Prevention of nevirapine-associated exanthema using slow dose escalation and/or corticosteroids

Objective: The appearance of rash is one of the most frequent and limiting side-effects during the first 4 weeks of treatment with nevirapine (NVP). W e explored the efficacy and safety of Four different strategies for reducin g the incidence of this complication. Patients and methods: Four-hundred and sixty-nine patients were assigned ra ndomly to accomplish the induction phase of NVP following either the standa rd recommendation of 200 mg daily during the first 2 weeks (n = 166), or an y of three new strategies: adding prednisone 50 mg each other day during th e first 2 weeks in = 93); using a slowly escalating dose, beginning with 10 0 mg daily the first week, and increasing the dose by 100 mg/week up to the Cull daily dose of 400 mg (n = 107); and combining both the addition of pr ednisone with the slowly escalating dose in = 103). A pharmacokinetic subst udy was performed in seven patients receiving 100 mg of NVP during the firs t week. Results: The incidence of rash diminished from 18.7% using the standard rec ommendation to 9.2% using the alternative approaches (P = 0.003). Rash appe ared in 11.2%, 8.6%, and 7.7% of subjects assigned to receive the slowly es calating dose, prednisone, or both, respectively, without significant diffe rences among them. The rate of drug discontinuation was also diminished by one-half using the new approaches (8.5% versus 4.3%; P = 0.06). NVP plasma concentrations within the first week of treatment using 100 mg daily were a bove the 90% inhibitory concentration for wildtype HIV-1 in all instances. Conclusion: The incidence of rash complicating the first few weeks of treat ment with NVP can be diminished by adding corticosteroids for 2 weeks to th e standard recommendation, or by using a slowly escalating dose. This secon d approach is proven to be pharmacokinetically safe. (C) 2000 Lippincott Wi lliams & Wilkins.