Maltese.pdf

Annex I lists veterinary medicinal product details, including name, strength, pharmaceutical form, animal species, and route of administration, for various EU/EEA member states. The product, Adjusol TMP Sulfa, contains trimethoprim and sulfadiazine, and is indicated for infections caused by susceptible bacteria in cattle, sheep, pigs, rabbits, and poultry.

Annex II provides scientific conclusions and grounds for amendment of the summary of product characteristics, labelling, and package leaflet. The European Commission referred the issue to the CVMP/European Medicines Agency due to divergent national decisions resulting in discrepancies in product information.

The main areas of disharmony relate to target species, indications, and posology. The marketing authorisation holder provided data, including in vitro susceptibility, pharmacokinetic, and pharmacokinetic/pharmacodynamic modelling, to support proposed indications. However, clinical data on efficacy is scarce, and the provided literature was considered supportive, not pivotal.

A PK/PD model was presented to justify indications and dosage regimens, using AUC/MIC as the PK/PD index, which was considered acceptable by CVMP. The breakpoint value for AUC/MIC to achieve a bactericidal effect was estimated at higher than 25 hours, based on a publication by Cheng et al. (2009).

The CVMP accepted the PD target value proposed by the MAH and the extrapolations made in the PK/PD model, considering the antimicrobial combination has been used for several decades. The numerical approach and formula were considered acceptable, and the values above MIC determined by the MAH could be accepted.

The proposed indication for pre-ruminant calves was 'Treatment and metaphylaxis of respiratory infections caused by Pasteurella multocida or Mannheimia haemolytica, and acute enteritis caused by Salmonella spp., and acute enteritis and arthritis caused by Escherichia coli or septicaemia due to the same bacteria species susceptible to trimethoprim and sulfadiazine'.