PROPAFENONE IN A USUAL DOSE PRODUCES SEVERE SIDE-EFFECTS - THE IMPACTOF GENETICALLY-DETERMINED METABOLIC STATUS ON DRUG-THERAPY

We report the case of an elderly lady presenting with dizziness, a hea d injury resulting from a fall and bradycardia. Propafenone 150 mg t.i .d. had been prescribed for atrial fibrillation with tachyarrhythmia, induced by hyperthyroidism, 18 months earlier. A toxic concentration o f parent propafenone, and no 5-hydroxy metabolite, was detected in a p lasma sample. Symptoms disappeared after the discontinuation of propaf enone. The poor metaboliser (PM) phenotype of sparteine/debrisoquine w as assumed and subsequently confirmed by phenotyping (sparteine test) and genotyping (allele-specific polymerase chain reaction). The PM phe notype is common in European populations, with a prevalence of about 7 %. If drugs with narrow therapeutic ranges undergo genetically polymor phic metabolism, toxicity may arise even with recommended doses. Indiv idualization of doses is required to avoid adverse effects.