Europe and America approve once-a-day stavudine (d4T, Zerit)

Graham McKerrow, HIV i-Base

European and American authorities have approved a new once-a-day formulation of stavudine (d4T, Zerit) but it will not be launched until later in the year.

The new slow-release formulation will have slightly different names on each side of the Atlantic. In Europe it will be called stavudine prolonged release capsule (stavudine PRC, Zerit PRC) while in the US it will be know as stavudine extended release (stavudine XR, Zerit XR).

The new formulation was approved by the European Medicines Evaluation Agency, based in London, in October, and the US Food and Drug Administration followed suit on 31 December.

Bristol-Myers Squibb, the manufacturer, told HIV Treatment Bulletin that it was “validating the manufacturing process” which involved quality control checks on the capsules of tiny, coated beads of the drug.

There will not be an early access programme for the new formulation because the slow-release formulation is not regarded as a significant enough advantage over ordinary stavudine, said the company.

Stavudine PRC will be available in the following sizes: 37.5 mg, 50 mg, 75 mg, and 100 mg.

Stavudine PRC maintains measurable plasma concentrations for 24 hours after once-daily dosing. The recommended doses of stavudine PRC are 100 mg once daily for individuals weighing at least 60 kg and 75 mg once daily for individuals weighing less than 60 kg.

Once daily stavudine studies

In a randomised, controlled clinical study conducted in 783 treatment-naïve, HIV-infected individuals, stavudine PRC was comparable to the previously approved twice-daily formulation of the drug, according to Bristol-Myers Squibb. In this study, participants were randomised to either the extended release or standard formulation, in combination with lamivudine and efavirenz. The proportion of patients with HIV viral load levels below 400 copies/mL at 48 weeks was 79% and 76% for the extended release and immediate release-containing regimens, respectively.

For viral load under 50, the response rates were 55% and 57% for the new and old formulations, respectively. The tolerability and safety profile of the new once daily, extended release formulation is comparable to that of the previously approved twice-daily formulation, according to the company.

The study results were supported by a second, smaller study in 150 treatment naïve patients. It is widely believed that once daily formulations may help patients adhere to treatment regimens due to the increased convenience of the dosing schedule.

The full label for Zerit XR will soon be available at the FDA website.

Source of study information: Richard Klein. Office of Special Health Issues. US Food and Drug Administration.


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