WC500185968

habdomyolysis and related terms reported for donepezil with a view to amend the product information
for donezepil-containing medicines.
The PRAC appointed Julie Williams (UK) as Rapporteur for the signal.
Summary of recommendation(s)
The MAH for Aricept (donezepil) should submit to the EMA, within 60 days, a cumulative review
of all cases of rhabdomyolysis and related terms reported for donepezil. The review should
include reports in the MAH’s clinical trial and post-marketing safety databases and the
published literature. If applicable, the MAH should make a proposal to update the product
information.
A 60-day timetable was recommended for the assessment of this review leading to a further
PRAC recommendation.
4.2.4. Fingolimod - GILENYA (CAP)
Signal of progressive multifocal leukoencephalopathy (PML)
Regulatory details:
PRAC Rapporteur: Arnaud Batz (FR)
Administrative details:
EPITT 18241– New signal
MAH(s): Novartis Europharm Ltd
Lead MS: FR
Background
Fingolimod is a sphingosine 1-phosphate receptor modulator indicated as single disease modifying
therapy in highly active relapsing remitting multiple sclerosis (MS) under certain conditions.
The exposure for Gilenya a centrally authorised medicine containing fingolimod, is estimated to have
been more than 135,800 patient years worldwide, in the period from first authorisation in 2011 up to
February 2014.
During routine signal detection activities, a signal of progressive multifocal leukoencephalopathy (PML)
was identified by France, based on a spontaneous report of PML in a patient treated with fingolimod for
multiple sclerosis for 4 years in Germany. The Rapporteur confirmed that the signal needed initial
analysis and prioritisation by the PRAC.
Discussion
The PRAC discussed the information on the newly reported case of PML associated with long-term
treatment with fingolimod. The diagnosis was confirmed and based on magnetic resonance imaging
(MRI) findings and John Cunningham virus (JCV) DNA polymerase chain reaction (PCR) results. It was
notable that the patient experienced weakness but no clinical sign or symptoms related to PML. The
lack of previous immunosuppressive treatment further pointed towards a possible causal association
with Gilenya . The PRAC also discussed twelve other cases of PML with fingolimod reported in the last
PSUR (DLP: 28/02/2014). Among these, no case was previously reported without a history of
natalizumab or another immunosuppressant treatment. Only one patient had no prior history of
natalizumab use but was treated with another immunosuppressant. PML is currently included as an
important potential risk in the fingolimod Risk Management Plan.
Pharmacovigilance Risk Assessment Committee (PRAC)
EMA/PRAC/257790/2015 Page 18/89