Lovenox and associated names - referral

Current status

European Commission final decision

Overview

Questions and answers on Lovenox and associated names (enoxaparin, solution for injection)

Outcome of a procedure under Article 30 of Directive 2001/83/EC

On 15 December 2016, the European Medicines Agency completed a review of Lovenox and associated names. The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that there is a need to harmonise the prescribing information for Lovenox in the European Union (EU).

What is Lovenox?

Lovenox is an anticoagulant medicine (a medicine to prevent blood clots) used in adults to prevent and treat conditions associated with blood clots such as deep vein thrombosis (where the clot develops in a deep vein, usually in the leg), as well as unstable angina (a severe type of chest pain caused by problems with the blood flow to the heart) and certain types of myocardial infarction (heart attack);
Lovenox contains the active substance enoxaparin. It is available as vials, ampoules, prefilled syringes and pens and is given by injection under the skin or into a vein.

Lovenox is available in all EU countries. It is also available under other trade names: Clexane, Clexane T, Clexane Forte, Klexane, Qualiop, Enoxaparin Sanofi and Enoxaparine Sanofi. The company that markets these medicines is Sanofi.

Why was Lovenox reviewed?

Lovenox 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.

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

On 12 November 2015, France referred the matter to the CHMP in order to harmonise the marketing authorisations for Lovenox in the EU.

What are the conclusions of the CHMP?

The CHMP, in 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:

The CHMP agreed that the strength of the active substance enoxaparin will now be expressed both in international units (IU) and in milligram (mg) throughout the product information.

4.1 Therapeutic indications

The CHMP agreed that Lovenox can be used for the following uses:

• to prevent venous thromboembolism (blood clots that form inside the veins, obstructing blood flow), especially in patients who are having surgery or who are at greater risk of clots because they have reduced mobility due to illness;
• to treat conditions associated with blood clots such as deep vein thrombosis (where the clot develops in a deep vein, usually in the leg) or pulmonary embolism (clot in a blood vessel supplying the lung);
• to treat unstable angina (a severe type of chest pain caused by problems with the blood flow to the heart);
• to treat certain types of myocardial infarction (heart attack);
• to prevent clots forming when blood is circulated through a haemodialysis machine to remove toxic substances.

4.2 Posology and method of administration

For the treatment of deep vein thrombosis and pulmonary embolism, the CHMP also clarified that the dose regimen of 150 IU/kg (1.5 mg/kg) given once daily should only be used only in uncomplicated patients who have a low risk of a further venous thromboembolism. Patients at higher risk should be given 100 IU/kg (1 mg/kg) twice daily.

The regimen should be selected by the physician based on an individual assessment including evaluation of the thromboembolic risk and of the risk of bleeding.

This section was also updated to reflect that outside its approved use in haemodialysis Lovenox is not recommended in patients with end stage kidney disease. A table with dosing recommendations in this group was included.

4.3 Contraindications

A contraindication that existed in some EU member states for use in patients with severe kidney impairment was removed.

The Committee also harmonised other sections of the SmPC including sections 4.4 (special warning and precautions), 4.5 (interaction with other medicinal products and other forms of interaction), 4.6 (fertility, pregnancy and lactation), 4.7 (effects on ability to drive and use of machines) and 4.8 (undesirable effects).

The European Commission issued a decision on this opinion on 9/03/2017.

Lovenox Article 30 referral - Questions and answers on Lovenox and associated names (enoxaparin, solution for injection)

Reference Number: EMA/837288/2016

Key facts

About this medicine

• Approved name:
  Lovenox and associated names
• International non-proprietary name (INN) or common name:
  enoxaparin

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-30/1429
• 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:
  15/12/2016
• EC decision date:
  09/03/2017

All documents

Opinion provided by Committee for Medicinal Products for human Use

Lovenox Article 30 referral - Annex III

Lovenox Article 30 referral - Questions and answers on Lovenox and associated names (enoxaparin, solution for injection)

Reference Number: EMA/837288/2016

European Commission final decision

Lovenox Article 30 referral - Assessment report

Reference Number: EMA/134171/2017

Lovenox Article 30 referral - Annex I

Lovenox Article 30 referral - Annex II

Lovenox Article 30 referral - Annex IV

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.