Switch to nevirapine can happen at any CD4 count, says European drug regulator

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People with HIV who have an undetectable viral load can safely switch to nevirapine (Viramune) at any CD4 cell count, the European Medicines Agency has concluded.

The agency has issued a revised Summary of Product Characteristics to allow switching in people with suppressed viral load who want to switch to nevirapine for reasons of tolerability or cost.

The agency’s Committee for Medical Products for Human Use reviewed evidence from clinical studies to determine whether people who switched to nevirapine from an existing antiretroviral regimen had an increased risk of liver toxicity or hypersensitivity reaction at higher CD4 cell counts.

Glossary

formulation

The physical form in which a drug is manufactured or administered. Examples of formulations include tablets, capsules, powders, and oral and injectable solutions. A drug may be available in multiple formulations.

toxicity

Side-effects.

equivalence trial

A clinical trial which aims to demonstrate that a new treatment is no better or worse than an existing treatment. While the two drugs may have similar results in terms of virological response, the new drug may have fewer side-effects, be cheaper or have other advantages. 

tolerability

Term used to indicate how well a particular drug is tolerated when taken by people at the usual dosage. Good tolerability means that drug side-effects do not cause people to stop using the drug.

rash

A rash is an area of irritated or swollen skin, affecting its colour, appearance, or texture. It may be localised in one part of the body or affect all the skin. Rashes are usually caused by inflammation of the skin, which can have many causes, including an allergic reaction to a medicine.

People who have never taken antiretroviral treatment are at increased risk of these reactions at higher CD4 cell counts. Women with CD4 counts above 250 and men with CD4 counts above 400 should not start treatment with the drug, regulatory agencies have ruled.

However, evidence from cohort studies conducted prior to the ruling has demonstrated that switching to nevirapine after achieving an undetectable viral load is not associated with an increased risk of toxicity, even if a person’s CD4 count has risen above the CD4 count thresholds that rule out use of the drug in untreated people.

Being able to switch to nevirapine after initial treatment with another drug may be attractive to some patients. Nevirapine treatment is much less likely to result in increases in lipid levels than other antiretroviral drugs, and the drug is well-tolerated, apart from the risk of transient rash in the first month of treatment in up to 16% of patients.

Nevirapine is currently licensed only for twice-daily dosing, due to concerns about the increased risk of liver toxicity in people who took the drug once a day in the 2NN study, a large trial that compared different dosing options for nevirapine.

However a randomised study of switching to once-daily nevirapine in virally suppressed patients showed that once-daily dosing of the existing formulation resulted in a non-inferior rate of hepatotoxicity after 48 weeks.

The drug’s manufacturer, Boehringer-Ingelheim, is currently testing a once-daily extended-release formulation called Viramune XR. Forty-eight week results of a study of the new formulation show that it is equivalent to twice-daily dosing with the old formulation.

Nevirapine remains one of the cheaper antiretroviral drugs, and is due to go off patent in Europe in 2012, which will greatly reduce the cost of the older formulation.

Further information on nevirapine is available here..