Dosing & Uses
Dosage Forms & Strengths
tablet
- 150mg
Pharmacokinetic Enhancer for HIV Treatment
Indicated to increase systemic exposure of atazanavir or darunavir (once-daily dosing regimen) in combination with other antiretroviral agents (ARTs) 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 plus other ARTs
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 plus other ARTs
Dosage Modifications
Refer to prescribing information for darunavir and atazanavir for dosage modifications
Renal impairment
- Mild-to-severe: No dosage adjustment necessary
-
Coadministered with tenofovir DF
- CrCl <70 mL/min: Coadministration with tenofovir DF not recommended
- Dose adjustment of tenofovir is required for CrCl <50 mL/min, and such dose adjustments not established for coadministration with cobicistat
Hepatic impairment
- Mild-to-moderate: No dosage adjustment necessary
- Severe: No data
Dosing Considerations
Limitations of use
- Cobicistat is not interchangeable with ritonavir and cobicistat use is not recommended to increase systemic exposure of darunavir 600 mg BID, fosamprenavir, saquinavir, or tipranavir due to lack of exposure data
- Complex or unknown mechanisms of drug interactions preclude extrapolation of ritonavir drug interactions to certain cobicistat interactions
- Cobicistat and ritonavir when administered with either atazanavir or darunavir may result in different drug interactions when used with concomitant medications
Laboratory testing before and during treatment
- Before initiating: Test for hepatitis B infection
- Before initiating and during treatment: Assess eCrCl; cobicistat decreases eCrCl because of tubular secretion inhibition of creatinine; however, it does not affect actual renal glomerular function
- Coadministration with tenofovir DF: Assess eCrCl, urine glucose, and urine protein at baseline
- Patients with chronic kidney disease: Assess eCrCl, urine glucose, urine protein, and serum phosphorus at baseline
Not recommended during pregnancy
- Do not initiate cobicistat with darunavir or atazanavir during pregnancy
- Coadministered with darunavir or atazanavir is not recommended during pregnancy owing to substantially lower systemic exposures of darunavir and cobicistat during the second and third trimesters
Dosage Forms & Strengths
tablet
- 150mg
Pharmacokinetic Enhancer for HIV Treatment
Indicated to increase systemic exposure of atazanavir or darunavir (once daily dosing regimen) in combination with other antiretroviral agents (ARTs) in the treatment of HIV-1 infection in pediatric patients
Coadministration with atazanavir
- Indicated for treatment-naïve or treatment experienced patients
- <35 kg: Safety and efficacy not established
- ≥35 kg: Cobicistat 150 mg PO qDay plus atazanavir (300 mg PO qDay) plus other ARTs
Coadministration with darunavir
- Indicated for treatment-naïve or treatment experienced patients with no darunavir resistance-associated substitutions
- <40 kg: Safety and efficacy not established
- ≥40 kg: Cobicistat 150 mg PO qDay plus darunavir (800 mg PO qDay) plus other ARTs
Dosage Modifications
Refer to prescribing information for darunavir and atazanavir for dosage modifications
Renal impairment
- Mild-to-severe: No dosage adjustment necessary
-
Coadministered with tenofovir DF
- CrCl <70 mL/min: Coadministration with tenofovir DF not recommended
- Dose adjustment of tenofovir is required for CrCl <50 mL/min, and such dose adjustments not established for coadministration with cobicistat
Hepatic impairment
- Mild-to-moderate: No dosage adjustment necessary
- Severe: No data
Dosing Considerations
Limitations of use
- Cobicistat is not interchangeable with ritonavir and cobicistat use is not recommended to increase systemic exposure of darunavir 600 mg BID, fosamprenavir, saquinavir, or tipranavir due to lack of exposure data
- Complex or unknown mechanisms of drug interactions preclude extrapolation of ritonavir drug interactions to certain cobicistat interactions
- Cobicistat and ritonavir when administered with either atazanavir or darunavir may result in different drug interactions when used with concomitant medications
Laboratory testing before and during treatment
- Before initiating: Test for hepatitis B infection
- Before initiating and during treatment: Assess eCrCl; cobicistat decreases eCrCl because of tubular secretion inhibition of creatinine; however, it does not affect actual renal glomerular function
- Coadministration with tenofovir DF: Assess eCrCl, urine glucose, and urine protein at baseline
- Patients with chronic kidney disease: Assess eCrCl, urine glucose, urine protein, and serum phosphorus at baseline
Not recommended during pregnancy
- Do not initiate cobicistat with darunavir or atazanavir during pregnancy
- Coadministered with darunavir or atazanavir is not recommended during pregnancy owing to substantially lower systemic exposures of darunavir and cobicistat during the second and third trimesters
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 >2.5x ULN (65%)
Ocular icterus, all grades (15%)
Jaundice, all grades (13%)
Nausea, all grades (12%)
1-10%
Creatine kinase >10x ULN (5%)
Jaundice, Grades 2-4 (5%)
Rash, Grades 2-4 (5%)
Serum amylase >2x ULN (4%)
ALT or AST >5x ULN (3%)
Glycosuria >1000 mg/dL (3%)
Urine RBC >75 RBC/HPF (3%)
Ocular icterus Grades 2-4 (3%)
GGT >5x 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
Coadministration of cobicistat with atazanavir or darunavir and the following drugs is contraindicated owing to potential for serious and/or life-threatening events or loss of therapeutic effect
- Alfuzosin
- Amiodarone
- Carbamazepine, phenobarbital, phenytoin
- Rifampin
- Irinotecan (when administered with atazanavir)
- Lurasidone, pimozide
- Dihydroergotamine, ergotamine, methylergonovine
- Cisapride
- St. John’s wort (Hypericum perforatum)
- Drospirenone/ethinyl estradiol (when administered with atazanavir)
- Lomitapide, lovastatin, simvastatin
- Nevirapine (when administered with atazanavir)
- Sildenafil when administered for pulmonary arterial hypertension
- Indinavir (when administered with atazanavir)
- Triazolam, orally administered midazolam
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
Coadministration with darunavir or atazanavir is not recommended during pregnancy
In a clinical trial of individuals taking cobicistat coadministered with darunavir, exposures of cobicistat and darunavir were substantially lower during the second and third trimesters of pregnancy
Refer to prescribing information of darunavir and atazanavir about pregnancy
Animal data
- In animal reproduction studies in rats and rabbits, no evidence of fetal harm was observed with oral administration of cobicistat during organogenesis at doses that produced exposures up to 1.4x and 3.3x the maximal recommended human dose (MRHD) of 150 mg
ART pregnancy registry
- Pregnancy exposure registry that monitors fetal outcomes in individuals exposed to drug during pregnancy
- Encourage to register patients by calling Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263
Contraception
- Cobicistat interacts with certain oral contraceptives
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
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
Storage
Tablets: Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F)
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Patient Handout
Formulary
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