Drug withdrawal from market causes

Drug Withdrawals From the Market - Causes and Consequences... 

CH44 DRUG WITHDRAWALS FROM THE MARKET - CAUSES AND CONSEQUENCES... 

Practolol (Figure 8.13) was the prototype cardioselective p-adrenoceptor blocking agent. Selectivity was achieved by substitution in the para position with an acetyl anilino function. The similarity of this drug with those outlined above is obvious. Practolol caused severe skin and eye lesions in some patients which led to its withdrawal from the market [6]. These lesions manifested as a rash, hyperkeratosis, scarring, even perforation of the cornea and development of a fibrovascular mass in the conjunctiva, and sclerosing peritonitis. Some evidence is available that the drug is oxidatively metabolized to a reactive product that binds irreversibly to tissue pro-... 

In 1994, the animal slaughter class most often associated with residues were bob veal calves, culled dairy cows, both beef and cull cows, and market hogs. Residues associated with injectable drugs accounted for approximately 42% of the violations. This was followed by the oral route and the intramammary route. Most of the drugs that caused the residues were purchased from a feed/ farm supply store or veterinarian. The primary cause of residue violations was failure to adhere to the approved withdrawal periods. Other causes included failure to keep proper animal identification and treatment records and extralabel use exceeding recommended dosage. 

This was an important factor in the development of adverse reactions to the antiarthritis drug benoxaprofen (Opren), which caused serious toxicity in some elderly patients, necessitating withdrawal of the drug from the market. 

Tienilic acid is a uricosuric diuretic drug that may cause immunoallergic hepatitis in 1 in 10,000 patients, a side effect that resulted in its withdrawal from the market. The... 

The FDA requires Warner-Lambert, the maker of the diabetes drug Rezulin, to withdraw the drug from the market after evidence grows that it caused hundreds of users to die from liver failure. 

Toxicity is a major cause for the withdrawal of drugs from the market and it is a major concern for pharmaceutical researchers. Reactive metabolism is certainly a very hot topic within the whole approach to drug metabolism. The downstream consequences of not identifying reactive metabolites may be financially catastrophic. There is an increasing drive to have early prediction of the metabolic fate and interactions of candidate drug molecules. Factors such as metabolic stability, toxic metabolite production, and P450 inhibition and induction are all routinely monitored to prevent compounds with poor pharmacokinetic properties from progressing forward onto clinical trials. 

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