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.
Peg-Intron (Schering-Plough)
vials containing 50, 80, 100, 120 and 150 microgram as powder for injection
Approved indication: chronic hepatitis C
Australian Medicines Handbook section 14.2.2
The treatment of choice for chronic hepatitis C is ribavirin in combination with interferon alfa-2b.1 This interferon has to be given by injection three times a week. To reduce the frequency of injections interferon alfa-2b has been conjugated with polyethylene glycol to produce peginterferon which has a reduced renal clearance.
Peginterferon is injected once a week. The site of the subcutaneous injection should be varied with each dose. Plasma concentrations reach a maximum 15-44 hours after the injection and are sustained for 48-72 hours. The elimination half-life of interferon alfa-2b is about seven hours and renal clearance accounts for 80% of the total clearance. Conjugation with polyethylene glycol reduces renal clearance to 30% of the total and increases the elimination half-life to 40 hours.
The efficacy of peginterferon has been assessed in 1219 previously untreated patients with chronic hepatitis C confirmed by liver biopsy. Patients were randomised to receive interferon alfa-2b three times a week or a weekly injection of one of three different doses of peginterferon. They were treated for 48weeks. Six months after completing treatment, 12% of the patients taking interferonalfa-2b had undetectable concentrations of hepatitis C RNA and normal concentrations of alanine aminotransferase (see 'Hepatitis C: diagnosis and monitoring' Aust Prescr 1999;22:91-4). This response was significantly less than the 18-25% of the patients who responded to peginterferon.
Although all the doses of peginterferon were efficacious, the recommended dose is 0.5 microgram/kg. The dose may be doubled for patients infected with genotype 1 virus. (This genotype is associated with a poor response to interferon.)If the virus is still present after six months of treatment, peginterferon should be stopped.
Peginterferon causes more injection site reactions than interferon alfa-2b,but overall the pattern of adverse reactions is similar. Common complaints are flu-like symptoms in the first few weeks of treatment, headache, tiredness, myalgia and fevers. As granulocytopenia occurs in 4-7% of cases, patients with fever require investigation. Thrombocytopenia can also occur. Patients should have their eyes examined before treatment as the interferons can cause ophthalmological problems such as retinal haemorrhages. Interferon alfa-2b may also exacerbate psoriasis. Some patients develop depression during treatment, so a previous history of a serious psychiatric condition is a contraindication to treatment. While peginterferon is used to treat chronic hepatitis, it is not recommended for patients with severe hepatic dysfunction.
Although more patients respond to peginterferon than interferon alfa-2b the response rate is much lower than the 43% seen with the combination of interferonalfa-2b and ribavirin.1 Another trial therefore studied the effectiveness of peginterferon in combination with ribavirin.
This open trial randomised 1530 previously untreated patients to take either interferon alfa-2b and ribavirin or one of two regimens of peginterferon alfa-2band ribavirin. The patients were treated for 48 weeks then followed up for another 24 weeks. Viral RNA was undetectable in 47% of the patients given interferonalfa-2b or the lower dose regimen of peginterferon alfa-2b. In patients who had taken a higher dose (1.5 microgram/kg/week) of peginterferon the response was 54% - a statistically significant advantage. This regimen was also advantageous for patients with the genotype 1 virus. A sustained virological response was found in 42% compared with 33% of the patients given interferon alfa-2b. The higher dose, however, resulted in more frequent adverse reactions including neutropenia.2
Although the high dose regimen produces a bigger response in patients with genotype 1 virus it has no significant advantage over lower doses or interferonalfa-2b for patients infected with other genotypes. Identifying the best regimen will require further research to clarify the most effective dose of ribavirin. Despite these issues, the combination of peginterferon alfa-2b and ribavirin may become the treatment of choice for chronic hepatitis C, if it is found to be cost-effective.
