Dapsone

Evidence Level: L1

Predicted Indications: 1

Dapsone

Pharmacist Assessment Report

Dapsone: sulfone antibacterial (dihydropteroate synthase inhibitor) → pneumocystosis

One-Sentence Summary

Dapsone is a sulfone antibacterial and anti-inflammatory drug marketed in Canada. The TxGNN model predicts it may be effective for pneumocystosis, with 10 clinical trials and 20 publications compiled for this report supporting this direction. The trials include several completed Phase 3 studies of dapsone in Pneumocystis pneumonia prevention and treatment.

Quick Overview

Item	Content
Original Indication	Not recorded in the local data
Predicted New Indication	pneumocystosis
TxGNN Prediction Score	0.9973
Evidence Level	L1
Canada Market Status	Marketed (marketed DINs: 2 of 2)
Number of DINs	2 (marketed: 2)
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Detailed mechanism of action data is not available in the compiled record. Based on established pharmacology, dapsone is a sulfone that inhibits dihydropteroate synthase in the folate synthesis pathway, the same target as sulfonamides such as sulfamethoxazole.

Pneumocystis jirovecii depends on this folate pathway, so a drug acting there is mechanistically plausible. This fits the very high prediction score and the clinical activity of dapsone in Pneumocystis pneumonia prophylaxis and treatment.

This is effectively an already-established use, since dapsone is a guideline-recognized alternative to trimethoprim-sulfamethoxazole, rather than a novel repurposing signal. The mechanistic link comes from established pharmacology, not from the supplied record.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00000802	Phase 3	Completed	700	Daily dapsone vs daily atovaquone for PCP prophylaxis in HIV patients intolerant of trimethoprim/sulfonamides
NCT00001028	Phase 3	Completed	400	Monthly aerosolized pentamidine vs thrice-weekly dapsone for PCP prophylaxis
NCT00000640	Phase 3	Completed	290	Dapsone/trimethoprim and clindamycin/primaquine vs TMP-SMX for mild-to-moderate PCP
NCT00000991	Phase 3	Completed	600	Three anti-Pneumocystis regimens (dapsone among them) plus zidovudine for primary prevention in advanced HIV
NCT00000739	Phase 1	Completed	96	Daily vs weekly oral dapsone for PCP prophylaxis in HIV-infected children (toxicity, pharmacokinetics)
NCT00002120	Phase 1	Completed	20	Trimetrexate with leucovorin plus dapsone vs TMP-SMX in moderately severe PCP; dapsone is part of a combination
NCT00002283	Not applicable	Completed	Not reported	Dapsone plus trimethoprim vs TMP-SMX for first-episode PCP in AIDS patients
NCT00002043	Not applicable	Completed	Not reported	Dapsone 100 mg vs 50 mg for primary PCP prophylaxis
NCT02550080	Phase 4	Unknown	3130	HLA-B*1301 genetic screening to reduce dapsone hypersensitivity syndrome; a safety study, not an efficacy study

Literature Evidence

PMID	Year	Type	Journal	Key Findings
38583518	2024	Systematic review / network meta-analysis	Clin Microbiol Infect	Compares PCP prophylaxis regimens in people living with HIV, including dapsone-based regimens, TMP-SMX, pentamidine and atovaquone
39732393	2025	Systematic review / network meta-analysis	Clin Microbiol Infect	Compares treatment regimens for PCP in people living with HIV; TMP-SMX remains the primary treatment
27550992	2016	Guideline (ECIL)	J Antimicrob Chemother	Prophylaxis recommendations in haematological malignancy and stem cell transplant; TMP-SMX is the drug of choice
33870843	2021	Review	Expert Opin Pharmacother	Review of Pneumocystis jirovecii with a focus on prevention and treatment
11155588	2001	Review	Dermatol Clin	Dapsone is useful in PCP prophylaxis in HIV disease
18971152	2008	Review	J Formos Med Assoc	Overview of Pneumocystis pneumonia
10073326	1999	Pharmacokinetic study	J Clin Pharmacol	Pharmacokinetics of trimetrexate and dapsone in AIDS patients with PCP
7937279	1994	Review	Pharmacotherapy	PCP prophylaxis options during pregnancy, including dapsone
9606476	1998	Case report	Ann Pharmacother	Dapsone-induced methemoglobinemia during PCP prophylaxis
31631707	2021	Review	Drug Chem Toxicol	Dapsone-induced hepatic complications

Canada Market Information

DIN	Product Name	Dosage Form	Approved Indication
02481227	MAR-DAPSONE	Not recorded	Not recorded
02281074	ACZONE	Not recorded	Not recorded

Safety Considerations

Conditions of concern: Listed as contraindication-related conditions in the compiled data (not label text): liver disease, gallbladder disease, anemia, macrocytic anemia, G6PD deficiency, glycogen storage disease, cystinuria, galactosemia, pyruvate dehydrogenase E3 deficiency, and methemoglobinemia due to methemoglobin reductase deficiency.
Drug Interactions: 100 interactions were found. Moderate-level ones include aprepitant, metronidazole, picosulfuric acid, nateglinide, nitisinone, rosuvastatin, simvastatin, tinidazole, activated charcoal and troglitazone.
Reported adverse events in the literature: methemoglobinemia with hypoxia, hepatic complications, acute pancreatitis, and hypersensitivity syndrome.

Please also refer to the package insert for full safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Several completed Phase 3 trials (about 2,000 participants combined) directly study dapsone in Pneumocystis pneumonia prevention and treatment, and network meta-analyses include dapsone-based regimens. Guidelines favour TMP-SMX first, so dapsone is best viewed as an alternative for patients who cannot take it.

To proceed, the following is needed:

Package insert warnings and contraindications from Health Canada
Mechanism of action data confirmed from a primary source
G6PD deficiency screening before use, plus monitoring for methemoglobinemia and hemolysis
Review of the high drug-interaction burden against the intended patient population
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.