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.
250 mg tablets
50 mg/g oral powder
Indication: HIV infection
Drugs for HIV infection tend to reach the market more rapidly than previously. Nelfinavir is the latest to be approved on the basis of its effects on surrogate end-points. Like the other protease inhibitors (indinavir, ritonavir and saquinavir1), nelfinavir should only be used in combination with other treatments. (Combination helps to reduce the risks of the virus becoming resistant.)
The tablets should be taken with a meal as this will at least double the plasma concentration. Children (over 2 years old) who cannot swallow tablets can mix the oral powder with a small amount of food or fluid. The drug has a half-life of 3-5 hours with most of the dose being metabolised. This metabolism involves many isoforms of cytochrome P450.
In view of potential interactions, nelfinavir should not be given with astemizole, terfenadine, cisapride, midazolam, triazolam, ergot derivatives or rifampicin. Other drugs which interact include oral contraceptives, phenytoin, carbamazepine and rifabutin. There may be other possible interactions due to the potential ability of nelfinavir to inhibit hepatic enzymes. For example, fluvoxamine and fluoxetine have the potential to inhibit cytochrome P450 3A4. Alprazolam is also metabolised by this isoenzyme.
Inhibition of HIV protease prevents the production of mature virus. This results in a fall in viral RNA concentrations. These concentrations can be used to follow the activity of the disease. One study compared zidovudine and lamivudine alone and in combination with nelfinavir. The decrease in viral RNA was significantly greater in the patients who took all 3 drugs. They also had a significantly larger increase in CD4 lymphocytes.
Another study compared stavudine (a nucleoside analogue) and nelfinavir with stavudine alone. Again, the combination therapy had a significantly better effect on the surrogate markers.
Over 1500 patients were involved in the trials of nelfinavir. Diarrhoea was the main adverse reaction they experienced. Patients may also complain of headache, abdominal pain or asthenia. As safety data are limited, the relationship of some adverse events to the drug is unclear. Serious adverse events have included pancreatitis, altered liver function, anaemia, leucopenia, thrombocytopenia and, in patients with haemophilia, an increased bleeding tendency. Some patients develop hyperglycaemia and may require insulin or oral hypoglycaemic drugs.
The marketing approval is based on studies lasting up to24 weeks so there are no long-term clinical outcomes. The pattern of resistance to nelfinavir may differ from those of the other protease inhibitors. More studies are needed to find out if nelfinavir should be used when other protease inhibitors fail or if it should be used first.
- Deeks SG, Smith M, Holodniy M, Kahn JO. HIV-1 protease inhibitors. JAMA 1997;277:145-53.