WC500185968

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.
6.2. Follow-up to PSUR procedures 21
6.2.1. Tacrolimus – PROTOPIC (CAP)
Evaluation of a follow-up to a PSUR procedure
Regulatory details:
PRAC Rapporteur: Almath Spooner (IE)
Administrative details:
Procedure number(s): EMEA/H/C/000374/LEG 056
Procedure scope: MAH’s responses to the outcome of the evaluation of PSU 055 as adopted in October
2014
MAH(s): Astellas Pharma Europe B.V.
Background
Following the most recent assessment of a PSUR for the above mentioned medicines, the PRAC
requested the MAH to provide detailed reviews of cases of non-cutaneous infection and of cases of
more generalised infection secondary to cutaneous infection or infected atopic dermatitis; a detailed
analysis of cases of lentigo as well as a comprehensive review of cases of skin pigmentation
abnormalities with a discussion of this issue in relation to topical calcineurin inhibitor (CNI) use,
including potential mechanisms and relevant non-clinical data and data from the scientific literature.
Finally the PRAC requested the MAH to provide detailed reviews of cases of off-label use, generalised
lymphadenopathy in association with long-term use of tacrolimus ointment, increased creatinine and
osteomyelitis. The MAH was also requested to provide a discussion on the use of the targeted
lymphoma questionnaire including the gathering of data on such cases and to provide the
questionnaire responses in its discussion of reported cases. In addition, the MAH was requested to
provide further details on the prescription of tacrolimus ointment by non-specialists particularly in
children under 2 years and between 2 and 16 years. Finally, the MAH was requested to provide a
detailed discussion on first line use of tacrolimus ointment in relation to the European market (see
PRAC Minutes October 2014). The responses were assessed by the Rapporteur for further PRAC advice.
Summary of advice/conclusion(s)
Based on the review of the data submitted by the MAH, the PRAC agreed that the MAH should submit
within two months a variation to include lentigo as an undesirable effect with an unknown frequency.
In addition the PRAC agreed that the MAH should monitor and review cases of skin pigmentation
abnormalities associated with the use of Protopic should further relevant data emerge, and present
cases of selected infections for review in the next PSUR (DLP: 31/03/2015).
6.2.2. Telmisartan, amlodopine – TWYNSTA (CAP)
Evaluation of a follow-up to a PSUR procedure
Regulatory details:
PRAC Rapporteur: Valerie Strassmann (DE)
21 Follow-up as per the conclusions of the previous PSUR procedure, assessed outside of the next PSUR procedure
Pharmacovigilance Risk Assessment Committee (PRAC)
EMA/PRAC/257790/2015 Page 46/89