site reactions (ISRs). If clinically significant ISRs occur, evaluate and institute appropriate therapy and follow-up.

Manifestations of ISRs may include swelling, pain, erythema, nodule, induration, pruritus, extravasation or mass. Nodules and indurations at the injection site may take longer to resolve than other ISRs. In clinical studies, after a median follow-up of 553 days, 30% of nodules and 13% of indurations (in 10% and 1% of subjects, respectively) associated with the first injections of lenacapavir had not fully resolved. Measurements and qualitative assessments of ISRs were not routinely reported. Where described, the majority of the injection site nodules and indurations were palpable but not visible, and had a maximum size of approximately 1 to 4 cm.

The mechanism driving the persistence of injection site nodules and indurations in some patients is not fully understood, but based on available data, they may be related to the presence of the subcutaneous drug depot. In some patients who had a skin biopsy performed of an injection site nodule or induration, dermatopathology revealed foreign body inflammation or granulomatous response.

Specific Populations

Pregnancy

There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to lenacapavir during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.

There are insufficient human data on the use of lenacapavir during pregnancy to inform a drug-associated risk of birth defects and miscarriage. In animal reproduction studies, no adverse developmental effects were observed when lenacapavir was administered to rats and rabbits at exposures (AUC) ≥16 times the exposure in humans at the recommended human dose (RHD) of lenacapavir sodium.

The background risk of major birth defects and miscarriage for the indicated population is unknown. The background rate of major birth defects in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) is 2.7%. The rate of miscarriage is not reported in the APR. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15 to 20%.

Lenacapavir was administered intravenously to pregnant rabbits (up to 20 mg/kg/day on gestation days (GD) 7 to 19), orally to rats (up to 300 mg/kg/day on GD 6 to 17), and subcutaneously to rats (up to 300 mg/kg on GD 6). No significant toxicological effects on embryo-fetal (rats and rabbits) or pre/postnatal (rats) development were observed at exposures (AUC) approximately 16 times (rats) and 39 times (rabbits) the exposure in humans at the RHD of lenacapavir sodium.

Lactation

The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection.

It is not known whether lenacapavir is present in human breast milk, affects human milk production, or has effects on the breastfed infant. After administration to pregnant rats, lenacapavir was detected in the plasma of nursing rat pups, without effects on these nursing pups.

Because of the potential for 1) HIV transmission (in HIV-negative infants); 2) developing viral resistance (in HIV-positive infants); and 3) adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed if they are receiving lenacapavir sodium.

Lenacapavir was detected at low levels in the plasma of nursing rat pups in the pre/postnatal development study (post-natal day 10).

Pediatric Use

The safety and effectiveness of lenacapavir sodium have not been established in pediatric patients.

Geriatric Use

Clinical studies of lenacapavir sodium did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Renal Impairment

No dosage adjustment of lenacapavir is recommended in patients with mild, moderate, or severe renal impairment (estimated creatinine clearance greater than or equal to 15 mL per minute). Lenacapavir has not been studied in patients with ESRD (estimated creatinine clearance less than 15 mL per minute).

Hepatic Impairment

No dosage adjustment of lenacapavir sodium is recommended in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. Lenacapavir has not been studied in patients with severe hepatic impairment (Child-Pugh Class C).

Common Adverse Effects

Most common adverse reactions (incidence ≥3%, all grades) are nausea and injection site reactions.

General

Lenacapavir sodium is available in the following dosage form(s) and strength(s):

Tablets: 300 mg (of lenacapavir)

Injection: 463.5 mg (of lenacapavir)/1.5 mL (309 mg/mL) in single-dose vials.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• Lenacapavir is administered orally and as subcutaneous injections.

• Recommended dosage: Initiate with one of two options followed by once every 6-months maintenance dosing. Tablets may be taken without regard to food.

• Missed dose: If more than 28 weeks have elapsed since the last injection and if clinically appropriate to continue lenacapavir treatment, restart the initiation dosage regimen from Day 1, using either Option 1 or Option 2.

• Two 1.5 mL subcutaneous injections are required for complete dose.

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

• Consult the Full Prescribing Information prior to and during treatment for important drug interactions.