Table 1.
Aims of post-marketing drug safety (pharmacovigilance) information reporting and management (adapted from Bate A et al., 2008 [28]).
Table 2.
Sex and age distribution in 226 cases of spontaneously reported suspected ADRs to the German Federal Institute for Drugs and Medical Devices.
Figure 1.
Annually reported cases of flupirtine induced liver injury.
Annually spontaneously hepatobiliary adverse events reported for flupirtine (black) and proportion of cases rated to be ‘highly probable’ or ‘probable’ according to the CIOMS score (grey).
Table 3.
Causality assessment according to the adapted Bradford-Hill criteria.
Figure 2.
Results of liver function tests of spontaneously reported ADRs.
Scatter plots of maximum AST (A), ALT (B), and bilirubin (C) levels (given in×ULN) in relation to the daily dose (left panel), cumulative doses (daily dose (mg)×duration of drug exposure (days), middle panel), and in relation to the time to onset (right panel) of the ADRs in cases of suspected hepatobiliary adverse events associated with flupirtine exposure.
Table 4.
Incidence of viral disease and cases with positive autoimmune titres in 226 cases of liver ADR linked to flupirtine treatment.
Table 5.
The 10 most common co-medications with a potential for hepatobiliary ADRs in n = 151 reported cases with co-medications possibly responsible or contributing factor(s) for hepatobiliary ADRs.
Table 6.
The 10 most common co-medications of n = 51 cases reported by physicians as a possible cause of hepatic ADRs.
Figure 3.
Flupirtine hyper-sensitivity of a 53-year-old female patient.
Laboratory results of a 53-year-old female patient after exposure and re-exposure to flupirtine. She experienced icterus with markedly increased serum transaminase levels. Upon discontinuation transaminase levels decreased. On day 6 of hospital admission re-exposure to an unknown dose of flupirtine resulted in a recurrent increase of laboratory values.
Table 7.
Histopathological findings in liver biopsies taken from n = 49 patients with reported hepatobiliary ADRs (multiple histological findings were listed for one patient).
Table 8.
Evaluation of 226 cases with suspected hepatobiliary ADRs reported for flupirtine obtained with the CIOMS score and the WHO-UMC causality assessment system.
Figure 4.
Reporting scheme and critical issues in the management of suspected ADRs.