Introduction - Uppsala Monitoring Centre

Withdrawn: USA 1962
Availability: nil
Drug Lifespan: three years
Delay in recognition: despite the fact that both subacute and chronic toxicity
studies in animals (rats and dogs) showed clear evidence of toxicity in doses
dangerously close to those proposed for use in humans (approximately 4
mgm/kg/day) the application was approved in April 1960. Subsequently 40
mgm/kg/day in rats produced cataracts within 3 months and 20–40
mgm/kg/day caused cataracts in dogs in 3-4 months (Nestor, 1975).
Cataracts were first reported in patients in April 1962 (Kirby, 1962). The FDA
had been tipped off to investigate the manufacturer’s records. The
manufacturers, William S Merrill, had failed to reveal the fact that they had
found that it had produced cataracts in both rats and dogs (JAMA July 1962).
Damages were paid to the injured patients and the company paid the
maximum fine.
Delay in regulatory action: the drug should not have been approved for human
use.
Comment: the evidence was ignored by the company. MER/29 had some
similarities with Coralgil.
Nialamide (Niamid)
Use: a monoamine oxidase inhibitor. Antidepressant.
ADR: cytolytic hepatitis (Hammer et al., 1969) and drug interaction with food
(tyramine) causing hypertensive crises was recognised in 1959 (Davies, 1959).
SED 1960 and SED 1963: no mention
SED 1966: hypertensive crises have been reported.
Withdrawn: in Canada in 1963, the USA and Japan in 1974, UK in 1978, India in
1983, in France in 1987, and Norway in 1995, also in Cuba, Denmark, Saudi
Arabia, Thailand and Venezuela. HAI: banned in 7 countries.
Availability: in Belgium (Martindale)
Drug Lifespan: 4 years
Delay in recognition: 10 years for hepatitis
Delay in regulatory action: 4 years
Time span of withdrawals: 32 years
Comment: a class ADR + a specific ADR. All MAOIs interact with tyramine.
Analysis
Delay in recognition (Time to first case)
There were several factors that hindered the early recognition of new ADRs.