Dosing & Uses
Dosage Forms & Strengths
tablet
- 150mg
Pharmacokinetic Enhancer for HIV Treatment
CYP3A inhibitor indicated to increase systemic exposure of atazanavir or darunavir (once-daily dosing regimen) in combination with other antiretroviral agents in the treatment of HIV-1 infection
Coadministered with atazanavir
- May use for treatment-naïve or experienced
- 150 mg PO qDay with atazanavir 300 mg PO qDay
Coadministered with darunavir
- May use for treatment-naïve or treatment-experienced with no darunavir resistance-associated substitutions
- 150 mg PO qDay with darunavir 800 mg PO qDay
Assess CrCl before initiating
- Assess estimated creatinine clearance (eCrCl)
- Cobicistat decreases eCrCl because of tubular secretion inhibition of creatinine
- Does not affect actual renal glomerular function
- If administering with tenofovir, assess eCrCl, urine glucose, and urine protein at baseline
Dosage Modifications
CrCl <70 mL/min: Coadministration with tenofovir not recommended
Note: Dose adjustment of tenofovir is required for CrCl <50 mL/min, and such dose adjustments have not been established for coadministration with cobicistat
Dosing Considerations
Not interchangeable with ritonavir or recommended to increase systemic exposure of darunavir 600 mg BID, fosamprenavir, saquinavir, or tipranavir, owing to lack of exposure data
Complex or unknown mechanisms of drug interactions preclude extrapolation of ritonavir drug interactions to certain cobicistat interactions; when administered with either atazanavir or darunavir, cobicistat may result in different drug interactions when used with concomitant medications
Safety and efficacy not established
HIV-1 Infection (Orphan)
Orphan designation teatment of human immunodeficiency virus type 1 (HIV-1) infection in pediatric patients
Sponsor
- Gilead Sciences, Inc; 333 Lakeside Drive;Foster City, California 94404
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
Note: Adverse effects listed below are for cobicistat coadministered with atazanavir
>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
Warnings
Contraindications
Alfuzosin: Potential for increased alfuzosin concentrations, which can result in serious or life-threatening reactions (eg, hypotension)
Dronedarone: Potential for increased dronedarone concentrations
CYP inducers (rifampin, carbamazepine, phenobarbital, phenytoin, St. John’s wort): Coadministration with CYP inducers may cause a significant decrease in the plasma concentrations of atazanavir or darunavir and result in loss of therapeutic effect and development of resistance
Irinotecan: Only contraindicated when cobicistat is coadministered with atazanavir; UGT1A1 inhibition by atazanavir may interfere with the metabolism of irinotecan, resulting in increased toxicity
Ergot derivatives (dihydroergotamine, ergotamine, methylergonovine): Potential for serious and/or life-threatening reactions (eg, acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues)
Cisapride, lurasidone, pimozide: Potential for serious and/or life-threatening reactions (eg, cardiac arrhythmias)
HMG-CoA reductase inhibitors (lovastatin, simvastatin): Potential for serious reactions (eg, myopathy, including rhabdomyolysis)
PDE5 inhibitors (long-term administration [eg, sildenafil as Revatio for PAH]): Potential for sildenafil-associated adverse reactions (eg, visual disturbances, hypotension, priapism, syncope)
Indinavir: Only contraindicated when cobicistat is coadministered with atazanavir; both atazanavir and indinavir are associated with indirect (unconjugated) hyperbilirubinemia
Triazolam, midazolam PO: These are extensively metabolized by CYP3A4; potential for prolonged or increased sedation or respiratory depression
Hormonal contraceptives (drospirenone/ethinyl estradiol)
Concomitant administration with ranolazine, has potential for serious and/or life-threatening reactions
Concomitant use with colchicine; contraindicated in patients with renal and/or hepatic impairment due to potential for serious and/or life-threatening reactions
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
Antiretrovirals that are not recommended
- The following are NOT recommended in combination with cobicistat because dosing recommendations for the combinations have not been established
- Coadministration may result in decreased plasma concentrations of the antiretroviral agents, leading to loss of therapeutic effect and development of resistance
- -More than 1 antiretroviral that requires pharmacokinetic enhancement (ie, 2 protease inhibitors or a protease inhibitor in combination with elvitegravir)
- -Darunavir in combination with efavirenz, nevirapine, or etravirine
- -Atazanavir in combination with etravirine
- -Atazanavir in combination with efavirenz in treatment-experienced patients
- -Darunavir 600 mg BID
- -Other HIV-1 protease inhibitors, including fosamprenavir, saquinavir, or tipranavir
- -Stribild fixed-dose combination tablets (elvitegravir, cobicistat, emtricitabine, tenofovir) are not recommended because cobicistat is a component of Stribild
- -Cobicistat in combination with lopinavir/ritonavir or regimens containing ritonavir are not recommended, owing to similar effects of cobicistat and ritonavir on CYP3A
Pregnancy & Lactation
Pregnancy Category: B
Lactation: Unknown whether distributed in breast milk
In the United States, the CDC recommends that HIV-infected mothers not breastfeed their infants, to avoid risking postnatal transmission of HIV
Pregnancy Categories
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Pharmacology
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
Administration
Oral Administration
Must be coadministered with atazanavir or darunavir at the same time, with food, and in combination with other HIV-1 antiretroviral agents
Coadministration with acid-modifying drugs
- Atazanavir systemic exposure is decreased if administered comcomitantly with acid modifying drugs
- Antacids containing aluminum or magnesium hydroxide: Administer antacids at least 2 hr before or after cobicistat with atazanavir
- H2-receptor antagonists: Administer either at the same time or take cobicistat with atazanavir a minimum of 10 hr after administering H2-receptor antagonists
- Proton pump inhibitors: Take cobicistat with atazanavir a minimum of 12 hr after administering proton pump inhibitors
Images
Patient Handout
Formulary
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