SMON Tragedy in ]apan
One of history’s most horrifying cases of pharmaceutical-related corporate negligence involved the Swiss multinational giant Ciba Geigy and its drug clioquinol (also known as Mexaform, Enterovioform, Enteroquinol). Ciba started marketing clioquinol in 1934 to fight amoebic dysentery. By the time the company entered the lucrative Japanese market in 1953, it was pushing clioquinol worldwide for all forms of dysentery. Ciba was permitted to market the drug in for all types of abdominal trouble, with no limitation as to dosage or length of treatment. Ciba promoted the drug throughout the 1950s and 1960s as being safe and effective, even for children, and as having no adverse permanent side effects. Clioquinol is known to cause Sub-Acute Myelo-Optic Neuropathy (SMON), a serious side effect affecting the nervous system, causing damage to the spinal cords and the nerves, including the optic nerve.
Andrew Chetley, in his Problem Drugs, explains what happened in Japan in the 1970s:’When 19-year-old Mieko Hoshi came down with diarrhoea… she was eventually given a halogenated hydroxyquinoline drug called iodochlorhydroxyquin (or clioquinol). Shortly afterwards, she suffered from a temporary paralysis of facial muscles… When that problem disappeared, she began to suffer from a growing numbness in her legs which spread to an almost complete paralysis of her body…she also lost her eyesight… It was clear that she was one of more than 11,000 victims of a disease called sub acute myelo-optic neuropathy (SMON).’Chetley then states: ‘Japanese scientists reported that clioquinol was the probable cause. Within a month, the Japanese government banned all of the 186 halogenated hydroxyquinolines products on the market… Japanese victims began to take legal action against Ciba- Geigy, but it was not until six years later that the company both apologised to them, and paid substantial damages.’
SMON litigation began in May 1971 in Tokyo. In response, Ciba-Geigy stated: ‘the SMON problem is a peculiarly Japanese one and they are not responsible to Japanese patients. ’However, Ciba-Geigy Japan, was a subsidiary of the Swiss multinational giant.
Further, a worldwide study of clioquinol, its brand names and information sheets accompanying the drug, by IOCU, found critical differences in drug information being supplied in different countries. For instance, drug information accompanying Enterovioform, manufactured in Switzerland and sold also in Greece, Portugal, Kenya,
South Africa, Hong Kong, Malaysia and Singapore, limited the maximum dosage to 750 mg.; listed the four main contraindications – hyperthyroidism, iodine allergy and impaired liver or kidney function; mentioned the side effects – peripheral and optic neuritis; and warned that the drug must be stopped at the first signs of abnormal sensations and visual disturbances. However, when exported from Switzerland to Thailand and Indonesia the instructions specified a maximum dose of 1500 mg, omitted malfunctioning of liver or kidneys from the list of contraindications, and failed to warn the user to stop the drug at the first signs of neuritis. Similarly, Entero-Vioform manufactured in U.K., and sold there and in Bahamas, Belize, and New Zealand, limited the course of treatment to a total of 3 g (1000 mg for 3 days). On the other hand, when exported to Tanzania their instructions specified a maximum of 15 g.
The Clioquinol campaign, initiated by Dr. Olle Hansson and the Japanese victims, soon built up as a global campaign. As Ciba-Geigy continued to market clioquinol in spite of known hazards and doubtful hazards, 3000 Swedish doctors boycotted Ciba-Geigy products, causing the company to lose 25% of its market in Sweden. Clinicians from England, Australia, Switzerland, Sweden, Denmark, the Netherlands, and the United States described patients who developed neurological symptoms while taking clioquinol. Their clinical symptoms were similar to those noted in the histories of Japanese patients with SMON. In August 1978, the Tokyo District Court ruled in favour of the SMON victims and ordered Ciba-Geigy to make a settlement, which will adequately compensate for their sufferings and to submit an apology to the SMON victims. The Court noted:
‘The Ciba Geigy head office in Basel investigated reports that dogs given Entero-Vioform or Mexaform often developed epileptic seizures and died, and the company circulated a warning among veterinarians not to use these drugs in veterinary treatment. However, although ‘these drugs were produced for human use’, they not only did not take any measures to warn about the dangers of use by humans, but also, they continued to stress thereafter the safety of Entero-Vioform and Mexaform in Japan, which can be considered deplorable. ‘If Ciba Geigy had taken the appropriate measures at that time, it is probable that the suffering of most or at least a considerable number of SMON patients could have been avoided. Under such conditions, this must be considered as a matter of deep regret with respect to the Defendant Ciba-Geigy.’
Under intense pressure, Ciba-Geigy finally announced in November 1982 its intention to ‘phase out’ the production and sale of clioquinol oral preparations over a 3-5 year period.
Ciba Geigy finally gave a written apology to the Japanese victims; the apology states ‘… [the plaintiffs’] grievances were all earnest expressions of their pain, distress, and anger; appeals were made for redress. They were heart rending cries that made us realise anew that SMON has caused the patients and their families unimaginable suffering…In view of the fact that medical products manufactured and sold by us have been responsible for the occurrence of this tragedy in Japan, we extend our apologies, frankly and without reservation to the Plaintiffs and their families… We have also realised, with regret, that when we recently asked the court to act as mediator we neglected to adequately express our sincerity. Again, we deeply apologise to the plaintiffs and their families.’– edited excerpts from Andrew Chetley’s Problem Drugs and Locost’s Lay Person’s Guide to Medicine, www.locostindia.com