Dosage and Administration Overview

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APRETUDE contains cabotegravir extended-release injectable suspension in a single-dose vial [see Dosage Forms and Strengths (3)].

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APRETUDE must be administered by a healthcare provider by gluteal intramuscular injection [see Dosage and Administration (2.7)].

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APRETUDE may be initiated with oral cabotegravir prior to the intramuscular injections or the patient may proceed directly to injection of APRETUDE without an oral lead-in [see Dosage and Administration (2.4)].

HIV-1 Screening for Individuals Receiving APRETUDE for HIV-1 PrEP

Individuals must be tested for HIV-1 infection prior to initiating APRETUDE or oral cabotegravir, and with each subsequent injection of APRETUDE, using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection. If an antigen/antibody-specific test is used and provides negative results, then such negative results should be confirmed using an RNA-specific assay, even if the results of the RNA-assay are available after APRETUDE or oral cabotegravir administration [see Contraindications (4), Warnings and Precautions (5.1)].

Adherence to APRETUDE

Prior to starting APRETUDE, healthcare providers should carefully select individuals who agree to the required injection dosing and testing schedule and counsel individuals about the importance of adherence to scheduled dosing visits to help reduce the risk of acquiring HIV-1 infection and development of resistance [see Dosage and Administration (2.1), Warnings and Precautions (5.1, 5.3), Microbiology (12.4)].

Optional Oral Lead-in Dosing to Assess Tolerability of APRETUDE

The healthcare provider and individual may decide to use an oral lead-in with oral cabotegravir prior to the initiation of APRETUDE to assess the tolerability of cabotegravir or the healthcare provider and individual may proceed directly to injection of APRETUDE without the use of an oral lead-in [see Dosage and Administration (2.5)].

No safety and efficacy data are available for use of APRETUDE without an oral lead-in [see Warnings and Precautions (5.3), Adverse Reactions (6.1)]. However, in HIV-1 treatment clinical trials, data show that an oral lead-in is not needed to ensure adequate plasma cabotegravir exposure upon initiation of injections and that the safety and efficacy results of CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) were similar when administered with and without an oral lead-in.

Gluteal Intramuscular Injection Dosing with APRETUDE

Initiation Injections

If an oral lead-in is used, initiation injections should be administered on the last day of oral lead‑in or within 3 days thereafter. The recommended initiation injection doses of APRETUDE in individuals is a single 600‑mg (3-mL) intramuscular injection of APRETUDE given 1 month apart for 2 consecutive months (Table 1 and Table 2). Individuals may be given the second APRETUDE initiation injection up to 7 days before or after the date the individual is scheduled to receive the injections.

Continuation Injections

After the 2 initiation injection doses given consecutively 1 month apart, the recommended continuation injection dose of APRETUDE is a single 600-mg (3-mL) intramuscular injection of APRETUDE every 2 months (Table 2). Individuals may be given APRETUDE up to 7 days before or after the date the individual is scheduled to receive the injections.

Recommended Dosing Schedule for Missed Injections

Adherence to the injection dosing schedule is strongly recommended [see Dosage and Administration (2.3)]. Individuals who miss a scheduled injection visit should be clinically reassessed to ensure resumption of APRETUDE remains appropriate [see Dosage and Administration (2.2), Warnings and Precautions (5.1, 5.2)]. Refer to Table 3 for dosing recommendations after missed injections.

Planned Missed Injections

If an individual plans to miss a scheduled every-2-month continuation injection visit by more than 7 days, take daily oral cabotegravir for up to 2 months to replace 1 missed scheduled every-2-month injection. The recommended oral daily dose is one 30-mg tablet of oral cabotegravir. The first dose of oral PrEP should be taken approximately 2 months after the last injection dose of APRETUDE. Restart injection with APRETUDE on the day oral dosing completes or within 3 days; thereafter, as recommended in Table 3. For oral PrEP durations greater than 2 months, an alternative oral regimen is recommended.

Unplanned Missed Injections

If a scheduled injection visit is missed or delayed by more than 7 days and oral dosing has not been taken in the interim, clinically reassess the individual to determine if resumption of injection dosing remains appropriate [see Warnings and Precautions (5.1)]. If the injection dosing schedule will be continued, see Table 3 for dosing recommendations.

Administration Instructions

Refer to the Instructions for Use for complete administration instructions with illustrations.

APRETUDE is a suspension for gluteal intramuscular injection that does not need further dilution or reconstitution.

The ventrogluteal site is recommended for injection. A dorsogluteal approach (upper outer quadrant) is acceptable, if preferred by the healthcare professional. Do not administer by any other route or anatomical site. Consider the body mass index (BMI) of the individual to ensure that the needle length is sufficient to reach the gluteus muscle. Longer needle lengths (not included in the dosing kit) may be required for individuals with higher BMI (e.g., >30 kg/m2) to ensure that the injection is administered intramuscularly as opposed to subcutaneously.

If the pack has been stored in the refrigerator, the vial should be brought to room temperature prior to administration (not to exceed 30°C [86°F]).

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. The APRETUDE vial has a brown tint to the glass that may limit visual inspection. Discard the vial if the medicine exhibits particulate matter or discoloration.

Shake the vial vigorously so that the suspension looks uniform before injecting. Small air bubbles are expected and acceptable.

Once the suspension has been drawn into the syringe, the injection should be administered as soon as possible, but may remain in the syringe for up to 2 hours. The filled syringe should not be placed in the refrigerator. If the medicine remains in the syringe for more than 2 hours, the filled syringe and needle must be discarded [see How Supplied/Storage and Handling (16)].