European Medicines Agency recommends restricting use of thiocolchicoside by mouth or injection
Press release
Human
Medicines
Medicine only to be used at low doses for additional short-term relief of painful muscle contractures
The European Medicines Agency's Committee on Human Medicinal Products (CHMP) has recommended that the authorised uses for thiocolchicoside-containing medicines for use by mouth or injection should be restricted across the European Union (EU). These medicines are now recommended only as an add-on treatment for painful muscle contractures (permanent tightening of the muscle tissue) resulting from spinal conditions in adults and adolescents 16 years of age or older. In addition, the dose of thiocolchicoside by mouth or injection should be restricted.
Thiocolchicoside is a muscle relaxant that has been authorised by national procedures in several EU Member States1 for use by mouth or injection into the muscles in the treatment of painful muscular disorders.
The review of thiocolchicoside was triggered by the Italian medicines regulatory agency, AIFA, following new experimental evidence which suggested that thiocolchicoside was broken down in the body into a metabolite called M2 or SL59.0955 that could damage dividing cells, resulting in aneuploidy (an abnormal number or arrangement of chromosomes). As a result AIFA asked the CHMP to examine the safety profile of this medicine and consider what regulatory action might be appropriate.
The CHMP reviewed the evidence, including the opinions of experts in the field of medicines safety, and concluded that aneuploidy could occur with M2 at levels not much greater than those seen after recommended doses of thiocolchicoside taken by mouth. Aneuploidy is a risk factor for harm to the developing fetus, reduced fertility in men and in theory could increase the risk of developing cancer. The CHMP therefore recommended measures to ensure thiocolchicoside-containing medicines are used as safely as possible. These include restricting the maximum dose and number of days of treatment when given by mouth or injection. Use is also contra-indicated in pregnancy and lactation or in women of childbearing potential not using contraception, as well as in children or for chronic (long-term) conditions. Preparations for local application to the skin, which do not produce substantial levels of M2 in the body, are not affected by this review.
The CHMP opinion will now be forwarded to the European Commission, which will issue a final decision in due course.
Information to patients
Information to healthcare professionals
The Committee's recommendations were based on a review of available data from pre-clinical and clinical studies, published literature and post-marketing experience, and consultations with an expert working party on medicines safety. Preclinical studies indicated that the thiocolchicoside metabolite 3-demethylthiocolchicine (M2, SL59.0955) may be associated with aneuploidy (abnormal chromosome number and loss of heterozygosity) in dividing cells, at levels of exposure not much greater than those achieved in the body with maximum recommended oral doses. Aneuploidy is an established risk factor for teratogenicity, embryotoxicity or spontaneous abortion, and impaired male fertility. In theory it also increases the risk of cancer, although any significantly increased cancer risk would in general be dependent on long-term exposure to the causative substance. Thiocolchicoside metabolites were not associated with mutagenicity (changes to genes) or clastogenicity (structural damage to chromosomes). The Committee concluded that in the light of current evidence the benefit-risk for the medicine remained positive provided appropriate risk-mitigating measures were taken, including restricting the maximum dose and duration of use and contra-indicating use during pregnancy and lactation and in children
More about the medicine
Thiocolchicoside is used as a muscle relaxant in the treatment of painful muscular conditions. It is thought to act on receptors in the nervous system that are involved in the regulation of muscle function.
Thiocolchicoside is authorised through national procedures in the Czech Republic, France, Greece, Hungary, Italy, Malta, Portugal and Spain. It is available for use by mouth or by injection into the muscles. In some countries it is also available as preparations to be applied to the skin, but these latter preparations are not affected by this review.
More about the procedure
The review of systemic thiocolchicoside-containing medicines was triggered on 15 February 2013 at the request of Italy, under Article 31 of Directive 2001/83/EC. This followed new evidence from experimental studies carried out by a marketing authorisation holder which suggested an effect on chromosomes by a metabolite of thiocolchicoside. The Italian medicines regulatory authority therefore requested the CHMP to carry out a full assessment of the benefit-risk balance of systemic medicines containing thiocolchicoside, and issue an opinion on whether their marketing authorisations should be maintained, varied, suspended or withdrawn across the European Union.
The CHMP opinion will now be forwarded to the European Commission, which will issue a final decision in due course.
1Czech Republic, France, Greece, Hungary, Italy, Malta, Portugal and Spain.