Cobicistat

Mechanism :

Cobicistat is a mechanism-based inhibitor of cytochrome P450 3A (CYP3A).
Inhibition of CYP3A-mediated metabolism by cobicistat and increases the systemic exposure of CYP3A substrates atazanavir and darunavir.

Indication :

Treatment of HIV-1 infection to increase systemic exposure of atazanavir or darunavir (once-daily dosing regimen)

Contraindications :

Concomitant use of cobicistat with atazanavir or darunavir with alfuzosin, carbamazepine, cisapride, colchicine (in patients with renal and/or hepatic impairment), dronedarone, ergot derivatives (e.g., dihydroergotamine, ergotamine, methylergonovine), lovastatin, lurasidone, midazolam (oral), phenobarbital, phenytoin, pimozide, ranolazine, rifampin, sildenafil (when used for pulmonary arterial hypertension), simvastatin, St. John wort, triazolam; concomitant use of cobicistat and atazanavir with drospirenone/ethinyl estradiol, indinavir, irinotecan, or nevirapine.

Dosing :

Safety and efficacy not established in pediatric patients.

Adults:

With atazanavir 300 mg give 150 mg PO OD.

With darunavir 800 mg give 150 mg PO OD.

Adverse Effect :

Hyperbilirubinemia, increased creatine kinase, rash, increased serum amylase, GGT, AST and ALT, glycosuria, hematuria, nausea, diarrhea, vomiting, fatigue, rhabdomyolysis, depression, insomnia.

Interaction :

CYP3A4 Inducers: May increase the metabolism of CYP3A4 Substrates.
CYP3A4 Substrates: CYP3A4 Inhibitors may decrease the metabolism of CYP3A4 Substrates .
Dexamethasone (Systemic): May decrease the serum concentration of Cobicistat.
Digoxin: Cobicistat may increase the serum concentration of Digoxin.
Warfarin: Cobicistat may increase the serum concentration of Warfarin.

Hepatic Dose :

Use with caution or preferably avoid in severe hepatic impairment as it has not been studied in these patients.