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Launched in Europe in the summer of 1999, Econor® (valnemulin) was the first antibiotic feed premix for disease control to be approved through the centralized registration procedure in all member states of the EU.
 

The product - a new-generation pleuromutilin with claims for swine dysentery and enzootic pneumonia - was well received in all major EU pig markets, as well as in eastern Europe, Latin America and the Pacific Rim.
 

"Unlike most other antibiotics used for enteric and respiratory disease control in animals, Econor is unique in that it was developed specifically for use in food animals," says Dr. Ulrich Klein, a professional services veterinarian for the company. "It is not related to any antibiotic used in human medicine."
 

From a disease-management standpoint, Econor proved to be the most active product for preventing and treating swine dysentery, including that caused by tylosin- and lincomycin-resistant strains of Brachyspira hyodysenteriae, the causative organism for this costly disease. Research has also shown that Econor has potent activity against spirochaetal colitis and ileitis.
 

The arrival of Econor in the EU also gave the pig industry a new class of antibiotic for preventing and treating enzootic pneumonia.
 

Studies throughout the EU show that pigs medicated with Econor have significantly improved productivity with better daily gain and feed conversion efficiency than untreated controls.
 

Isolated reactions
Sales of Econor grew steadily during its first year as it was gradually launched in all major pig markets in the EU.
 

In Scandinavia, however, a number of cases of adverse reactions to Econor began to be reported. In all, there were 36 cases; 34 - more than 94% - occurred in Denmark and Sweden. One was reported in Finland and another in Ireland. The overall incidence of ADRs in the affected countries ranged from 0.03% to 1.76% of all pigs treated. Mortality in affected herds ranged from 0.7% in Sweden to 1.2% in Denmark.
 

"The ADRs in Denmark and Sweden were really puzzling," Klein says. "With the exception of two isolated cases, we had not seen these types of reactions - fever, lack of coordination, depression, oedema, to name a few - anywhere else in the EU, nor had any been reported in Eastern Europe, Latin America or the Pacific Rim."
 

"Furthermore, while the ADRs in the affected countries seemed to be associated in some way with the use of Econor, the product alone could not have accounted for all the observed effects we were seeing in Scandinavia."
 

Due to the higher number of unexplained ADRs in Denmark (24), local regulatory authorities decided to suspend Econor marketing authorization in August 2000. Authorities in Sweden, where 10 such cases had been reported, and in Finland, which had one case, followed suit in September. In October, the European Commission decided to suspend Econor marketing authorization in the European Union.
 

Novartis Animal Health, which had been reporting all the suspected ADRs to the European Medicine Evaluation Agency (EMEA) and the authorities of all EU member states, then collaborated with various specialists to investigate the cause of the problem. This effort involved an epidemiological survey, tolerability studies and a review of feed ingredients used in the rations of affected pigs.
 

(Note to editors: See editorial backgrounders, "One of a Kind - Unique Breeding Schemes in Denmark and Sweden May Be Factor in Mystery ADRs," and "Novartis Completes Extensive Investigation Of Mysterious Adverse Drug Reactions" for more information.)
 

Tracing the source
Initially, Klein says, many thought the ADRs in Scandinavia might be linked to vitamin E deficiency or possibly interaction with high concentrations of zinc oxide, which is commonly used to control E. coli after the removal of antibiotic growth promoters.
 

Since then, however, investigators have trained their sights on the unique breeding programmes used in Denmark and Sweden and, more specifically, a deficiency in the liver enzyme CYP2A P450. This deficiency can slow the metabolic processes of the liver in swine and, in turn, make pigs more susceptible to ADRs.
 

"Scientists are still conducting studies to identify the exact cause of the problem in Scandinavia," Klein says. "In the meantime, statistics and circumstantial evidence strongly suggest that ADRs seen in Denmark and Sweden may be unique to pigs bred for those markets. We do not expect this phenomenon to spill over to other markets, unless the pigs being raised are of Scandinavian genetic origin."
 

Nevertheless, Novartis Animal Health has re-emphasised its ongoing pharmacovigilance programme to ensure a fast response to any suspected ADRs that might be reported after use of Econor. Company sales representatives have been instructed to quickly forward any reports of ADRs to the appropriate Novartis Animal Health regional pharmacovigilance manager or deputy; Novartis Animal Health headquarters must be notified within 5 days, as well as local authorities as required by local law.
 

There will be complete investigations and handling of any ADRs that might occur, including on-farm visits by an investigating veterinarian and a thorough examination of pigs and the feed.
 

Although Econor was suspended in the EU for 19 months, Novartis Animal Health says the product has continued to set new sales records in Brazil, Colombia, Hungary and the Czech Republic. Excellent growth has also been seen in the Philippines, Poland, Venezuela, Argentina, Peru and Slovakia. With the relaunch in the EU, Econor is now registered in more than 25 countries worldwide.
 

For more information about Econor, contact the company at Novartis Animal Health, Inc., WRO 1032.3.41/AH 6.4, CH-4002, Basel, Switzerland. Tel: +41-61-697-7851.