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

• Published in: AIDS (London) Vol. 14; no. 14; pp. 2153 - 2157
• Main Authors: BARREIRO, Pablo, SORIANO, Vincent, CASAS, Esperanza, ESTRADA, Vicente, TELLEZ, Maria Jesus, HOETELMANS, Richard, GONZALEZ DE REQUENA, Daniel, JIMENEZ-NACHER, Inmaculada, GONZALEZ-LAHOZ, Juan
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 29-09-2000
• Subjects: Anti-HIV Agents - adverse effects; Anti-Inflammatory Agents - therapeutic use; Biological and medical sciences; Drug toxicity and drugs side effects treatment; Exanthema - chemically induced; Exanthema - prevention & control; HIV Infections - complications; HIV Infections - drug therapy; Human immunodeficiency virus 1; Humans; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); nevirapine; Nevirapine - administration & dosage; Nevirapine - adverse effects; Pharmacology. Drug treatments; Prednisone - therapeutic use; Prospective Studies; Human; Corticosteroid; Skin disease; Chemoprophylaxis; RNA-directed DNA polymerase; Nevirapine; Enzyme; Toxicity; Transferases; Non nucleoside compound; Exanthema; Enzyme inhibitor; Method; Progressive; Prevention; Increasing dose; Nucleotidyltransferases; Efficiency; Antiviral
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/00002030-200009290-00012

The appearance of rash is one of the most frequent and limiting side-effects during the first 4 weeks of treatment with nevirapine (NVP). We explored the efficacy and safety of four different strategies for reducing the incidence of this complication.
Four-hundred and sixty-nine patients were assigned randomly to accomplish the induction phase of NVP following either the standard recommendation of 200 mg daily during the first 2 weeks (n = 166), or any of three new strategies: adding prednisone 50 mg each other day during the first 2 weeks (n = 93); using a slowly escalating dose, beginning with 100 mg daily the first week, and increasing the dose by 100 mg/week up to the full daily dose of 400 mg (n = 107); and combining both the addition of prednisone with the slowly escalating dose (n = 103). A pharmacokinetic substudy was performed in seven patients receiving 100 mg of NVP during the first week.
The incidence of rash diminished from 18.7% using the standard recommendation to 9.2% using the alternative approaches (P = 0.003). Rash appeared in 11.2%, 8.6%, and 7.7% of subjects assigned to receive the slowly escalating dose, prednisone, or both, respectively, without significant differences 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 above the 90% inhibitory concentration for wild-type HIV-1 in all instances.
The incidence of rash complicating the first few weeks of treatment with NVP can be diminished by adding corticosteroids for 2 weeks to the standard recommendation, or by using a slowly escalating dose. This second approach is proven to be pharmacokinetically safe.