Parenteral iron-containing medicinal products - referral

Current status

Procedure started

Overview

PRAC starts review of injectable iron-containing medicines.

Review will assess risk of low blood phosphate levels and related bone problems. 

Background

EMA’s safety committee, PRAC, has started a review of injectable iron-containing medicines following concerns about the risk of hypophosphataemia (low blood phosphate levels) and related bone problems, including osteomalacia (softening of the bones). Phosphate is important for keeping bones healthy. When phosphate levels become too low, osteomalacia can occur causing symptoms such as bone pain. In some cases, it can result in fractures. 

Injectable iron-containing medicines are used to treat iron deficiency and iron deficiency anaemia (low red blood cell levels) when iron taken by mouth does not work well enough, cannot be used, or when iron levels need to be restored quickly.

Hypophosphataemia and hypophosphataemic osteomalacia (softening of the bones caused by low blood phosphate levels) are known side effects of injectable iron medicines containing the active substance ferric carboxymaltose. Hypophosphataemia is listed as a common side effect in the product information, meaning it affects up to 1 in 10 people taking the medicine. However, the frequency of hypophosphataemic osteomalacia is unknown because the available data do not allow an estimate of how often it occurs. The product information also includes measures to reduce the risk of hypophosphataemic osteomalacia including recommendations to monitor blood phosphate levels in people receiving high doses or long-term treatment and those with known risk factors. 

The review was triggered following reports that raised concerns about the effectiveness of the current measures to reduce this risk for medicines containing ferric carboxymaltose. These included serious cases of hypophosphataemia, some of which resulted in osteomalacia, including in people who had received only one or two doses of ferric carboxymaltose and who did not have recognised risk factors. Furthermore, in some cases there were delays in diagnosing hypophosphataemia. This could be because symptoms of hypophosphataemia such as tiredness, muscle pain and bone pain may overlap with those of iron deficiency. In addition, the bone problems reported in these cases, such as osteomalacia, may not always be visible on X-rays. 

As similar cases have also been reported with other injectable iron-containing medicines, the scope of the review covers all of these medicines rather than only those containing ferric carboxymaltose. 

PRAC will now review the risk of hypophosphataemia and related bone disorders associated with injectable iron-containing medicines, as well as the effectiveness of existing measures to reduce these risks. The Committee will assess whether these risks affect the overall benefit-risk balance of the medicines and determine whether any changes to their marketing authorisations are needed.

More about the medicines

Injectable iron-containing medicines are used to treat iron deficiency and iron deficiency anaemia (low red blood cell counts). They are used when there is a need to increase iron levels quickly or when iron supplements taken by mouth cannot be used or do not work well enough, especially in people receiving dialysis for kidney failure, before and after operations, people with heart failure, women with severe iron deficiency during or after pregnancy or in cases of disorders that affect the absorption of nutrients from the gut. Depending on the medicine, they may be given as an injection into a vein, as a drip (infusion) into a vein, as an injection into a muscle, or through the dialysis machine during a dialysis session.

These medicines contain iron bound to for example sugar molecules, forming iron complexes. The review covers medicines containing the active substances ferric carboxymaltose, ferric derisomaltose, iron dextran, ferric gluconate, ferric hydroxide polymaltose complex and iron sucrose. These medicines are authorised in EU Member States under various trade names. 

Iron-containing medicines taken by mouth are not included in the review because they provide considerably lower amounts of iron over time than injectable medicines and are therefore less likely to cause hypophosphataemia.

More about the procedure

The review of injectable iron-containing medicines has been initiated at the request of the Austrian medicines Agency, under Article 31 of Directive 2001/83/EC. 

The review is being carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for human medicines, which will make a set of recommendations. As these medicines are all authorised nationally, the PRAC recommendations will be forwarded to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a position. The CMDh is a body representing EU Member States as well as Iceland, Liechtenstein and Norway. It is responsible for ensuring harmonised safety standards for medicines authorised via national procedures across the EU.

Parenteral iron-containing medicinal products Article-31 referral - PRAC starts review of injectable iron-containing medicines

Reference Number: EMA/196849/2026

Key facts

About this medicine

• Approved name:
  Parenteral iron-containing medicinal products
• International non-proprietary name (INN) or common name:
  • ferric carboxymaltose
  • ferric derisomaltose
  • ferric gluconate
  • ferric hydroxide polymaltose complex
  • iron dextran
  • iron sucrose
• Class:
  iron, parenteral preparations

About this procedure

• Current status:
  Procedure started
• Reference number:
  EMA/REF/0000369747
• Type:
  Article 31 referrals

  This type of referral is triggered when the interest of the Union is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.

• Authorisation model:
  Nationally authorised product(s)
• Decision making model:
  PRAC-CMDh

Key dates and outcomes

• Procedure start date:
  03/09/2026

All documents

Procedure started

Parenteral iron-containing medicinal products Article-31 referral - Annex I

Reference Number: EMADOC-1700519818-3433507

Parenteral iron-containing medicinal products Article-31 referral - Timetable for the procedure

Reference Number: EMADOC-1700519818-3419993

Parenteral iron-containing medicinal products Article-31 referral - PRAC list of questions

Reference Number: EMADOC-1700519818-3419982

Parenteral iron-containing medicinal products Article-31 referral - Notification

Parenteral iron-containing medicinal products Article-31 referral - PRAC starts review of injectable iron-containing medicines

Reference Number: EMA/196849/2026

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.