Novantrone and associated names - referral

Current status

European Commission final decision

Overview

On 28 April 2016, the European Medicines Agency completed a review of Novantrone. The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that there is a need to harmonise the prescribing information for Novantrone in the European Union (EU).

What is Novantrone?

Novantrone is a medicine that is used in the treatment of cancers including breast cancer, non-Hodgkin's lymphoma (a cancer of the lymphatic system, which is part of the immune system) and certain types of blood cancer, as well as pain caused by prostate cancer. It is also used to treat patients with worsening multiple sclerosis when no alternative treatments are available.

Novantrone contains the active substance mitoxantrone and it is available as a concentrate to be made into a solution for infusion (drip) into a vein.
Novantrone is marketed in the following EU member states: Cyprus, Finland, France, Germany, Greece, Italy, Romania, Slovenia, Spain and Sweden, as well as Iceland and Norway. It is also available in the EU under the trade names Elsep and Ralenova.

The company that markets these medicines is MEDA.

Why was Novantrone reviewed?

Novantrone has been authorised in the EU via national procedures. This has led to divergences across Member States in the medicine's authorised uses, as seen in the differences in the summaries of product characteristics (SmPCs), labelling and package leaflets.

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

On 1 October 2014, the European Commission referred the matter to the CHMP in order to harmonise the marketing authorisations for Novantrone 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, considered that the SmPCs, labelling and package leaflets should be harmonised across the EU.

The areas harmonised include:

4.1 Therapeutic indications

The CHMP agreed that Novantrone can be used for the treatment of the following conditions:

• Metastatic breast cancer (breast cancer that has spread to other parts of the body);
• Non-Hodgkin's lymphoma;
• Acute myeloid leukaemia (cancer of a type of white blood cell called myeloid cells);
• 'Blast crisis' in chronic myeloid leukaemia (the final, rapidly progressive stage of another type of cancer of white blood cells);
• Relief of pain in patients with advanced prostate cancer;
• Highly active relapsing multiple sclerosis associated with rapidly evolving disability, in patients for whom no alternative treatments are available.

The CHMP also agreed that Novantrone should no longer be approved for the treatment of acute lymphocytic leukaemia (a cancer of a different type of white blood cells) and liver cancer.

4.2 Posology and method of administration

The CHMP also harmonised the recommendations on how to use Novantrone for the different indications. The recommended dose of Novantrone and the duration of treatment depend on the disease it is used for, whether it is used in combination with other medicines, on the height and weight of the patient, and on the response to treatment. Daily doses vary from 6 to 14 mg per square metre of body surface area (calculated using the patient's height and weight). Novantrone should only be given by infusion into a vein.

4.3 Contra-indications

Mitoxantrone, the active substance in Novantrone, passes into breast milk and has been detected in breast milk for up to one month after the medicine was discontinued. Therefore, to avoid potential serious side effects in breastfed infants, breastfeeding must be discontinued before starting treatment with Novantrone.

Additionally, Novantrone must not be used for the treatment of multiple sclerosis in pregnant women.

Other changes

The Committee also harmonised other sections of the SmPC including sections 4.4 (special warnings and precautions for use), 4.5 (interactions), 4.6 (fertility, pregnancy and lactation), 4.7 (effects on ability to drive and use machines), 4.8 (side effects) and 5.1 (pharmacodynamic properties).

A risk management plan will be developed to ensure that Novantrone is used as safely as possible. As part of this plan, the company will provide educational materials about the use of Novantrone in patients with multiple sclerosis. The educational materials will include a guide and checklist for healthcare professionals informing of the risks of cardiotoxicity (harm to the heart) and leukaemia with the medicine, and how patients should be monitored. Patients will receive a guide to the risks and an alert card describing the signs and symptoms to watch out for. The company will prepare a survey for healthcare professionals to check how well these materials work.

The amended information to doctors and patients is available in Annex III under 'All Documents' tab.

A European Commission decision on this opinion will be issued in due course.

Questions and answers on Novantrone and associated names (mitoxantrone 2 mg/ml concentrate for solution for infusion)

Reference Number: EMA/55368/2016

Key facts

About this medicine

• Approved name:
  Novantrone and associated names
• International non-proprietary name (INN) or common name:
  mitoxantrone
• Associated names:
  • Elsep
  • Ralenova
• Class:
  Antineoplastic agent

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-30/1399
• 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:
  28/04/2016
• EC decision date:
  24/06/2016

All documents

Opinion provided by Committee for Medicinal Products for human Use

Novantrone Article-30 referral - Annex III

Questions and answers on Novantrone and associated names (mitoxantrone 2 mg/ml concentrate for solution for infusion)

Reference Number: EMA/55368/2016

European Commission final decision

Novantrone and associated names Article-30 referral - Assessment report

Reference Number: EMA/CHMP/427120/2016

Novantrone Article-30 referral - Annex I

Novantrone Article-30 referral - Annex II

Novantrone 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.