Dosing nevirapine in children

Dosing antiretrovirals in children is notoriously confusing, utilising different dose calculations, and guidelines are rarely harmonious.

In Europe the PENTA guidelines recommend 150mg/m² nevirapine BID with a maximum dose of 200mg/m² BID. The PACTG has evaluated doses of 120mg/m² and 200mg/m² BID and the FDA licensed dose is 7mg/kg BID for children age 2 months to 8 years and 4 mg/kg BID 8 years and above. Nevirapine is included in international generic products (and in pipeline paediatric generic fixed dose combinations).

Edmund Capparelli from the University of California presented findings from a population pharmacokinetic evaluation of datasets from five PACTG studies to better characterise nevirapine and assess optimum doses [1]. These five studies contained 2449 nevirapine concentrations from 495 infants and children who were aged between one month and 19.5 years (mean 6.6 years).

There were 54% boys and 46% girls in the group evaluated and 40 children were <6 months; 46 children 6 months to 2 years; 152 children 2 to 6 years; 206 children 6 to 12 years and 51 children >12 years old.

Nevirapine concentrations <1000ng/mL(12%) were excluded from the analysis due to suspected non-adherence.

The population pharmacokinetic analysis was performed using NONMEN (Laplacian) and NLME, both methods had excellent concordance and identified age (a 30% drop from age 5 to 18), ritonavir (a 23% decrease across all age groups) and nelfinavir (a 28% decrease in infants) as covariates associated with lower nevirapine clearance.

The final model predicted an AUC of 63.6 ug.h/mL for a typical 6.6 year-old (weighing 21.7kg/0.80m²) using nevirapine in combination therapy without ritonavir or nelfinavir. The predicted AUC12hr following 150mg/m² was 63.9 ng x hr/mL, which is close to adult exposure receiving 400mg/day.

Dr Capparelli concluded that a body surface area (BSA) calculation was slightly more consistent than weight based dosing across all age bands. A dose of 150mg/m² is less likely to under dose older children than the FDA recommendation based on weight. He added that due to inter patient variability TDM may be useful for children receiving nevirapine.

Capparelli E, Blanchard S, Aweeka F et al. Population pharmacokinetics of nevirapine in infants and childrenthe impact of body size, age, and concomitant therapies. 6th International Workshop on Clinical Pharmacology of HIV Therapy. 28-30 April 2005. Quebec. Abstract 37.