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.
Norvir (Abbott Australasia)
100 mg capsules
Indication: HIV infection
The approval of ritonavir adds to the choice of HIV protease inhibitors in Australia. While most of the efficacy data for this class of drugs are based on surrogate markers, there is some evidence that ritonavir reduces mortality.
The drug acts by inhibiting the HIV-1 protease. This results in the formation of non-infectious HIV particles. The drug is metabolised with most of each dose being excreted in the faeces. Only 4% is excreted unchanged in the urine.
Several studies, including an Australian study1,show that treatment with ritonavir increases the number of lymphocytes. Inpatients who have not previously taken antiretroviral drugs, ritonavir has a greater effect than zidovudine. Ritonavir alone also appears to be more effective than a combination with zidovudine. For patients with advanced disease, one study, with a median duration of 6 months, has found a reduction in mortality and clinical progression of HIV disease. During the study, 26 (4.8%) of the543 patients who had ritonavir added to their therapy died, compared with 46(8.4%) of the 547 who had a placebo added.
One of the problems with treating HIV is the development of resistant strains. While ritonavir and other HIV protease inhibitors are unlikely to develop cross-resistance with reverse transcriptase inhibitors, it is not known if cross-resistance will develop between the protease inhibitors. Viral clones with reduced susceptibility to ritonavir have already been isolated.
The long-term effects of ritonavir are not known, but several adverse effects are associated with treatment. Common adverse effects are vomiting, diarrhoea, asthenia and paraesthesia. Nausea is the most frequent adverse reaction and is moderate or severe in at least 25% of patients. Ritonavir increases the concentrations of triglycerides and liver enzymes. The metabolism of ritonavir by the cytochrome P450 system creates a potential for many drug interactions. Commonly used drugs which may interact include macrolide antibiotics, calcium channel blockers, oral contraceptives containing ethinyloestradiol, warfarin and many antidepressants.