Translation of "Rafoxanide" in German

Half-lives reported for rafoxanide range between 7 and 16.6 days.

Based on this study, the parent compound, rafoxanide, was concluded to be the appropriate marker residue in milk, and a ratio of marker to total residues of 0.3 was established.

It should be noted that many (155) of the clorsulon, closantel, nitroxinil, rafoxanide or triclabendazole containing products are combination products containing other active substances.

The flukicidal substances for which a MRL has not been established in milk and that are included as active substances in authorised veterinary medicinal products in the Member States (EU/EEA) are clorsulon, closantel, nitroxinil, rafoxanide and triclabendazole.

Based on this it was estimated that the safe level in milk (6 µg/l) would occur when the plasma concentration of rafoxanide is 0.18 µg/ml.

It is concluded that use of rafoxanide containing products administered orally should take place during the first or second trimesters (and not during the third trimester) of the gestation period in order to ensure that residues in milk would not be at a level that could result in total exposure to residues over the ADI.

Assuming consumption of 1.5 l of milk per day and a marker to total residues ratio of 0.3, it is concluded that the concentration of rafoxanide in milk that can be considered safe is 6 µg/l.

It is therefore considered that the only acceptable subcutaneous use of rafoxanide in cattle intended for production of milk for human consumption would involve administration to young animals before the first pregnancy and at least 1 year before the first calving.

It is concluded that the only acceptable use of rafoxanide in ewes intended for production of milk for human consumption would involve administration to young animals before the first pregnancy and at least 1 year before the first lambing.

On 14 June 2012 the CVMP adopted a final opinion confirming the recommendation, included in its opinion of 8 March 2012, that variations are necessary in the marketing authorisations for the veterinary medicinal products containing clorsulon, closantel, nitroxinil, rafoxanide or triclabendazole as a single active substance and for the veterinary medicinal products administered as pour-on to cattle containing triclabendazole and moxidectin in order to amend the summaries of product characteristics and package leaflets in line with recommended by the CVMP changes in the product information.

Having considered all the overall package of data submitted the CVMP concluded that the benefit-risk balance for the veterinary medicinal products containing clorsulon, closantel, nitroxinil, rafoxanide or triclabendazole as single active substances (see Annex I) was positive provided that adequate instructions concerning use in dairy animals are included in section 4.11 Withdrawal period(s) of the SPC of the relevant products based on the time spans shown in the above table.

The flukicidal substances for which a maximum residue limit has not been established in milk and that are included as active substances in authorised veterinary medicinal products in the Member States (EU/EEA) are clorsulon, closantel, nitroxinil, rafoxanide and triclabendazole.

The CVMP was therefore requested to give its opinion as to whether measures are necessary to ensure that the use, during the non-lactating period, of veterinary medicinal products containing clorsulon, closantel, nitroxinil, rafoxanide and triclabendazole, would not lead to residues in milk that, combined with residues of these flukicidal substances from other foodstuffs, would result in consumer exposure exceeding the acceptable daily intake.

Based on the evaluation of the available data, the CVMP adopted, on 8 March 2012, an opinion recommending variations of the marketing authorisations for the veterinary medicinal products containing clorsulon, closantel, nitroxinil, rafoxanide or triclabendazole as a single active substance and for the veterinary medicinal products administered as pour-on to cattle containing triclabendazole and moxidectin.

Rafoxanide is currently included in that table as an allowed substance, for bovine and ovine species, applicable to muscle, fat, liver, kidney and milk.

An application for the extension of the time period applying to the provisional MRL for rafoxanide in bovine and ovine milk has been submitted to the European Medicines Agency (hereinafter ‘EMA’).

The EMA, based on the opinion of the Committee for Medicinal Products for Veterinary Use has considered that an extension of the existing provisional MRL for rafoxanide in bovine and ovine milk would allow completion of scientific studies in progress and has therefore recommended the extension of the provisional MRL until 31 December 2017.

Since the provisional MRL for rafoxanide in bovine and ovine milk expired on 31 December 2015 and in order to protect the legitimate expectations of market operators regarding the use of that substance, the extension of the provisional MRL should enter into force as a matter of urgency and should apply with effect from 1 January 2016.

A request for an opinion on the extrapolation of the existing entry for rafoxanide applicable to bovine milk has been submitted to the European Medicines Agency.

The entry for rafoxanide in Table 1 of the Annex to Regulation (EU) No 37/2010 should therefore be amended to include the recommended provisional MRL for bovine and ovine milk and to remove the prohibition to use that substance from animals from which milk is produced for human consumption.