WC500185968

6.1.2. Brimonidine – MIRVASO (CAP)
Evaluation of a PSUSA procedure
Regulatory details:
PRAC Rapporteur: Rafe Suvarna (UK)
Administrative details:
Procedure number(s): EMEA/H/C/002642/PSUSA/10093/201408
MAH(s): Galderma International
Background
Brimonidine is a selective alpha2-adrenergic receptor agonist (dermatological agent) indicated for the
symptomatic treatment of facial erythema of rosacea in adult patients.
Based on the assessment of the PSUR, the PRAC reviewed the benefit-risk balance of Mirvaso, a
centrally authorised medicine containing brimonidine, 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 Mirvaso
(brimonidine) in the approved indication(s) remains favourable.
Nevertheless, the product information should be updated to include a new warning that cases
of aggravated erythema, flushing and skin burning sensation have been reported during the
post-marketing period. In addition, symptoms of allergic reaction including urticaria and facial
swelling should be included as undesirable effects with an uncommon frequency. Therefore the
current terms of the marketing authorisation(s) should be varied 10 .
In the next PSUR, the MAH should include as new important identified risk ‘condition
aggravated (erythema, flushing, skin burning sensation)’ and upgrade the safety concern
‘allergic reactions’ from an important potential to an important identified risk in a revised RMP.
The MAH should also provide an evidence-based review of the value of recommending that a
small test dose of Mirvaso should be applied to test tolerability prior to initiation of treatment,
taking into account the time to onset of aggravated symptoms and a consideration of whether
any of the excipients (as well as the active ingredient) might be involved. An appropriate
duration for the test period should be proposed. The MAH should discuss how patient exposure
could be better estimated, given that many patients are likely to be receiving long-term
treatment with Mirvaso.
Regarding the use of a targeted questionnaire for follow-up of cases of aggravated erythema
and flushing, it would be helpful for this to incorporate a question on any treatment given, and
its effectiveness. The MAH should include a mock-up of the questionnaire in the revised RMP.
Finally the MAH should specifically follow-up adverse event reports suggestive of a
haemodynamic effect for blood pressure measurements where appropriate, and should
carefully review cases of dizziness taking into account the time to onset from first dose of
Mirvaso and the possible effects of other drugs.
10 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 34/89