Introduction

Antiretroviral agent; HIV-1 capsid inhibitor.

Uses for Lenacapavir (Systemic)

Treatment of HIV Infection

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. Used in combination with other antiretrovirals.

Current guidelines on the treatment of HIV in adults include lenacapavir among other agents with a novel mechanism of action that can be used as part of a new treatment regimen following virologic failure of an existing regimen; consult guidelines for the most current information on recommended regimens.

Lenacapavir (Systemic) Dosage and Administration

General

Pretreatment Screening

• Review current medication regimen to evaluate the need for dosage adjustment or change in therapy due to drug interactions.

Patient Monitoring

• Monitor for injection site reactions such as swelling, pain, erythema, nodule, induration, pruritus, extravasation, or mass.

Administration

Administered orally and by sub-Q injection. Use the oral formulation as part of the initiation regimen only; not intended for long-term maintenance dosing.

Oral Administration

Administer with or without food.

Sub-Q Administration

Administer sub-Q lenacapavir by a trained medical professional. Administer into the abdomen at least 2 inches from the navel. Two 1.5 mL injections required for a complete dose; give each injection at a different site on the abdomen.

Supplied in a dosing kit containing 2 single-dose vials of lenacapavir (each containing 463.5 mg/1.5 mL of lenacapavir), 2 vial access devices, 2 disposable syringes, and 2 injection safety needles. Contents of the injection kits are for single use only. Injection solution should appear clear and yellow with no visible particles. Do not use if solution is discolored or contains particles. Use provided vial access devices to withdraw medication from the vials into the syringes for administration. Consult the prescribing information for detailed preparation and administration instructions.

Dosage

Adults

Treatment of HIV Infection

Oral, then Sub-Q

Initiate using 1 of 2 initiation dosage regimens, then begin once every 6-months maintenance dosing (See Table 1).

During the maintenance period, 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 one of the recommended initation regimens.

Special Populations

Hepatic Impairment

No dosage adjustment for mild or moderate hepatic impairment (Child-Pugh Class A or B); not evaluated in severe hepatic impairment (Child-Pugh Class C).

Renal Impairment

No dosage adjustment for mild, moderate, or severe renal impairment (estimated Cl_cr ≥15 mL/minute); not evaluated in end stage renal disease (estimated Cl_cr<15 mL/minute).

Geriatric Use

No specific dosage recommendations.

Contraindications

• Concomitant administration with strong CYP3A inducers.

Warnings/Precautions

Immune Reconstitution Syndrome

Immune reconstitution syndrome 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 in the setting of immune reconstitution; however, 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 systemic circulation for prolonged periods (up to 12 months or longer after the last sub-Q dose). Counsel patients that maintenance dosing by injection is required every 6 months; 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 exposure to, and therefore potential risk of adverse reactions from, drugs primarily metabolized by CYP3A initiated within 9 months after the last sub-Q dose of lenacapavir.

If lenacapavir is discontinued, 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

Sub-Q administration of lenacapavir may result in local injection site reactions including swelling, pain, erythema, nodule, induration, pruritus, extravastion, or mass. If clinically significant injection site reactions occur, evaluate and institute appropriate therapy and follow-up. Nodules and indurations at the injection site may take longer to resolve than other injection site reactions.

Specific Populations

Pregnancy

Enroll pregnant patients in the Antiretroviral Pregnancy Registry at 1-800-258-4263.

Insufficient human data on the use of lenacapavir during pregnancy exist 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 of lenacapavir.

Lactation

Not known whether lenacapavir is present in human breast milk, affects human milk production, or has effects on the breastfed infant. Animal data indicate low levels of lenacapavir in plasma of nursing rat pups.

The Centers for Disease Control and Prevention recommend that HIV-1-infected patients in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection. Because of the potential for HIV transmission (in HIV-negative infants), development of viral resistance (in HIV-positive infants), and adverse reactions in a breastfed infant similar to those seen in adults, instruct patients not to breastfeed if they are receiving lenacapavir.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Sufficient numbers of patients ≥65 years of age not evaluated in clinical studies.

Renal Impairment

Pharmacokinetics of lenacapavir not significantly impacted by severe renal impairment (Cl_cr 15 to <30 mL/minute). No dosage adjustment of lenacapavir recommended in patients with Cl_cr ≥15 mL/minute. Not studied in patients with estimated Cl_cr <15 mL/minute.

Hepatic Impairment

Pharmacokinetics of lenacapavir not significantly impacted by moderate hepatic impairment (Child-Pugh Class B). No dosage adjustment recommended in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. Not studied in patients with severe hepatic impairment (Child-Pugh Class C).

Common Adverse Effects

Most common adverse reactions (≥3%): nausea, injection site reactions.

General

Pretreatment Screening

• Review current medication regimen to evaluate the need for dosage adjustment or change in therapy due to drug interactions.

Patient Monitoring

• Monitor for injection site reactions such as swelling, pain, erythema, nodule, induration, pruritus, extravasation, or mass.

Administration

Administered orally and by sub-Q injection. Use the oral formulation as part of the initiation regimen only; not intended for long-term maintenance dosing.

Oral Administration

Administer with or without food.

Sub-Q Administration

Administer sub-Q lenacapavir by a trained medical professional. Administer into the abdomen at least 2 inches from the navel. Two 1.5 mL injections required for a complete dose; give each injection at a different site on the abdomen.

Supplied in a dosing kit containing 2 single-dose vials of lenacapavir (each containing 463.5 mg/1.5 mL of lenacapavir), 2 vial access devices, 2 disposable syringes, and 2 injection safety needles. Contents of the injection kits are for single use only. Injection solution should appear clear and yellow with no visible particles. Do not use if solution is discolored or contains particles. Use provided vial access devices to withdraw medication from the vials into the syringes for administration. Consult the prescribing information for detailed preparation and administration instructions.

Dosage

Adults

Treatment of HIV Infection

Oral, then Sub-Q

Initiate using 1 of 2 initiation dosage regimens, then begin once every 6-months maintenance dosing (See Table 1).

During the maintenance period, 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 one of the recommended initation regimens.

Special Populations

Hepatic Impairment

No dosage adjustment for mild or moderate hepatic impairment (Child-Pugh Class A or B); not evaluated in severe hepatic impairment (Child-Pugh Class C).

Renal Impairment

No dosage adjustment for mild, moderate, or severe renal impairment (estimated Cl_cr ≥15 mL/minute); not evaluated in end stage renal disease (estimated Cl_cr<15 mL/minute).

Geriatric Use

No specific dosage recommendations.

Substrate of CYP3A, P-glycoprotein (P-gp), and UGT1A1; moderate inhibitor of CYP3A; and inhibitor of P-gp and breast cancer resistance protein (BCRP).

Not a substrate, inducer, or inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2D6. Not an inducer of CYP3A4 or an inhibitor of UGT1A1. Not an inhibitor of organic anion transporting polypeptide (OATP), organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 1, OCT2, multidrug and toxin extrusion transporter (MATE) 1, or MATE 2-K. Not a substrate of BCRP, OATP1B1, or OATP1B3.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Strong or Moderate CYP3A Inducers

Strong or moderate CYP3A inducers may significantly decrease lenacapavir plasma concentrations, which may result in loss of therapeutic effect and development of resistance. Concomitant administration of strong CYP3A inducers and lenacapavir contraindicated. Concomitant administration of moderate CYP3A inducers and lenacapavir not recommended.

Combined P-gp, UGT1A1, and Strong CYP3A Inhibitors

Combined P-gp, UGT1A1, and strong CYP3A inhibitors may significantly increase lenacapavir plasma concentrations. Concomitant administration of these agents and lenacapavir not recommended.

Drugs Primarily Metabolized by CYP3A

Lenacapavir is a moderate inhibitor of CYP3A. Due to its long half-life following sub-Q administration, lenacapavir may increase the exposure and risk of adverse effects of drugs primarily metabolized by CYP3A initiated within 9 months after the last sub-Q dose of lenacapavir. Dosage adjustments of the CYP3A substrate may be needed.

Specific Drugs