Protium - referral

Current status

European Commission final decision

Overview

The European Medicines Agency has completed a review of Protium and associated names. The Agency's Committee for Medicinal Products for Human Use (CHMP) has concluded that there is a need to harmonise the prescribing information for Protium and associated names in the European Union (EU) and the European Economic Area (EEA).

The review was carried out under an 'Article 30' referral¹.

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¹ Article 30 of Directive 2001/83/EC as amended, referral on the grounds of divergent decisions adopted by member States.

What is Protium?

Protium is used to treat diseases where the stomach produces too much acid. These include:

• reflux disease to treat symptoms such as heartburn and acid regurgitation (acid flowing up in the mouth),
• reflux oesophagitis (inflammation of the gullet, due to acid),
• stomach or duodenal ulcer,
• Zollinger-Ellison syndrome (a condition caused by oversecretion of acid in the stomach).

Protium can also be used for the prevention of the stomach ulcers that can be caused by some medicines used to treat pain and inflammations called non-selective non-steroidal anti-inflammatory drugs (NSAIDs), when the patient needs continuous NSAID treatment, and to help rid the stomach of a bacterium called Helicobacter pylori, which is known to cause stomach ulcers.

The active substance in Protium, pantoprazole, is a proton pump inhibitor (PPI). It works by blocking 'proton pumps', proteins found in specialised cells in the stomach lining that pump acid into the stomach. By blocking the pumps, pantoprazole reduces acid production.

Protium is also available in the EU and EEA under other trade names: Anagastra, Apton, Controloc, Eupantol, Inipomp, Pantec, Pantecta, Pantipp, Panto-Byk-20, Panto-Byk-40, Panto-Byk-IV, Pantoc, Pantoloc, PantoLomberg, Pantopan, Pantoprazol 20 mg Byk, Pantoprazol NYC, Pantoprazol Nycomed, Pantoprazol-Byk, Pantoprazole ALTANA, Pantoprazole Lomberg, Pantorc, Pantozol, Peptazol, Rifun, Somac, Ulcotenal, Zurcal, Zurcale and Zurcazol.

The company that markets these medicines is Nycomed.

Why was Protium reviewed?

Protium is authorised in the EU via national procedures. This has led to divergences among 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 product is marketed. Protium has been identified as needing harmonisation by the Co-ordination Group on the Mutual and Decentralised Procedures – Human (CMD(h)).

On 3 September 2008, the European Commission referred the matter to the CHMP in order to harmonise the marketing authorisations for Protium and associated names in the EU and the EEA.

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 main areas harmonised include:

4.1 Therapeutic indications
The CHMP agreed on a harmonised indication (the disease for which the medicine may be used). The Committee recommended that the 20-mg gastro-resistant tablets should be used for the treatment of symptomatic gastro-oesophageal reflux disease, the long-term management and prevention of relapse in reflux oesophagitis and the prevention of gastroduodenal ulcers induced by non-selective NSAIDs in patients at risk with a need for continuous NSAID treatment.

The Committee recommended that the 40-mg gastro-resistant tablets and the 40 mg powder for solution for injection should be used to treat reflux oesophagitis, gastric and duodenal ulcer, and Zollinger-Ellison syndrome and other pathological hypersecretory conditions. The 40-mg gastro-resistant tablets can also be used to eradicate H. pylori in combination with appropriate antibiotic therapy in patients with H. pylori-associated ulcers.

4.2 Posology and method of administration
The recommended dosage for the treatment of symptomatic gastro-oesophageal reflux disease, the long-term management of reflux oesophagitis and the prevention of gastroduodenal ulcers in patients taking NSAIDs, the recommended dose is one 20-mg tablet once daily. This can be increased to 40 mg a day in cases where symptoms of reflux oesophagitis relapse.

The recommended dose for reflux oesophagitis and gastric or duodenal ulcers is one 40 mg tablet or one 40 mg injection daily. The dose of the tablets may be doubled in cases where there has been no response to treatment. Zollinger-Ellison syndrome and other pathological hypersecretory conditions are treated with a daily dose of 80 mg of pantoprazole, either as two 40-mg tablets or an injection. The dose can be adjusted depending on the amount of acid being secreted in the stomach. To eradicate H. pylori in the stomach, the recommended dose is one 40-mg gastro-resistant tablet taken twice a day in combination with appropriate antibiotic treatment.

4.3 Contra-indications
The CHMP also agreed on a harmonised wording for the contra-indications (situations where the medicine must not be used). The Committee was of the opinion that the concomitant use of atazanavir and other anti-HIV medicines should not be contraindicated, but that a warning should be added in section 4.4.

4.4 Special warnings and precautions for use
Co-administration of atazanavir with PPIs is not recommended. However, if the combination of atazanavir with a PPI is judged unavoidable, close clinical monitoring (e.g. virus load) is recommended while high doses of PPI should be avoided. The CHMP also included a warning that treatment with Protium and other PPIs may lead to an increase in infections of the gut.

4.5 Interactions with other medicinal products
The CHMP noted that, due to interactions, the concomitant use of PPIs may affect the efficacy of atazanavir and other HIV medications whose absorption is pH-dependent.

Other changes
The CHMP harmonised the SmPC sections on pregnancy and lactation, the ability to drive and use machines, undesirable effects and overdose.

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

The European Commission issued a decision on 15 April 2010.

Questions and answers on the referral for Protium and associated names - pantoprazole, 20 or 40 mg gastro-resistant tablets and 40 mg powder for solution for injection

Adopted Reference Number: EMA/CHMP/565104/2009

Key facts

About this medicine

• Approved name:
  Protium
• International non-proprietary name (INN) or common name:
  pantoprazole
• Associated names:
  • Anagastra
  • Apton
  • Controloc
  • Eupantol
  • Inipomp
  • Pantec
  • Pantecta
  • Pantipp
  • Panto-Byk-20 / 40 / IV
  • Pantoc
  • Pantoloc
  • PantoLomberg
  • Pantopan
  • Pantorc
  • Pantozol
  • Peptazol
  • Rifun
  • Somac
  • Ulcotenal
  • Zurcal
  • Zurcale
  • Zurcazol

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-30/1002
• 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:
  17/12/2009
• EC decision date:
  15/04/2010

All documents

Protium - Article 30 referrals - Annex I

Protium - Article 30 referrals - Annex II

Protium - Article 30 referrals - Annex IV

Protium - Article 30 referrals - Annex III

Adopted

Questions and answers on the referral for Protium and associated names - pantoprazole, 20 or 40 mg gastro-resistant tablets and 40 mg powder for solution for injection

Adopted Reference Number: EMA/CHMP/565104/2009

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.