Also found in: Acronyms.
Pregnancy Category: B
Pharmacologic: enzyme inhibitors
ClassificationTherapeutic: temporary class
Pharmacologic: enzyme inhibitors
To increase blood levels of atazanivir and darunavir (in combination with other antiretrovirals) in the treatment of HIV-1 infection.
By strongly inhibiting CYP3A enzymes, enhances systemic exposure to atazanivir and darunavir.
Slowed progression of HIV infection and decreased occurrence of sequelae.
Absorption: Absorption follows oral administration.
Protein Binding: 97–98%.
Metabolism and Excretion: Metabolized by CYP3A and to a small extent by CYP2D6; 86.2 eliminated in feces, 8.2% in urine.
Half-life: 3–4 hr.
|PO||unknown||3 hr||24 hr|
Contraindicated in: Concurrent use of other drugs for which ↑ or ↓ blood levels would be associated with serious/life-threatening toxicity/adverse reactions or loss of effectiveness including alfuzosin, dronedarone, rifampin, irinotecan, dihydroergotamine, ergotamine, methylergonovine, cisapride, St. John's wort, lovastatin, simvastatin, pimozide, nevirapine, sidenafil (when used for pulmonary hypertension), indinavir, triazolam, and midazolam (oral); Concurrent use with other antiretrovirals whose blood levels/effectiveness may be ↓ or risk of resistance ↑; Lactation: HIV-infected women should not breastfeed due to risk of viral transmission.
Use Cautiously in: Concurrent use of tenofovir (↑ risk of acute renal failure or Fanconi syndrome); Obstetric: Use during pregnancy only if potential benefits justify fetal risks; Pediatric: Safety and effectiveness not established.
Adverse Reactions/Side EffectsNoted for combination use with atazanavir
Ear, Eye, Nose, Throat
- ocular icterus (most frequent)
- jaundice (most frequent)
- acute renal failure (↑ with tenofovir)
- Fanconi syndrome (↑ with tenofovir)
InteractionsDue 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, those interactions are considered here.
Drug-Drug interactionConcurrent use with alfuzosin ↑ risk of potentially life threatening reactions and is contraindicated.↑ blood levels/risk of potentially dangerous adverse reactions with dronedarone ; concurrent use is contraindicated.Rifampin may ↓ blood levels/antiretroviral effectiveness of atazanavir or darunavir; concurrent use in a regimen with cobistat is contraindicated.↑ blood levels and risk of serious toxicity from irinotecan when used in a regimen containing atazanavir and cobicistat; concurrent use is contraindicated (due to atazanivir decreasing metabolism of irinotecan). ↑ risk of serious toxicity including peripheral vasospasm/ischemia from dihydroergotamine, ergotamine, and methylergonovine ; concurrent use is contraindicated. ↑ risk of serious arrhythmias with cisapride and pimozide ; concurrent use is contraindicated.↑ risk of myopathy/rhabdomyolysis with lovastatin and simvastatin ; concurrent use is contraindicated; other HMG-CoA reductase inhibitors should be initiated at the lowest recommended dose and carefully titrated.Concurrent use with nevirapine may ↓ levels/effectiveness of atazanavir and ↑ levels/risk of adverse reactions from nevirapine; concurrent use is contraindicated.↑ risk of adverse reactions including visual disturbances, hypotension, priapism and syncope with sildenafil (contraindicated when used for pulmonary hypertension).Concurrent use with indinavir in a regimen containing atazanavir ↑ risk of hyperbilirubinemia and is contraindicated.↑ risk of prolonged sedation/respiratory depression with oral midazolam and triazolam ; concurrent use is contraindicated.Concurrent use of more than one antiretroviral that requires another agent to ↑ blood levels, such as two protease inhibitors or a protease inhibitor in conjunction with elvitegravir may ↓ antiretroviral effectiveness; concurrent use is not recommended. Concurrent use of darunavir concurrently 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, saquinavir, 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 combinations due to cumulative effects on CYP3A.↑ levels of maraviroc (when used concurrently ↓ maraviroc dose to 150 mg twice daily). Anatacids ↓ absorption of atazanavir (separate doses by 2 hr).↑ level/risk of toxicity/adverse reactions with antiarrhythmics including amiodarone, digoxin, disopyrramide, flecainide, mexiletine, propafenone, and quindine ; careful monitoring and titration is recommended. Clarithromycin, erythromycin, and telithromycin may ↑ levels of ataznavir, darunavir and cobicistat; consider alternative anti-infectives.↑ blood levels/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. Effect on warfarin is not know; monitor INR.Carbamazepine and oxcarbazepine ↓ levels of cobicistat and atazanavir; consider alternative anticonvulsants or antiretroviral.May ↑ levels of clonazepam and carbamazepine ; careful anticonvulsant monitoring recommended.May ↑ levels/effects of tricyclic antidepressants and trazodone ; careful dosing of antidepressants recommended (effect on SSRIs in 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; voriconazole use not recommended. ↑ levels/risk of adverse reactions with colchicine ; concurrent use in patients with renal/hepatic impairment not recommended, for others decrease 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 flare—if dose was originally 0.6 mg twice daily, decrease to 0.3 mg once daily, if original regimen was 0.6 mg once daily, decrease to 0.3 mg every other day, treatment of familial Mediterranean fever—daily dose should not exceed 0.6 mg or 0.3 mg twice daily).↑ levels/effects/risk of adverse reaction including neutropenia and uveitis with rifabutin ; lower rifabutin dose to 150 mg every other day.↑ levels/effects of metoprolol, carvedilol, timolol, or any other beta-blockers metabolized by CYP2D6 ; clinical monitoring recommended.↑ levels/effects of amlodipine, diltiazem, felodipine, nifedipine, verapamil, or any other calcium channel blocker metabolized by CYP3A ; careful monitoring recommended.Concurrent use of dexamethasone or other corticosteroids that induce CYP3A may ↓ levels/effectiveness and ↑risk of resistance to azatanavir or darunavir (consider use of other corticosteroids).Concurrent use of corticosteroids that are metabolized by CYP3A including inhaled fluticasone and budenosde may result in ↑ steroid effects.Concurrent use with bosentan may result in ↑ levels/toxicity of bosentan and ↓ levels of atazanaivr, 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 including famotidine may decrease levels/effectiveness and ↑ risk of resistance; administer simultaneously or at least 10 hr after h2–receptor antagonist (dose of h2–receptor antagonist should not exceed famotidine 40 mg [or equivalent] twice daily in treatment-naïve patients or famotidine 20 mg [or equivalent] twice daily in treatment-experienced patients; atazanavir dose should be increased to 400 mg daily). ↑ levels/risk of toxicity from immunosuppressants metabolized by CYP3A including cyclosporine, everolimus, sirolimus, and tacrolimus ; therapeutic monitoring recommended.↑ levels of salmeterol and may ↑risk of serious adverse cardiovascular events; concurrent use is not recommended. May ↑ levels/risk of respiratory depression with opioids including buprenorphine, buprenorphine/naloxone, fentanyl, and tramadol ; carefully monitor opioid affects when cobicistat with atazanavir or darunavir is initiated, dose adjustment of opioid may be necessary.May ↑ levels/effects of neuroleptics that are metabolized by CYP3A or CYP2D6 including perphenazine, risperidone, and thioridazine ; dose decrease of neuroleptic may be necessary.May ↑ levels and risk of adverse cardiovascular, ophthalmic and genitourinary effects of PDE-5 inhibitors including avanafil, sildenafil, tadalafil, and vardenafil ; avanafil use 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 atazanvir and darunavir for at least 7 days— 20 mg once daily initially, may be titrated to 40 mg once daily, 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; verdenafil—for erectile dysfunction single dose should not exceed 2.5mg/72 hr.Proton-pump inhibitors including omeprazole ↓ levels/effectiveness and ↑risk of resistance; in treatment–naïve patients, administer cobicistat with atazanavir or darunavir at least 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/ effects and risk of excess sedation/respiratory depression from some sedative/hypnotics metabolized by CYP3A including buspirone, diazepam, and parenteral midazolam ; concurrent use with oral midazolam is contraindated, concurrent with other sedative/hypnotics metabolized by CYP3A should be undertaken with caution, dose reduction may be necessary.St. John's wort may ↓ blood levels and antiretroviral effectiveness of atazanavir or darunavir; concurrent use with a regimen including cobistat is contraindicated.
Oral (Adults (treatment-naïve or experienced) 150 mg once daily with atazanavir 300 mg once daily.with darunavir
Oral (Adults treatment-naïve, treatment-experienced with no darunavir resistance substitutions) 150 mg once daily with darunavir 800 mg once daily.
Tablets: 150 mg
- Assess patient for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
- Lab Test Considerations: Assess estimated creatinine clearance before starting therapy; cocicistat decreases estimated creatinine clearance by inhibiting tubular secretion of creatinine without affecting actual renal function.
- Assess estimated creatinine clearance, urine glucose, and urine protein if cobicistat administered with tenofovir.
- May cause ↑ total bilirubin, creatine kinase, serum amylase, ALT, AST, GGT, urine glucose and urine RBC.
Potential Nursing DiagnosesRisk for infection (Indications)
Deficient knowledge, related to medication regimen (Patient/Family Teaching)
- Oral: Administer with atazanavir or darunavir once daily with food.
- Administer antacids containing aluminum or magnesium at least 2 hr before or after cobicistat and atazanavir.
- Administer H2 receptor antagonists at same time or take cobicistat with atazanavir 10 hr after taking H2 receptor antagonists.
- Administer cobicistat and atazanavir at least 12 hr after administering proton pump inhibitors.
- Explain purpose of cobicistat to patient; cobicistat does not treat HIV and must be taken with antiretroviral medications. Instruct patient to take cobicistat as directed with food and with atazanavir or darunavir on a regular dosing schedule. Take missed doses as soon as remembered if within 12 hr; if more than 12 hr, skip dose and take next dose as scheduled; do not double doses. Do not stop taking cobicistat without consulting health care professional. Advise patient to read Patient Information prior to starting therapy and with each Rx refill in case of change. Also read Patient Information for atazanavir or darunavir.
- Instruct patient that cobicistat should not be shared with others.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's Wort. Cobicistat interacts with many other drugs. Follow instructions for specific timing of or avoiding other medications.
- Advise female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
- Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.
- Increased blood levels of atazanavir or darunavir leading to slowed progression of HIV infection and decreased occurrence of sequelae.
Drug Guide, © 2015 Farlex and Partners