Acetamonophen and G-6-PD Deficiency

Dr. Ernest Beutler, Department of Basic and Clinical Research, Scripps Clinic and Research Foundation, 10666 N. Torrey Pines Road, La Jolla‚CA 92037 (USA) Recent correspondence [1,2] readdresses the issue of whether acetaminophen (Tylenol, paracetamol) is a safe medication for patients with glucose-6-phosphate dehydrogenase (G-6PD) deficiency. When we reviewed the evidence concerning this drug in 1978 [3], we concluded, on the basis of its experimental administration to patients both with G-6-PD A[4] and G-6-PD Canton [5] that it did not produce significant hemolytic anemia. In addition, it has been shown that administration of 2,000 mg of acetaminophen daily failed to effect the survival of G-6-PD Hillbrow red cells [6]. 1 This publication is manuscript No. 3569 BCR from the Research Institute of Scripps Clinic. This work has been supported in part by grant HL25552 from the National Institutes of Health, Division of Heart, Lung and Blood. research setting, our experience with drug administration and hemolysis was that the latter did not occur until the drug had been given for at least 2 days [7]. On the basis of the history provided, therefore, it seems very unlikely that acetaminophen was the cause of hemolysis in this patient. Observing the in vivo effect of drug administration on 51Cr-labelled G-6-PD-deficient red cells is still the only reliable way of appraising a cause-and-effect relationship between drug and hemolysis. The subsequent letter from Pootrakul and Panich [2] is therefore particularly instructive. In contrast to the three earlier studies [3–5] evidence is presented that acetaminophen does, indeed, destroy G-6-PD-defi-cient red cells. But the critical consideration is that only about 10% of the cells were destroyed and a very large dose, 3,000 mg daily for 14 days was required to achieve this effect. Pootrakul and Panich [2] imply that in a G-6-PD-deficient individual such cell destruction would be greater. In point of fact it would, if anything, be less. All of the labelled cells were, after all, G-6-PD-deficient and the proportion of a G-6-PD-deficient subject’s red cells would be expected to be similar. Cell destruction is age-dependent and the 51Cr-labelled red cells were allowed to age in the recipient for some 6 days before exposing them to a course of drug. Therefore a correction which reduces the effect somewhat needs to be applied [8]. We consider it extremely unlikely that the magnitude of cell destruction revealed by the 51Cr studies would be attended by any clinical effect. Dosages of drugs which produce red cell destruction of this magnitude do not produce clinical hemolytic anemia. This should hardly be considered surprising, since red cell destruction takes place over a period of 212 Correspondence