HIV infection (in combination with other antiretrovirals).
- Atazanavir–Inhibits the action of HIV protease, preventing maturation of virions.
- Cobicistat–↑ blood levels of atazanavir .
↑ CD4 cell counts and ↓ viral load with subsequent slowed progression of HIV and its sequelae.
Absorption: Rapidly absorbed (↑ by food).
Distribution: Enters cerebrospinal fluid and semen.
Metabolism and Excretion: 80% metabolized (CYP3A); 13% excreted unchanged in urine.
Half-life: 7 hr.
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.
TIME/ACTION PROFILE (blood levels)
|atazanavir PO||rapid||2.5 hr||24 hr|
|cobicistat PO||unknown||3 hr||24 hr|
- Previous hypersensitivity, including Stevens-Johnson syndrome, erythema multiforme or other serious skin reactions
- Concurrent use of alfuzosin, carbamazepine, colchicine, dihydroergotamine, dronedarone, elbasvir/grazoprevir, ergotamine, indinavir, irinotecan, lovastatin, lurasidone, methylergonovine, nevirapine, phenobarbital, phenytoin, pimozide, ranolazine, rifampin, sildenafil (for pulmonary hypertension), simvastatin, St. John's wort and triazolam;
- Renal impairment (CCr <70 mL/min) (when used concomitantly with tenofovir disoproxil fumarate);
- End-stage renal disease managed by dialysis (treatment-experienced patients)
- Hepatic impairment.
Use Cautiously in:
- History of pre-existing cardiac conduction disease (marked first-degree AV block, second-or third-degree AV block; ECG monitoring recommended)
- Renal impairment (consider alterative medications)
- Hepatitis B or C co-infection (↑ risk of further hepatic impairment)
- Diabetes mellitus (↑ risk of new onset/ exacerbation)
- Hemophilia (risk of spontaneous bleeding and need for additional factor VIII)
- OB: Use during pregnancy only if potential benefits justify potential risks
- Lactation: Breastfeeding should be avoided by HIV-infected mothers;
- Pedi: Safety and effectiveness not established (use in atazanavir in infants <3 mo may ↑ risk of kernicterus).
Adverse Reactions/Side Effects
CV: cardiac conduction abnormalities
EENT: ocular icterus
GI: cholelithiasis, hepatotoxicity, hyperbilirubinemia, jaundice, nausea
GU: nephrolithiasis, new onset/worsening renal impairment
Derm: DRESS SYNDROME, ERYTHEMA MULTIFORME, STEVENS-JOHNSON SYNDROME, rash
Metabolic: accumulation/redistribution of body fat
Misc: immune reconstitution syndrome
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Carbamazepine, phenobarbital, phenytoin, rifampin and nevirapine ↓ blood levels and effectiveness; concurrent use contraindicated.
- ↑ blood levels and risk of serious toxicity with alfuzosin, dihydroergotamine, dronedarone, ergotamine, irinotecan, lovastatin, lurasidone, methylergonovine, pimozide, ranolazine, sildenafil (for pulmonary hypertension), simvastatin, and triazolam; concurrent use contraindicated.
- ↑ blood levels and risk of serious toxicity with colchicine; concurrent use contraindicated in patients with renal or hepatic impairment.
- ↑ risk of indirect hyperbilirubinemia with indinavir; concurrent use contraindicated.
- ↑ risk of hepatotoxicity with elbasvir/grazoprevir; concurrent use contraindicated.
- ↑ risk of renal impairment with tenofovir disoproxil fumarate; avoid concurrent use with nephrotoxic agents.
- Concurrent use with other antiretrovirals that require inhibition of CYP3A for adequate exposure especially protease inhibitors (may ↓ antiretroviral effectiveness).
- ↑ levels and risk of toxicity from some antiarrhythmics (including amiodarone, digoxin, disopyramide, flecainide, mexiletine and propafenone, antineoplastics (including dasatinib, nilotinib, vinblastine and vincristine), anticonvulsants metabolized by CYP3A (including clonazepam); monitor drug effects carefully, titrate if necessary and consider alternatives.
- ↑ risk of sedation with sedative/hypnotics, including buspirone, diazepam, midazolam, zolpidem and others metabolized by CYP3A (careful monitoring with dose reduction recommended).
- 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 equilvalent in treatment-experienced patients]).
- Concurrent use with didanosine (buffered)↓ atazanavir levels (administer 1 hr before or 2 hr after atazanavir/cobicistat.
- ↓ levels of concurrent didanosine EC (administer at different times).
- Concurrent use with efavirenzor etravirine may ↓ levels and effectiveness (concurrent use is not recommended).
- ↑ levels of maraviroc (↓ dose of maraviroc to 150 mg twice daily).
- Effects on simeprevirare unknown (concurrent use is not recommended).
- ↑ levels and risk of adverse reactions from clarithromyicn anderythromycin; concurrent use may also ↑ levels of atazanavir and cobicistat; consider alternative anti-infectives.
- ↑ levels and risk of bleeding with apixaban, rivaroxaban and dabigatran (concurrent use of apixaban and rivaroxaban not recommended, dose adjustments or alternatives necessary for dabigatran).
- 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 CYP3Aincluding amlodipine, diltiazem, felodipine, nifedipineand 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(use lowest effective dose, monitor for adverse effects, rosuvastatin dose not >10 mg/day).
- ↑ levels and effects of immunosuppressants including cyclosporine, everolimus, sirolimus. tacrolimus (blood level monitoring recommended).
- ↑ risk of adverse cardiovascular effects with inhaled salmeterol (concurrent use not recommended.
- ↑ risk of corticosteroid effects with inhaled/nasal corticosteroids metabolized by CYP3A including and budesonide and fluticasone (consider alternative corticosteroids).
- 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, risperidoneand thioridazine (dose reduction may be necessary).
- ↑ levels and risk of adverse cardiovascular effects with PDE-5 inhibitors including avanafil, sildenafil, tadalafiland 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
St. John's wort ↓ blood levels and effectiveness; concurrent use contraindicated.
PO: (Adults) One tablet (atazanavir 300 mg/cobicistat 150 mg) once daily.
Tablets: atazanavir 300 mg/cobicistat 150 mg
- Assess for change in severity of HIV symptoms and for symptoms of opportunistic infections throughout 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.
Lab Test Considerations: Monitor creatinine clearance 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 ↑ creatine kinase.
- May cause ↑ in unconjugated bilirubin; reversible on discontinuation.
- PO: Administer once daily with food.
- Take with other antiretroviral agents as prescribed.
- 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 does not 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.
- Instruct females using hormonal contraceptives to use an alternative nonhormonal method of contraception. Advise patient to notify health care professional 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.
- Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.
- Delayed progression of HIV and decreased opportunistic infections in patients with HIV.
- Decrease in viral load and increase in CD4 cell counts.
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