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.

Pegasys (Pegasys-RBV) (Roche)

Pre-filled syringes containing 135 microgram/0.5 mL and 180 microgram/0.5 mL

(Pegasys-RBV is packaged as pre-filled syringes with 200 mg tablets of ribavirin)

Approved indication: chronic hepatitis C

Australian Medicines Handbook section 14.2.2

The interferons are cytokines which can enhance the immune response. They have been used to treat patients with hepatitis to try and halt the progression to cirrhosis. To prolong the effect of a dose of interferon the genetically engineered molecule has been conjugated to polyethylene glycol. Peginterferon alfa-2b and ribavirin is an effective combination for treating chronic hepatitis C.1

Peginterferon alfa-2a has also been studied as a treatment for hepatitis C. One trial compared weekly injections of peginterferon alfa-2a with thrice weekly interferon alfa-2a in 531 previously untreated patients. After 48 weeks of treatment and a further 24 weeks of follow-up, 38% of the peginterferon group and 17% of the interferon group had normal aminotransferase concentrations and no detectable viral RNA. Liver biopsies showed a response in 63% of the peginterferon group and 55% of the interferon group.2

Peginterferon alfa-2a has also been compared with interferon alfa-2b. All 444 patients randomised to take interferon alfa-2b and 453 of the patients randomised to take peginterferon alfa-2a also received ribavirin. The other 224 patients took peginterferon alfa-2a and a placebo for up to 48 weeks. When the patients were assessed at 72 weeks, 56% of the patients treated with peginterferon alfa-2a and ribavirin had no detectable viral RNA. This was significantly greater than the sustained virological response seen in patients taking a placebo (29%) or interferon alfa-2b and ribavirin (44%). 3The sustained response rate in patients with genotype 1 virus was lower (46%), but still significantly greater than in the other groups.

Doses of peginterferon alfa-2a are injected subcutaneously into the abdomen or thigh. The serum concentration peaks after 6-8 days and accumulates during the first two months of treatment. As the half-life is 50-130 hours the serum concentrations are sustained between each weekly injection.

Injection site reactions are among the many common adverse reactions reported in clinical trials. Other common complaints are fever, fatigue, myalgia and headache. Treatment was discontinued by 22% of the patients taking peginterferon alfa-2a with ribavirin and 32% of these withdrawals were because of adverse events. Laboratory abnormalities accounted for another 12% of withdrawals. 3These abnormalities included neutropenia and thrombocytopenia, so it is important that haematological and biochemical tests are monitored during treatment. Peginterferon alfa-2a may also alter thyroid function and exacerbate autoimmune disease. It can also cause depression and patients' quality of life reduces during the 48 weeks of treatment.

While peginterferon alfa-2a may be superior to interferon alfa-2b 3, peginterferon alfa-2b can also induce sustained virological responses in more than 50% of patients 1so a direct comparison of their effectiveness would be useful. Both drugs should be used in combination with ribavirin unless ribavirin is contraindicated or not tolerated. Even if the treatment is tolerated, it should probably be stopped if it has not significantly reduced viral RNA within 12 weeks.