Due to the potential for interactions, regimens should be reviewed during any changes (starting or stopping medications or altering dose). Because cobicistat is used in conjunction with darunavir or atazanavir, those interactions are considered here.

Drug-drug:

• Alfuzosin↑ risk of potentially life-threatening reactions; concurrent use contraindicated.
• ↑levels and risk of potentially dangerous adverse reactions with dronedarone; concurrent use contraindicated.
• Rifampin, carbamazepine, phenobarbital, or phenytoinmay ↓ levels and effectiveness of atazanavir or darunavir; concurrent use in a regimen with cobicistat is contraindicated.
• ↑levels and risk of serious toxicity from irinotecan when used in a regimen containing atazanavir and cobicistat; concurrent use contraindicated.
• ↑risk of serious toxicity, including peripheral vasospasm/ischemia, from dihydroergotamine, ergotamine, and methylergonovine; concurrent use contraindicated.
• ↑risk of serious arrhythmias with pimozide; concurrent use contraindicated.
• ↑risk of hepatotoxicity with lomitapide; concurrent use contraindicated.
• ↑risk of myopathy/rhabdomyolysis with lovastatin and simvastatin; concurrent use contraindicated.
• Concurrent use with nevirapine may ↓ levels and effectiveness of atazanavir and ↑ levels and risk of toxicity from nevirapine; concurrent use contraindicated.
• ↑risk of visual disturbances, hypotension, priapism, and syncope with sildenafil; concurrent use contraindicated when sildenafil used for pulmonary hypertension.
• ↑levels and risk of potentially life-threatening reactions from ranolazine; concurrent use contraindicated.
• ↑levels and risk of potentially life-threatening reactions from colchicine; concurrent use contraindicated in patients with renal and/or hepatic impairment.
• ↑levels and risk of potentially life-threatening reactions from lurasidone; concurrent use contraindicated.
• ↑risk of prolonged sedation/respiratory depression with oral midazolam and triazolam; concurrent use contraindicated.
• ↑risk of hyperkalemia from drospirenone/ethinyl estradiol when used in a regimen containing atazanavir and cobicistat; concurrent use contraindicated.
• Concurrent use of more than one antiretroviral that requires another agent to ↑ levels, such as two protease inhibitors, may ↓ antiretroviral effectiveness; concurrent use is not recommended.
• Concurrent use of darunavir with efavirenz, nevirapine, or etravirine may ↓ antiretroviral effectiveness and ↑ risk of resistance; concurrent use is not recommended.
• Concurrent use of atazanavir with etravirine or efavirenz (in treatment-experienced patients) may ↓ antiretroviral effectiveness and ↑ risk of resistance; concurrent use is not recommended.
• Concurrent use of darunavir at a dose of 600 mg twice daily may ↓ antiretroviral effectiveness and ↑ risk of resistance; concurrent use at that dose is not recommended.
• Concurrent use of other protease inhibitors, including fosamprenavir and tipranavir, may ↓ antiretroviral effectiveness and ↑ risk of resistance; concurrent use is not recommended.
• Should not be used concurrently with other cobicistat-containing fixed-dose combinations or ritonavir-containing regimens or fixed-dose combinationsdue to cumulative effects on CYP3A.
• ↑levels of maraviroc; ↓ maraviroc dose to 150 mg twice daily.
• Antacids↓ absorption of atazanavir; separate doses by 2 hr.
• ↑levels and risk of toxicity of amiodarone, digoxin, disopyramide, flecainide, mexiletine, propafenone, and quinidine; careful monitoring and titration are recommended.
• Clarithromycin and erythromycin may ↑ levels of atazanavir, darunavir, and cobicistat; consider alternative anti-infectives.
• ↑levels and risk of toxicity with dasatinib, nilotinib, vinblastine, and vincristine; careful monitoring for toxicity and dose adjustments recommended.
• May ↑ bleeding risk with rivaroxaban; avoid concurrent use.
• May ↑ bleeding risk with apixaban when coadministered with atazanavir or darunavir; if taking apixaban 5–10 mg twice daily, ↓ apixaban dose by 50%; if taking apixaban 2.5 mg twice daily, avoid concurrent use.
• May ↑ bleeding risk with dabigatran when coadministered with atazanavir; may need to avoid concurrent use if patient has moderate or severe renal impairment (depends on dabigatran indication).
• May ↑ bleeding risk with edoxaban when coadministered with atazanavir; ↓ edoxaban dose by 50% when used for VTE treatment in patients with moderate or severe renal impairment.
• Effect on warfarin is not known; monitor INR.
• Oxcarbazepine↓ levels and effectiveness of cobicistat and atazanavir; consider alternative anticonvulsants or antiretroviral.
• May ↑ levels and risk of toxicity of clonazepam; careful anticonvulsant monitoring recommended.
• May ↑ levels and risk of toxicity of tricyclic antidepressants and trazodone; careful dosing of antidepressants recommended (effect on SSRIs is unknown).
• Concurrent use with itraconazole, ketoconazole, and voriconazole may result in ↑ levels of itraconazole and ketoconazole (effect on voriconazole is unknown) and ↑ levels of atazanavir, cobicistat, and darunavir; concurrent use with voriconazole not recommended.
• ↑levels and risk of toxicity with colchicine; concurrent use in patients with renal/hepatic impairment not recommended; for others, ↓ dose (for gout flare: 0.6 mg followed by 0.3 mg one hr later; may repeat no sooner than 3 days; for prophylaxis of gout flare: if dose was originally 0.6 mg twice daily, ↓ to 0.3 mg once daily; if original regimen was 0.6 mg once daily, ↓ to 0.3 mg every other day; for treatment of familial Mediterranean fever: daily dose should not exceed 0.6 mg or 0.3 mg twice daily).
• ↑levels and risk of toxicity of rifabutin; ↓ rifabutin dose to 150 mg every other day.
• ↑levels and risk of toxicity of metoprolol, carvedilol, timolol, or any other beta blockers metabolized by CYP2D6; clinical monitoring recommended.
• ↑levels and risk of toxicity of amlodipine, diltiazem, felodipine, nifedipine, verapamil, or any other calcium channel blocker metabolized by CYP3A; careful monitoring recommended.
• Concurrent use of corticosteroids that induce CYP3A, including betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, and triamcinolone, may ↓ levels and effectiveness and ↑ risk of resistance to atazanavir or darunavir (consider use of other corticosteroids, such as beclomethasone, prednisone, or prednisolone).
• Concurrent use of corticosteroids that are metabolized by CYP3A, including betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, and triamcinolone, may ↑ risk of Cushing's disease and adrenal suppression (consider use of other corticosteroids, such as beclomethasone, prednisone, or prednisolone).
• Concurrent use with bosentan may result in ↑ levels/toxicity of bosentan and ↓ levels of atazanavir, darunavir, and cobicistat; dose alteration is required (initiating bosentan in patients already receiving cobicistat with atazanavir or darunavir for 10 days or more: bosentan 62.5 mg daily or every other day, depending on tolerance; initiating cobicistat with atazanavir or darunavir in patient already receiving bosentan : discontinue bosentan for 10 days; resume bosentan at 62.5 mg daily or every other day, depending on tolerance.
• H2-receptor antagonists may ↓ levels and effectiveness; administer simultaneously or ≥ 10 hr after H₂-receptor antagonist (dose of H₂-receptor antagonist should not exceed famotidine 40 mg [or equivalent] twice daily in treatment-naive patients or famotidine 20 mg [or equivalent] twice daily in treatment-experienced patients; atazanavir dose should be ↑ to 400 mg daily).
• ↑levels and risk of toxicity of immunosuppressants metabolized by CYP3A, including cyclosporine, everolimus, sirolimus, and tacrolimus; therapeutic monitoring recommended.
• ↑levels and risk of toxicity of salmeterol; concurrent use is not recommended.
• May ↑ levels and risk of respiratory depression with opioids, including buprenorphine, buprenorphine/naloxone, fentanyl, and tramadol; carefully monitor opioid effects when cobicistat with atazanavir or darunavir is initiated; dose adjustment of opioid may be necessary.
• May ↑ levels and risk of toxicity of neuroleptics that are metabolized by CYP3A or CYP2D6, including perphenazine, risperidone, and thioridazine; may need to ↓ dose of neuroleptic.
• May ↑ levels and risk of toxicity of PDE-5 inhibitors , including avanafil, sildenafil, tadalafil, and vardenafil; concurrent use with avanafil is not recommended; sildenafil : use for pulmonary hypertension is contraindicated; when used for erectile dysfunction, single dose should not exceed 25 mg/48 hr, tadalafil: (for pulmonary hypertension—initiating tadalafil in patients receiving cobicistat with atazanavir and darunavir for at least 7 days)—20 mg once daily initially; may be titrated to 40 mg once daily; (for pulmonary hypertension—initiating cobicistat with atazanavir or darunavir in patients receiving tadalafil)—discontinue tadalafil 24 hr prior to initiating cobicistat with atazanavir or darunavir; after 7 days, reinstitute tadalafil at 20 mg once daily; may be increased to 40 mg once daily; (for erectile dysfunction)—single dose should not exceed 10 mg/72 hr; vardenafil: (for erectile dysfunction)—single dose should not exceed 2.5 mg/72 hr.
• Proton-pump inhibitors↓ levels and effectiveness; in treatment-naive patients; administer cobicistat with atazanavir or darunavir ≥12 hr after proton-pump inhibitors; dose of proton-pump inhibitor should not exceed omeprazole 20 mg daily or equivalent; in treatment-experienced patients, concurrent use with proton-pump inhibitors is not recommended.
• ↑levels and risk of excess sedation/respiratory depression from some sedative/hypnotics metabolized by CYP3A, including buspirone, diazepam, and parenteral midazolam; concurrent use with other sedative/hypnotics metabolized by CYP3A should be undertaken with caution; dose ↓ may be necessary.
• May ↑ levels and risk of toxicity of quetiapine; ↓ quetiapine dose to ⅙ of current dose.
• ↑risk of hyperkalemia from drospirenone/ethinyl estradiol when used in a regimen containing darunavir and cobicistat; closely monitor serum potassium concentrations.
• ↑risk of myopathy with atorvastatin and rosuvastatin; avoid concurrent use of atorvastatin with atazanavir and cobicistat; for atazanavir/cobicistat regimens, do not exceed rosuvastatin dose of 10 mg/day; for darunavir/cobicistat regimens, do not exceed atorvastatin or rosuvastatin dose of 20 mg/day.
• May ↑ levels of and risk of bleeding with ticagrelor; concurrent use not recommended.
• May ↓ antiplatelet effects of clopidogrel, which may ↑ risk of thrombosis; concurrent use not recommended.

Drug-Natural Products:

• St. John's wort may ↓ blood levels and effectiveness of atazanavir or darunavir; concurrent use with a regimen including cobicistat is contraindicated.