Precautions of Lenacapavir

Immune Reconstitution Inflammatory Syndrome

Immune reconstitution inflammatory syndrome has been reported in patients receiving combination antiretroviral therapy. During the initial phase of combination antiretroviral treatment, patients with an immune system response may develop inflammatory reactions to latent or residual opportunistic infections (such as Mycobacterium avium complex infection, cytomegalovirus, Pneumocystis jirovecii pneumonia, or tuberculosis), which may require further evaluation and treatment.

Autoimmune diseases (such as Graves’ disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) have also been reported to occur in the context of immune reconstitution; however, the onset time is more variable and may occur months after the start of treatment.

Long-Acting Properties of Lenacapavir and Potentially Associated Risks

Residual concentrations of lenacapavir may persist in the patient’s systemic circulation for an extended period (up to 12 months or longer after the last subcutaneous injection). Patients must be informed of the need to receive a maintenance dose every 6 months, as missed doses or non-adherence to injections may lead to loss of virological response and development of drug resistance.

Lenacapavir is a moderate CYP3A inhibitor. Initiation of drugs primarily metabolized by CYP3A within 9 months after the last subcutaneous injection of lenacapavir may increase the exposure of these drugs, thereby elevating the potential risk of adverse reactions.

If lenacapavir is discontinued, to minimize the potential risk of developing viral resistance, an alternative, fully suppressive antiretroviral treatment regimen must be initiated no later than 28 weeks after the last injection of lenacapavir. In the event of virological failure during treatment, patients should be switched to an alternative regimen whenever possible.

Injection Site Reactions

Administration of lenacapavir may result in local injection site reactions. If a clinically significant injection site reaction occurs, evaluation should be performed, and appropriate treatment and follow-up should be implemented.

Manifestations of injection site reactions may include swelling, pain, erythema, nodules, induration, pruritus, extravasation, or masses. Nodules and indurations at the injection site may take longer to resolve than other injection site reactions. In clinical studies, after a median follow-up of 553 days, 30% and 13% of nodules and indurations associated with the first injection of lenacapavir (corresponding to 10% and 1% of subjects, respectively) had not fully resolved. Measurement and qualitative assessment of injection site reactions were not routinely reported. In the described cases, most injection site nodules and indurations were palpable but not visible, with maximum dimensions of approximately 1 to 4 centimeters.

The mechanism underlying the persistence of injection site nodules and indurations in some patients is not fully understood, but based on available data, it may be related to the presence of a subcutaneous drug depot. In some patients who underwent skin biopsy of injection site nodules or indurations, skin pathology showed foreign body inflammation or granulomatous reactions.

Incorrect administration (intradermal injection) is associated with severe injection site reactions, including necrosis and ulceration. Ensure that lenacapavir is administered only as a subcutaneous injection in the abdomen.

FDA，2024.11