Flolan - referral

Current status

European Commission final decision

Overview

On 24 May 2012, the European Medicines Agency completed a review of Flolan. The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that there is a need to harmonise the prescribing information for Flolan in the European Union (EU).

What is Flolan?

Flolan is a medicine that contains the active substance epoprostenol. It is used to prevent blood clotting during haemodialysis (a technique for removing waste products from the blood used in patients with kidney disease). Flolan is also used to treat a lung condition called 'pulmonary arterial hypertension' (high blood pressure in the lungs).

The active substance in Flolan, epoprostenol, is a naturally occurring prostaglandin that works by stopping the blood from clotting. It stops the activation of the blood-clotting mechanism by preventing platelets (components that help the blood to clot) from sticking together. Epoprostenol also widens the blood vessels which helps to lower the blood pressure in the lungs.

Flolan is marketed in the following EU Member States: Austria, Belgium, the Czech Republic, Denmark, Estonia, France, Ireland, Italy, Luxembourg, Malta, the Netherlands, Spain and the United Kingdom, as well as Norway. It is also available under the trade name Epoprostenol.

The company that markets these medicines is GlaxoSmithKline.

Why was Flolan reviewed?

Flolan is authorised in the EU via national procedures. This has led to divergences across Member States in the way the medicine can be used, as seen in the differences in the summaries of product characteristics (SmPCs), labelling and package leaflets in the countries where the medicine is marketed.

Flolan was identified as needing harmonisation by the Co-ordination Group on the Mutual and Decentralised Procedures – Human (CMDh).

On 15 June 2011, the European Commission referred the matter to the CHMP in order to harmonise the marketing authorisations for Flolan in the EU.

What are the conclusions of the CHMP?

The CHMP, in the light of the data submitted and the scientific discussion within the Committee, was of the opinion that the SmPCs, labelling and package leaflets should be harmonised across the EU.

The areas harmonised include:

4.1 Therapeutic indications

After reviewing the available data supporting the use of the medicine, the CHMP agreed that Flolan should be used for the following:

• treatment of pulmonary arterial hypertension (PAH) (idiopathic or heritable PAH and PAH associated with connective tissue diseases) in patients with World Health Organization functional class III-IV symptoms to improve exercise capacity;
• haemodialysis in emergency situations when the use of heparin carries a high risk of causing or exacerbating bleeding, or when heparin is otherwise contraindicated.

4.2 Posology and method of administration

Having harmonised the indications, the CHMP also harmonised the recommendations on the use of Flolan in the elderly and patients with reduced kidney and liver function.

4.3 Contra-indications

In harmonising the contraindications, the CHMP decided to remove three contraindications that were in the SmPCs of some EU countries: pulmonary veno-occlusive disease, hypotension and angina. The CHMP was of the view that patients with pulmonary veno-occlusive disease could benefit from treatment with Flolan and that for hypotension and angina it was more appropriate to include relevant warnings in section 4.4.

Other changes

The CHMP also harmonised other sections of the SmPC including sections 4.6 (pregnancy and lactation), 4.5 (interaction with other medicinal products and other forms of interaction) and 4.8 (side effects).

The amended information to doctors and patients is available under the 'All documents' tab.

A European Commission issued a decision on 8 August 2012.

Questions and answers on Flolan and associated names (epoprostenol, 0.5 and 1.5 mg powder for solution for infusion)

AdoptedReference Number: EMA/CHMP/329168/2012 Rev.1Summary:

On 24 May 2012, the European Medicines Agency completed a review of Flolan. The Agency’s Committee for Medicinal Products for Human Use (CHMP) concluded that there is a need to harmonise the prescribing information for Flolan in the European Union (EU).

Key facts

About this medicine

• Approved name:
  Flolan
• International non-proprietary name (INN) or common name:
  epoprostenol
• Associated names:
  Epoprostenol

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-30/1299
• Type:
  Article 30 referrals

  This type of referral is triggered when Member States have adopted different decisions over the years for some medicines (e.g. different indications, contraindications or posology) and there is a need to harmonise across the EU.

Key dates and outcomes

• CHMP opinion date:
  24/05/2012
• EC decision date:
  08/08/2012

All documents

Flolan - Article 30 - Annex III

European Commission final decision

Flolan - Article 30 - Annex I

Flolan - Article 30 - Annex II

Questions and answers on Flolan and associated names (epoprostenol, 0.5 and 1.5 mg powder for solution for infusion)

AdoptedReference Number: EMA/CHMP/329168/2012 Rev.1Summary:

On 24 May 2012, the European Medicines Agency completed a review of Flolan. The Agency’s Committee for Medicinal Products for Human Use (CHMP) concluded that there is a need to harmonise the prescribing information for Flolan in the European Union (EU).

Description of documents published

Please note that some of the listed documents apply only to certain procedures.

• Overview - lay-language summary of the stage of the procedure
• Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
• Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
• List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
• Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
• List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
• List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
• Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
• Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
• Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
• Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
• Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
• Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
• Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
• Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)

Note that older documents may have different titles.