Complications Related to Dapsone Use for Pneumocystis Jirovecii Pneumonia Prophylaxis in Solid Organ Transplant Recipients

Abstract

Dapsone, used for prevention of Pneumocystis jirovecii infections, has been reported to cause hemolytic anemia and methemoglobinemia; its tolerability in solid organ transplant recipients is not well described. We investigated dapsone-related adverse events in patients undergoing solid organ transplantation from 1999 to 2004. Transplant providers identified patients for the investigators who then reviewed the patients' hospital and outpatient records. Sixteen solid organ transplant recipients fit case definitions for dapsonerelated hemolytic anemia (n = 11) or methemoglobinemia (n = 5). Median time from event to dapsone discontinuation was 15 days; all patients improved after drug discontinuation. G6PD enzyme activity was normal in all patients whose test results were available. Dapsone may be associated with hemolytic anemia or methemoglobinemia, even with normal G6PD levels. These events are often not promptly recognized, and drug discontinuation is delayed. Dapsone-related hemolytic anemia or methemoglobinemia should be considered in solid organ transplant recipients with unexplained anemia or hypoxia.

Dapsone-induced Hemolytic Anemia in Lung Allograft Recipients

“…However, they were unable to determine the prevalence of dapsoneinduced hemolysis. 5 Dapsone-induced hemolysis is thought to involve oxygen free radicals, 6 through one of the major therapeutically inactive metabolites, dapsone hydroxylamine. It is this metabolite that has been shown to cause a direct hemolytic effect on the red blood cell, 6,11,16,17 which can occur independently of G6PD levels.…”

“…Some studies have suggested an increased rate of hematologic toxicity in SOT recipients as compared with human immunodeficiency virus (HIV) patients, but prevalence has not been reported. 5 Dapsone is a synthetic sulfone that inhibits folate synthesis. Its use in humans was first documented in the 1940s to treat leprosy.…”

Dapsone induced hemolysis in a patient with ANCA associated glomerulonephritis and normal G6PD level and implications for clinical practice: case report and review of the literature

“…Oxidant hemolysis caused by its metabolite hydroxylamine is a reported side effect in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency and therefore screening for G6PD deficiency is recommended before the drug is started. Although dapsone induced hemolytic anemia is mostly reported in patients with G6PD deficiency, there are reports of dapsone induced hemolytic anemia in literature regarding transplant recipients who have normal G6PD levels (Lee et al 2005; Naik et al 2008; Olteanu et al 2012). Dapsone is also often used for PJP prophylaxis in patients with AAV who receive immunosuppressive drug therapy to induce remission.…”

Profilaxis de neumonía por Pneumocystis jiroveci en niños y adultos sometidos a trasplante de órganos sólidos y de precursores hematopoyéticos

“…Es posible que los pacientes que experimentan estos eventos adversos tengan una predisposición individual y déficit de glucosa-6-fosfato deshidrogenasa. El metabolismo de dapsona, sirolimus y tacrolimus ocurre en la misma isoenzima del citocromo P-450 (CYP3A4) lo que puede aumentar la incidencia de efectos adversos en pacientes expuestos a estos inmunosupresores 13 . Un estudio caso control mostró un riesgo 18 veces mayor de desarrollar neumonía por P. jiroveci en TPH alogénico cuando se realiza profilaxis con dapsona vs cotrimoxazol 83 .…”