Introduction - Uppsala Monitoring Centre

SED 1952: no mention. A warning was given in 1956 of neurotoxicity [Worm
wobble] (Combes et al., 1956). Severe neurotoxicity (Yohai and Barnett,
1989) consisting of absences and atonic seizures. It also caused
hypersensitivity and possible carcinogenicity. It is still considered sufficiently
safe for use; although in most industrialised countries it has been abandoned,
primarily because of concern about possible carcinogenicity and
electroencephalographic changes (Kaddu, 2000; Parsons, 1971; Belloni,
1967; Miller, 1967; Savage, 1967).
SED 1960 : mention of incoordination, muscle weakness, tremors and
headache
SED 1963 : they had added: abnormal limb movements, myoclonus,
dyskinesia and purpura.
Withdrawn: in Italy in 1977, in Sweden in 1983, Denmark in 1984 (prescription
control), Netherlands in 1985, Malaysia and Thailand (use severely restricted)
in 1996, Armenia in 2000. It is not manufactured in the USA.
Availability: in some countries where ascariasis is not endemic and where
piperazine was used predominantly for the treatment of pinworm it has been
withdrawn from use on the grounds that other more effective and less toxic
drugs are now available. In other such countries, however, piperazine
remains available in over-the-counter preparations: Canada, France, Ireland,
Spain, Portugal, Belgium, Thailand, Turkey, Venezuela, Brazil, Mexico,
Indonesia and South Africa (WHO, 2003). It was used in the UK for
threadworms and roundworms (BNF, 1999). It is still available in India but
with restrictions.
Drug Lifespan: c89 years
Delay in recognition: 64 years
Delay in regulatory action: 25 years
Time span of withdrawals: 23 years
Comment: the side effects, which are dose-related only appeared after the drug
was used as an antihelmintic some 64 years after its appearance on the
market for the treatment of gout and this needs some explanation. Piperazine
in 1894 cost 12 shillings an ounce–‘scarcely affordable for public practice’.
The dose used then was 5-10 grains three times daily, which in 2008 terms
would mean £17. 37 per day (Gordon, 1894), whilst the dose now for round
worms is two doses of 4 G or 61. 2 grains, two weeks apart and for thread
worms at a dose of 2.5 G daily for seven days. It is probable that piperazine
was little used in the treatment of gout because its inefficacy, the price and the
availability of colchicum. Some confirmation this is found in the lack of articles
in the BMJ of this period and that there is no mention of piperazine in a book
of household remedies of 1896. (Thompson et al., 1896). The potential
carcinogenicity is based on the possibility that some nitrososamine may be