WC500185968

The exposure for Kepivance, a centrally authorised medicine containing palifermin, is estimated to
have been more than 17,287 patients worldwide, in the period from first authorisation in 2005 up to
January 2012.
A signal of increased mortality associated with the unlicensed use of palifermin in acute lung injury was
identified by EMA, based on the results of the recently completed keratinocyte growth factor in acute
lung injury to reduce pulmonary dysfunction (KARE) study. The MAH provided EMA with a summary of
the results of this investigator-sponsored randomised placebo-controlled study in patients with acute
lung injury conducted in Northern Ireland. The study results showed that intensive care unit (ICU) and
28-day survival were significantly lower in the palifermin group compared to placebo. In addition, the
palifermin group had a longer duration of ventilator use, ICU stay and hospital stay. The Rapporteur
confirmed that the signal needed initial analysis and prioritisation by the PRAC.
Discussion
The PRAC discussed the information provided by the MAH on the KARE study and noted that the
approved indication and the KARE study differ in terms of patient population, conditions treated and
posology. Randomised clinical trials, observational studies and spontaneous reports in patients with
haematological malignancies have not raised a signal of increased mortality or pulmonary events with
palifermin. Pulmonary events, both infectious and non-infectious, are currently included as an
important potential risk in the RMP. The PRAC agreed that no regulatory action was necessary based
on this study report and that the MAH should continue to closely monitor pulmonary adverse events
including fatal cases in future PSURs. The PRAC considered that the investigator should be encouraged
to promptly publish the results in a suitable peer reviewed publication of the KARE study.
Summary of recommendation(s)
No regulatory action was considered necessary based on this study report; however the MAH
should continue to closely monitor pulmonary adverse events including fatal cases in future
PSURs.
4.2.6. Warfarin (NAP)
Signal of bone density decrease
Regulatory details:
PRAC Rapporteur: Torbjörn Callreus (DK)
Administrative details:
EPITT 18173 – New signal
MAH(s): various
Lead MS: DK
Background
Warfarin is an oral anticoagulant used for short and long term prevention of thrombo-embolic
disorders, including treatment and prevention of deep venous thrombosis and pulmonary embolism,
secondary prevention of myocardial infarction and prevention of thromboembolic complications (stroke
or systemic embolism) after myocardial infarction, and prevention of thromboembolic complications in
patients with atrial fibrillation, cardiac valvular disease and or prosthetic heart valves.
The worldwide exposure for medicines containing warfarin is estimated to have been very large, since
the medicine has been extensively prescribed since its first authorisation in the mid-1950s.
Pharmacovigilance Risk Assessment Committee (PRAC)
EMA/PRAC/257790/2015 Page 20/89