Tenofovir disoproxil fumarat
- Aust Prescr 2002;25:147-51
- 1 December 2002
- DOI: 10.18773/austprescr.2002.146
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.
Viread (Gilead Sciences)
300 mg tablets
Approved indication: HIV infection
Australian Medicines Handbook section 5.3
Patients with HIV are now treated with combinations of antiviral drugs (see 'New approaches in the treatment of HIV infection' Aust Prescr 1998;21:44-6).The combination each patient uses may need to be changed when resistance develops. There are no drugs which will eliminate multi resistant HIV, buttenofovir can be added to the patient's usual regimen.
Tenofovir is an analogue of adenosine monophosphate. By competing with the usual substrate of HIV reverse transcriptase it inhibits the enzyme. This stops the conversion of viral RNA into DNA.
Early trials showed that tenofovir could reduce plasma concentrations of viral RNA. It was therefore tried in patients who had evidence of ongoing viral replication despite antiretroviral therapy. In a dose-ranging study tenofovir or a placebo was added to the combination therapy of 186 patients. After 24weeks, 19% of the patients taking tenofovir had less than 400 viral copies/mL and 11% had less than 50 viral copies/mL. In the placebo group only 7% of patients achieved less than 400 viral copies/mL.
A larger trial added 300 mg tenofovir to the treatment of 368 patients while another 182 patients had a placebo added. After 24 weeks 40% of the patients taking tenofovir and 11% of the patients taking placebo had less than 400 viral copies/mL. Only 1% of the placebo group had less than 50 copies/mL compared with 19% of the tenofovir group.
As tenofovir is not well absorbed the tablets contain tenofovir disoproxilfumarate. This compound is a prodrug which is rapidly converted in the liver and plasma. It should be taken with food as this increases bioavailability. Most of a dose is excreted in the urine as tenofovir. Unlike some antiretroviraldrugs, tenofovir does not inhibit cytochrome P450, but it does compete with other drugs excreted by renal tubular secretion. These competing drugs include ganciclovir, valaciclovir and aciclovir. Tenofovir can increase the concentrations of didanosine by more than 40%, but the mechanism is unknown.
As some renal toxicity (e.g. phosphaturia) occurred in animal studies, kidney function should be monitored. These studies also reported osteomalacia, but the significance of this finding for patients is not yet known. Most of the adverse effects of tenofovir are gastrointestinal (nausea, vomiting, flatulence and diarrhoea).
There are no long-term safety data for tenofovir and its efficacy is based on surrogate end-points. Although there has been little viral resistance to tenofovir so far, the benefits of tenofovir are still uncertain. In the dose-ranging study the effect of tenofovir on CD4 lymphocytes was not significantly different from that of placebo.