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The CMDh position on diacerein (see EMA/162540/2014), which followed the related PRAC
recommendations, was adopted in March 2014 by majority vote and sent to the European Commission
for a final legally binding decision valid throughout the European Union (EU).
Summary of recommendation(s)/conclusions
The PRAC noted a letter from the EC addressed to the PRAC and CMDh asking for review of the CMDh
position and PRAC recommendations in light of some scientific points raised by the Standing
Committee on Medicinal Products for Human Use. It was agreed that the Rapporteurs would prepare a
reply to the letter to be discussed at the July 2014 PRAC.
4. Signals assessment and prioritisation 3
4.1. New signals detected from EU spontaneous reporting systems
4.1.1. Vildagliptin – GALVUS (CAP), JALRA (CAP), XILIARX (CAP)
Vildagliptin, metformin - EUCREAS (CAP), ICANDRA (CAP), ZOMARIST (CAP)
Signal of rhabdomyolysis
Regulatory details:
PRAC Rapporteur: Qun-Ying Yue (SE)
Administrative details:
EPITT 17959 – New signal
Leading MS: SE
MAH(s): Novartis Europharm Ltd
Background
Vildagliptin is a dipeptidyl peptidase 4 (DPP-4) -inhibitor indicated in the treatment of type 2 diabetes
mellitus in adults.
The exposure for centrally authorised medicine containing vildagliptin (alone or in combination with
metformin) is estimated to have been more than 7.8 million patient-years worldwide, in the period
from first authorisation in 2007 to 2014.
During routine signal detection activities, a signal of rhabdomyolysis was identified by the EMA, based
on 8 cases retrieved from EudraVigilance. The Rapporteur confirmed that the signal needed initial
analysis and prioritisation by the PRAC.
Discussion
The PRAC noted that the suspected cases of rhabdomyolysis described were generally well
documented, all providing information on positive de-challenge and, in one case, on re-challenge.
Although there could have been confounding by the medication reported in a number of cases, the
temporal relationship with vildagliptin treatment as well as the reports of positive dechallenge and
rechallenge indicated a plausible link between vildagliptin and rhabdomyolysis/myalgia. A possible
biological explanation can be suggested by findings from a phase I dose-ranging study and non-clinical
3 Each signal refers to a substance or therapeutic class. The route of marketing authorisation is indicated in
brackets (CAP for Centrally Authorised Products; NAP for Nationally Authorised Products including products
authorised via Mutual Recognition Procedures and Decentralised Procedure). Product names are listed for reference
Centrally Authorised Products (CAP) only. PRAC recommendations will specify the products concerned in case of any
regulatory action required
Pharmacovigilance Risk Assessment Committee (PRAC)
EMA/PRAC/438418/2014 Page 15/75