PRAC Starts Review on Ambroxol, Bromhexine Meds

Larry Hand


April 11, 2014

The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has started a safety review of medicines that contain ambroxol and bromhexine.

The medicines are used as expectorants and for sore throat. In addition, some are used in treating breathing disorders in premature and newborn babies, as well as to increase lung maturation prenatally.

The Belgian medicines agency requested the review by PRAC after it received reports of allergic reactions, including anaphylactic, associated with ambroxol. Other reports have also linked ambroxol with severe adverse skin reactions.

The Belgian agency also expressed concern over use of ambroxol in children under 6 years of age and questioned whether benefits outweighed risks.

Bromhexine is largely converted into ambroxol by the body, and some reports have associated bromhexine with allergic reactions. PRAC therefore decided to include it in the review.

The primary use of these drugs is oral intake to help thin mucus so it can be cleared more easily by patients with short- or long-term lung or airway problems. A lozenge formulation is available for sore throat. Injection formulations are available for use in premature and newborn babies to treat respiratory distress syndrome, in which a baby's lungs are immaturely developed.

The drugs are authorized in 28 European jurisdictions.

The committee will be looking into how the medicines are being used, such as prescription or over the counter, dosages, and whether manufacturers have issued any warnings. They will ask about specific sales figures, stratified by age bracket, geographic area, and the indications for which the drugs are being used.

Other questions will include potential benefits that are being achieved, and possible risks, to arrive at a risk/benefit ratio. PRAC also wants to know whether any "risk minimization" efforts are ongoing.

PRAC is asking marketing authorization holders specific questions, as summarized below:

  • Question 1: How are ambroxol and bromhexine being used? PRAC is requesting a summary of product characteristics and the package leaflet, and whether they vary by jurisdiction.

  • Question 2: Please provide evidence of therapeutic benefits and, when applicable, stratified by age groups, 0 to 6 years, 6 to 12 years, and older than 12 years.

  • Question 3: Regarding risks of immediate hypersensitivity and delayed hypersensitivities associated with cutaneous adverse events, please provide all of this information since launch of products.

  • Question 4: Please provide a benefit/risk balance evaluation in each of the medicines license indications.

  • Question 5: Please provide proposals and justifications with supportive evidence for any risk minimization measures that may improve the benefit/risk balance.

After PRAC completes the review, the committee will issue an opinion on whether marketing authorizations should be maintained, varied, suspended, or withdrawn across the European Union. The recommendation will be forwarded to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human, which will adopt a final position.


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