cobicistat (Rx)

>10%

Total bilirubin, >2.5 x ULN (65%)

Ocular icterus, all grades (15%)

Jaundice, all grades (13%)

Nausea, all grades (12%)

1-10%

Creatine kinase, >10 x ULN (5%)

Jaundice, grades 2-4 (5%)

Rash, grades 2-4 (5%)

Serum amylase, >2 x ULN (4%)

ALT or AST, >5 x ULN (3%)

Glycosuria, >1000 mg/dL (3%)

Urine RBC, >75 RBC/HPF (3%)

Ocular icterus, grades 2-4 (3%)

GGT, >5 x ULN (2%)

Nausea, grades 2-4 (2%)

<2%

Gastrointestinal disorders: Diarrhea, vomiting, upper abdominal pain

General disorders and administration site conditions: Fatigue

Musculoskeletal and connective-tissue disorders: Rhabdomyolysis

Nervous system disorders: Headache

Psychiatric disorders: Depression, abnormal dreams, insomnia

Renal and urinary disorders: Nephropathy, Fanconi syndrome acquired

Frequency Not Defined

Increased triglycerides, +15 from baseline

Increased LDL-C, +5 from baseline

Increased total cholesterol, +4 from baseline

Increased HDL-C, +3 from baseline

Contraindications

Cautions

Cobicistat may cause modest increases in serum creatinine and modest declines in CrCl without affecting renal glomerular function; serum creatinine >0.4 mg/dL from baseline should be closely monitored for renal safety; assess CrCl before administering

New-onset or worsening renal impairment reported when used with antiretroviral regimens containing tenofovir; do not use with tenofovir if CrCl <70 mL/min

Assess urine glucose and urine protein at baseline and monitor ClCr, urine glucose, and urine protein when using with tenofovir; monitor serum phosphorus in patients with or at risk for renal impairment

CYP inducers may lower systemic exposure of cobicistat and atazanavir or darunavir, resulting in loss of virologic response

Cobicistat is an inhibitor of CYP3A, CYP2D6, p-glycoprotein (P-gp), BCRP, OATP1B1, and OATP1B3; plasma concentration of drugs that are substrates of the aforementioned isoenzymes or transporters may be increased if coadministered with cobicistat

Pregnancy

An ART pregnancy registry has been established (1-800-258-4263); prospective pregnancy data from the Antiviral Pregnancy Registry (APR) not sufficient to adequately assess risk of birth defects or miscarriage

Not recommended for use during pregnancy because of substantially lower exposures of cobicistat during second and third trimesters

Avoid use in pregnant individuals; an alternative regimen is recommended for individuals who become pregnant during therapy

Lactation

There is no information regarding presence of cobicistat in human milk, the effects on the breastfed infant, or the effects on milk production

The Centers for Disease Control and Prevention do not recommend HIV-infected mothers breastfeed their infants due to potential risk for postnatal transmission of HIV

Mechanism of Action

CYP3A4 inhibitor; mechanism-based pharmaco-enhancer, first product to be developed and submitted solely as pharmacokinetic booster for elvitegravir; enhances the systemic exposure of ART CYP3A substrates (ie, atazanavir, darunavir), where bioavailability is limited and half-life is shortened by CYP3A-dependent metabolism

Absorption

Peak Plasma Time: 3.5 hr

Peak Plasma Concentration: 0.99 mcg/mL

Trough Plasma Concentration: 0.03 mcg/mL

AUC: 7.6 mcg•hr/mL

Distribution

Protein bound: 97-98%

Metabolism

Metabolized by CYP3A4 and CYP2D6 (minor)

Inhibits CYP3A, CYP2D6, p-glycoprotein (P-gp), BCRP, OATP1B1, and OATP1B3

Elimination

Half-life: 3-4 hr

Excretion: 86.2% feces; 8.2% urine

Oral Administration

Must be coadministered with atazanavir or darunavir at the same time, with food, and in combination with other HIV-1 antiretroviral agents

Storage

Tablets: Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F)