Enliven: Pharmacovigilance and Drug Safety

Background:
Nevirapine’s (NVP) pharmaceutical manufacturer recommended the avoidance of NVP in females and males with baseline CD4 counts >250 and >400, respectively. This safety measure was challenged by research results that showed similar proportions of adverse events in high and low baseline CD4 count patients. WHO’s antiretroviral therapy guidelines recommended the use of NVP in patients with CD4 counts <350. Whether this recommendation would result in increase of NVP-related adverse reaction reports in Namibia was not known. Consequently, the pharmacovigilance centre monitored the NVP-related reaction reports for change in number and severity.

Methods:
We accessed adverse reaction reports in VigiFlow®. NVP-related skin and liver adverse reaction reports received in 2011 were compared with those received in the Previous Years. Also, NVP-related reaction reports were compared with the same reactions associated with other medicines. The comparisons were made by using reporting ratio, proportional reporting ratio, and the Students T-Test.

Results:
1,074 adverse reaction reports were accessed. NVP-related liver and skin reactions were 208 (2011) and 99 (Previous Years). The proportions of reports related to ARV in 2011 and Previous Years were comparable (RR=1; p=0.87). The NVP-related reactions were greater in 2011 than in the Previous Years (43.2% vs. 16.7%: RR = 2.6; p <0.0001). Grade3 and 4 reactions related to NVP were greater in 2011 than in the Previous Years (SKIN: 22.7% vs. 5.6%: RR = 4.1; p <0.0001; LIVER: 8.5% vs. 2.2%: RR = 3.9; p <0.0001), but not for grade1 & 2 reactions (SKIN: 8.5% vs. 6.2%; RR = 1.4; p =0.16; LIVER: 2.7% vs. 2.4%; RR = 1.1; p = 0.73).The increase in reports was observed for both female and male patients (p<0.01). The increase ingrade 3 and 4 reactions were unique to NVP.

Conclusion:
The significant increase in proportions of grade3 and 4 liver and skin reaction reports in patients on NVP was detected as a safety signal after shifting ART initiation to higher CD4 counts. The Ministry of Health halted the plan of initiating NVP-based ART in pregnant females, and recommended the avoidance of NVP in ART-naïve patients with high baseline CD4 counts. Through locally derived data, pharmacovigilance centres can protect patients from drug-induced harm.