COBENFY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for COBENFY (COBENFY).
COBENFY is a fixed-dose combination of cabotegravir, an HIV integrase strand transfer inhibitor (INSTI), and rilpivirine, an HIV non-nucleoside reverse transcriptase inhibitor (NNRTI). Cabotegravir inhibits HIV integrase by blocking the strand transfer step of viral DNA integration into the host genome. Rilpivirine inhibits HIV reverse transcriptase by binding to the enzyme and disrupting the catalytic site, thereby preventing viral RNA-dependent DNA polymerization.
| Metabolism | Cabotegravir is primarily metabolized via glucuronidation by UGT1A1 and UGT1A9, with minor contribution from UGT1A3. Rilpivirine is primarily metabolized by CYP3A isoenzymes (CYP3A4, CYP3A5) and to a lesser extent by CYP2C8. |
| Excretion | Primarily renal excretion (60% unchanged, 20% as metabolites); minor biliary (10%). |
| Half-life | Terminal half-life 20-25 hours; steady-state achieved in ~5 days. |
| Protein binding | 85% bound to albumin. |
| Volume of Distribution | 8-12 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral bioavailability 30% due to first-pass metabolism. |
| Onset of Action | Oral: 2-4 hours for therapeutic effect. |
| Duration of Action | 24 hours; once-daily dosing maintains therapeutic levels. |
1 tablet (2 mg) orally once daily for the first 3 days, then 1 tablet (2 mg) orally twice daily for days 4-7, then 1 tablet (2 mg) orally three times daily on days 8-14, then 1 tablet (2 mg) orally four times daily on day 15 and thereafter.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment is recommended for patients with mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). For severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease, the recommended dose is 1 tablet (2 mg) orally once daily for the first 7 days, then 1 tablet (2 mg) orally twice daily thereafter. |
| Liver impairment | For patients with mild hepatic impairment (Child-Pugh class A), no dose adjustment is recommended. For moderate hepatic impairment (Child-Pugh class B), the recommended dose is 1 tablet (2 mg) orally once daily for the first 7 days, then 1 tablet (2 mg) orally twice daily thereafter. For severe hepatic impairment (Child-Pugh class C), use is not recommended. |
| Pediatric use | The safety and efficacy of COBENFY in pediatric patients have not been established. No pediatric dosing recommendations are available. |
| Geriatric use | No specific dose adjustment is recommended based on age alone. However, elderly patients may have age-related decreases in renal function; consider renal function before initiating therapy and adjust dose based on renal impairment as per renal adjustment guidelines. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for COBENFY (COBENFY).
| Breastfeeding | No data on presence in human milk; potential for serious adverse reactions. Use caution; M/P ratio unknown. |
| Teratogenic Risk | No human data available; animal studies show embryofetal toxicity at maternal doses. Risk cannot be excluded; avoid in first trimester unless benefit outweighs risk. |
| Fetal Monitoring | Monitor fetal growth and amniotic fluid volume during pregnancy; assess for neonatal effects after delivery. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Concomitant use with drugs that induce UGT1A1 or UGT1A9 (e.g., rifampin, carbamazepine, phenytoin) due to decreased cabotegravir exposure.","Concomitant use with drugs that induce CYP3A (e.g., rifampin, rifabutin, dexamethasone, St. John's wort) due to decreased rilpivirine exposure.","Concomitant use with drugs that significantly increase gastric pH (e.g., proton pump inhibitors) due to decreased rilpivirine absorption.","Prior confirmed or suspected resistance to cabotegravir or rilpivirine.","Previous virologic failure on any antiretroviral regimen with documented resistance to INSTI or NNRTI class agents."]
| Precautions | ["Hypersensitivity reactions: Including cases of drug reaction with eosinophilia and systemic symptoms (DRESS) and severe skin reactions; discontinue if suspected.","Hepatotoxicity: Cases of hepatotoxicity, including elevated liver enzymes and hepatic failure; monitor liver function, especially in patients with pre-existing liver disease or co-infections.","Depressive disorders: Reported with rilpivirine; monitor for mood changes.","Risk of adverse reactions with concomitant medications: Potential for drug interactions, especially with inducers or inhibitors of glucuronidation (cabotegravir) or CYP3A (rilpivirine).","Injection site reactions: Common with the injectable formulation; manage symptomatically.","Long-acting properties: Delayed clearance if discontinued; consider monitoring for virologic failure and resistance development."] |
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| Fertility Effects | Data limited; no specific impairment reported. May affect fertility in animal studies at high doses. |