Introduction - Uppsala Monitoring Centre

acetphenetidine (Phenacetin) in ‘ Headache Cures’. These drugs Depress the
heart–Injure the blood–Produce a habit. DANGER.’ There is limited evidence
that Phenacetin is carcinogenic in animals (IARC vol 24, 1980).
Withdrawn: in Finland in 1965, it was removed from one Australian product in
1967 and the other product in 1975, withdrawn in Italy and Kuwait in 1973,
1974 first UK regulatory warning, but withdrawn in New Zealand and Canada
in 1977, Nigeria in 1978, Cyprus and Yemen in 1979, France, Philippines and
UK in 1980, Norway, Brazil, Argentina and Israel in 1981, Romania, Turkey,
Bangladesh, Mauritius, Sweden, Hongkong, Japan, India, Nepal, Thailand,
Rwanda and USA in 1983, Chile, Ethiopia, Greece and Denmark in 1984,
Panama, Germany and Malaysia in 1986, Oman in 1987, Austria and Belgium
in 1988, and also in Bahrain, Egypt, Switzerland, Ireland, Israel, Netherlands,
Saudi Arabia, and Surinam because of analgesic nephropathy (Stolley, 1991).
The various reasons for withdrawal included: carcinogenicity, hepatotoxicity,
renal toxicity and methemoglobinemia (WHO). HAI: banned in 41 countries
and restricted in one.
Availability: Hungary, Spain, Czechoslovakia, and France (Martindale).
Drug Lifespan: 78 years
Delay in recognition: 65 years
Delay in regulatory action: 12 years (since the Spühler & Zollinger paper) or,
56 years after the AMA warning. Venning said that the avoidable delay was
21 years; that is since the Larsen and Moller study in 1959 (Venning II, 1983).
Time span of withdrawals: 23 years
Comment: doubt lingered on as to whether Phenacetin was solely to blame for the
nephropathy or whether the other drugs, with which it was combined, might have
played a part (Prescott, 1970). This doubt seems to have vanished as Aspirin
and paracetamol have been cleared of responsibility.
1888 Piperazine C 4 H 10 N 2 (Antepar, Pripsen)
Was introduced. It was discovered by Schreiber in 1878.
Use: originally for gout and rheumatism because it had been shown in vitro to
dissolve urate in stones (Mapother, 1894). Its use as an antihelmintic drug
was discovered in 1951.
ADR: marked toxic effects after a drachm or more were reported in 1894
(Stewart, 1894). A booklet published by Pipérazine Midy in 1910 said: ‘the
innocuity of piperazine is absolute, so tolerance always perfect.’ (Midy, 1910).
1915 Seifert mentioned headache (Seifert,1915). The first gastrointestinal,
allergic and neurological side effects were reported in 1952. The neurological
symptoms were: lack of coordination resulting in dropping things, sickness,
inability to focus and a sense of detachment ? due to overdose (Standen &
White, 1952).