Flash VIG-news: risk of haemolysis associated with the use of hydroxychloroquine (PLAQUENIL) in the treatment of COVID-19

Physicians should be alert to the signs and symptoms of haemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency treated with hydroxychloroquine for the treatment of COVID-19.

The FAMHP has been notified of an adverse reaction occurring during the use of hydroxychloroquine in the treatment of COVID-19, according to Sciensano’s Belgian guidelines. A 32-year-old patient showed stigmata of haemolysis two days after starting treatment. The nadir haemoglobin level was 7.1g/dL. The patient received a transfusion of red blood cells and folic acid. Treatment with hydroxychloroquine was continued, as provided for by the Sciensano guidelines (five days of treatment in total). The patient's condition improved, and he was able to leave the hospital. In this patient, a biological examination revealed a G6PD deficiency, suggesting that hydroxychloroquine may have favoured haemolysis in this context.

Hydroxychloroquine in patients with G6PD deficiency

Hydroxychloroquine is not contraindicated in patients with G6PD deficiency, but it should be used with caution.

The data on the causal link between the use of hydroxychloroquine and the risk of haemolysis in patients with systemic lupus erythematosus, rheumatoid arthritis and inflammatory arthritis are contradictory. Data on the use of hydroxychloroquine in the very specific setting of COVID-19 treatment are still very limited. 

There are several forms of G6PD deficiency. The Mediterranean form is probably the one that presents the greatest risk of drug-induced haemolysis.

To date, no other case of haemolysis under hydroxychloroquine, in the indication for coronavirus infection, has been submitted to the European pharmacovigilance database, EudraVigilance.

We have not found any articles in scientific literature mentioning such a case of haemolysis in patients with COVID-19.

Recommendations

Sciensano guidelines do not recommend a systematic biological search for G6PD deficiency before initiating treatment with hydroxychloroquine to avoid it being delayed. But it does include this deficiency in the precautions to be taken into account.

It is likely that some patients with G6PD deficiency are already aware of this deficiency. The question should be asked at the time of admission.

In patients with G6PD deficiency, special attention should be paid to the signs and symptoms of haemolysis during treatment with hydroxychloroquine. Given the long elimination half-life of hydroxychloroquine, this attention should continue after treatment has been discontinued.

Signs and symptoms of haemolysis 

Systemic manifestations include pallor, fatigue, dizziness and occasionally hypotension. Scleral jaundice (yellowing of the whites of the eye) and/or jaundice may occur and the spleen may be enlarged.

Haemolytic crisis (acute, severe haemolysis) may be accompanied by chills, fever, lower back and abdominal pain, prostration and shock. Haemoglobinuria causes red or reddish-brown urine.

Report all adverse reactions to the FAMHP

Patients and healthcare professionals are encouraged to report suspected adverse reactions via www.notifieruneffetindésirable.be

References

1. RCP PLAQUENIL, accessible via the authorised medicinal product database

2. ANSM medicinal product and G6PD deficiency reference

3. Examination of Hydroxychloroquine Use and Hemolytic Anemia in G6PDH-Deficient Patients . Mohammad S, Clowse MEB, Eudy AM, Criscione-Schreiber LG. Arthritis Care Res (Hoboken). 2018 Mar; 70 (3): 481-485. doi: 10.1002 / acr.23296. Epub 2018 Feb 9.

4. Glucose-6-phosphate dehydrogenase deficiency: Clinical presentation and eliciting factors. Dors N., Rodrigues Pereira R., Van Zwieten R., Fijnvandraat K., Peters M.

Nederlands Tijdschrift voor Geneeskunde 2008 152: 18 (1029-1033)

5. Retrospective Study: Association of Hydroxychloroquine Use and Hemolytic Anemia in Patients with Low Levels of Glucose-6- Phosphate Dehydrogenase (G6PD ). Mejia Saldarriaga M, Ramirez de Oleo IE, Johnson B Arthritis Rheumatol. 2018; 70 (suppl 10).

 

Last updated on
23/04/2020