Dapsone safety in hematology patients: Pathways to optimizing Pneumocystis jirovecii pneumonia prophylaxis in hematology malignancy and transplant recipients

Abstract

Dapsone may be used for Pneumocystis jirovecii pneumonia (PJP) prophylaxis in hematology patients receiving immunosuppressive therapy or after hematopoietic stem cell transplant (HSCT) in the setting of trimethoprim-sulfamethoxazole (TMP-SMX) adverse drug reaction (ADR) history. Dapsone-induced hematological toxicities such as oxidative hemolysis may limit use in these patients and modern assessments of dapsone allergy cross-reactivity in non-HIV patients with a sulfonamide allergy are largely absent. The aim of this single-centre, retrospective study was to describe dapsone usage in hematology patients requiring PJP prophylaxis, including HSCT recipients, over a 12-month period in terms of indications, incidence of dapsone-attributed oxidative hemolysis, and immune cross-reactivity in those previously labeled with a sulfonamide allergy, as well as describing potential opportunities for first-line TMP-SMX PJP prophylaxis reintroduction. Of 24 patients meeting the study inclusion criteria, 12 (50%) were receiving dapsone PJP prophylaxis post-HSCT. No cases of breakthrough PJP infection were noted. Sixteen patients (67%) were initiated on dapsone to avoid the perceived risk of further myelosuppression with TMP-SMX and five patients (21%) because of prior delayed immune-mediated allergy to TMP-SMX. None experienced rash with dapsone therapy. Six patients (25%) were successfully rechallenged on TMP-SMX, including one patient with prior TMP-SMX-associated rash. Four (17%) patients had confirmed oxidative hemolysis, all resulting in dapsone cessation. Dapsone PJP prophylaxis in hematology patients was effective and safe, with nonlife threatening dapsone-related hemolysis noted in a small number. An absence of sulfonamide allergy cross-reactivity was noted, suggesting greater TMP-SMX rechallenges or desensitization could be considered in those receiving dapsone.

Sulfonamide desensitization in solid organ transplant recipients: A protocol‐driven approach during the index transplant hospitalization

“…Our institution opted for 3‐day desensitization during the index transplant hospitalization, though it is likely that an expedited protocol (eg, 6 hours) would be similarly tolerated and effective. While our center's protocol includes pentamidine as second line for PJP prophylaxis in SOT recipients unable to tolerate TMP‐SMX, dapsone is an alternative option . Although the risk for cross‐reactivity between sulfonamide antibiotics and dapsone is low, there is a small but present risk of hemolytic anemia or methemoglobinemia …”

An evaluation of PJP prophylaxis and anemia among renal transplant recipients

“…The incidence of dapsone-associated methemoglobinemia (8%) that we report is relatively similar to previous analyses. 6,8,9 Very few dapsone-treated patients in this cohort had evaluable lactate dehydrogenase, haptoglobin, or bilirubin assessments around the time of drug initiation of discontinuation. However, our assumption is that the mechanism for dapsone-associated anemia is likely hemolytic in nature.…”

Pneumocystis jiroveci in Transplant: Recognizing Risk, Understanding Prevention, and Implementing Treatment

“…A significant proportion of patients with hypersensitivity to TMP/SMX will also react to dapsone (up to 50%), so it should be avoided in those with lifethreatening reactions to TMP/SMX [14]. More recently, a study found no breakthrough PJP or cross-reactivity with TMP/SMX; however, it included only a small number of patients [56]. Other toxicities include methemoglobinemia, hemolytic anemia in those with glucose-6-phophate dehydrogenase deficiency, aplastic anemia, agranulocytosis, rash, nausea, and hepatitis.…”