Delavirdine mesylate

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.

Rescriptor (Pharmacia & Upjohn)

100 mg tablets

Indication: HIV infection
Combination therapy is the currently favoured approach to treating HIV infections. The combinations can include non-nucleoside reverse transcriptase inhibitors. Nevirapine is already available and now delavirdine has been approved for use in combination with nucleoside analogues.

Delavirdine is a selective non-competitive inhibitor of HIV 1 reverse transcriptase. Its effect is to reduce viral replication. Unfortunately, the virus rapidly develops resistance if delavirdine is used as monotherapy.

Approval for marketing is based on two double-blind trials of delavirdine, one of which is still in progress. This trial is comparing the combination of delavirdine and zidovudine with zidovudine alone. The combination appears to be more effective in reducing viral RNA and increasing CD4 lymphocyte counts. The other trial has compared didanosine with a combination of didanosine and delavirdine in patients who have previously taken zidovudine. During the first 8 weeks of treatment, the CD4 lymphocyte count was significantly higher and the reduction in RNA significantly greater in the patients given the combination.

Delavirdine is taken 3 times a day. If didanosine is also being taken, it should not be taken simultaneously. Delavirdine is metabolised by cytochrome P450 3A and possibly P450 2D6, so there is a potential for other interactions. The drugs which interact include rifampicin, rifabutin, phenytoin, carbamazepine, warfarin and calcium channel blockers. Plasma concentrations of delavirdine may also be affected by fluconazole, ketoconazole and saquinavir. Zidovudine and ritonavir have no significant effect on delavirdine concentrations, but delavirdine may increase the concentrations of indinavir. The manufacturers also advise that delavirdine should not be taken with terfenadine, astemizole, triazolam, alprazolam, midazolam or cisapride.

Up to half the patients taking delavirdine will develop a rash. Patients with lower CD4 cell counts are more likely to develop the rash. In most cases, the rash resolves in a few weeks. Other adverse effects include nausea, headache and dizziness.

Overall, delavirdine has a modest benefit. Its efficacy is mainly based on surrogate end-points and in the comparison with didanosine there was no improvement in survival. The role of delavirdine in combination therapy, e.g. with protease inhibitors, will require more trials.