Table 5.

Recommended therapeutic use of low-to-no risk drugs^a in relation to G6PD phenotype

Predicted G6PD phenotype based on genotype	Implications for phenotypic measures	Therapeutic recommendations for low-to-no risk drugs	Classification of recommendationsb	Considerations
Normal	Low-to-no risk of acute hemolytic anemia	No reason to avoid low-to-no risk drugs based on G6PD status	Strong
Deficient	Low-to-no risk of acute hemolytic anemia	No reason to avoid a low-to-no risk drug based on G6PD status at standard doses	See Table 2 for drug-specific strength of recommendations	Closer monitoring may be indicated for higher-than-normal dosages, and in the setting of infection or other oxidative stress, including concomitant use of multiple medium and low-to-no risk drugs.
Deficient with CNSHA	High risk of acute exacerbation of chronic hemolysis	Use all drugs cautiously in this group; if a drug is used, close monitoring for acute exacerbation of chronic hemolysis is recommended.	Optional	There are insufficient data in patients with the G6PD Deficient with CNSHA phenotype, but the risk of using any drug should be weighed carefully against the benefits in these rare patients due to the underlying pathophysiology that confers high risk for acute exacerbation of chronic hemolysis.
Variable	Low-to-no risk of acute hemolytic anemia	No reason to avoid low-to-no risk drugs based on G6PD status at standard doses	Moderate	Due to X-linked mosaicism, individuals with more than one X chromosome (e.g., females, individuals with Klinefelter syndrome) and heterozygous for one non-deficient (class IV) and one deficient (class I–III) allele may display a normal or a deficient phenotype.
Indeterminate	Unknown risk of acute hemolytic anemia	To ascertain G6PD status, enzyme activity must be measured. Drug use should be guided per the recommendations based on the activity-based phenotype.	Moderate

CNSHA, chronic non-spherocytic hemolytic anemia; G6PD, glucose-6-phosphate dehydrogenase

^aDrugs are classified as high, medium, or low-to-no risk for acute hemolytic anemia based on evidence review and on assumptions of normal dosing regimens. Drug-induced hemolysis in G6PD deficiency is generally related to drug dosage (the higher the dose, the more the oxidative stress and the more likely anemia is to occur). Because primaquine has been well studied at high, medium and low dosages, see Table 6 for primaquine-specific recommendations.

^bRating scheme described in Supplement (see Strength of Recommendations material)