cobicistat

V03AX03

Forms & Strengths

Adult Dosing

150 mg orally once daily administered with food as a pharmacokinetic enhancer of atazanavir (300 mg) or darunavir (800 mg) in HIV-1 regimens
150 mg orally once daily as a component of fixed-dose combination products (e.g., Stribild, Genvoya, Symtuza)

Pediatric Dosing

Safety and efficacy not established in pediatric patients weighing less than specified thresholds for fixed-dose combinations
Weight-based dosing utilized strictly via approved fixed-dose combination tablets in pediatric patients aged 12 years and older and weighing >= 35 kg

Indications

Pharmacokinetic enhancer (booster) of CYP3A substrates atazanavir or darunavir in the treatment of HIV-1 infection
Component of fixed-dose combination regimens for the treatment of HIV-1 infection in adults and pediatric patients aged >= 12 years

Mechanism of Action

Mechanism-based inhibitor of cytochrome P450 3A (CYP3A) enzymes (CYP3A4 and CYP3A5)
Inhibits intestinal and hepatic CYP3A metabolism, significantly increasing systemic exposure and half-life of co-administered antiretrovirals (atazanavir, darunavir)
Inhibits drug transporters including P-glycoprotein, BCRP, OATP1B1, and OATP1B3; lacks anti-HIV activity of its own

Contraindications

Co-administration with drugs highly dependent on CYP3A for clearance where elevated concentrations cause serious/life-threatening events (e.g., alfuzosin, amiodarone, colchicine, cisapride, dronedarone)
Co-administration with potent CYP3A inducers (e.g., rifampin, St. John's wort, carbamazepine, phenobarbital, phenytoin) due to risk of decreased efficacy
Hypersensitivity to cobicistat

Adverse Reactions

Nausea
Fatigue
Jaundice and ocular icterus (secondary to atazanavir boosting)
Indirect hyperbilirubinemia
Transient, modest increases in serum creatinine due to inhibition of renal tubular secretion of creatinine without true impairment of glomerular filtration rate (eGFR)

Drug Interactions

Potent CYP3A inhibitors/inducers significantly alter cobicistat plasma concentrations
Potent CYP3A4 inhibitors/inducers alter clearance of boosted agents
Contraindicated with HMG-CoA reductase inhibitors heavily reliant on CYP3A4 (simvastatin, lovastatin) due to risk of myopathy/rhabdomyolysis
Contraindicated with oral midazolam or triazolam due to risk of prolonged sedation
May increase concentrations of certain direct-acting oral anticoagulants, antiarrhythmics, and anticonvulsants

Curated Content: Needs Vetting Before Put to Clinical Use