The Italian Medicines Agency AIFA withdraws the paediatric indication for domperidone-containing products

The Italian Medicines Agency AIFA withdraws the paediatric indication for domperidone-containing products

The Italian Medicines Agency AIFA has just released a safety communication about the use of medicines containing domperidone. Domperidone-containing medicines have been authorised nationally in individual Member States of the EU for the treatment of nausea and vomiting of various causes since 1970s, with the first approval in Belgium in March 1978.

The AIFA communication is aimed to remind the recommendations for the use of domperidone-containing medicines in order to reduce the risk of cardiac severe adverse events already published on 07/03/2014 by AIFA in agreement with the European Medicines Agency (EMA) and to inform health care professionals on the results of a new paediatric study.

The profile risk/benefit of domperidone has been studied for a long time. The injectable form of domperidone was already withdrawn in 1985 because of cardiac adverse events. In 2007, the AIFA Experts Group on “Drugs and Children” carried out a review of the efficacy and safety data on antiemetic drugs in children, in order to provide recommendations for clinical practice (Drug Information Bulletin No. 5/2007). The review showed that efficacy data in children were few and poorly documented by clinical trials, while the risk of adverse reactions was well known and well documented.

Moreover, domperidone-containing products are also used to increase the secretion of milk of lactating mothers as off-label and also in this case, the French medicines agency “Agence française de sécurité sanitaire des produits de santé” (Afssaps) highlighted the risk associated with this use in 2011. A communication has also been released by the Italian Epidemiology and Preventive Pharmacology Centre (SEFAP) underlining that the risk/benefit ratio of domperidone used to increase the secretion of milk have not been demonstrated.

On 23 April 2014, the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) endorsed the Pharmacovigilance Risk Assessment Committee (PRAC) recommendations to restrict the use of domperidone-containing medicines. The review of domperidone was carried out at the request of the Belgian medicines authority, the Federal Agency for Medicines and Health Products (FAGG-AFMPS) over concerns about the medicine’s effects on the heart.

The PRAC was asked to examine whether the benefits outweighed the risks for these medicines in their approved uses and forms, and whether their marketing authorisations should be maintained or changed across the EU. The review confirmed that domperidone-containing medicines may continue to be used in the EU only for the management of the symptoms of nausea and vomiting, but the recommended dose should be reduced to 10 mg up to three times daily by mouth with a maximum daily dose of 30mg in adults and adolescents weighing 35 kg or more.

Products licensed in children and adolescents weighing less than 35 kg were not suspended but it was recommended to use only oral formulation at a dose of 0.25 mg per kg bodyweight up to three times daily. Nevertheless, CMDh underlined that there were limited data to support paediatric use in this indication, therefore studies to provide further data to support efficacy in this population have been requested.

We asked Prof Adriana Ceci* as previous member of the AIFA Experts Group on “Drugs and Children” to provide her consideration about this AIFA communication:

“The CMDh position, dated back to 2014, did not withdraw the use of domperidone in children <12 years/35 Kg allowing to a jeopardised situation in EU since a paediatric indication has not been granted in all the Member State. However where not granted under 12 years, domperidone has been, largely used as off-label.

The AIFA communication goas behind and taking into account the new data collected in children clarifies that under 12 years of age the risk-benefit ratio remains negative and that also in older children the health professionals should avoid inappropriate uses and incorrect dosages.

This communication is long overdue considering the review on efficacy and safety data of antiemetic drugs in children carried out in 2007 by the AIFA Experts Group on “Drugs and Children” providing similar conclusions.

We can only hope that the AIFA position will be largely disseminated among the paediatricians in charge to prescribe domperidone-containing medicines. The paediatricians should evaluate carefully the overall risk/benefit profile in every child before starting a treatment based on domperidone-containing medicines, in order to avoid unneeded exposure among children. We also hope that the package leaflets revisions will be concluded very soon”

What remains to be done and which can be the contribution of TEDDY in this field?

“Now it is important to evaluate whether the benefit-risk balance of domperidone remains positive also in children over 12-year-old for the still approved indications. Within TEDDY, we can promote an analysis of the use of domperidone-containing medicines in all the Member States to push for a common decision at European level, as a case study for other uses not supported by scientific evidence”.

* Adriana Ceci, is funder member of TEDDY – European Network of Excellence for Paediatric Clinical Research, President of the Gianni Benzi Foundation Onlus, Past member of the Italian – Commissione Unica del Farmaco and of the Paediatric Committee at EMA.

June 5th, 2019|