Generic Name
Cabotegravir
Brand Names
Apretude, Vocabria
FDA approval date: January 21, 2021
Classification: Human Immunodeficiency Virus Integrase Strand Transfer Inhibitor
Form: Tablet, Kit
What is Apretude (Cabotegravir)?
APRETUDE is indicated for pre‑exposure prophylaxis to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating APRETUDE for HIV-1 PrEP [see Dosage and Administration.
Approved To Treat
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Brand Information
Apretude (Cabotegravir)
WARNING: RISK OF DRUG RESISTANCE WITH USE OF APRETUDE FOR HIV-1 PRE‑EXPOSURE PROPHYLAXIS (PrEP) IN UNDIAGNOSED HIV-1 INFECTION
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. Drug-resistant HIV-1 variants have been identified with use of APRETUDE by individuals with undiagnosed HIV-1 infection. Do not initiate APRETUDE for HIV-1 PrEP unless negative infection status is confirmed. Individuals who acquire HIV-1 while receiving APRETUDE for PrEP must transition to a complete HIV-1 treatment regimen
1INDICATIONS AND USAGE
APRETUDE is indicated for pre‑exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating APRETUDE (with or without an oral lead-in with oral cabotegravir) for HIV-1 PrEP
2DOSAGE FORMS AND STRENGTHS
Injection: Single-dose vial containing 600 mg/3 mL (200 mg/mL) of cabotegravir extended‑release injectable suspension.
3CONTRAINDICATIONS
APRETUDE is contraindicated in individuals:
- with unknown or positive HIV-1 status
- with previous hypersensitivity reaction to cabotegravir
- receiving the following coadministered drugs for which significant decreases in cabotegravir plasma concentrations may occur due to uridine diphosphate glucuronosyltransferase (UGT)1A1 enzyme induction, which may result in reduced effectiveness
4ADVERSE REACTIONS
The following adverse reactions are described below and in other sections of the labeling:
- Hypersensitivity reactions
- Hepatotoxicity
- Depressive disorders
4.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect rates observed in practice.
Clinical Trials Experience in Adults
The safety assessment of APRETUDE is based on the analysis of data from 2 international, multicenter, double-blind trials, HPTN 083 and HPTN 084
Adverse reactions were reported while on blinded study product following exposure to APRETUDE extended-release injectable suspension and oral cabotegravir tablets as oral lead-in. The median time on blinded study product in HPTN 083 was 65 weeks and 2 days (range: 1 day to 156 weeks and 1 day), with a total exposure on cabotegravir of 3,231 person‑years. The median time on blinded study product in HPTN 084 was 64 weeks and 1 day (range: 1 day to 153 weeks and 1 day), with a total exposure on cabotegravir of 2,009 person‑years.
The most common adverse reactions regardless of severity reported in at least 1% of participants in HPTN 083 or HPTN 084 are presented in
In HPTN 083, 6% of participants in the group receiving APRETUDE intramuscular injection every 2 months and 4% of participants receiving oral TRUVADA [emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF)] once daily discontinued due to adverse events (all causality). Non-injection-site–associated adverse events leading to discontinuation and occurring in ≥1% of participants were increased alanine aminotransferase with APRETUDE and TRUVADA.
In HPTN 084, 1% of participants receiving APRETUDE and 1% of participants receiving TRUVADA discontinued due to adverse events. The most commonly reported adverse event (all causality) leading to discontinuation was increased alanine aminotransferase (<1%) with APRETUDE and TRUVADA. The side-by-side tabulation is to simplify presentation; direct comparison across trials should not be made due to differing trials.
Injection-Associated Adverse Reactions: Local Injection Site Reactions (ISRs) with APRETUDE: The most frequent adverse reactions associated with the intramuscular administration of APRETUDE in HPTN 083 were ISRs. After 20,286 injections, 8,900 ISRs were reported. Of the 2,117 participants who received at least one injection of APRETUDE, 1,740 (82%) participants experienced at least one ISR, of which a total of 3% of participants discontinued APRETUDE because of ISRs. Among the participants who received APRETUDE and experienced at least one ISR, the maximum severity of reactions was mild (Grade 1) in 41% of participants, moderate (Grade 2) in 56% of participants, and severe (Grade 3) in 3% of participants. The median duration of overall ISR events was 4 days. The proportion of participants reporting ISRs at each visit and the severity of the ISRs decreased over time. The most commonly reported ISRs (all causality and grades) in at least 1% of participants who received APRETUDE and experienced at least one ISR from HPTN 083 are presented in Table 5.
The most frequent adverse reactions associated with the intramuscular administration of APRETUDE in HPTN 084 were ISRs. After 13,068 injections, 1,171 ISRs were reported. Of the 1,519 participants who received at least one injection of APRETUDE, 578 (38%) participants experienced at least one ISR. No participants discontinued APRETUDE because of ISRs. Among the participants who received APRETUDE and experienced at least one ISR, the maximum severity of reactions was mild (Grade 1) in 66% of participants, moderate (Grade 2) in 34% of participants, and severe (Grade 3) in less than 1% of participants. The median duration of overall ISR events was 8 days. The proportion of participants reporting ISRs at each visit and the severity of the ISRs generally decreased over time. The most commonly reported ISRs (all causality and grades) in at least 1% of participants who received APRETUDE and experienced at least one ISR from HPTN 084 are presented in
Other Injection-Associated Adverse Reactions: In the HPTN 083 clinical trial, an increased incidence of pyrexia (including pyrexia, feeling hot, chills, influenza-like illness) (4%) was reported by participants receiving APRETUDE compared with participants receiving TRUVADA (<1%). There were no differences reported in the incidence of pyrexia between groups in HPTN 084.
Vasovagal or pre-syncopal reactions considered treatment related were reported in <1% of participants after injection with APRETUDE in HPTN 083. None were reported as treatment related by the investigators in HPTN 084.
Less Common Adverse Reactions: The following select adverse reactions (regardless of severity) occurred in <1% of participants receiving APRETUDE in HPTN 083 or HPTN 084.
Hepatobiliary Disorders: Hepatotoxicity.
Investigations: Weight increase (see below).
Psychiatric Disorders: Depression; suicidal ideation, and suicide attempt (these events were observed primarily in participants with a pre‑existing history of depression or other psychiatric illness).
Weight Increase: At the Week 41 and Week 97 timepoints in HPTN 083, participants who received APRETUDE gained a median of 1.2 kg (Interquartile Range [IQR]; -1.0, 3.5; n = 1,623) and 2.1 kg (IQR; -0.9, 5.9; n = 601) in weight from baseline. Those who received TRUVADA gained a median of 0 kg (IQR; -2.1, 2.4; n = 1,611) and 1 kg (IQR; -1.9, 4.0; n = 598) in weight from baseline, respectively.
At the Week 41 and 97 timepoints in HPTN 084, participants who received APRETUDE gained a median of 2 kg (IQR; 0.0, 5.0; n = 1,151) and 4 kg (IQR; 0.0, 8.0; n = 216) in weight from baseline, respectively. Those who received TRUVADA gained a median of 1 kg (IQR; -1.0, 4.0; n = 1,131) and 3 kg (IQR; -1.0, 6.0; n = 218) in weight from baseline, respectively.
Laboratory Abnormalities: Grade 3 or 4 post-baseline maximum toxicity laboratory abnormalities for HPTN 083 or HPTN 084 are summarized in Table 6.
Serum Lipids: Changes from baseline to Month 15 in total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and total cholesterol to HDL ratio in HPTN 083 and HPTN 084 are presented in Table 7.
Clinical Trials Experience in Adolescents
In adolescents receiving APRETUDE for HIV-1 PrEP, the safety data were comparable to the safety data reported in adults receiving APRETUDE for HIV-1 PrEP
4.2Postmarketing Experience
The following adverse reactions have been identified during postmarketing use of APRETUDE or cabotegravir-containing regimens. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Immune System Disorders
Hypersensitivity reactions (including angioedema and urticaria)
Skin and Subcutaneous Tissue Disorders
Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)
5OVERDOSAGE
There is no known specific treatment for overdose with APRETUDE. If overdose occurs, monitor the individual and apply standard supportive treatment as required as well as observation of the clinical status of the individual. As APRETUDE is highly bound to plasma proteins, it is unlikely that it will be significantly removed by dialysis. Consider the prolonged exposure to APRETUDE following an injection when assessing treatment needs and recovery
6DESCRIPTION
APRETUDE contains cabotegravir extended-release injectable suspension, an HIV INSTI.
The chemical name of cabotegravir is (
Cabotegravir extended-release injectable suspension is a white to light pink free-flowing suspension for intramuscular injection in a sterile single-dose vial. Each vial contains 3 mL of the following: cabotegravir 200 mg/mL and the inactive ingredients mannitol (35 mg/mL), polyethylene glycol (PEG) 3350 (20 mg/mL), polysorbate 20 (20 mg/mL), and Water for Injection.
The vial stoppers are not made with natural rubber latex.
7HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
APRETUDE is supplied in a kit containing one 600-mg/3-mL single-dose (200-mg/mL) vial of cabotegravir extended-release injectable suspension, 1 syringe, 1 vial adapter, and 1 needle for intramuscular injection (23 gauge, 1½ inch) (NDC 49702-264-23). The vial stopper is not made with natural rubber latex.
Storage and Handling
Store APRETUDE at 2°C to 25°C (36°F to 77°F) in the original carton until ready to use. Exposure up to 30°C permitted. Do not freeze. Do not mix with any other product or diluent.
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]).
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 syringes 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
8PATIENT COUNSELING INFORMATION
Advise the individual to read the FDA-approved patient labeling (Patient Information).
Important Information for Individuals without HIV-1 Taking APRETUDE for HIV-1 Pre‑Exposure Prophylaxis
Advise individuals without HIV-1 about the following
- APRETUDE should be used for PrEP as part of an overall HIV-1 infection prevention strategy, including adherence to the administration schedule and safer sex practices, including condoms, to reduce the risk of STIs.
- APRETUDE is not always effective in preventing HIV-1 acquisition
- Counsel individuals on the use of other prevention measures (e.g., knowledge of partner HIV-1 status, testing for STIs condom use). Inform individuals about and support their efforts in reducing sexual risk behavior.
- APRETUDE should be used to reduce the risk of acquiring HIV-1 only in individuals confirmed to be HIV-1 negative
- If recent (<1 month) exposures to HIV-1 are suspected or clinical symptoms consistent with acute HIV-1 infection are present, use a test approved or cleared by the FDA as an aid in the diagnosis of acute or primary HIV-1 infection.
- When using APRETUDE for HIV-1 PrEP, HIV-1 testing should be repeated prior to each injection of APRETUDE, and upon diagnosis of any other STIs.
- If an HIV-1 test indicates possible HIV-1 infection, or if symptoms consistent with acute HIV-1 infection develop following an exposure event, additional HIV testing to determine HIV status is needed. If an individual has confirmed HIV-1 infection, then the individual must be transitioned to a complete HIV-1 treatment regimen.
- Some individuals, such as adolescents, may benefit from frequent visits and counseling to support adherence.
Potential Risk of Resistance with APRETUDE
Advise individuals there is a potential risk of developing resistance to APRETUDE if HIV-1 is acquired either before or while taking APRETUDE or following discontinuation of APRETUDE
To minimize this, it is essential that individuals are clinically reassessed for risk of HIV-1 acquisition and tested frequently to confirm HIV-1 negative status. Advise individuals who are confirmed to have with HIV-1 infection to consult with their healthcare professional, as HIV-1 treatment must be initiated
Inform individuals that alternative forms of PrEP should be considered following discontinuation of APRETUDE for those at continuing risk of HIV-1 acquisition and initiated within 2 months of the final injection of APRETUDE
Long-Acting Properties of APRETUDE
Advise individuals that APRETUDE is an extended-release injectable that may be systemically present for 12 months or longer and consideration should be taken regarding the prolonged release characteristics when APRETUDE is discontinued
Adherence to APRETUDE
Counsel individuals about the importance of continued medication adherence and scheduled visits to help reduce the risk of acquiring HIV-1 infection and development of resistance
Hypersensitivity Reactions
Advise individuals to immediately contact their healthcare provider if they develop a rash. Instruct individuals to immediately stop taking APRETUDE and seek medical attention if they develop a rash associated with any of the following symptoms as it may be a sign of a more serious reaction such as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN): fever; generally ill feeling; extreme tiredness; muscle or joint aches; blisters; oral blisters or lesions; eye inflammation; facial swelling; swelling of the eyes, lips, tongue, or mouth; difficulty breathing; and/or signs and symptoms of liver problems (e.g., yellowing of the skin or whites of the eyes; dark or tea‑colored urine; pale-colored stools or bowel movements; nausea; vomiting; loss of appetite; or pain, aching, or sensitivity on the right side below the ribs). Advise individuals that if hypersensitivity occurs, they will be closely monitored, laboratory tests will be ordered, and appropriate therapy will be initiated
Hepatotoxicity
Inform individuals that hepatotoxicity has been reported with cabotegravir
Depressive Disorders
Inform individuals that depressive disorders (including depression, depressed mood, major depression, persistent depressive disorder, suicidal ideation, suicide attempt) have been reported with APRETUDE
Drug Interactions
Inform individuals that APRETUDE may interact with other drugs and may reduce exposure of APRETUDE; therefore, advise individuals to report to their healthcare provider the use of any other prescription or nonprescription medication
Missed Dose
Inform individuals that APRETUDE can remain in the body for up to 12 months or longer after receiving their last injection. Advise individuals that they should contact their healthcare provider if they miss or plan to miss a scheduled monthly injection visit and that oral dosing may be used to replace up to 2 consecutive monthly injections. Advise individuals that if they discontinue use of APRETUDE, they will need to take other medicines for HIV-1 PrEP
Pregnancy Registry
Inform individuals that there is an antiretroviral pregnancy registry to monitor fetal outcomes in those exposed to APRETUDE during pregnancy. Individuals who are of reproductive potential should be informed of the long duration of exposure of APRETUDE and that there is very limited clinical experience in human pregnancy
Lactation
Inform individuals that due to the potential for adverse reactions and residual concentrations in the systemic circulation for up to 12 months or longer after discontinuing injections of APRETUDE, it is recommended that mothers breastfeed only if the expected benefit justifies the potential risk to the infant. The benefits and risks of APRETUDE while breastfeeding should be evaluated, including the risk of HIV-1 acquisition due to medication nonadherence and subsequent mother to child transmission. Instruct mothers not to breastfeed if acute HIV-1 infection is suspected because of the risk of passing the HIV-1 virus to the baby
APRETUDE, CABENUVA, and VOCABRIA are trademarks owned by or licensed to the ViiV Healthcare group of companies.
The other brand listed is a trademark owned by or licensed to its respective owner and is not a trademark owned by or licensed to the ViiV Healthcare group of companies. The maker of this brand is not affiliated with and does not endorse the ViiV Healthcare group of companies or its products.
Manufactured for:
ViiV Healthcare
©2025 ViiV Healthcare group of companies or its licensor.
APR:5PI