1u7kf0g

leukoencephalopathy and non-specific encephalopathy reported, and agreed that although other
factors or concomitant conditions could have explained the development of the reaction in some cases,
in others it was not possible to exclude a causal association.
Therefore the signal should be further investigated.
Summary of recommendation(s)
The MAH for Yervoy (ipilimumab) should submit to the EMA a cumulative review of the signal
of PRES/leukoencephalopathy, including related MedDRA terms or relevant SMQ within the
next PSUR (DLP 24/9/2014).
4.3. Signals follow-up and prioritisation
4.3.1. Dexmedetomidine – DEXDOR (CAP)
Signal of infantile apnoeic attack
Regulatory details:
PRAC Rapporteur: Julie Williams (UK)
Administrative details:
EPITT 17657 – Follow-up January 2014
MAH(s): Orion Corporation
Background
For background information, see PRAC minutes of 6-9 January 2014.
The MAH replied to the request for further information on the signal infantile apnoeic attack and the
responses were assessed by the Rapporteur.
Discussion
The PRAC noted that the number of suspected cases was small against the population exposure and
concluded that the available data submitted by the MAH of respiratory related events in the paediatric
population did not provide strong evidence of a causal association.
However, due to the fact that dexmedetomidine is used off-label in neonates, adverse reaction
reporting in this population was considered less likely and this may have led to the small number of
cases reported. Furthermore, the cases reported in adults did provide some evidence to support a
causal association particularly the cases with no obvious alternative explanation for the respiratoryrelated
events.
The PRAC acknowledged that the mechanism of action of respiratory-related effects remains unclear
and therefore it was possible that any risk that occurs in adult patients would also apply to paediatric
patients. Overall the PRAC considered that in the context of additional data, a causal association
between respiratory depression/apnoea and dexmedetomidine cannot be ruled out and it was
considered possible that dexmedetomidine, in combination with other factors, may have contributed to
the development of apnoea. Co-administration of dexmedetomidine with anaesthetics, sedatives,
hypnotics, and opioids is likely to lead to enhancement of its effects.
Based on these conclusions the PRAC agreed that it would be important to update the product
information for dexmedetomidine containing products to reflect these findings.
Pharmacovigilance Risk Assessment Committee (PRAC)
EMA/PRAC/438418/2014 Page 18/75