Sandimmun Neoral and associated names - referral

Current status

European Commission final decision

Overview

On 27 June 2013, the European Medicines Agency completed a review of Sandimmun and Sandimmun Neoral. The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that there is a need to harmonise the prescribing information for Sandimmun and Sandimmun Neoral in the European Union (EU).

What are Sandimmun and Sandimmun Neoral?

Sandimmun and Sandimmun Neoral are immunosuppressive medicines (medicines that reduce the activity of the immune system, the body's natural defences). Both medicines contain the active substance ciclosporin. However, while Sandimmun is an oil-based formulation of ciclosporin, Sandimmun Neoral is a microemulsified formulation, which allows for a more uniform absorption of ciclosporin by the body.

Sandimmun and Sandimmun Neoral are used in patients who have had a transplant, to prevent rejection (when the immune system attacks the transplanted organ) and to treat or prevent graft-versus-host disease (when the immune system of the transplanted organ attacks the patient's tissues). They are also used to treat autoimmune diseases. An autoimmune disease is a disease which is caused by the body's own defence system attacking normal tissue.

The active substance in Sandimmun and Sandimmun Neoral, ciclosporin, acts on some special cells in the immune system called T-cells that are responsible for attacking transplanted organs or, in auto-immune diseases, normal tissue.
Sandimmun and Sandimmun Neoral are available as capsules (10, 25, 50 and 100 mg) and oral solution (100 mg/ml). Sandimmun is also available as a concentrate for solution for infusion (50 mg/ml). Both medicines are available in the EU under other trade names: Immunosporin, Neoral, Neoral – Sandimmun, Sandimmun Optoral and Sandimmune.

The companies that market these medicines are Novartis group of companies and associated companies.

Why were Sandimmun and Sandimmun Neoral reviewed?

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

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

On 15 December 2011, the European Commission referred the matter to the CHMP in order to harmonise the marketing authorisations for Sandimmun and Sandimmun Neoral 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

The CHMP agreed that Sandimmun and Sandimmun Neoral should be used in the following indications, which were already approved in several but not all EU Member States:

• Solid organ transplantation (for the prevention and treatment of graft rejection);
• Bone marrow transplantation (for the prevention of graft rejection and prevention or treatment of graft-versus-host disease).

In addition, the capsules and oral solutions may also be used to treat the following autoimmune diseases:

• Endogenous uveitis (inflammation of the uvea, the middle layer of the eye);
• Nephrotic syndrome (a kidney disease);
• Severe rheumatoid arthritis (a disease causing damage and inflammation in the joints);
• Severe psoriasis (a disease causing red, scaly patches on the skin);
• Severe atopic dermatitis (eczema, an itchy red rash of the skin).

The CHMP did not recommend use in aplastic anaemia (a blood disorder in which the bone marrow doesn't make enough new blood cells), which was approved in only one Member State.

4.2 Posology and method of administration

The CHMP agreed on specific dose ranges for the various indications, which should serve as guidelines only, and recommended that these medicines should be given in two divided doses equally distributed throughout the day.

Sandimmun and Sandimmun Neoral should only be prescribed by, or in close collaboration with, a doctor experienced in the diseases that these medicines are used to treat.

Information on how to switch between different ciclosporin medicines was also included in the product information of these medicines.

4.3 Contra-indications

The CHMP agreed that Sandimmun and Sandimmun Neoral should not be used in patients who are hypersensitive (allergic) to the active substance. They should also not be given in combination with a herbal medicine called St John's wort (used to treat depression) nor with medicines whose blood levels may be increased by ciclosporin and lead to serious side effects, such as dabigatran etexilate (used to prevent the formation of blood clots after surgery) or bosentan and aliskiren (used to treat high blood pressure).

Other changes

The Committee also harmonised other sections of the SmPC, including sections 4.4 (special warnings and precautions for use), 4.5 (interactions with other medicines) and 4.6 (use in pregnancy and breast feeding). The package leaflet was amended accordingly.

Questions and answers on Sandimmun, Sandimmun Neoral and associated names (ciclosporin, 10, 25, 50 and 100 mg capsules, 100 mg/ml oral solution and 50 mg/ml concentrate for solution for infusion)

Reference Number: EMA/391239/2013

Key facts

About this medicine

• Approved name:
  Sandimmun Neoral and associated names
• International non-proprietary name (INN) or common name:
  ciclosporin

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-30/1300, EMEA/H/A-30/1320
• 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:
  27/06/2013
• EC decision date:
  31/10/2013

All documents

Opinion provided by Committee for Medicinal Products for human Use

Sandimmun Neoral Article-30 referral - Assessment report

AdoptedReference Number: EMA/589501/2013

Sandimmun Neoral Article-30 referral - Annex III

Questions and answers on Sandimmun, Sandimmun Neoral and associated names (ciclosporin, 10, 25, 50 and 100 mg capsules, 100 mg/ml oral solution and 50 mg/ml concentrate for solution for infusion)

Reference Number: EMA/391239/2013

European Commission final decision

Sandimmun Neoral Article-30 referral - Annex I

Sandimmun Neoral Article-30 referral - Annex II

Reference Number: EMEA/H/A-30/1300

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.