Drug regulatory authorities in the US have issued revised dosing recommendations for the use of the protease inhibitor atazanavir (Reyataz) in children.
The Food and Drug Administration (FDA) now recommends that atazanavir should not be given to babies aged under three months because of a risk of a type of brain damage, called kernicterus, that is caused by excess levels of bilirubin. Bilirubin is a waste product produced by the liver and a build-up of bilirubin in the blood, called hyperbilirubinaemia, is a harmless, but sometimes cosmetically distressing, side-effect of atazanavir therapy in adults.
Other revisions to atazanavir’s prescribing information concern the use of the capsule formulation of the drug by children and adolescents aged between six and 18 years. The FDA’s update stresses that dosing of atazanavir capsules in patients between these ages is based upon body weight, but should never exceed the recommended adult dose. Atazanavir capsules should, the FDA recommend, be taken with food
There are insufficient data, the guidance states, to support prescribing atazanavir capsules to the following three categories: children under six; children under 13 without ritonavir boosting; and, to treatment-experienced children with a body weight below 25kg.
Guidance about the appropriate weight-adjusted dose of atazanavir capsules for both treatment-naïve and treatment-experienced patients is also provided by the FDA.
Atazanavir’s safety profile is similar in children to adults, the FDA notes. The most commonly observed moderate to severe side-effects being cough (21%), fever (19%), jaundice (13%), diarrhoea (8%), vomiting (8%), headache (7%) and runny nose (6%). Increased levels of bilirubin were found in the blood of 49% of patients.
Information on the effectiveness of atazanavir capsules in a clinical trial involving 99 children is also provided in the updated FDA information.
The proportion of treatment-naïve six-to-18 year olds treated with atazanavir or atazanavir/ritonavir who achieved a viral load below 50 copies/ml after 24 weeks of treatment was 59% (24/41). Of the treatment-experienced children treated with atazanavir or atazanavir/ritonavir, 24% (14/58) experienced a fall in their viral load to below 50copies/ml. After 20 weeks, the median increase in CD4 cell count was 171 cells/mm3 in treatment-naïve children, and 116 cells/mm3 in treatment-experienced patients.