Emtricitabine

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.

Emtriva (Gilead)
200 mg capsules
Approved indication: HIV infection
Australian Medicines Handbook section 5.4.1

The current treatment of HIV infection involves giving antiviral drugs from different classes. This may require the patient to take medications several times a day.¹ Most of the regimens include nucleoside reverse transcriptase inhibitors to prevent viral replication. This class is now expanded by the addition of emtricitabine, an analogue of cytosine.

Emtricitabine is taken once a day. It is rapidly absorbed and then phosphorylated within cells to its active form. While the elimination half-life of emtricitabine is 10 hours the intracellular half-life of emtricitabine-triphosphate is 39 hours. Most of the drug is excreted in the urine so the dose requires adjustment in patients with renal impairment.

A multinational double-blind trial studied emtricitabine in 571 patients who had not previously been treated with antiretroviral drugs. These patients were randomised to take emtricitabine or stavudine, in addition to didanosine and efavirenz. After 48 weeks 78% of the emtricitabine group and 59% of the stavudine group had fewer than 50 copies of viral RNA/mL.²

Another trial studied 440 patients who were already taking combinations of antiviral drugs including lamivudine. The patients were randomised to either continue lamivudine or to switch to emtricitabine. After 48 weeks 72% of the patients taking lamivudine and 67% of those taking emtricitabine had fewer than 50 copies of viral RNA/mL.

Common adverse effects are diarrhoea, nausea, abdominal pain and nightmares, but these may occur less frequently than with stavudine. Skin discolouration was observed in 3% of the previously untreated patients given emtricitabine.² Liver function, blood cell counts and triglyceride concentrations may be affected by emtricitabine.

Resistance can develop during treatment. In previously untreated patients, viral mutations occurred in 4% of those taking emtricitabine and 11% of those taking stavudine.² As emtricitabine is structurally similar to lamivudine, a virus which is resistant to lamivudine will probably be resistant to emtricitabine.

While a once-daily treatment may improve compliance, it will require further study to see if emtricitabine has a clinically significant advantage. At present, its efficacy has only been proven with surrogate end points.