WC500169468

consequence of low testosterone levels. Therefore it was agreed that the issue should be further
evaluated taking into account information concerning all active substances from the same therapeutic
class.
The PRAC appointed Martin Huber (DE) as Rapporteur for the signal.
Summary of recommendation(s)
The PRAC Rapporteur, with support of the EMA secretariat, should perform further analysis of
the signal in order to assess whether the pharmacological mechanism - decreased testosterone
and other androgens serum levels - shared by all medicinal products of the class, that could be
associated with QT interval prolongation. This further analysis should include products from the
ATC codes L02AE Gonadotropin releasing hormone analogues, L02BX other hormone
antagonists and related agents and L02BB Anti-androgens.
A 4 month timetable was recommended for the assessment of this review leading to a further
PRAC recommendation.
4.1.2. Atazanavir – REYATAZ (CAP)
Signal of haemolytic anaemia
Regulatory details:
PRAC Rapporteur: Isabelle Robine (FR)
Administrative details:
EPITT 17921 – New signal
MAH(s): Bristol-Myers Squibb Pharma EEIG
Background
Atazanavir is a protease inhibitor co-administered with low-dose ritonavir, which is indicated for the
treatment of HIV‐1-infected adults and paediatric patients 6 years of age and older in combination with
other antiretroviral medicinal products.
The exposure for Reyataz, a centrally authorised medicine containing atazanavir, is estimated to have
been more than 1.200.000 patients worldwide, in the period from 2003 to 2012.
During routine signal detection activities, a signal of haemolytic anaemia was identified by the EMA,
based on 20 cases retrieved from EudraVigilance. The Rapporteur confirmed that the signal needed
initial analysis and prioritisation by the PRAC.
Discussion
The PRAC discussed the information on the suspected cases of haemolytic anaemia reported and noted
that the number of cases in consideration of wide population exposure of the product was low in
absolute terms, however the reactions reported were serious since some patients required transfusion
and in some other cases, for which information is available, patients experienced severe anaemia.
Therefore the PRAC agreed that the signal should be further investigated.
Summary of recommendation(s)
The MAH for Reyataz (atazanavir) should submit to the EMA, within 60 days, a comprehensive
and detailed cumulative review of the risk of haemolytic anaemia reported in post-marketing
and in clinical trials.
Pharmacovigilance Risk Assessment Committee (PRAC)
EMA/PRAC/324055/2014 Page 16/73