The European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) will be conducting a review of Rifadin 20 mg/ml oral suspension and syrup following concerns about the levels of one of its ingredients, diethanolamine (DEA).

Rifadin (Sanofi) is a rifampicin-containing medicine that is used to treat tuberculosis and other serious infections. DEA is used to ensure that the antibiotic is evenly distributed within the liquid and to maintain the acidity required for the medicine’s stability and tolerability. It has been classified as a possible carcinogen based on studies involving rodents that were exposed to very high doses over a long period of time. The EMA pointed out that the doses used in these studies were much higher than the amounts people would normally be exposed to when taking medicines that contain DEA.

The review was initiated at the request of the Dutch medicines agency, which is concerned about the carcinogenic risk posed by DEA on the benefit-risk balance of Rifadin oral suspension.

The CHMP will conduct an assessment and issue a recommendation on whether the marketing authorization in the EU should be maintained, amended, suspended, or revoked.

Proposals for New Formulation Absent 

In 2019, the EMA’s Coordination Group for Mutual Recognition and Decentralised Procedures requested that marketing authorization holders assess the risks associated with DEA and either reformulate affected medicines so they don’t contain this ingredient or justify why DEA could not be replaced with an alternative.

The current EMA review was commenced because, to date, the company that markets Rifadin 20 mg/ml oral suspension and syrup had not submitted a proposal for a new formulation of the medicine. In addition, the Netherlands considered that all possible options to replace DEA had not been sufficiently investigated and that DEA should be removed from the drug product formula.

More Information Needed 

Rifadin is authorized in Austria, France, Ireland, Italy, Netherlands, Northern Ireland, Portugal, and Spain. In Austria, France, and Spain, the medicine is marketed under the trade names, Rifoldin, Rifadine, and Rifaldin, respectively. 

Other medicines containing rifampicin and authorized in the European Economic Area are available in different pharmaceutical forms: capsules or powder and solvent for concentrate for solution for infusion.

The new EMA review is limited to one formulation of Rifadin — 20 mg/ml oral suspension and syrup — which is mainly used in children.

The marketing authorization holders are now requested to provide further information. This includes a review of all available preclinical and toxicological data related to the potential carcinogenic risk associated with oral exposure to DEA in general, and in Rifadin oral suspension and syrup. Also requested are proposals for potential reformulation strategies aimed at eliminating the presence of DEA in Rifadin oral suspension and syrup, and proposals for any other mitigation strategies that may improve benefit-risk balance of the product.

Rob Hicks is a retired National Health Service doctor. A well-known TV and radio broadcaster, he has written several books and has regularly contributed to national newspapers, magazines, and online publications. He is based in the United Kingdom.