ATAZANAVIR SULFATE (atazanavir sulfate)

There are 0 contraindications.

There are 5 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Hemophilia
Kidney stone
Lactic acidosis
Prolonged PR interval

There are 6 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Atrioventricular block
Biliary calculus
Chronic hepatitis B
Chronic hepatitis C
Diabetes mellitus
Hyperbilirubinemia

There are 36 severe adverse reactions.

More Frequent	Less Frequent
None.	None.

Rare/Very Rare

Abnormal hepatic function tests Acute pancreatitis Angioedema Atrioventricular block Autoimmune hepatitis Biliary calculus Cholecystitis Cholestasis Diabetes mellitus Dream disorder DRESS syndrome Dysgeusia Eczema Edema Eosinophilia Erythema multiforme Flatulence Graves' disease Guillain-barre syndrome Gynecomastia Hematuria Hyperglycemia Interstitial nephritis Kidney disease with reduction in glomerular filtration rate (GFr) Kidney stone Left bundle branch block Palpitations Polymyositis Proteinuria Renal pain Sleep disorder Splenomegaly Stevens-johnson syndrome Syncope Thrombocytopenic disorder Xerostomia

There are 23 less severe adverse reactions.

More Frequent	Less Frequent
Acute abdominal pain Depression Diarrhea Dizziness Fever Headache disorder Hyperbilirubinemia Insomnia Jaundice Lipodystrophy associated with human immunodeficiency virus infection Myalgia Nausea Peripheral neuropathy Scleral icterus Skin rash Vomiting	Pain

Rare/Very Rare
Alopecia Arthralgia Hypertriglyceridemia Maculopapular rash Prolonged PR interval Pruritus of skin

The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to atazanavir during pregnancy. Clinicians are encouraged to register patients in the APR by calling 800-258-4263 or visiting https://www.apregistry.com/.

Atazanavir has been evaluated in a limited number of women during pregnancy. Available human and animal data suggest that atazanavir does not increase the risk of major birth defects overall compared to the background rate. No treatment-related malformations were observed in rats and rabbits using dosages that resulted in atazanavir exposures 0.7-1.2

times those reported with the usual human dosage of ritonavir-boosted atazanavir (300 mg of atazanavir once daily with ritonavir 100 mg once daily). Based on prospective reports from the APR of approximately 1600 live births following exposure to atazanavir-containing antiretroviral regimens during pregnancy (including 1037 first-trimester exposures), there was no difference in the rate of overall birth defects in those exposed to atazanavir-containing regimens compared with the estimated background risk of major birth defects (2-4% in the US population). Dosage adjustments may be necessary in certain pregnant women.

Lactic acidosis, sometimes fatal, and symptomatic hyperlactatemia have occurred in pregnant patients receiving atazanavir in conjunction with NRTIs. Hyperbilirubinemia has occurred in pregnant patients receiving atazanavir. Advise pregnant patients of the potential risks of lactic acidosis syndrome and hyperbilirubinemia. Closely monitor postpartum women for adverse effects during the first 2 months after delivery since atazanavir concentrations and AUC may be increased approximately 28-43% during the postpartum period (4-12 weeks).

Atazanavir is distributed into human milk. It is not known whether atazanavir affects human milk production. Atazanavir is distributed into milk in rats and was associated with neonatal growth retardation that reversed after weaning.

The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding. The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant.

Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.

The manufacturer makes no specific dosage recommendations for geriatric patients. Exercise caution in administration and monitoring because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy. Experience in patients >=65 years of age is insufficient to determine whether they respond differently to atazanavir than younger adults.

Exercise caution in administration and monitoring because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease or drug therapy in geriatric patients. No clinically important differences in pharmacokinetics of atazanavir have been reported in those >65 years of age compared with younger adults.