APRETUDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for APRETUDE (APRETUDE).
Apretude (cabotegravir) is an HIV-1 integrase strand transfer inhibitor (INSTI) that inhibits the integration of HIV-1 DNA into host genomic DNA, which is essential for viral replication. It binds to the active site of integrase and blocks the strand transfer step of retroviral DNA integration.
| Metabolism | Cabotegravir is primarily metabolized by UDP-glucuronosyltransferase (UGT) 1A1, with minor contributions from UGT1A9. It is not a substrate for CYP450 enzymes. |
| Excretion | Renal (approximately 30% as unchanged drug) and fecal (approximately 50% as metabolites and unchanged drug) following oral administration. |
| Half-life | Terminal elimination half-life is approximately 40 hours following subcutaneous injection, supporting monthly dosing. |
| Protein binding | Approximately 99.9% bound to serum proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 12.2 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Subcutaneous injection: 100% bioavailability; oral: not applicable (only approved as injectable). |
| Onset of Action | Subcutaneous injection: achieves therapeutic concentrations within 1 week; peak plasma concentrations at 4–6 weeks post-dose. |
| Duration of Action | With monthly dosing, protection against HIV-1 acquisition is maintained for the entire dosing interval; clinical efficacy sustained with adherence. |
600 mg IM every 2 months, initiated as two consecutive monthly loading doses of 600 mg each, for HIV-1 pre-exposure prophylaxis.
| Dosage form | SUSPENSION, EXTENDED RELEASE |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in patients with CrCl <30 mL/min or end-stage renal disease, as safety and efficacy not established. |
| Liver impairment | No dosage adjustment required for mild hepatic impairment (Child-Pugh A). Not recommended in moderate to severe hepatic impairment (Child-Pugh B or C), as safety and efficacy not established. |
| Pediatric use | Not approved for use in pediatric patients weighing less than 35 kg. For adolescents weighing ≥35 kg, same dosing as adults: 600 mg IM every 2 months after two monthly loading doses. |
| Geriatric use | No specific dose adjustment recommended based on age alone, but caution due to age-related renal and hepatic function decline; monitor adverse effects closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for APRETUDE (APRETUDE).
| Breastfeeding | Unknown if excreted in human breast milk; M/P ratio not established. Weigh benefits of breastfeeding against potential exposure to infant. |
| Teratogenic Risk | No evidence of teratogenicity in animal studies; insufficient human data in pregnant women. Avoid in first trimester unless benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal HIV viral load and CD4 count; fetal ultrasound for growth and anatomy if exposed during pregnancy. |
■ FDA Black Box Warning
None
| Serious Effects |
["Previous hypersensitivity reaction to cabotegravir","Concomitant use with certain drugs that are strong UGT1A1 inducers (e.g., rifampin, carbamazepine, phenytoin) due to decreased cabotegravir exposure and risk of reduced efficacy"]
| Precautions | ["Hypersensitivity reactions including cases of drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported","Hepatotoxicity has been reported in patients with or without pre-existing hepatic impairment or other risk factors","Risk of development of HIV-1 resistance if used for PrEP in undiagnosed HIV-1 infection; must confirm negative HIV-1 test before initiation and during use","Long-acting properties: if discontinued, cabotegravir may remain in systemic circulation for up to 12 months or longer; clinical monitoring and appropriate testing are recommended to detect HIV-1 infection","Risk of injection site reactions (most common adverse reaction leading to discontinuation)","Caution in patients with liver disease or risk factors for liver disease","Caution in patients with a history of depression; may exacerbate depression"] |
| Food/Dietary |
Loading safety data…
| Fertility Effects | No known adverse effects on fertility based on animal studies and limited human data. |
| No food interactions reported. Oral cabotegravir lead-in can be taken with or without food. |
| Clinical Pearls | APRETUDE (cabotegravir extended-release injectable suspension) is an integrase strand transfer inhibitor (INSTI) for HIV-1 PrEP. Administer as two gluteal intramuscular injections (600 mg total) at initiation, then every 2 months after the first injection. Must be initiated with oral cabotegravir lead-in (30 mg daily for ~4 weeks) to assess tolerability. Do not miss scheduled injections—late doses (>7 days) require oral bridging. Monitor for hepatitis B virus (HBV) co-infection; APRETUDE is not active against HBV. |
| Patient Advice | APRETUDE is injected into your buttocks by a healthcare provider every 2 months to prevent HIV infection. · You must start with 4 weeks of daily oral cabotegravir pills to check for side effects before switching to injections. · Do not miss your injection appointment; if delayed more than 7 days, you may need to take oral medication until your next injection. · APRETUDE does not protect against other sexually transmitted infections or prevent pregnancy. · If you stop APRETUDE, discuss alternative HIV prevention methods immediately to avoid risk of infection. |