Lenacapavir 463.5 mg/1.5 mL Injection contains Lenacapavir, a first-in-class human immunodeficiency virus type 1 (HIV-1) capsid inhibitor indicated, in combination with other antiretroviral agents, for the treatment of multidrug-resistant HIV-1 infection in heavily treatment-experienced adults whose current antiretroviral regimen is failing due to resistance, intolerance, or safety considerations. Lenacapavir acts by targeting the HIV-1 capsid protein, a critical component of the viral life cycle, thereby inhibiting multiple stages of viral replication, including viral capsid assembly, disassembly, nuclear transport, and virus production. This unique mechanism of action distinguishes Lenacapavir from other classes of antiretroviral medicines and provides an effective treatment option for patients with limited therapeutic alternatives.

Lenacapavir injection is administered as a long-acting subcutaneous injection every six months following an initiation regimen. Its extended dosing interval helps improve treatment adherence and reduces the burden of frequent dosing for eligible patients. Because of its prolonged duration of action, Lenacapavir should always be administered according to the prescribed schedule by a qualified healthcare professional and used in combination with an optimized background antiretroviral regimen. It is not intended for use as monotherapy.

Lenacapavir has demonstrated significant antiviral efficacy in clinical studies by producing substantial reductions in HIV-1 viral load and improving virologic suppression in heavily treatment-experienced patients with multidrug-resistant HIV infection. Its novel capsid-targeting mechanism offers an important therapeutic advancement for patients who have developed resistance to multiple existing antiretroviral drug classes.

Before initiating treatment, patients should inform their healthcare provider about all existing medical conditions, previous antiretroviral therapies, known drug allergies, pregnancy or breastfeeding status, and all prescription medicines, over-the-counter medications, vitamins, and herbal supplements they are currently taking. Particular attention should be given to medicines that strongly induce the CYP3A enzyme, as these may significantly reduce Lenacapavir concentrations and compromise treatment effectiveness.

Regular clinical monitoring, including assessment of HIV viral load, CD4 cell count, treatment response, and possible adverse reactions, is recommended throughout therapy. Patients should continue all accompanying antiretroviral medications exactly as prescribed and should not discontinue Lenacapavir or any component of their HIV treatment regimen without consulting their healthcare provider.

Lenacapavir injection should only be administered under the supervision of a qualified healthcare professional experienced in the management of HIV infection. When used as part of a comprehensive antiretroviral treatment plan, Lenacapavir provides an innovative long-acting therapeutic option that helps achieve sustained viral suppression and supports long-term HIV disease management in appropriate patients.

• Treat multidrug-resistant HIV-1 infection in heavily treatment-experienced adults as part of a combination antiretroviral regimen.
• Suppress HIV viral replication by inhibiting the HIV-1 capsid protein, an essential component required for multiple stages of the viral life cycle.
• Reduce HIV-1 viral load, helping patients achieve and maintain virologic suppression when used together with an optimized background antiretroviral regimen.
• Provide a long-acting treatment option, requiring administration only once every six months after completion of the recommended initiation regimen, thereby reducing treatment burden and supporting adherence.
• Offer an effective therapeutic option for patients with limited treatment choices due to resistance to multiple classes of antiretroviral medicines.
• Support long-term HIV disease management by maintaining sustained antiviral activity when administered according to the prescribed dosing schedule and in combination with other active antiretroviral agents.

Important: Lenacapavir injection must not be used as monotherapy. It should always be administered in combination with other active antiretroviral medicines to reduce the risk of treatment failure and the development of viral resistance. Treatment should be initiated and monitored by a healthcare professional experienced in the management of HIV infection.

By binding directly to the HIV-1 capsid protein, Lenacapavir disrupts several critical viral processes, including capsid assembly, capsid disassembly (uncoating), nuclear import of viral genetic material, viral particle maturation, and the production of infectious virions. This multi-stage mechanism effectively suppresses HIV replication and reduces the production of new virus particles.

The therapeutic effects of Lenacapavir include:

• Potent suppression of HIV-1 viral replication by targeting the viral capsid protein at multiple stages of the viral life cycle.
• Significant reduction in plasma HIV-1 viral load when administered in combination with an optimized background antiretroviral regimen.
• Achievement and maintenance of virologic suppression in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection.
• Reduction in the risk of further disease progression by effectively controlling viral replication and preserving immune function.
• Long-acting antiviral activity, allowing subcutaneous administration only once every six months following the recommended initiation regimen, thereby improving treatment adherence and reducing dosing frequency.
• Clinical efficacy against HIV-1 strains resistant to multiple antiretroviral drug classes, providing an important therapeutic option for patients with limited remaining treatment choices.

Clinical studies have demonstrated that, when used as part of a combination antiretroviral therapy (ART) regimen, Lenacapavir produces rapid and sustained reductions in HIV-1 viral load while maintaining durable antiviral activity over prolonged treatment periods. Because of its unique mechanism of action and prolonged pharmacokinetic profile, Lenacapavir contributes to long-term viral suppression and supports improved treatment outcomes in patients with multidrug-resistant HIV infection.

Lenacapavir does not eradicate HIV infection or cure AIDS. Patients should continue taking all prescribed antiretroviral medicines and remain under regular medical supervision, including routine monitoring of HIV viral load, CD4 cell count, treatment response, and potential adverse effects, to achieve optimal long-term therapeutic outcomes.

Lenacapavir 463.5 mg/1.5 mL injection should be used exactly as prescribed by your healthcare provider. Treatment should be initiated and supervised by a physician experienced in the management of HIV-1 infection. Lenacapavir is not used alone and must always be administered in combination with an optimized background antiretroviral regimen (ART) to achieve and maintain virologic suppression.

Administration:

• Lenacapavir injection is administered as a subcutaneous (under the skin) injection into the abdomen by a trained healthcare professional.
• The medicine must not be administered intravenously (IV), intramuscularly (IM), or intradermally.
• Following the recommended initiation regimen, Lenacapavir is administered once every 6 months (26 weeks) as two consecutive subcutaneous injections (each containing 1.5 mL) during the same visit.

Recommended Dosing:

Patients should receive the recommended oral initiation regimen, followed by the initial subcutaneous injection according to the prescribing information.

Maintenance Dose:

463.5 mg (3 mL total) administered as two 1.5 mL subcutaneous injections every 6 months (26 weeks).

Missed Dose:

• It is important not to miss scheduled injection appointments.
• If a scheduled injection is missed, contact your healthcare provider as soon as possible to reschedule treatment.
• Depending on the length of the delay, your healthcare provider may recommend oral Lenacapavir bridging therapy before resuming injections.
• Missing or delaying treatment may increase the risk of virologic failure and the development of HIV drug resistance.

Before Receiving Lenacapavir:

Inform your healthcare provider if you:

• Have liver or kidney disease.
• Are pregnant, planning to become pregnant, or breastfeeding.
• Have any known allergies to Lenacapavir or its ingredients.
• Are taking prescription medicines, over-the-counter medicines, vitamins, herbal supplements, or traditional medicines, particularly strong CYP3A inducers, which are contraindicated with Lenacapavir.

During Treatment:

• Continue taking all other prescribed antiretroviral medicines exactly as directed.
• Attend all scheduled follow-up appointments for monitoring of HIV viral load, CD4 cell count, and treatment response.
• Report any persistent injection-site reactions, allergic reactions, or other unusual symptoms to your healthcare provider promptly.
• Do not stop treatment or change your HIV medication regimen without consulting your physician.

Important Instructions:

• Lenacapavir is not a cure for HIV infection or AIDS. Continue practicing appropriate measures to reduce the risk of HIV transmission.
• Because Lenacapavir remains in the body for 12 months or longer after the last injection, drug interactions and treatment considerations may persist after discontinuation.
• Maintain regular medical follow-up to ensure continued viral suppression and monitor for potential adverse effects.
• This medicine should be administered only by a qualified healthcare professional in an appropriate clinical setting. Self-administration is not recommended.

Common:

The most frequently reported side effects associated with Lenacapavir Injection include:

• Injection-site reactions (pain, swelling, redness, induration, itching, bruising, or nodules)
• Nausea
• Diarrhea
• Headache
• Fatigue
• Dizziness

Injection-site reactions are the most commonly reported adverse events and are generally mild to moderate in severity. Most reactions resolve without specific treatment within a few days or weeks.

Less Common:

Some patients may also experience:

• Vomiting
• Abdominal discomfort
• Constipation
• Rash
• Pruritus (itching)
• Mild hypersensitivity reactions
• Decreased appetite
• Muscle pain (myalgia)
• Joint pain (arthralgia)

These side effects are generally manageable but should be reported if they persist or become bothersome.

Serious:

Although uncommon, patients should seek immediate medical attention if they experience:

• Severe allergic (hypersensitivity) reactions, including swelling of the face, lips, tongue, or throat, difficulty breathing, or severe skin rash.
• Severe or persistent injection-site reactions, such as extensive swelling, ulceration, skin necrosis, severe pain, or signs of infection.
• Signs of liver problems, including yellowing of the skin or eyes (jaundice), dark urine, persistent nausea or vomiting, severe fatigue, or pain in the upper right abdomen.
• Virologic failure, indicated by increasing HIV viral load or worsening HIV-related symptoms, particularly if treatment doses are missed or delayed.
• Immune Reconstitution Inflammatory Syndrome (IRIS), where the recovering immune system may cause an inflammatory response to previously undiagnosed or treated opportunistic infections. Patients should promptly report new or worsening symptoms after initiating treatment.

Injection-Site Reactions:

Because Lenacapavir is administered as a long-acting subcutaneous injection, some patients may develop:

• Pain or tenderness
• Swelling
• Redness
• Hardening (induration)
• Small nodules
• Bruising
• Itching

These reactions are usually temporary and resolve over time. Patients should notify their healthcare provider if symptoms become severe, worsen, or persist for an extended period.

When to Contact Your Healthcare Provider:

Contact your healthcare provider immediately if you:

• Experience symptoms of a serious allergic reaction.
• Develop persistent or severe injection-site reactions.
• Notice symptoms suggestive of liver dysfunction.
• Develop unexplained fever, persistent rash, or other unusual symptoms.
• Miss a scheduled injection appointment or believe your HIV symptoms are worsening.

Regular monitoring of HIV viral load, CD4 cell count, liver function, and overall clinical status is recommended throughout treatment to ensure continued safety and effectiveness.

Lenacapavir 463.5 mg/1.5 mL Injection may interact with certain medicines that affect its metabolism or transport within the body. Lenacapavir is primarily metabolized by CYP3A and is also a substrate of P-glycoprotein (P-gp) and UGT1A1. Because Lenacapavir remains in the body for an extended period after administration, clinically significant drug interactions may persist for up to 9–12 months after the last injection. Patients should inform their healthcare provider about all prescription medicines, over-the-counter drugs, vitamins, and herbal supplements they are taking before starting treatment.

Lenacapavir injection may interact with the following medicines:

Contraindicated Medicines:

1) The concomitant use of strong CYP3A inducers is contraindicated, as these medicines can significantly decrease Lenacapavir plasma concentrations, resulting in reduced antiviral activity and an increased risk of treatment failure and development of viral resistance.

Examples include:

• Rifampicin (Rifampin)
• Carbamazepine
• Phenytoin
• Phenobarbital
• Primidone
• St. John's Wort (Hypericum perforatum)

These medicines should not be used together with Lenacapavir Injection.

2) Healthcare professionals should monitor patients for potential adverse reactions when these medicines are used concomitantly.

Examples include:

• Ketoconazole
• Itraconazole
• Voriconazole
• Clarithromycin
• Ritonavir
• Cobicistat

3) Caution is advised, particularly for drugs with a narrow therapeutic index.

Examples include:

• Midazolam
• Triazolam
• Tacrolimus
• Cyclosporine
• Sirolimus
• Everolimus

Dose adjustment or additional clinical monitoring may be required.

4) Lenacapavir may increase exposure to medicines transported by P-glycoprotein (P-gp) or Breast Cancer Resistance Protein (BCRP).

Examples include:

• Digoxin
• Dabigatran
• Rosuvastatin

Patients receiving these medicines should be monitored according to standard clinical practice.

Other Antiretroviral Medicines:

Lenacapavir is intended to be used only as part of combination antiretroviral therapy (ART). The accompanying background regimen should be selected based on the patient's resistance profile and previous treatment history to maximize virologic suppression and reduce the risk of resistance development.

Important Clinical Considerations:

• Inform your healthcare provider about all medicines, including prescription drugs, non-prescription medicines, herbal products, and dietary supplements, before receiving Lenacapavir.
• Because Lenacapavir has a very long elimination half-life, clinically significant drug interactions may continue for 9–12 months after the final injection.
• Do not start, stop, or change any medicine without consulting your healthcare provider.
• Patients receiving medicines with a narrow therapeutic index should undergo appropriate clinical monitoring if co-administered with Lenacapavir.
• Avoid self-medication with herbal products, especially St. John's Wort, as it may significantly reduce Lenacapavir effectiveness.
• Healthcare providers should carefully evaluate all concomitant medications before initiating Lenacapavir therapy and throughout treatment to minimize the risk of clinically significant drug interactions.

• Store Lenacapavir Injection at 2°C to 8°C (36°F to 46°F) in a refrigerator. Do not freeze.
• Keep the vial in the original carton to protect it from light until ready for use.
• Before administration, allow the vial to reach room temperature naturally for approximately 30 minutes. Do not use external heat sources such as microwaves, hot water, or direct sunlight to warm the medicine.
• Inspect the solution visually before administration. The solution should be clear to yellow and free from visible particles. Do not use the injection if it appears cloudy, discolored, or contains particulate matter.
• The product is supplied as a single-dose vial. Once the vial has been punctured, it should be used immediately. Any unused portion should be discarded in accordance with local regulations.
• Keep the medicine out of the reach and sight of children.
• Do not use the medicine after the expiry date printed on the carton and vial label.
• Dispose of unused or expired medicine and all injection materials safely according to local biomedical waste regulations or as directed by a pharmacist or healthcare professional.

Note: Proper storage and handling of Lenacapavir Injection are essential to maintain its stability, potency, and sterility throughout its shelf life. Always follow the manufacturer's storage recommendations and the healthcare provider's instructions.

Lenacapavir is the first FDA-approved HIV-1 capsid inhibitor offering a novel mechanism of action by targeting multiple stages of the HIV replication cycle and represents a significant advancement in HIV therapy because it targets multiple stages of the viral life cycle while offering long-acting, twice-yearly dosing after the initiation regimen. For optimal treatment outcomes, strict adherence to both the injection schedule and the accompanying antiretroviral regimen is essential. When administered on schedule and combined with an optimized antiretroviral regimen, it provides durable viral suppression and an important treatment option for heavily treatment-experienced patients with multidrug-resistant HIV-1 infection. Patients should maintain regular communication with their HIV specialist and promptly report any concerns or adverse effects during treatment.