G6PD deficiency

Drugs and chemicals to be avoided in Glucose-6-phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest enzyme disorder of human beings and a globally important cause of neonatal jaundice, which can lead to kernicterus and death or spastic cerebral palsy. It can also lead to life-threatening haemolytic crises in childhood and at later ages, by interacting with specific drugs and with fava beans in the diet.

The best known morbid effect of G6PD deficiency is hemolysis induced by oxidative drugs. When prescribing drugs for G6PD-deficient subjects, two points should be kept in mind: (1) different genetic variants of G6PD deficiency entail different susceptibility to the hemolytic risk from drugs; thus a drug found to be safe in some G6PD-deficient subjects may not be equally safe in others; (2) the risk and severity of hemolysis is almost always dose-related.

Drugs and chemicals may be separated into those that must be avoided by G6PD-deficient subjects (such as sulphonamides, quinolones, nitrofurantoin), and those that do not readily precipitate hemolysis but must nevertheless be prescribed with caution.

Very few G6PD-deficient individuals with chronic non-spherocytic haemolytic anaemia have haemolysis even in the absence of an exogenous trigger. These patients must be regarded as being at high risk of severe exacerbation of haemolysis following administration of ANY of the drugs listed in the following tables¹:

Drugs & chemicals with definite risk of haemolysis in most G6PD-deficient individuals:

Drugs & chemicals with possible risk of haemolysis in most G6PD-deficient individuals^g

Footnotes:

1. Higher doses for dermatitis herpetiformis more likely to cause problems¹;
2. In mothball;
3. Chemicals;
4. 30mg weekly for 8 weeks has been found to be without undue harmful effects in African and Asian people¹;
5. Quinolones include: ciprofloxacin¹, levofloxacin³, moxifloxacin³, nalidixic acid¹, norfloxacin¹ & ofloxacin¹;
6. Including co-trimoxazole; some sulphonamides, e.g. sulfadiazine, have been tested and found not to be haemolytic in many G6PD-deficient individuals¹;
7. Drugs in this table can probably be given in normal therapeutic doses to G6PD deficiency without non-spherocytic haemolytic anaemia²
8. Acceptable up to a dose at least 1g daily in most G6PD-deficiency individuals¹
9. Very high therapeutic doses (~80g administered intravenously) have precipitated severe, even fatal, haemolysis²
10. Acceptable in acute malaria¹.

The tables in this bulletin are compiled based on the most updated reference materials available at the time of publication, and are therefore not intended to be comprehensive. Other drugs and chemicals might later found to be incompatible with G-6PD deficiency, the reader is advised to exercise caution and clinical judgment when using these tables.

Reference

1. British National Formulary 46; September 2003, p447-448.
2. Beutler E. "G6PD deficiency." Blood 1994; 84: p3613-3636.
3. Micromedex Healthcare Series, Volume 119, 2004.