REYATAZ

What it is

REYATAZ contains atazanavir sulfate as the active ingredient, available in capsules of 150 mg, 200 mg or 300 mg. REYATAZ capsules must be taken with food and should be taken whole.

Approved indications

— HIV-1 infection, in combination with other antiretroviral agents.

Dosing overview

For therapy-naïve adult patients, the recommended dose is atazanavir 400 mg once daily or atazanavir 300 mg with ritonavir 100 mg once daily. For therapy-experienced adult patients, the recommended dose is atazanavir 300 mg with ritonavir 100 mg once daily. For paediatric patients aged 6 to 18 years, dosing depends on body weight: patients weighing 15 to less than 35 kg receive atazanavir 200 mg with ritonavir 100 mg once daily; those weighing at least 35 kg receive atazanavir 300 mg with ritonavir 100 mg once daily. For treatment-naïve patients aged at least 13 years and at least 40 kg who are unable to tolerate ritonavir, the recommended dose is atazanavir 400 mg without ritonavir once daily with food.

Key safety warnings

Most patients taking REYATAZ experience asymptomatic elevations in indirect (unconjugated) bilirubin, which may be associated with scleral icterus and jaundice in some patients. This isolated hyperbilirubinaemia is reversible upon discontinuation of atazanavir. Alternative antiretroviral therapy to atazanavir may be considered if jaundice or scleral icterus associated with bilirubin elevations presents cosmetic concerns for patients. REYATAZ has been shown to prolong the PR interval of the electrocardiogram in some patients. In healthy volunteers and in patients, abnormalities in atrioventricular (AV) conduction were asymptomatic and generally limited to first-degree AV block. There have been rare reports of second-degree AV block and other conduction abnormalities and no reports of third-degree AV block. Because of limited clinical experience, atazanavir should be used with caution in patients with pre-existing conduction system disease. In controlled clinical trials, rash (all grades, regardless of causality) occurred in 21% of patients treated with atazanavir. Rashes are usually mild-to-moderate maculopapular skin eruptions that occur within the first 3 weeks of initiating therapy. In most patients, rash resolves within 2 weeks while continuing atazanavir therapy. Cases of Stevens-Johnson syndrome, erythema multiforme, and toxic skin eruptions including drug rash, eosinophilia, and systemic symptoms (DRESS) syndrome have been reported in patients receiving atazanavir. Patients should be advised of the signs and symptoms and monitored closely for skin reactions. Cases of lactic acidosis, sometimes fatal, and symptomatic hyperlactatemia have been reported in patients receiving atazanavir in combination with nucleoside analogues, which are known to be associated with increased risk of lactic acidosis. In studies where didanosine and stavudine were administered with atazanavir to patients without prior antiretroviral therapy, lactic acidosis/symptomatic hyperlactatemia was observed in 2.2% of subjects. Chronic kidney disease in HIV-infected patients treated with atazanavir, with or without ritonavir, has been reported during post-marketing surveillance. Atazanavir should be used with caution, particularly in those patients with other risk factors for chronic kidney disease.

Contraindications

Hypersensitivity to atazanavir or to any of the excipients. Patients with severe hepatic insufficiency. REYATAZ is contraindicated in combination with: rifampicin, lurasidone, simvastatin or lovastatin, lomitapide, medicinal products that are substrates of the CYP3A4 isoform of cytochrome P450 and have narrow therapeutic windows, products containing St. John's wort, alfuzosin, salmeterol, and elbasvir/grazoprevir. Glecaprevir/pibrentasvir is contraindicated because co-administration may result in increased ALT elevations due to an increase in glecaprevir and pibrentasvir plasma concentrations. The PDE5 inhibitor sildenafil when used for the treatment of pulmonary arterial hypertension is contraindicated.

PBS listing

REYATAZ 300 mg capsules are listed on the PBS as 1 item with streamlined restriction at an ex-manufacturer price of A$300.43. REYATAZ 200 mg capsules are listed on the PBS as 1 item with streamlined restriction at an ex-manufacturer price of A$400.59.

Regulatory history

REYATAZ 200 mg capsules were first listed on the ARTG on 12 January 2004, and REYATAZ 300 mg capsules were first listed on 14 August 2007. The TGA approved a major variation to REYATAZ on 17 July 2013, involving changes to the paediatric dosage regimen and updates to the Product Information. This decision allowed for simplified dosing recommendations for HIV-infected paediatric patients, lowering the age limit and revising weight restrictions.