WC500185968

Summary of recommendation(s)
The MAHs of aripiprazole-containing medicinal products should submit a variation within 60
days to include ‘aggression’ 5 as an undesirable effect with an unknown frequency in the
product information.
The MAH for Abilify and Abilify Maintena should submit in the next PSUR (DLP: 16/07/2015), a
cumulative review of aripiprazole overdose and the risk of aggression and related events.
For the full PRAC recommendations, see EMA/PRAC/176901/2015 published on the EMA website.
4.3.3. Infliximab – INFLECTRA (CAP), REMICADE (CAP), REMSIMA (CAP)
Signal of rhabdomyolysis
Regulatory details:
PRAC Rapporteur: Ulla Wändel Liminga (SE)
Administrative details:
EPITT 18129 – Follow-up November 2014
Procedure number(s): EMEA/H/C/002778/SDA/020, EMEA/H/C/000240/SDA/152,
EMEA/H/C/002576/SDA/019
MAH(s): Hospira UK Limited (Inflectra), Janssen Biologics B.V. (Remicade), Celltrion Healthcare
Hungary Kft. (Remsima)
Background
For background information, see PRAC Minutes November 2014. The MAH replied to the request for
information on the signal of rhabdomyolysis and the responses were assessed by the Rapporteur.
Discussion
The PRAC discussed the cumulative review of the signal of rhabdomyolysis provided by the MAH. Three
cases of possible rhabdomyolysis were reported from clinical trials in infliximab treated subjects,
versus one case reported among placebo treated patients. Regarding the 53 post marketing reported
cases, no clear sentinel case was identified. For one case from Japan, a positive rechallenge was
reported. However, the information regarding relationship timing of the first dose of infliximab in
relation to the event, and concomitant administration of ciprofloxacin contradicts a causal relationship.
In total, six patients treated with infliximab in registries were reported to experience rhabdomyolysis.
It is not known if these cases were confounded. Due to the time frame for responding, no rheumatoid
arthritis registry data were included in the review provided. No relevant cases were described in the
literature. Based on the available evidence, the PRAC considered that there is insufficient evidence at
present to add rhabdomyolysis to the product information of infliximab-containing medicinal products.
However further clarifications from the MAH are required to address this signal fully.
Summary of recommendation(s)
The MAH for Remicade should submit to EMA, within 60 days, the rationale for classifying an
event of rhabdomyolysis emerging in a clinical trial as an adverse drug reaction (ADR),
clarification whether the cases retrieved from the clinical trials represent verified cases of
rhabdomyolysis, and what criteria were used to identify these, considering the medical coding
5 Section 4.8 of the Summary of Product Characteristics
Pharmacovigilance Risk Assessment Committee (PRAC)
EMA/PRAC/257790/2015 Page 23/89