- Aust Prescr 2002;25:44-7
- 1 March 2002
- DOI: 10.18773/austprescr.2002.041
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.
Agenerase (Glaxo Wellcome)
150 mg capsules, and 240 mL bottles containing 15 mg/mL oral solution
Approved indication: HIV-1
Australian Medicines Handbook Section 5.3.5
Amprenavir is the fifth protease inhibitor to be approved for use in Australia. It can be used to treat HIV infection in combination with other antiretroviral drugs, such as zidovudine and lamivudine. By inhibiting the protease in HIV-1, amprenavir results in the production of non-infectious virions.
Patients take amprenavir twice a day. As the dose is 20 mg/kg the patients need to take several capsules. The oral solution is less bioavailable than the capsules, so the doses are not equivalent. Although absorption is affected by food, amprenavir can be taken with or without food. The volume of distribution is large, but amprenavir does not greatly penetrate the blood brain barrier. Concentrations in cerebrospinal fluid are less than 1% of the plasma concentration.
Amprenavir is eliminated by hepatic metabolism and has a half-life of 7-11hours. The metabolism of amprenavir involves cytochrome CYP3A4. It therefore has many potential interactions including those with other drugs used to treat HIV. Patients taking amprenavir should not be given drugs such as midazolam, triazolam, ergot derivatives and rifampicin.
Clinical trials show that adding amprenavir to a combination of zidovudine and lamivudine in previously untreated patients is more efficacious than the combination alone. Almost 60% of patients will have concentrations of viral RNA less than 400 copies/mL after 16 weeks of treatment. An open label extension of this study resulted in 43% of the patients being at or below the target concentration after 48 weeks.1
In patients who have previously had treatment, but not with a protease inhibitor,30% will have less than 400 copies/mL after 48 weeks. If amprenavir is given to patients who have already been treated with a protease inhibitor, 34% will have less than 200 copies/mL after 24 weeks of taking the dual protease inhibitor regimen. The response rate is reduced if the patients have previously taken a non-nucleoside reverse transcriptase inhibitor.
Adverse effects are common and include nausea, vomiting and diarrhoea. Some patients will develop rashes. These usually resolve spontaneously, but the Stevens-Johnstone syndrome has been reported. Other uncommon adverse effects include lipodystrophy, hyperlipidaemia and diabetes mellitus.
The capsule formulation contains vitamin E, so patients are advised not to take supplements of vitamin E. The oral solution is not suitable for young children and pregnant women because it contains the potentially toxic propyleneglycol. This formulation is also contraindicated in patients with hepatic or renal impairment.
In patients who have not previously had a protease inhibitor as part of their treatment, indinavir may be better tolerated and have greater efficacy than amprenavir. However, it is only approved for patients who have previously been treated with a protease inhibitor. HIV can become resistant to protease inhibitors, however the profile of resistance to amprenavir differs from that of other protease inhibitors. It may therefore have a role in 'salvage therapy' when resistance to other protease inhibitors has developed