Usual Adult Dose for HIV Infection

1 tablet orally once a day with food

Comments:

• For therapy-naive and therapy-experienced patients
• The number of baseline primary protease inhibitor resistance substitutions should guide use in therapy-experienced patients.
• Use of this drug during pregnancy results in considerably lower exposures of cobicistat (and thus lower exposures of atazanavir) during the second and third trimesters. This drug is not recommended for use during pregnancy and should not be started in pregnant patients; an alternative regimen is recommended for patients who become pregnant during therapy with this drug.

Use: In combination with other antiretroviral agents, for the treatment of HIV-1 infection

Usual Pediatric Dose for HIV Infection

At least 35 kg: 1 tablet orally once a day with food

Comments:

• For therapy-naive and therapy-experienced patients
• The number of baseline primary protease inhibitor resistance substitutions should guide use in therapy-experienced patients.
• Use of this drug during pregnancy results in considerably lower exposures of cobicistat (and thus lower exposures of atazanavir) during the second and third trimesters. This drug is not recommended for use during pregnancy and should not be started in pregnant patients; an alternative regimen is recommended for patients who become pregnant during therapy with this drug.

Use: In combination with other antiretroviral agents, for the treatment of HIV-1 infection

Renal Dose Adjustments

Data not available

When used with tenofovir disoproxil fumarate (DF):

• Estimated CrCl less than 70 mL/min: Not recommended.
• In combination with concomitant or recent use of nephrotoxic agent: Not recommended.

Liver Dose Adjustments

Any degree of liver dysfunction: Not recommended.

Precautions

CONTRAINDICATIONS:

• Previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, toxic skin eruptions) to either active component or to any of the ingredients
• Coadministration with drugs highly dependent on CYP450 3A or UGT1A1 for clearance and for which elevated plasma levels are associated with serious and/or life-threatening events
• Coadministration with strong CYP450 3A inducers that may result in lower exposure and loss of efficacy of this drug
• Due to potential for serious and/or life-threatening events or loss of therapeutic effect, coadministration with alfuzosin, ranolazine, dronedarone, carbamazepine, phenobarbital, phenytoin, colchicine (in patients with renal and/or liver dysfunction), rifampin, irinotecan, lurasidone, pimozide, oral midazolam, triazolam, dihydroergotamine, ergotamine, methylergonovine, cisapride, elbasvir-grazoprevir, glecaprevir-pibrentasvir, St. John's wort, lomitapide, lovastatin, simvastatin, drospirenone-ethinyl estradiol, nevirapine, indinavir, sildenafil (for treatment of pulmonary arterial hypertension)

Safety and efficacy have not been established in pediatric patients weighing less than 35 kg; this drug is not recommended for use in patients younger than 3 months (due to risk of kernicterus).

Consult WARNINGS section for additional precautions.

Dialysis

Therapy-experienced patients with HIV-1 infection who have ESRD managed with hemodialysis: Not recommended.

Comments:

• The components of this drug are highly protein-bound; significant removal via hemodialysis or peritoneal dialysis is not likely.

Other Comments

Administration advice:

• Perform renal laboratory testing (including serum creatinine, estimated CrCl, and urinalysis with microscopic examination) in all patients before starting this drug and continue during therapy.
• When used with tenofovir DF, assess estimated CrCl, urine glucose, and urine protein at baseline then monitor routinely during therapy; in patients with chronic kidney disease, also monitor serum phosphorus.
• Perform hepatic laboratory testing in patients with underlying liver disease before starting this drug and continue during therapy.
• Use in combination with other antiretroviral agents.
• Administer with food; maintain adequate hydration.
• Dose separation may be necessary when coadministered with H2-receptor antagonists or proton-pump inhibitors; consult the manufacturer product information for further guidance.
• Consult the manufacturer product information regarding missed doses.

Storage requirements:

• Store at 25C (77F); excursions permitted to 15C to 30C (59F to 86F).
• Keep bottle tightly closed.

General:

• Each fixed-dose combination tablet contains atazanavir 300 mg and cobicistat 150 mg.
• Cobicistat decreases estimated CrCl; it inhibits tubular secretion of creatinine without affecting actual renal glomerular function.

Monitoring:

• Cardiovascular: ECG in patients with preexisting conduction disorders
• Hepatic: Hepatic laboratory testing in patients with underlying liver disease (before starting and during therapy); hepatic laboratory tests in patients with HBV, HCV, or marked transaminase elevations at baseline (before starting and during therapy)
• Metabolic: Serum phosphorus in patients with chronic kidney disease (when used with tenofovir DF)
• Renal: Renal laboratory testing, including serum creatinine, estimated CrCl, and urinalysis with microscopic examination, in all patients (before starting and during therapy); for renal safety (if serum creatinine increases more than 0.4 mg/dL from baseline); estimated CrCl, urine glucose, and urine protein (at baseline and routinely during therapy [when used with tenofovir DF])

Patient advice:

• Read the US FDA-approved patient labeling (Patient Information).
• Take this drug with food on a regular dosing schedule; do not miss or skip doses as resistance may develop. Do not stop therapy without consulting healthcare provider.
• Patients of childbearing potential: If taking hormonal contraceptives, use additional or alternative nonhormonal contraceptive measures during therapy; if you become pregnant during therapy, notify healthcare provider.
• This drug may cause changes in ECG (e.g., PR prolongation); consult healthcare provider if dizziness/lightheadedness occurs.
• Seek medical evaluation at once if signs/symptoms of severe skin reactions or hypersensitivity reactions develop (including, but not limited to, severe rash or rash with fever, general malaise, muscle/joint aches, blisters, oral lesions, conjunctivitis, facial edema).
• Drink plenty of fluids while using this drug.
• Notify healthcare provider at once of any symptoms of infection.