Atazanavir sulfate

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Reyataz (Bristol-Myers Squibb)

150 mg and 200 mg capsules

Approved indication: HIV infection

Australian Medicines Handbook section 5.3.4

HIV infections are best managed with combinations of antiviral drugs.1 As treatment may involve taking medication several times a day, there is an interest in simpler regimens. Atazanavir is a protease inhibitor which only needs to be taken once a day.

The daily dose should be taken with food as this increases bioavailability. Steady state concentrations are reached in 4-8 days. Most of the dose is metabolised and then excreted in the faeces.

A dose-ranging study compared atazanavir with nelfinavir in previously untreated patients. The 467 patients also received lamivudine and stavudine. After 48 weeks approximately 35% of all patients had less than 50 copies of viral RNA/mL and CD4 cell counts had increased.2

Another study compared atazanavir with nelfinavir in 420 previously untreated patients who were also given didanosine and stavudine. After 48 weeks 36% of the patients taking 400 mg atazanavir daily and 39% of those taking nelfinavir had less than 50 copies of viral RNA/mL. CD4 cell counts increased in all treatment groups.3

In patients who have previously been treated with a regimen containing a protease inhibitor, atazanavir may be less effective than adding lopinavir and ritonavir to therapy with two nucleoside reverse transcriptase inhibitors. After 48 weeks 35% of the 144 patients taking atazanavir had less than 50 copies of viral RNA/mL compared with 53% of the 146 patients taking lopinavir and ritonavir.

If atazanavir is used in a combination with ritonavir a lower dose is prescribed because of a drug interaction. As atazanavir is metabolised by cytochrome P450 3A4 it has the potential for several other interactions. It should not be prescribed with calcium channel blockers, HMG-CoA reductase inhibitors ('statins'), ergot derivatives, sildenafil, midazolam and triazolam.

Atazanavir inhibits an enzyme involved in bilirubin conjugation. Many patients will therefore have elevated bilirubin concentrations and up to 11% may develop jaundice while taking atazanavir 400 mg daily.2

Other adverse effects reported in clinical trials include nausea, rashes and heart block. Hyperlipidaemia may be less of a problem than it is with other protease inhibitors. As with other protease inhibitors, HIV can become resistant to atazanavir.

While atazanavir does have the advantage of a single daily dose, the best use of the drug in combination regimens, particularly in previously treated patients, will require further study.


  1. Palmer C. HIV treatments and highly active antiretroviral therapy. Aust Prescr 2003;26:59-61.
  2. Murphy RL, Sanne I, Cahn P, Phanuphak P, Percival L, Kelleher T, et al. Dose-ranging, randomized, clinical trial of atazanavir with lamivudine and stavudine in antiretroviralnaive subjects: 48-week results. AIDS 2003;17:2603-14.
  3. Sanne I, Piliero P, Squires K, Thiry A, Schnittman S. Results of a phase 2 clinical trial at 48 weeks (AI424-007): a dose-ranging, safety, and efficacy comparative trial of atazanavir at three doses in combination with didanosine and stavudine in antiretroviral-naive subjects. J AIDS 2003;32:18-29.