WC500185968

6.1.4. Enzalutamide – XTANDI (CAP)
Evaluation of a PSUSA procedure
Regulatory details:
PRAC Rapporteur: Dolores Montero Corominas (ES)
Administrative details:
Procedure number(s): EMEA/H/C/002639/PSUSA/10095/201408
MAH(s): Astellas Pharma Europe B.V.
Background
Enzalutamide is a potent androgen receptor signalling inhibitor that blocks several steps in the
androgen receptor signalling pathway indicated for the treatment of prostate cancer under certain
conditions.
Based on the assessment of the PSUR, the PRAC reviewed the benefit-risk balance of Xtandi, a
centrally authorised medicine containing enzalutamide, and issued a recommendation on its marketing
authorisation(s).
Summary of recommendation(s) and conclusions
Based on the review of the data on safety and efficacy, the risk-benefit balance of Xtandi
(enzalutamide) in the approved indication(s) remains favourable.
Nevertheless, the product information should be updated to include hypersensitivity reactions
as new warning and to include rash, tongue oedema, lip oedema, pharyngeal oedema, nausea
and vomiting as undesirable effects with an unknown frequency. Therefore the current terms of
the marketing authorisation(s) should be varied 12 .
In the next PSUR, the MAH should provide the number of cases excluded (patients who did not
receive the study drug) providing a brief description of those cases. The MAH should provide a
definition of thrombocytopenia and platelet count decreased also including the platelet count
level taken into consideration to define both terms. The MAH should present a detailed
description of the 7 cases from study CRPC2, where the patients who were in the enzalutamide
arm developed thrombocytopenia during the first and second months of treatment. The MAH
should include relevant safety information or information with a potential impact on the
benefit-risk assessment retrieved from the fixed-combination therapies studies and from noninterventional
studies, if available. The MAH should provide a cumulative review of peripheral
oedema, and of asthenia and fatigue to assess if there is a causal relationship between
enzalutamide treatment and these adverse events. Based on the outcome of these reviews,
proposals for updating the product information should be provided. The MAH should provide a
cumulative review of all cases which contain combined androgen antagonism (gonadotropinreleasing
hormone agonists) with oral anti-androgens to evaluate if there could be a relevant
association which could impact on the increased risk of acute kidney injury.
The next PSUR should be submitted in accordance with the requirements set out in the list of Union
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC.
12 Update of SmPC sections 4.4 and 4.8. The package leaflet is updated accordingly. The PRAC AR and PRAC
recommendation are transmitted to the CHMP for adoption of an opinion
Pharmacovigilance Risk Assessment Committee (PRAC)
EMA/PRAC/257790/2015 Page 36/89