Prevention of nevirapine-associated rash using slow dose escalation, antihistaminics or corticosteroids

This data was reported by P Barreiro and a Spanish research group. The pharmacology was performed in Amsterdam (Slotervaart Hosp). The appearance of a rash is one of the most frequent and limiting side effects during the first 4 weeks of treatment with nevirapine (NVP). They explored the efficacy and safety of four different strategies for reducing the incidence of this complication. Prior studies have shown conflicting reports about the benefits of these interventions. A recent study showed they did not reduce rash but made it worse.

Five-hundred and sixty-two patients were randomly assigned to accomplish the induction phase of NVP following either the standard (std) recommendation of 200 mg daily during the first 2 weeks (n=166), or any of four new strategies:

1) adding loratadine 10 mg/12hours during the first 2 weeks (n=93),

2) adding prednisone 50 mg each other day during the first 2 weeks (n=93),

3) using an slow escalating dosing, beginning with 100 mg daily the first week, and increasing the dose 100 mg weekly up to the full daily dose of 400 mg (n=107), and

4) combining both the addition of prednisone with the slow escalating dosing (n=103).

A pharmacokinetic substudy was performed in 8 patients receiving 100 mg of NVP during the first week. The incidence of rash and NVP discontinuation standard recommendation and the alternative approaches was:

Results:

The incidence of rash is reported as 18.7% using standard recommendation of 200 mg daily during the first 2 weeks (n=166). But this rate is cut in half by any of the other approaches of using antihistimines or corticosteroids 7.7% to 8.8%.

P values compare the standard induction of NVP with the different new interventions. NVP plasma concentrations within the first week of treatment using 100 mg daily were above the IC90 for wild type HIV-1 in all instances.

The authors concluded, the incidence of rash complicating the first few weeks of treatment with NVP can be diminished adding corticosteroids or antihista-minics for two weeks to the standard recommendation, or using a slow escalating dosing. This third approach is proven to  be pharma-cokinetically safe.