Closamectin Pour-on Solution and associated names - referral

Current status

European Commission final decision

Overview

On 8 October 2015, the European Medicines Agency (the Agency) completed a review of the animal safety of Closamectin Pour-On Solution and associated names. The Agency's Committee for Medicinal Products for Veterinary Use (CVMP) concluded that the benefits of Closamectin Pour-On Solution and associated names continue to outweigh their risks subject to variation of the marketing authorisations to include new adverse reactions and precautionary measures and conditions concerning risk mitigation and surveillance measures.

What is Closamectin Pour-On Solution and associated names?

Closamectin Pour-On Solution and associated names contain closantel and ivermectin and are authorised in several European Union (EU) Member States¹ via decentralised and national procedures. The products are effective for use in beef cattle for the treatment of mixed trematode (fluke) and nematode or arthropod infestations due to roundworms, lungworms, eyeworms, warbles, mites and lice.

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¹Austria, Belgium, Czech Republic, Denmark, France, Germany, Greece, Ireland, Italy, Poland, Portugal, Romania, Spain, Sweden, Slovenia, Slovakia and the United Kingdom

Why were Closamectin Pour-On Solution and associated names reviewed?

Between 25 May 2011 and 31 May 2015 the French medicines regulatory agency (Agence Nationale du Médicament Vétérinaire (ANMV)) received a total of 123 adverse event reports involving Closamectin Pour-On Pour Bovins in which 401 animals were affected and 121 died. The adverse events principally related to neurological signs (ataxia, recumbency, paresis/paralysis and blindness) and/or gastrointestinal disorders (diarrhoea, anorexia etc.) some of which had a fatal outcome. The nature of the reported clinical signs was considered by ANMV to be indicative of the clinical signs associated with overdose toxicity of closantel. Although the overall incidence of adverse events was considered to be within acceptable limits (0.006% in the last annual periodic safety update report ) the continued occurrence of serious adverse events and the severity of subsequent losses on farms in France were considered significant, which led to the suspension of the marketing authorisation in France on 6 July 2015. The product was also recalled at veterinary clinic and wholesale level.

On 19 June 2015, France triggered a procedure under Article 78 of Directive 2001/82/EC for Closamectin Pour-On Solution and associated names following evaluation of pharmacovigilance data indicating serious concerns for animal safety and subsequent suspension of the marketing authorisation for the product. Accordingly, the CVMP was requested to give its opinion on the matter concerning animal safety.

Which data has the CVMP reviewed?

To investigate the potential relation between the adverse events observed and Closamectin Pour-On Solution and associated names, the CVMP considered the data provided by the marketing authorisation holder (MAH). This included a review of scientific literature regarding the pharmacology and toxicology of ivermectin and closantel, cumulative pharmacovigilance experience following use of the products in the EU since 2009, a comparison with ivermectin-based products and with ivermectin/closantel injectable formulations held by the MAH, investigations carried out by the MAH to identify possible factors involved in reported adverse events and proposals for risk mitigation measures and actions.

What are the conclusions of the CVMP?

Based on the evaluation of the currently available data and the scientific discussion within the Committee, the CVMP concluded that the benefits of Closamectin Pour-On Solution and associated names continue to outweigh their risks subject to:

• variation of the marketing authorisations for Closamectin Pour-On Solution and associated names to amend the summary of product characteristics and package leaflet to include new precautionary measures and adverse reactions; and
• conditions of the marketing authorisations concerning risk mitigation and surveillance measures.

It was also recommended that the suspension of the marketing authorisation for Closamectin Pour-On Solution Pour Bovins in France be lifted.

The European Commission issued a decision on 22 March 2016.

Questions and answers on Closamectin Pour-On Solution and associated names

Reference Number: EMA/672999/2015 Summary:

EMEA/V/A/113

Key facts

About this medicine

• Approved name:
  Closamectin Pour-on Solution and associated names
• International non-proprietary name (INN) or common name:
  • ivermectin
  • closantel

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/V/A/113
• Type:
  Article 78 referrals (prior to January 2022)

  This type of referral is initiated when, as a result of the evaluation of veterinary pharmacovigilance data, a Member State considers that a marketing authorisation should be suspended, withdrawn or varied to restrict the indications or availability, amend the posology, add a contraindication or add a new precautionary measure.

Key dates and outcomes

• Opinion date:
  08/10/2015
• EC decision date:
  22/03/2016

All documents

European Commission final decision

Opinion following an Article-78 procedure for Closamectin Pour-On Solution and associated names

Reference Number: EMA/CVMP/511375/2015

Closamectin Article-78 referral - Annex I-IV

Reference Number: EMEA/V/A/113

Questions and answers on Closamectin Pour-On Solution and associated names

Reference Number: EMA/672999/2015 Summary:

EMEA/V/A/113

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
• 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. veterinary healthcare professionals, farmers, academia) (if applicable)
• Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
• Scientific conclusions – scientific conclusions of CVMP
• Divergent positions – divergent positions of the CVMP members (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)