From the Guidelines
G6PD levels should be checked before starting hydroxychloroquine therapy, but routine monitoring is not required during treatment if the initial test is normal. According to the kdigo 2024 clinical practice guideline for the management of lupus nephritis 1, measurement of G6PD levels is preferred in men, especially those of African, Asian, or Middle Eastern origin, before starting hydroxychloroquine due to the risk of hemolysis in patients who have glucose-6-phosphate dehydrogenase (G6PD) deficiency. However, this risk appeared low, according to the findings of a recent report 1.
Key Considerations
- Methotrexate's mechanism of action involves inhibiting dihydrofolate reductase and does not directly affect the pentose phosphate pathway that is compromised in G6PD deficiency, therefore G6PD testing is not routinely recommended for patients on methotrexate 1.
- If a patient develops unexplained anemia, jaundice, or hemolysis while on either medication, G6PD levels should be checked immediately.
- Hydroxychloroquine can potentially cause hemolysis in patients with G6PD deficiency, though this risk is lower compared to other antimalarials like primaquine 1.
Monitoring and Dosing
- Updated guidelines from the Royal College of Ophthalmologists in the United Kingdom published in 2020 do not recommend baseline examination prior to initiating treatment, and yearly monitoring should begin after 1 year of therapy in patients with additional risk factors or after 5 years of therapy otherwise 1.
- The recommended starting dose of hydroxychloroquine is around 5 mg/kg/d, and doses of 2–3 mg/kg/d may not achieve adequate blood levels and could be associated with higher flare rates 1.
From the Research
Monitoring G6PD Levels in Patients Taking Methotrexate and Hydroxychloroquine
- There is limited research directly addressing the frequency of monitoring Glucose-6-phosphate dehydrogenase (G6PD) levels in patients taking both Methotrexate and Hydroxychloroquine.
- Studies have investigated the risk of hemolytic anemia in patients with G6PD deficiency taking Hydroxychloroquine, with varying conclusions:
- A study published in 2020 2 found that the frequency of G6PD deficiency in rheumatic patients is similar to that of the general population, and the risk of hemolytic anemia associated with Hydroxychloroquine is extremely rare.
- Another study from 2018 3 found no reported episodes of hemolysis in over 700 months of Hydroxychloroquine exposure among 11 G6PDH-deficient patients.
- However, case reports have highlighted the potential risk of hemolytic anemia in G6PD-deficient patients taking Hydroxychloroquine, particularly in the context of COVID-19 treatment 4, 5, 6.
- The current evidence does not provide a clear recommendation for the frequency of monitoring G6PD levels in patients taking Methotrexate and Hydroxychloroquine, but it suggests that the risk of hemolytic anemia associated with Hydroxychloroquine in G6PD-deficient patients may be rare but not negligible.