Usual Adult Dose for HIV Infection

CAPSULES:
THERAPY-NAIVE PATIENTS: Atazanavir 300 mg plus ritonavir 100 mg orally once a day

• If unable to tolerate ritonavir: 400 mg orally once a day
• If used with efavirenz: Atazanavir 400 mg plus ritonavir 100 mg orally once a day

THERAPY-EXPERIENCED PATIENTS: Atazanavir 300 mg plus ritonavir 100 mg orally once a day

• If used with both an H2-receptor antagonist and tenofovir disoproxil fumarate (DF): Atazanavir 400 mg plus ritonavir 100 mg orally once a day

PREGNANT PATIENTS:
Therapy-Naive and Therapy-Experienced: Atazanavir 300 mg plus ritonavir 100 mg orally once a day

Therapy-Experienced During the Second or Third Trimester:

• If used with either an H2-receptor antagonist or tenofovir DF: Atazanavir 400 mg plus ritonavir 100 mg orally once a day
• If used with both an H2-receptor antagonist and tenofovir DF: Not recommended.

Comments:

• For patients unable to swallow the capsules, the oral powder is administered once a day with food at the same recommended dose as the capsules with ritonavir.
• This drug must be used with ritonavir during pregnancy.
• No dose adjustment needed for pregnant patients with the above exceptions.
• No dose adjustment needed for postpartum patients; close monitoring for side effects recommended (higher drug exposures possible during first 2 months after delivery).

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

Usual Adult Dose for Nonoccupational Exposure

US CDC Recommendations: Atazanavir 300 mg plus ritonavir 100 mg orally once a day
Duration of therapy: 28 days

Comments:

• If other alternative regimens for nonoccupational postexposure prophylaxis of HIV infection are considered, this drug (plus ritonavir) is recommended as a component in various regimens.
• Prophylaxis should be started as soon as possible, within 72 hours of exposure.
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Occupational Exposure

US Public Health Service Working Group Recommendations: Atazanavir 300 mg plus ritonavir 100 mg orally once a day
Duration of therapy: 28 days, if tolerated

Comments:

• This drug (plus ritonavir) is recommended as a component in various alternative regimens for HIV postexposure prophylaxis.
• Prophylaxis should be started as soon as possible, preferably within hours after exposure.
• The optimal duration of prophylaxis is unknown and may differ based on institution protocol.
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for HIV Infection

ORAL POWDER:
Therapy-Naive and Therapy-Experienced Patients:
3 months or older:

• Weight 5 to less than 15 kg: Atazanavir 200 mg plus ritonavir 80 mg orally once a day
• Weight 15 to less than 25 kg: Atazanavir 250 mg plus ritonavir 80 mg orally once a day
• Weight at least 25 kg (and unable to swallow capsule formulation): Atazanavir 300 mg plus ritonavir 100 mg orally once a day

CAPSULES:
Therapy-Naive and Therapy-Experienced Patients:
6 to less than 18 years:

• Weight at least 15 to less than 35 kg: Atazanavir 200 mg plus ritonavir 100 mg orally once a day
• Weight at least 35 kg: Atazanavir 300 mg plus ritonavir 100 mg orally once a day

Therapy-Naive Patients Unable to Tolerate Ritonavir:
13 to less than 18 years:

• At least 40 kg: 400 mg orally once a day

Comments:

• The oral powder is not recommended for patients weighing less than 5 kg.
• Only patients weighing 5 to less than 10 kg who do not tolerate 200 mg of the oral powder and have not previously used an HIV protease inhibitor may use 150 mg of the oral powder with close monitoring of HIV viral load.
• The capsules and ritonavir should be administered simultaneously with food.
• The capsules must be used with ritonavir in therapy-experienced patients.
• When switching between formulations, a dose adjustment may be needed; dosing for the specific formulation should be reviewed.

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

Renal Dose Adjustments

Without hemodialysis: No adjustment recommended.

Liver Dose Adjustments

Therapy-naive adults:

• Mild liver dysfunction (Child-Pugh A): 400 mg orally once a day
• Moderate liver dysfunction (Child-Pugh B): 300 mg orally once a day
• Severe liver dysfunction (Child-Pugh C): Not recommended.

When used with ritonavir:

• Any degree of liver dysfunction: Not recommended.

Dose Adjustments

The manufacturer product information should be consulted regarding coadministration with acid-reducing agents (e.g., H2-receptor antagonists, proton-pump inhibitors) and other antiretroviral drugs (e.g., efavirenz, tenofovir DF, didanosine).

Precautions

CONTRAINDICATIONS:

• Prior clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, toxic skin eruptions) to the active component or 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 where significant decreases in atazanavir plasma levels may occur, which may result in loss of virologic response and possible resistance
• With or without ritonavir: Coadministration with St. John's wort, rifampin, alfuzosin, irinotecan, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, pimozide, oral midazolam, triazolam, elbasvir-grazoprevir, glecaprevir-pibrentasvir, lovastatin, simvastatin, indinavir, nevirapine, sildenafil (for treatment of pulmonary arterial hypertension)
• With ritonavir: Coadministration with lurasidone

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

ESRD Managed with Hemodialysis:

• Therapy-naive patients: Atazanavir 300 mg plus ritonavir 100 mg orally once a day
• Therapy-experienced patients: Not recommended.

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.
• Perform hepatic laboratory testing in patients with underlying liver disease before starting this drug and continue during therapy.
• Use in combination with other antiretroviral drugs.
• Administer the capsules and oral powder with food; maintain adequate hydration.
• Do not open the capsules.
• Do not use the capsule formulation without ritonavir in therapy-experienced patients with previous virologic failure.
• Do not use the oral powder formulation without ritonavir; administer the oral powder after mixing with food or beverage and administer ritonavir immediately after that.
• Administer the entire dose of the oral powder (mixed with food or beverage) within 1 hour of preparation; ensure patient eats or drinks all the food or beverage containing the powder (including residual mixture); may give more food after the entire mixture has been consumed
• For infants younger than 6 months who cannot eat solid food or drink from a cup: Use an oral dosing syringe to administer the oral powder mixed with infant formula; do not use an infant bottle as the full dose may not be delivered.
• Dose depends on treatment history of patient and use of concomitant drugs; dose separation may be necessary 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:

• Oral powder: Store below 30C (86F) in the original packet (do not open until ready to use); once mixed with food or beverage, may keep at 20C to 30C (68F to 86F) for up to 1 hour before administration

Reconstitution/preparation techniques:

• The oral powder should preferably be mixed with food such as applesauce or yogurt; may mix with a beverage (milk, infant formula, water) for infants who can drink from a cup; for infants younger than 6 months who cannot eat solid food or drink from a cup, should mix with infant formula.
• The manufacturer product information should be consulted for further guidance preparing the oral powder.

General:

• Use of atazanavir/ritonavir in therapy-experienced patients should be guided by the number of baseline primary protease inhibitor resistance substitutions.
• Use of ritonavir doses greater than 100 mg/day is not recommended (higher doses may alter the safety of this drug); the manufacturer product information for ritonavir should be consulted.
• Each packet of the oral powder contains 50 mg of atazanavir and 35 mg of phenylalanine.

Monitoring:

• Cardiovascular: ECG in patients with preexisting conduction disorders
• General: For side effects in postpartum patients (at least first 2 months after delivery)
• 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); for severe hyperbilirubinemia in all infants (first few days of life)
• Renal: Renal laboratory testing, including serum creatinine, estimated CrCl, and urinalysis with microscopic examination, in all patients (before starting and during therapy)

Patient advice:

• Read the US FDA-approved patient labeling (Patient Information and Instructions for Use).
• This drug may cause changes in ECG (e.g., PR prolongation); consult healthcare provider if dizziness/lightheadedness occurs.
• Stop this drug and seek medical evaluation at once if signs/symptoms of severe skin reactions or hypersensitivity reactions develop.
• Drink plenty of fluids while using this drug.
• Notify healthcare provider at once of any symptoms of infection.