Atazanavir

Indications

Atazanavir is used for: HIV-1 infection.

Adult Dose

Oral HIV-1 infection Adult: 300 mg once daily, given w/ ritonavir 100 mg. Alternatively, for treatment-naive patient: 400 mg once daily (if patient cannot tolerate ritonavir). Hepatic Impairment W/ ritonavir: Mild to severe: Contraindicated. W/o ritonavir (treatment-naive patient): Moderate (Child-Pugh category B): 300 mg daily. Severe (Child-Pugh category C): Contraindicated.

Child Dose

Oral HIV-1 infection Child: >3 mth As powd: 5-<15 kg: 200 mg once daily, given w/ ritonavir 80 mg; 15-<25 kg: 2250 mg once daily, given w/ ritonavir 80 mg. >6 yr As cap/powd: 15-<20 kg: 150 mg once daily, given w/ ritonavir 100 mg; 20-<40 kg: 200 mg once daily, given w/ ritonavir 100 mg; >40 kg: Same as adult dose.

Renal Dose

Renal Impairment Treatment-experienced patient on haemodialysis: Contraindicated.

Administration

Should be taken with food.

Contra Indications

Hypersensitivity. Treatment-experienced patient on haemodialysis. Mild to moderate (w/ ritonavir) and severe (w/ or w/o ritonavir) hepatic impairment. Lactation. Concomitant use w/ statins (e.g. simvastatin, lovastatin), antiarrhythmics (e.g. amiodarone, bepridil, quinidine, systemic lidocaine), antihistamines (e.g. astemizole, terfenadine), antipsychotics (e.g. pimozide, quetiapine), ergot derivatives (e.g. dihydroergotamine, ergometrine, ergotamine, methylergometrine), GI prokinetics (e.g. cisapride), sedative and hypnotics (e.g. triazolam, oral midazolam), alpha1-adrenergic antagonists (e.g. alfuzosin), sildenafil (for treatment of pulmonary arterial HTN), irinotecan, and indinavir.

Precautions

Patient w/ haemophilia A/B, pre-existing cardiac conduction disorder (e.g. 1st-3rd degree AV or complex bundle branch block), DM, bradycardia, long congenital QT, electrolyte imbalance. Hepatic impairment (including chronic hepatitis B or C). Pregnancy.

Pregnancy-Lactation

Pregnancy Atazanavir has been evaluated in a limited number of women during pregnancy; available human and animal data suggest that atazanavir does not increase risk of major birth defects overall compared to background rate Therapy must be administered with ritonavir in pregnant women Lactation The Centers for Disease Control and Prevention recommend that HIV-1 infected mothers not breastfeed infants to avoid risking postnatal transmission of HIV-1 Atazanavir has been detected in human milk; no data available regarding atazanavir effects on milk production; atazanavir was present in milk of lactating rats and was associated with neonatal growth retardation that reversed after weaning Because of both the potential for HIV-1 transmission and potential for serious adverse reactions in breastfed infants, advise women not to breastfeed

Interactions

Decreased concentration w/ PPIs, efavirenz, nevirapine, and rifampicin. May increase serum concentration of inhaled fluticasone and salmeterol. Potentially Fatal: Increased risk for myopathy (i.e. rhabdomyolysis) w/ simvastatin and lovastatin. Increased risk for cardiac arrhythmia w/ cisapride. May increase risk of hypotension w/ alfuzosin. May increase potential of serious AR of amiodarone, bepridil, quinidine, and systemic lidocaine. May increase serum concentration of astemizole, terfenadine, pimozide, quetiapine, dihydroergotamine, ergometrine, ergotamine, methylergometrine, triazolam, and oral midazolam. May increase risk for hypotension, visual changes, and priapism w/ sildenafil (when used for pulmonary arterial HTN). May inhibit UGT1A1 causing an increase toxicity of irinotecan. May cause indirect hyperbilirubinaemia w/ indinavir.

Adverse Effects

Side effects of Atazanavir : Incidence based on combination therapy >10% Total bilirubin increased (35-49%) Fever (19%) Rash (3-21%) Cholesterol is increased (6-25%) Nausea (4-14%) CPK increased (6-11%) Cough (21%) Diarrhea (3-11%) 1-10% Neutrophils decrease (6-10%) Jaundice (5-9%) Headache (1-7%) Peripheral neuropathy (1-4%) Insomnia (1-3%) Fever (2%) Vomiting (3-7%) Dizziness (1-2%) Myalgia (4%) Abdominal pain (2-4%) Depression (1-2%) <1% Prolonged PR interval New onset diabetes mellitus, exacerbation of diabetes mellitus & hyperglycemia

Mechanism of Action

Atazanavir, a synthetic azapeptide, is a selective, competitive, and reversible HIV-1 protease inhibitor. It inhibits the cleavage of viral Gag and Gag-Pol polyprotein precursors into individual functional proteins, preventing the processing of the polyproteins into mature and infectious virions.