Metabolism and Excretion: Primarily metabolized in this liver via the CYP3A isoenzyme, and to a lesser extent by the CYP2D6 isoenzyme; 86.2% excreted in feces, 8.2% excreted in urine.
Concurrent use with other antiretrovirals that require inhibition of CYP3A for adequate exposure especially protease inhibitors (may ↓ antiretroviral effectiveness).
Absorption of atazanavir may be ↓ by proton-pump inhibitors (administer 12 hr after PPI, dose should not >20 mg omeprazole or equivalent/day, not recommended in treatment-experienced patients), antacids (separate dose by 2 hr), buffered medications, H2 -receptor antagonists (administer famotidine at same time or at least 10 hr after famotidine [dose should not exceed famotidine 40 mg twice daily or equivalent in treatment-naïve patients or 20 mg twice daily or equivalent in treatment-experienced patients]).
Concurrent use with efavirenz or etravirine may ↓ levels and effectiveness (concurrent use is not recommended).
↑ levels of maraviroc (↓ dose of maraviroc to 150 mg twice daily).
↑ levels and risk of adverse reactions from clarithromycin and erythromycin ; concurrent use may also ↑ levels of atazanavir and cobicistat; consider alternative anti-infectives.
↑ levels and risk of bleeding with apixaban, dabigatran, edoxaban, and rivaroxaban (concurrent use of rivaroxaban not recommended, dose adjustments or alternatives necessary for apixaban, dabigatran, or edoxaban).
Levels and effectiveness may be ↓ by oxcarbazepine ; monitor levels and clinical response carefully, consider alternative anticonvulsants.
May ↑ or alter effects of antidepressants including SSRIs, tricyclic antidepressants and trazodone (monitor for drug effect and titrate to lowest effective dose).
↑ levels of ketoconazole and itraconazole (voriconazole not recommended unless benefits outweigh risks); ketoconazole and itraconazole may also ↑ levels of atazanavir and cobicistat.
↑ levels and risk of toxicity with rifabutin (↓ dose by 75% and monitor for adverse reactions).
↑ levels and risk of adverse reactions with beta-blockers metabolized by CYP2D6 including carvedilol, metoprolol and timolol (clinical monitoring for adverse cardiovascular effects recommended).
↑ levels and risk of adverse reactions with calcium channel blockers metabolized by CYP3A including amlodipine, diltiazem, felodipine, nifedipine and verapamil (clinical monitoring for adverse cardiovascular effects recommended).
Concurrent use with corticosteroids that induce CYP3A, including dexamethasone, ↓ effectiveness and ↑ corticosteroid effects (consider alternative corticosteroid).
Levels and effectiveness may be ↓ by bosentan while effects of bosentan are ↑ (specific dose alteration of bosentan is required).
↑ levels and risk of toxicity from atorvastatin, fluvastatin, pravastatin and rosuvastatin ; concurrent use with atorvastatin not recommended; rosuvastatin dose should not exceed 10 mg/day; for other statins, use lowest effective dose and monitor for adverse effects.
↑ risk of adverse cardiovascular effects with inhaled salmeterol (concurrent use not recommended.
↑ risk of corticosteroid effects with corticosteroids metabolized by CYP3A; consider alternative corticosteroids, including beclomethasone, prednisone, or prednisolone.
May ↑ CNS and respiratory depression with opioid analgesics or tramadol (dose reduction and careful titration recommended).
May ↑ levels and risk of adverse reactions with neuroleptics metabolized by CYP3A or CYP2D6 including perphenazine, risperidone and thioridazine (dose reduction may be necessary).
↑ levels and risk of adverse cardiovascular effects with PDE-5 inhibitors including avanafil, sildenafil, tadalafil and vardenafil (avanafil use not recommended, dose reductions required for sildenafil (for erectile dysfunction), tadalafil and vardenafil).
May ↑ quetiapine levels; ↓ quetiapine dose to 1/6 of current dose
Assess for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
Monitor ECG periodically in patients with first, second, or third-degree AV blocks.
Assess for rash which can occur within initial 8 wk of therapy. Usually resolves within 2 wk without altering therapy. Discontinue therapy if rash becomes severe.
Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling, associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.
Lab Test Considerations:
Monitor viral load and CD4 cell count regularly during therapy.
Monitor CCr prior to starting therapy and when atazanavir/cobicistat is co-administered with tenofovir disoproxil fumarate. Cobicistat causes modest ↑ serum creatinine and declines in estimated creatinine clearance without affecting renal glomerular function. If serum creatinine ↑ >0.4 mg/dL from baseline, monitor renal frequently.
Monitor urine glucose and urine protein when administering with tenofovir disoproxil fumarate at baseline and periodically during therapy. May cause ↑ serum amylase, lipase and hyperglycemia.
Assess liver function tests prior to starting therapy and periodically during therapy in patients with hepatitis B or C virus infections. May ↑ liver enzymes.
May ↑ CK.
May cause ↑ in unconjugated bilirubin; reversible on discontinuation.
Emphasize the importance of taking atazanavir/cobicistat with food as directed. Advise patient to read the Patient Information before taking and with each Rx refill; in case of changes. Atazanavir/cobicistat must always be used in combination with other antiretroviral drugs. Do not take more than prescribed amount and do not stop taking without consulting health care professional. Take missed doses as soon as remembered if less than 12 hrs of dose, then return to regular dose schedule. If within 12 hr of next dose, omit dose and take next dose at regular time. Do not double doses.
Instruct patient that atazanavir/cobicistat should not be shared with others.
Inform patient that atazanavir/cobicistat does not cure HIV or prevent associated or opportunistic infections. Atazanavir/cobicistat may reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom and to avoid sharing needles or donating blood to prevent spreading the HIV virus to others.
Instruct 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; interactions may be fatal.
May cause dizziness. Caution patient to notify health care professional if this occurs and to avoid driving and other activities requiring alertness until response to medication is known.
Instruct patient to notify health care professional immediately if signs and symptoms of hepatitis (flu-like symptoms, tiredness, nausea, lack of appetite, yellow skin or eyes, dark urine, pale stools, pain or sensitivity to touch on right side below ribs), skin reactions with symptoms (fever, general malaise, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema), gallbladder disorder (right or middle upper stomach pain, fever, nausea, vomiting, or yellowing of skin and whites of eyes), kidney stones (side pain, blood in urine, pain upon urination), change in heart rhythm, high blood sugar, or signs of immune reconstitution syndrome (signs and symptoms of an infection) occur.
Inform patient that redistribution and accumulation of body fat may occur, causing central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance. The cause and long-term effects are not known.
Rep: May cause fetal harm. Advise females of reproductive potential to avoid pregnancy and breastfeeding during therapy. Instruct females using hormonal contraceptives to use an effective alternative nonhormonal method of contraception. Advise patient to notify health care professional immediately if pregnancy is planned or suspected or if breastfeeding. If pregnant patient is exposed to atazanavir/cobicistat, register patient in Antiretroviral Pregnancy Registry by calling 1-800-258-4263. Monitor neonates exposed to atazanavir in utero for development of severe hyperbilirubinemia during first few days of life.
Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.