Introduction - Uppsala Monitoring Centre

hypnotic-sedative product, pyrithyldione and diphenhydramine. Although
evidence was weak, the Centre suspected that agranulocytosis might have
been caused by pyrithyldione, and warned that the benefit-risk profile of this
product might have been unfavourable as a consequence (Butlletí grog,
1996). The adjusted odds ratio found in a case control study was 200 (CI 95%
22–infinity). There were eight cases of which none were fatal and the National
Commission of Pharmacovigilance recommended withdrawal, but the Ministry
of Health took more than 2 years to withdraw the drug and six more cases
occurred in this time (Ibáñez et al., 2000).
Withdrawn: in Spain in 1997 because of the eight cases of agranulocytosis.
Availability: by the end of the 1980s it was still marketed in Belgium, Denmark,
Germany, Sweden and Switzerland (Martindale).
Drug Lifespan: 57 years
Delay in recognition: 9 years
Delay in regulatory action: 48 years
Comment: no trace of further cases
1941 Sulfathiazole (Cibazol, Thiazomide, Tresamide)
Use: an antibacterial drug used for pneumococcal pneumonia, gonorrhoea,
staplococcus septicaemia, and urinary tract infections
ADR: the toxic effects of sulfathiazole on the kidneys (nitrogen retention,
haematuria, oliguria and crystals in the urine) were known soon after its
discovery in 1939 (Simon & Kaufman, 1943). Agranulocytosis was recognised
in 1941 (Hoyne & Larrimore, 1941). Hepatotoxicity in 1942. All sulphonamides
can cause hepatitis. (Lederer & Rosenblatt, 1942). Liver lesions include:
granulomas and necrosis (Rios Sanchez, 1971). Other ADRs were aplastic
anaemia and haemolytic anaemia, exfoliative dermatitis, erythema multiforme
and fever.
SED 1952: generalised dermatitis, erythema nodosum, crystalluria, fatal anuria
due to damage to the renal parenchyma, hepatitis, thrombocytopenia,
haemoglobinuria and necrotising arteritis. The older sulphonamides, e.g.
sulfathiazole, are more harmful than the modern preparations. There are no
sulphonamides known which cannot cause renal damage.
SED 1960: obstructive anuria with Sulfathiazole and 23 children had
haematuria.
Withdrawn: in the USA in 1970, Philippines in 1971 (because of the risk of
crystalluria), France and the United Arab Emirates in 1977, and Dominica in
1982.
Availability: in USA, Italy, Spain, Chile, Austria, Germany, Venezuela, Brazil,
Argentina and Vietnam (Martindale)
Drug Lifespan: 29 years