Higher nevirapine doses for children leads to better outcome

In a poster presentation from St Mary’s Family Clinic, Anet Alexanian reported better virological and immunological outcomes in children receiving higher doses of nevirapine than those recommended by the manufacturer.

The study was a case note review of children on nevirapine from whom blood samples had been sent for therapeutic drug monitoring to the Liverpool TDM service. Results of all NVP assays obtained from children from 1999 to September 2003 were examined and estimated trough concentrations were calculated.

Results of NVP TDM assays from 111 samples were available from 51 children. The median age of the children from which samples were taken was 4.8 years (range 1 month to 14.6 years). The authors reported an increase in trough levels of NVP with increasing dosage (P = 0.001). Sub-therapeutic trough levels were less frequent in children receiving doses higher than recommended by the manufacturers across age levels (P = 0.001). Higher trough levels were associated with lower viral loads (P = 0.012).

Additionally they found that children who achieved undetectable viral loads while receiving NVP-containing therapy had higher trough levels than children who never reached undetectable viral loads (P = 0.026).

They found no significant difference between the mean trough concentrations achieved in once and twice daily dosing groups (P = 0.064). Importantly, no correlation was seen between high plasma trough concentrations and liver or other toxicity. This was despite some astronomically high blood levels in some individuals.

The authors write: “Higher doses of NVP are associated with higher plasma trough concentrations which correlate with better virological and immunological outcomes with no dose-related hepatotoxicity. The data support the use of NVP doses greater than those currently recommended by the manufacturers.”

In practical terms this means maintaining doses above 300mg/m2/day in children, either once daily or divided b.d., provided the children children the initial induction period at 120 –150 mg/m² given once daily. This is reflected in the current PENTA guidelines, which recommends a dose between 300 – 400 mg/m²/day – PENTA guidelines

Alexanian A, Gibbons S, Lyall E.G.H., et al. Higher nevirapine doses correlate with improved outcomes in a paediatric population.7th ICDTHI,14-18 Nov, 2004, Glasgow. Abstract PL11.2.