CABENUVA KIT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CABENUVA KIT (CABENUVA KIT).
Cabotegravir is an HIV-1 integrase strand transfer inhibitor (INSTI) that inhibits viral DNA integration into the host genome. Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that allosterically inhibits HIV-1 reverse transcriptase.
| Metabolism | Cabotegravir is primarily metabolized by UGT1A1 with minor contribution from UGT1A9; rilpivirine is primarily metabolized by CYP3A4. |
| Excretion | Renal (minimal, <1% unchanged) and fecal (76% of dose, primarily as parent drug and metabolites). Biliary excretion is the primary route; renal clearance of unchanged drug is negligible. |
| Half-life | Cabotegravir: 40.9 days (intramuscular depot). Rilpivirine: 30.2 days (intramuscular depot). These long half-lives are due to slow absorption from the injection site and support monthly or every-2-month dosing. |
| Protein binding | Cabotegravir: >99% bound to plasma proteins (albumin, α1-acid glycoprotein). Rilpivirine: 99.7% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Cabotegravir: 12.5 L/kg (extensive tissue distribution). Rilpivirine: 6.3 L/kg (moderate tissue distribution). |
| Bioavailability | Intramuscular: Cabotegravir ~100% (depot formulation slowly absorbed). Rilpivirine ~100% (depot formulation slowly absorbed). Oral cabotegravir: ~63% (fed), oral rilpivirine: ~55% (fed). |
| Onset of Action | Intramuscular: Detectable plasma concentrations within 1 hour; clinically relevant concentrations achieved by day 3–7 for cabotegravir and day 7 for rilpivirine. |
| Duration of Action | Cabotegravir: 11.5 weeks (with oral lead-in) or 13.5 weeks (without oral lead-in) after last injection. Rilpivirine: 8.1 weeks (with oral lead-in) or 9.8 weeks (without oral lead-in). Clinical suppression of HIV RNA is maintained for the entire dosing interval (monthly or every 2 months). |
| Molecular Weight | Cabotegravir: 405.43 Da; Rilpivirine: 366.42 Da |
Two separate gluteal IM injections of cabotegravir 600 mg and rilpivirine 900 mg on the same day for initiation; then monthly maintenance: cabotegravir 400 mg and rilpivirine 600 mg IM.
| Dosage form | SUSPENSION, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl >=30 mL/min). Not recommended if CrCl <30 mL/min. |
| Liver impairment | No dose adjustment for mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Not recommended in severe (Child-Pugh C) impairment. |
| Pediatric use | Not approved for pediatric patients <18 years; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; limited data in patients >65 years, use with caution due to greater frequency of renal/hepatic impairment. |
| 1st trimester | Insufficient human data; animal studies show no teratogenicity but embryotoxicity at high doses. Use only if benefit outweighs risk. |
| 2nd trimester | Same as T1; limited human data, no known malformations. |
| 3rd trimester | Same as T1; may increase risk of HIV transmission to infant if viral load not suppressed. |
Clinical note
Comprehensive clinical and safety monograph for CABENUVA KIT (CABENUVA KIT).
| Placental transfer | Cabotegravir and rilpivirine cross the placenta in animal studies; human data limited but transfer likely. |
| Breastfeeding | Not recommended during breastfeeding. Both cabotegravir and rilpivirine are excreted in human milk; potential for HIV transmission and adverse effects in infant. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to cabotegravir, rilpivirine, or any componentConcurrent use with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, St. John's wort, or systemic dexamethasone (>1.5 mg/day for >2 weeks)
| Precautions | Hypersensitivity reactions, Hepatotoxicity, Depressive disorders, Risk of resistance if doses are missed, Injection site reactions |
| Food/Dietary | Take the oral lead-in (if prescribed) with a meal to improve absorption; avoid antacids or proton pump inhibitors with rilpivirine as they reduce its absorption. No specific food restrictions for the injectable form. |
Loading safety data…
| L5 |
| Teratogenic Risk | Cabenuva is not recommended during pregnancy unless benefit outweighs risk. In the Antiretroviral Pregnancy Registry, there is insufficient data to assess teratogenicity. Animal studies with cabotegravir and rilpivirine showed no evidence of teratogenicity at exposures up to 10-15 times human exposure. For rilpivirine, no teratogenic effects in rats or rabbits; for cabotegravir, no teratogenicity in rats or rabbits. Increased fetal resorptions and delayed ossification were seen only at maternally toxic doses. First trimester: limited data, not able to exclude risk. Second and third trimesters: no known specific risks. Use only if clearly needed. |
| Fetal Monitoring | Monitor HIV viral load and CD4 count throughout pregnancy. Perform fetal ultrasound to assess growth. Monitor for maternal adverse effects including injection site reactions, hepatotoxicity, depression, and hypersensitivity. No specific fetal monitoring required beyond routine prenatal care. |
| Fertility Effects | No human data on fertility effects. In animal studies, no adverse effects on fertility or early embryonic development were observed with cabotegravir or rilpivirine at exposures up to 10-15 times human exposure. |
| Clinical Pearls |
| Administer as two separate gluteal injections (cabotegravir and rilpivirine) on the same day. Observe patient for at least 10 minutes post-injection due to risk of post-injection reactions. Do not miss doses; if a dose is delayed >7 days, oral lead-in may be required. Monitor for hepatotoxicity, especially with underlying liver disease or co-infection with hepatitis B/C. |
| Patient Advice | This medication is given as two shots in the buttocks by a healthcare provider every month or every two months. · Do not miss your scheduled injections; if you miss an appointment, contact your healthcare provider immediately. · Common side effects include injection site pain, swelling, redness, headache, and fatigue; report any signs of allergic reaction or rash. · Inform your doctor of all medications you take, including over-the-counter drugs and supplements, as interactions may occur. · You may need to take oral forms of these medicines (cabotegravir and rilpivirine) for about one month before starting the injections. |