Lenacapavir (Monograph)

Brand name: Sunlenca
Drug class: HIV Capsid Inhibitors

Medically reviewed by Drugs.com on Sep 26, 2023. Written by ASHP.

Introduction

Antiretroviral agent; HIV-1 capsid inhibitor.

Uses for Lenacapavir

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 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).

Table 1. Initiation and Maintenance Dosage Regimens for Lenacapavir1
Initiation Dosage Regimen Option 1	Day 1: 927 mg by sub-Q injection (2 × 1.5 mL injections) and 600 mg orally (2 × 300 mg tablets Day 2: 600 mg orally (2 x 300 mg tablets)
Initiation Dosage Regimen Option 2	Day 1: 600 mg orally (2 x 300 mg tablets) Day 2: 600 mg orally (2 x 300 mg tablets) Day 8: 300 mg orally (1 x 300 mg tablet) Day 15: 927 mg by sub-Q injection (2 x 1.5 mL injections)
Maintenance Dosage	927 mg by sub-Q injection (2 × 1.5 mL injections) every 6 months (26 weeks) from the date of the last injection +/-2 weeks

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.

Cautions for Lenacapavir

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.

Drug Interactions

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

Drug	Interaction	Comments
Anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin)	Decreased lenacapavir concentrations, leading to loss of therapeutic effect and development of resistance	Co-administration with carbamazepine or phenytoin contraindicated Co-administration with oxcarbazepine or phenobarbital not recommended; consider use of alternative anticonvulsants
Antimycobacterials (rifampin, rifabutin, rifapentine)	Decreased lenacapavir concentrations, leading to loss of therapeutic effect and development of resistance	Co-administration with rifampin contraindicated Co-administration with rifabutin or rifapentine not recommended
Antiretrovirals (atazanavir/cobicistat, atazanavir/ritonavir, efavirenz, nevirapine, tipranavir/ritonavir)	Atanazavir/cobicistat, atazanavir/ritonavir; increased lenacapavir concentrations Efavirenz, nevirapine, tipranavir/ritonavir: decreased lenacapavir concentrations, leading to loss of therapeutic effect and development of resistance	No clinically significant interaction observed with darunavir/cobicistat, cobicistat, or tenofovir alafenamide
Corticosteroids, systemic (dexamethasone, hydrocortisone, cortisone)	Increased corticosteroid concentrations; increased risk of Cushing's syndrome and adrenal suppression.	Initiate with lowest corticosteroid dose and titrate carefully while monitoring for safety
Digoxin	Increased digoxin concentrations	Use with caution and monitor digoxin therapeutic concentrations
Direct oral anticoagulants (DOACs) (rivaroxaban, dabigatran, edoxaban)	Increased DOAC concentrations	Refer to the DOAC prescribing information for recommendations on concomitant administration with combined moderate CYP3A and P-gp inhibitors
Ergot derivatives (dihydroergotamine, ergotamine, methylergonovine)	Increased concentrations of ergot derivatives	Co-administration not recommended
HMG-CoA reductase inhibitors (lovastatin, simvastatin)	Increased concentrations of lovastatin or simvastatin No clinically significant interactions have been observed between lenacapavir and pitavastatin or rosuvastatin	Initiate lovastatin or simvastatin with the lowest starting dose and titrate while monitoring for safety (e.g., myopathy)
Naloxegol	Increased concentrations of naloxegol	Avoid concomitant use; if unavoidable, decrease dosage of naloxegol and monitor for adverse reactions
Opioid analgesics (buprenorphine, fentanyl, methadone, oxycodone, tramadol)	Fentanyl, oxycodone: increased concentrations of narcotics metabolized by CYP3A Tramadol: increased tramadol concentrations Burpenorphine, methadone: unknown effect on concentrations	Fentanyl, oxycodone: monitor therapeutic effects and adverse reactions (e.g., respiratory depression) Tramadol: dosage reduction may be needed Buprenorphine, methadone: when initiating analgesic, titrate carefully and use the lowest feasible initial or maintenance dose. When initiating lenacapavir, dosage adjustment of opioid analgesic may be needed; monitor clinical signs and symptoms
Phosphodiesterase (PDE-5) inhibitors (sildenafil, tadalafil, vardenafil)	Increased concentrations of PDE-5 inhibitors	For pulmonary arterial hypertension (PAH): co-administration with tadalafil is not recommended For erectile dysfunction: refer to prescribing information of the PDE-5 inhibitors for dosage recommendations
Sedative/hypnotics (midazolam [oral], triazolam)	Increased concentrations of orally administered midazolam and triazolam	Use with caution when co-administered
St. John's Wort	Decreased lenacapavir concentrations	Co-administration contraindicated

Lenacapavir Pharmacokinetics

Absorption

Bioavailability

Oral: 6-10%

Sub-Q: 100%

Distribution

Plasma Protein Binding

>98.5%

Elimination

Metabolism

CYP3A and UGT1A1; primarily excreted as unchanged drug in feces.

Elimination Route

76% excreted in feces (33% unchanged); <1% excreted in urine.

Half-life

Oral: 10–12 days.

Sub-Q: 8–12 weeks.

Special Populations

No clinically significant differences in pharmacokinetics based on age (18–78 years), sex, ethnicity, race, body weight (41.4–164 kg), severe renal impairment (Cl_cr 15 to <30 mL/minute), or moderate hepatic impairment (Child-Pugh Class B).

Effects of end-stage renal disease (including dialysis) or severe hepatic impairment (Child-Pugh Class C) unknown. Due to high plasma protein binding, dialysis not expected to alter drug exposure.

Stability

Storage

Oral

Tablets

20–25°C (excursions permitted between 15–30°C); store in original blister pack.

Parenteral

Solution for Injection

20–25°C (excursions permitted between 15–30°C). Store in original carton to protect from light.

Actions and Spectrum

Multistage, selective inhibitor of HIV-1 capsid function that directly binds to the interface between capsid protein (p24) subunits in hexamers.
Inhibits HIV-1 replication by interfering with multiple essential steps of the viral lifecycle, including capsid-mediated nuclear uptake of HIV-1 proviral DNA, virus assembly and release, and capsid core formation.
Has antiviral activity specific to human immunodeficiency virus (HIV-1 and HIV-2).
No antagonism of antiviral activity was observed in combination with major classes of antiretroviral agents.
HIV-1 variants with reduced susceptibility to lenacapavir have been selected in cell culture.
In heavily treatment-experienced patients with confirmed virologic failure, lenacapavir resistance-associated capsid substitutions identified.
In cell culture studies, lenacapavir remained fully active against all variants resistant to other antiretroviral agents, demonstrating a non-overlapping resistance profile.

Advice to Patients

Advise patients to inform their healthcare provider immediately of any symptoms of infection, as in some patients with advanced HIV infection (AIDS), signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started.
Counsel patients about the importance of continued medication adherence and scheduled visits to maintain viral suppression and to reduce risk of loss of virologic response and development of resistance. Advise patients to contact their healthcare provider immediately if they stop taking lenacapavir or any other drug in their antiretroviral regimen.
Inform patients that injection site reactions, such as swelling, pain, erythema, nodule, induration, pruritus, extravasation, or mass, may occur. Nodules and indurations at the injection site may take longer to resolve than other injection site reactions and may be persistent. Instruct patients to contact their healthcare provider about these reactions.
Advise patients to inform their clinician if they are or plan to become pregnant. Inform patients that there is an antiretroviral pregnancy registry to monitor fetal outcomes of pregnant individuals exposed to lenacapavir.
Instruct individuals with HIV-1 infection not to breastfeed because HIV-1 can be passed to the baby in breast milk.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.   If lenacapavir is discontinued, advise patients that the drug may remain in the body and affect certain other drugs for up to 9 months after receiving their last injection.
Advise patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Lenacapavir Sodium
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Kit	4 tablets, film-coated, 300 mg (of lenacapavir)	Sunlenca 4-Tablets	Gilead Sciences
		5 tablets, film-coated, 300 mg (of lenacapavir)	Sunlenca 5-Tablets	Gilead Sciences
Parenteral	Injection, for subcutaneous use	463.5 mg/1.5 mL (of lenacapavir)	Sunlenca (available as a kit containing 2 vials of drug with 2 vial access devices, 2 disposable syringes, and 2 safety needles for injection)	Gilead Sciences