COBICISTAT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for COBICISTAT (COBICISTAT).
Cobicistat is a mechanism-based inhibitor of cytochrome P450 3A (CYP3A) subfamily enzymes. It is used as a pharmacokinetic booster to increase systemic exposure of co-administered CYP3A substrates, such as certain antiretroviral agents.
| Metabolism | Cobicistat is metabolized primarily by CYP3A4/5 and to a lesser extent by CYP2D6. It is also a substrate of P-glycoprotein (P-gp). |
| Excretion | Primarily metabolized by CYP3A4 and to a lesser extent CYP2D6; 86.2% of dose excreted in feces (mainly as metabolites), 8.2% in urine. Less than 1% excreted unchanged. |
| Half-life | Terminal elimination half-life is approximately 3.5 hours when administered with atazanavir, but can be prolonged to 6-8 hours with boosted protease inhibitors due to enzyme saturation; supports once-daily dosing. |
| Protein binding | 97-98% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 0.99 L/kg (range 0.8-1.2 L/kg), indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is estimated at 70-80% under fed conditions; absorption is increased with a high-fat meal. |
| Onset of Action | Not applicable as cobicistat is a pharmacokinetic enhancer without intrinsic clinical effect; maximal enzyme inhibition occurs within 1-2 hours of oral administration. |
| Duration of Action | Enzyme inhibition persists for 24 hours with once-daily dosing, allowing coadministered HIV protease inhibitors or elvitegravir to be dosed once daily. |
Adults: 150 mg orally once daily, taken with food; used as pharmacokinetic booster in combination with other antiretroviral agents (e.g., protease inhibitors).
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. Not recommended for use in patients with GFR <30 mL/min due to lack of data. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Contraindicated in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Approved for children ≥12 years weighing ≥35 kg: 150 mg orally once daily with food. Safety and efficacy not established for children <12 years or <35 kg. |
| Geriatric use | Insufficient data for specific dose recommendations; use with caution due to age-related renal and hepatic function decline, limited clinical experience. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for COBICISTAT (COBICISTAT).
| Breastfeeding | It is unknown whether cobicistat is excreted in human breast milk. No specific M/P ratio data are available. Because cobicistat is a cytochrome P450 3A4 inhibitor, its presence in milk could theoretically affect infant drug metabolism, but clinical significance is unknown. In general, HIV-infected mothers should not breastfeed to avoid postnatal transmission of HIV, regardless of antiretroviral therapy. |
| Teratogenic Risk | Cobicistat is a pharmacokinetic enhancer, not a direct antiretroviral. Data in humans are limited. No teratogenicity was observed in animal studies at systemic exposures up to 5 times the human exposure. However, because cobicistat is always used in combination with other antiretrovirals (e.g., atazanavir, darunavir, elvitegravir), fetal risks are primarily determined by the companion drug. In general, antiretroviral therapy is recommended during pregnancy to prevent vertical transmission. No specific teratogenicity has been attributed to cobicistat based on available data from the Antiretroviral Pregnancy Registry. |
■ FDA Black Box Warning
There is no black box warning for cobicistat; however, the fixed-dose combinations containing cobicistat include warnings for other components (e.g., tenofovir disoproxil fumarate for hepatotoxicity and lactic acidosis, and tenofovir alafenamide for risk of lactic acidosis and severe hepatomegaly with steatosis).
| Serious Effects |
["Coadministration with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma levels are associated with serious adverse events (e.g., alfuzosin, amiodarone, ergot derivatives, lovastatin, simvastatin, sildenafil for pulmonary arterial hypertension, triazolam, midazolam oral).","Coadministration with drugs that strongly induce CYP3A (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, St. John's wort) because of potential loss of virologic response."]
| Precautions | ["Cobicistat decreases renal creatinine clearance and tubular secretion, leading to increased serum creatinine without affecting glomerular filtration rate; monitor renal function.","Cobicistat can cause nephrotoxicity due to increased exposure of co-administered tenofovir; avoid use with tenofovir disoproxil fumarate in patients with creatinine clearance <70 mL/min unless potential benefits outweigh risks.","Cobicistat is a strong inhibitor of CYP3A, potentially increasing exposure of co-administered drugs metabolized by CYP3A; monitor for toxicities and adjust doses as needed.","Cobicistat should be used with caution in patients with hepatic impairment; not recommended for severe hepatic impairment."] |
Loading safety data…
| Fetal Monitoring | No specific monitoring beyond standard prenatal care and monitoring of the antiretroviral regimen (e.g., viral load, CD4 count, hepatic and renal function) is required due to cobicistat alone. If coadministered with tenofovir alafenamide, monitor renal function and bone mineral density. If with atazanavir or darunavir, monitor bilirubin and hepatic parameters. Fetal ultrasound may be considered if indicated by the companion drug. |
| Fertility Effects | No human data on fertility effects. In animal studies (rats), cobicistat did not affect male or female fertility at systemic exposures up to 2.5 times the human exposure. No effect on reproductive organs or spermatogenesis observed. Clinical significance unknown. |