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 ivosidenib may significantly ↓ levels and effectiveness of atazanavir and cobicistat as well as significantly ↑ levels and risk of toxicity of ivosidenib; concurrent use contraindicated.
Concurrent use with encorafenib may significantly ↓ levels and effectiveness of atazanavir and cobicistat as well as significantly ↑ levels and risk of toxicity of encorafenib; concurrent use contraindicated.
Proton-pump inhibitors may ↓ absorption of atazanavir; administer 12 hr after PPI; do not use PPI doses >20 mg omeprazole or equivalent/day. Concurrent use not recommended in treatment-experienced patients.
Antacids (separate dose by 2 hr) and H2-receptor antagonists may ↓ absorption of atazanavir; separate from antacids by 2 hr. Administer at same time or ≥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).
Efavirenz or etravirine may ↓ levels and effectiveness; concurrent use not recommended.
May ↑ levels and risk of toxicity of maraviroc ; ↓ maraviroc dose to 150 mg twice daily).
Concurrent use with clarithromycin orerythromycin may ↑ levels and risk of toxicity of clarithromycin, erythromycin, atazanavir, and cobicistat; consider alternative anti-infective.
May ↑ levels and risk of bleeding with apixaban, dabigatran, edoxaban, and rivaroxaban ; concurrent use of rivaroxaban not recommended. Dose adjustments or alternatives necessary when considering use of apixaban, dabigatran, or edoxaban.
Oxcarbazepine may ↓ levels and effectiveness of atazanavir and cobicistatconsider alternative anticonvulsant.
May alter effects of antidepressants, including SSRIs, tricyclic antidepressants and trazodone ; monitor for drug effect and titrate to lowest effective dose.
Concurrent use may ↑ levels and risk of toxicity of ketoconazole and itraconazole, and voriconazole as well as those of atazanavir and cobicistat; concurrent use with voriconazole not recommended.
May ↑ levels and risk of toxicity of rifabutin ; ↓ rifabutin dose by 75%.
Concurrent use with corticosteroids, including dexamethasone, may ↓ levels and effectiveness of atazanavir and cobicistat and ↑ levels and risk of toxicity of corticosteroid; consider alternative corticosteroid, including beclomethasone, prednisone, or prednisolone.
Concurrent use with bosentan may ↑ levels and risk of toxicity of bosentan and ↓ levels and effectiveness of atazanavir and cobicistat; specific dose alteration of bosentan required.
May ↑ levels and risk of toxicity of 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.
May ↑ levels and risk of adverse cardiovascular effects of PDE-5 inhibitors, including avanafil, sildenafil, tadalafil and vardenafil ; concurrent use with avanafil not recommended; ↓ dose of sildenafil (for erectile dysfunction), tadalafil and vardenafil.
May ↑ levels and risk of toxicity of quetiapine ; ↓ 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 block.
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/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. If DRESS suspected, discontinue atazanavir/cobicistat.
Lab Test Considerations:
Monitor viral load and CD4 cell count regularly during therapy.
Monitor CCr before starting therapy and when atazanavir/cobicistat is co-administered with tenofovir disoproxil fumarate. Cobicistat causes modest ↑ serum creatinine and ↓ in estimated CCr without affecting renal glomerular function. If serum creatinine ↑ by >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 ↑ serum amylase, lipase; may also cause hyperglycemia.
Assess liver function tests before starting therapy and periodically during therapy in patients with hepatitis B or C virus infections. May ↑ liver enzymes.
May ↑ CK.
May ↑ unconjugated bilirubin; reversible on discontinuation.
Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy. 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 within 12 hr until next dose, omit dose and take next dose at regular time. Do not double doses.
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.
Advise patient that atazanavir/cobicistat should not be shared with others.
Advise patient that atazanavir/cobicistat does not cure HIV or prevent associated or opportunistic infections. Treatment may ↓ 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.
Advise patient to notify health care professional immediately if signs/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.
Advise 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 unknown.
Rep: May cause fetal harm. Advise women of reproductive potential to avoid pregnancy and breastfeeding during therapy. Instruct women using hormonal contraceptives to use an effective alternative nonhormonal method of contraception. If patient is exposed to atazanavir/cobicistat during pregnancy, 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 1st few days of life.
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.
Advise patient to notify health care professional immediately if signs/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.
Advise 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 unknown.
Rep: May cause fetal harm. Advise women of reproductive potential to avoid pregnancy and breastfeeding during therapy. Instruct women using hormonal contraceptives to use an effective alternative nonhormonal method of contraception. If patient is exposed to atazanavir/cobicistat during pregnancy, 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 1st few days of life.