{"site":"Dapsone Rx","url":"https://dapsonerx.com","format":"evidence-manifest/v1","claim_count":71,"claims":[{"id":"clm-001","text":"Dapsone is 4,4'-diaminodiphenyl sulfone (DDS), a synthetic sulfone with molecular formula C12H12N2O2S and molecular weight 248.30. It is a white or slightly yellow-white crystalline powder.","source_url":"https://pubchem.ncbi.nlm.nih.gov/compound/2955","grade":"chemical-reference","grade_label":"Chemical reference","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/entity"]},{"id":"clm-002","text":"Dapsone's antimicrobial activity was discovered in 1937 against the background of the sulfonamide era, and the molecule has dual actions: antimicrobial/antiprotozoal effects and anti-inflammatory features similar to non-steroidal anti-inflammatory drugs.","source_url":"https://europepmc.org/article/MED/24310318","grade":"review","grade_label":"Review or guideline","used_on":["https://dapsonerx.com/monograph"]},{"id":"clm-003","text":"Oral dapsone has been available for over 60 years (as of 2007) and its dose-dependent hematologic toxicity is the reason the oral form is reserved for diseases such as dermatitis herpetiformis and Hansen disease rather than acne.","source_url":"https://europepmc.org/article/MED/17655376","grade":"human-pk","grade_label":"Human PK","used_on":["https://dapsonerx.com/monograph"]},{"id":"clm-004","text":"ACZONE (dapsone) topical gel 5% was approved by FDA on July 7, 2005 under NDA 021794.","source_url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021794","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/faq"]},{"id":"clm-005","text":"ACZONE (dapsone) topical gel 7.5% was approved by FDA on February 24, 2016 under NDA 207154.","source_url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=207154","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/faq"]},{"id":"clm-006","text":"Drugs@FDA lists 29 dapsone applications spanning both routes: the two Aczone gel NDAs (021794 and 207154) plus generic topical gel ANDAs at 5% and 7.5%, and oral tablet ANDAs at 25 mg and 100 mg. Currently marketed prescription products include at least 7 generic 5% gels, 7 generic 7.5% gels, and 8 oral tablet applications.","source_url":"https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22dapsone%22&limit=50","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/comparisons"]},{"id":"clm-007","text":"The FDA-approved indication for dapsone gel 7.5% is topical treatment of acne vulgaris in patients 9 years of age and older; for the 5% gel it is topical treatment of acne vulgaris (12 years and older per its trial population).","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=22058b7d-a578-4eaa-a476-ac982337f02a","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/faq"]},{"id":"clm-008","text":"The FDA-approved indications for oral dapsone tablets are dermatitis herpetiformis and all forms of leprosy except cases of proven dapsone resistance. The oral label calls dapsone a primary treatment for dermatitis herpetiformis.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=13002250-b4c5-5890-e063-6394a90a2036","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/faq","https://dapsonerx.com/entity"]},{"id":"clm-009","text":"The G33 status disclosure for this site reads: Dapsone is FDA-approved both as a topical acne gel (Aczone and generics) and as oral tablets for dermatitis herpetiformis and leprosy.","source_url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021794","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com","https://dapsonerx.com/entity","https://dapsonerx.com/copy"]},{"id":"clm-010","text":"Dapsone gel is a prescription drug in the United States by both concentrations; there is no over-the-counter dapsone product, and dapsone is not an ingredient in FDA's over-the-counter topical acne monograph, which lists benzoyl peroxide at 2.5 to 10 percent among permitted OTC active ingredients.","source_url":"https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-333/subpart-D","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/comparisons"]},{"id":"clm-011","text":"Dapsone gel 5% was tested in two identically designed 12-week randomized, double-blind, vehicle-controlled trials totaling 3010 patients aged 12 and older, applied twice daily as monotherapy.","source_url":"https://europepmc.org/article/MED/17208334","grade":"human-rct","grade_label":"Human RCT","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies"]},{"id":"clm-012","text":"In the 5% gel pivotal trials, success on the Global Acne Assessment Score at week 12 was 42% vs 32% (study 1) and 35% vs 28% (study 2) for dapsone gel vs vehicle: absolute differences of 10 and 7 percentage points. Mean percent reduction in inflammatory lesions was 46% vs 42% and 48% vs 40%: vehicle-adjusted differences of 4 and 8 percentage points.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=b7d605cf-bf84-461b-939b-1f773a4cba65","grade":"human-rct","grade_label":"Human RCT","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies","https://dapsonerx.com/faq","https://dapsonerx.com"]},{"id":"clm-013","text":"Dapsone gel 7.5% was tested in two identically designed 12-week randomized, double-blind, vehicle-controlled trials with 2102 and 2238 patients in the intent-to-treat populations (4340 total assessed for efficacy), applied once daily.","source_url":"https://europepmc.org/article/MED/27168264","grade":"human-rct","grade_label":"Human RCT","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies"]},{"id":"clm-014","text":"In the 7.5% gel pivotal trials, GAAS success at week 12 was 29.9% vs 21.2% (trial 1) and 29.8% vs 20.9% (trial 2): absolute differences of 8.7 and 8.9 percentage points. Mean inflammatory lesion counts fell 55.5% vs 49.0% and 53.8% vs 47.3%. On the label's absolute counts, inflammatory lesions fell by 16.1 vs 14.3 and 15.6 vs 14.0: a vehicle-adjusted difference of about 1.6 to 1.8 lesions.","source_url":"https://europepmc.org/article/MED/27168264","grade":"human-rct","grade_label":"Human RCT","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies","https://dapsonerx.com/faq","https://dapsonerx.com"]},{"id":"clm-015","text":"A 2022 systematic review of 14 studies found topical dapsone monotherapy treatment success rates of 40.1 to 69.4% for the 5% gel and 29.8 to 47.0% for the 7.5% gel over 12 to 16 weeks, with inflammatory lesions responding more than noninflammatory in every study, and no major treatment-related adverse effects reported.","source_url":"https://europepmc.org/article/MED/35132625","grade":"systematic-review","grade_label":"Systematic review","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies"]},{"id":"clm-016","text":"In a 12-month open-label safety study, 486 acne patients applied dapsone gel 5% twice daily; inflammatory lesion counts fell 30.6% at one month and 58.2% at 12 months, treatment-related application-site reactions occurred in 8.2% of patients, and no significant changes in hematology or blood chemistry were observed.","source_url":"https://europepmc.org/article/MED/17966175","grade":"human-trial","grade_label":"Human trial","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies"]},{"id":"clm-017","text":"In the 7.5% gel trials the most common adverse reactions were application-site dryness (1.1% vs 1.0% on vehicle) and pruritus (0.9% vs 0.5%): local tolerability was nearly indistinguishable from the vehicle gel. Overall adverse-event incidence was also similar (19.1% vs 20.6% in trial 1; 17.6% vs 17.1% in trial 2).","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=22058b7d-a578-4eaa-a476-ac982337f02a","grade":"human-rct","grade_label":"Human RCT","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies"]},{"id":"clm-018","text":"A randomized combination study (301 patients, 12 weeks) added adapalene gel 0.1%, benzoyl peroxide gel 4%, or moisturizer to twice-daily dapsone gel 5%; adding adapalene or benzoyl peroxide did not significantly out-reduce inflammatory lesions versus adding moisturizer (P=0.052 for both).","source_url":"https://europepmc.org/article/MED/20120423","grade":"human-rct","grade_label":"Human RCT","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies","https://dapsonerx.com/comparisons"]},{"id":"clm-019","text":"The 2024 American Academy of Dermatology acne guideline issues strong recommendations for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline, and conditional recommendations for topical clascoterone, salicylic acid, and azelaic acid (plus several systemic options). Topical dapsone is not named in either recommendation list of the guideline abstract.","source_url":"https://europepmc.org/article/MED/38300170","grade":"review","grade_label":"Review or guideline","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/comparisons","https://dapsonerx.com/studies"]},{"id":"clm-020","text":"No head-to-head randomized trial of dapsone gel against benzoyl peroxide monotherapy or azelaic acid has been published: PubMed indexes only a combination study and a systematic review for dapsone gel plus benzoyl peroxide queries, and zero results for dapsone versus azelaic acid randomized queries.","source_url":"https://pubmed.ncbi.nlm.nih.gov/?term=%22dapsone+gel%22+AND+%22benzoyl+peroxide%22+AND+randomized","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/comparisons","https://dapsonerx.com/monograph"]},{"id":"clm-021","text":"In the crossover pharmacokinetic study, dapsone gel 5% applied twice daily for 14 days to about 22.5% of body surface area produced a day-14 AUC of 415 ng.h/mL, while a single 100 mg oral dapsone dose in the same study produced an AUC of 52,641 ng.h/mL: oral exposure approximately 100 times greater than topical.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=b7d605cf-bf84-461b-939b-1f773a4cba65","grade":"human-pk","grade_label":"Human PK","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies","https://dapsonerx.com/comparisons","https://dapsonerx.com","https://dapsonerx.com/tools"]},{"id":"clm-022","text":"At steady state, dapsone gel 7.5% applied once daily (2 g to face, upper chest, upper back and shoulders for 28 days) produced a mean Cmax of 13.0 ng/mL and AUC of 282 ng.h/mL; the label states systemic exposure from the 7.5% gel is expected to be about 1% of that from a 100 mg oral dose, even when co-administered with trimethoprim/sulfamethoxazole. Steady state was reached within 7 days.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=22058b7d-a578-4eaa-a476-ac982337f02a","grade":"human-pk","grade_label":"Human PK","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies","https://dapsonerx.com/comparisons","https://dapsonerx.com","https://dapsonerx.com/tools"]},{"id":"clm-023","text":"Oral dapsone reaches peak concentration in 4 to 8 hours; plasma half-life ranges from 10 to 50 hours (average 28); with 200 mg daily, blood levels averaged 2.3 mcg/mL (2,300 ng/mL), and about 85% of the daily intake is recoverable in urine.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=13002250-b4c5-5890-e063-6394a90a2036","grade":"human-pk","grade_label":"Human PK","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies","https://dapsonerx.com/comparisons","https://dapsonerx.com/tools"]},{"id":"clm-024","text":"Patients on chronic oral dapsone 50 to 100 mg daily carried mean plasma dapsone levels around 2,298 ng/mL, and their baseline methemoglobin averaged 5.5%; for comparison, steady-state Cmax on the 7.5% gel is 13.0 ng/mL, roughly 175 times lower than those chronic oral trough levels.","source_url":"https://europepmc.org/article/MED/7888363","grade":"human-trial","grade_label":"Human trial","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies","https://dapsonerx.com/comparisons","https://dapsonerx.com/tools"]},{"id":"clm-025","text":"Once-daily dapsone gel 7.5% delivers a lower systemic dose than twice-daily 5% gel despite the higher concentration: in a 28-day comparative PK study, daily systemic exposures of three 7.5% formulations were approximately 25% to 40% lower than that of the 5% gel, a statistically significant difference.","source_url":"https://europepmc.org/article/MED/27741344","grade":"human-pk","grade_label":"Human PK","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies","https://dapsonerx.com/comparisons","https://dapsonerx.com/faq"]},{"id":"clm-026","text":"Deaths associated with oral dapsone have been reported from agranulocytosis, aplastic anemia and other blood dyscrasias. The oral label instructs frequent complete blood counts: weekly for the first month, monthly for six months, and semi-annually thereafter, per the FDA Dermatology Advisory Committee recommendation.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=13002250-b4c5-5890-e063-6394a90a2036","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/warning_box","https://dapsonerx.com/comparisons","https://dapsonerx.com/tools"]},{"id":"clm-027","text":"Dose-related hemolysis is the most common adverse effect of oral dapsone: on treatment, almost all patients show a loss of 1 to 2 g of hemoglobin, a reticulocyte increase of 2 to 12%, shortened red-cell life span, and a rise in methemoglobin. G6PD-deficient patients have greater responses.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=13002250-b4c5-5890-e063-6394a90a2036","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/warning_box","https://dapsonerx.com/comparisons","https://dapsonerx.com","https://dapsonerx.com/tools"]},{"id":"clm-028","text":"In Sweden between 1972 and 1988, seven cases of agranulocytosis were reported during dapsone treatment of dermatitis herpetiformis: a crude relative risk of 50, a total risk of one case per 3,000 patient-years, and an estimated 1 case per 240 to 425 newly treated patients.","source_url":"https://europepmc.org/article/MED/2360840","grade":"human-obs","grade_label":"Human observational","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies","https://dapsonerx.com/warning_box"]},{"id":"clm-029","text":"A systematic review covering 336 patients found dapsone hypersensitivity reactions in 1.4% of treated patients (95% CI 1.2 to 1.7%) with an overall fatality rate of 9.9%; mucosal involvement, hepatitis, higher age and residence in non-affluent countries predicted fatal outcomes.","source_url":"https://europepmc.org/article/MED/22307940","grade":"systematic-review","grade_label":"Systematic review","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies","https://dapsonerx.com/warning_box"]},{"id":"clm-030","text":"A genome-wide association study in 872 leprosy patients (replicated in independent cohorts) identified HLA-B*13:01 as a risk factor for dapsone hypersensitivity syndrome with an odds ratio of 20.53; carrying the allele predicted the syndrome with 85.5% sensitivity and 85.7% specificity, and its absence lowered risk from 1.4% to 0.2%. The allele is present in about 2 to 20% of Chinese, 1.5% of Japanese, 1 to 12% of Indians, and 2 to 4% of Southeast Asians, but is largely absent in Europeans.","source_url":"https://europepmc.org/article/MED/24152261","grade":"human-obs","grade_label":"Human observational","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies"]},{"id":"clm-031","text":"The dapsone hypersensitivity syndrome develops in about 0.5 to 3.6% of persons treated with the drug, per the NEJM study's background statement.","source_url":"https://europepmc.org/article/MED/24152261","grade":"human-obs","grade_label":"Human observational","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/warning_box"]},{"id":"clm-032","text":"In a retrospective series of 138 acquired methemoglobinemia cases at two teaching hospitals over 28 months, dapsone was the most common cause, accounting for 42% of all cases, with a mean peak methemoglobin level of 7.6% among those patients. One fatality and 3 near-fatalities were attributable to methemoglobinemia overall.","source_url":"https://europepmc.org/article/MED/15342970","grade":"human-obs","grade_label":"Human observational","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies","https://dapsonerx.com/warning_box","https://dapsonerx.com/tools"]},{"id":"clm-033","text":"Methemoglobinemia with resultant hospitalization has been reported postmarketing with twice-daily dapsone gel 5%; the gel labels tell patients to stop and seek immediate care for slate grey cyanosis of the lips, nail beds or mouth, and to avoid the gel entirely in congenital or idiopathic methemoglobinemia.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=22058b7d-a578-4eaa-a476-ac982337f02a","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/warning_box","https://dapsonerx.com/faq","https://dapsonerx.com/tools"]},{"id":"clm-034","text":"Pediatric case reports document clinically significant methemoglobinemia from topical dapsone, including a previously healthy toddler after exposure to a sibling's Aczone gel who needed methylene blue plus a repeat dose for rebound methemoglobinemia, and a published NEJM case in an adult using the gel.","source_url":"https://europepmc.org/article/MED/27401099","grade":"human-case-report","grade_label":"Human case report","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies","https://dapsonerx.com/warning_box","https://dapsonerx.com/faq"]},{"id":"clm-035","text":"For dapsone overdose with methemoglobin-induced depression, convulsions or severe cyanosis, the oral label names intravenous methylene blue 1 to 2 mg/kg as the treatment of choice, repeatable if methemoglobin reaccumulates; it also warns that methylene blue reduction depends on G6PD and should not be given to fully expressed G6PD-deficient patients.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=13002250-b4c5-5890-e063-6394a90a2036","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/faq"]},{"id":"clm-036","text":"G6PD deficiency is the most prevalent human enzyme deficiency, affecting an estimated 400 million people worldwide, with the highest prevalence in Sub-Saharan Africa; most affected individuals are asymptomatic until an oxidative stressor such as certain drugs or infection triggers acute hemolysis.","source_url":"https://europepmc.org/article/MED/19233695","grade":"meta-analysis","grade_label":"Meta-analysis","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies","https://dapsonerx.com/tools"]},{"id":"clm-037","text":"The gel labels state G6PD deficiency is most prevalent in populations of African, South Asian, Middle Eastern, and Mediterranean ancestry, and that individuals with G6PD deficiency may be more prone to methemoglobinemia and hemolysis.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=22058b7d-a578-4eaa-a476-ac982337f02a","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/tools"]},{"id":"clm-038","text":"In the randomized, double-blind crossover trial of 64 G6PD-deficient acne patients, dapsone gel 5% twice daily produced a 0.32 g/dL hemoglobin drop at two weeks that resolved by week 12 despite continued treatment; drops of 1 g/dL or more were as common on vehicle as on dapsone (8 of 58 vs 7 of 56), the largest single drop was actually in the vehicle group (1.7 vs 1.5 g/dL), and there was no clinical or laboratory evidence of drug-induced hemolytic anemia.","source_url":"https://europepmc.org/article/MED/19075138","grade":"human-rct","grade_label":"Human RCT","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies","https://dapsonerx.com/faq","https://dapsonerx.com","https://dapsonerx.com/tools"]},{"id":"clm-039","text":"The original July 2005 Aczone label required G6PD screening: it stated that G6PD levels should be obtained prior to initiating therapy, in all patients. The March 2008 revised label removed that requirement after the 64-subject crossover study, and today's gel labels carry no G6PD testing requirement at all, only hematologic warnings.","source_url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021794lbl.pdf","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/faq","https://dapsonerx.com","https://dapsonerx.com/tools"]},{"id":"clm-040","text":"For oral dapsone the calculus differs: the oral label directs that hemolysis and Heinz body formation may be exaggerated in G6PD-deficient patients, that the reaction is frequently dose-related, and that dapsone should be given with caution to these patients; severe anemia should be treated before starting and hemoglobin monitored.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=13002250-b4c5-5890-e063-6394a90a2036","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/comparisons","https://dapsonerx.com/tools"]},{"id":"clm-041","text":"Topical dapsone labels instruct avoiding the gel in patients already taking oral dapsone or antimalarial medications because of the potential for hemolytic reactions, and note that combining the gel with trimethoprim/sulfamethoxazole may increase hemolysis likelihood in G6PD-deficient patients.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=22058b7d-a578-4eaa-a476-ac982337f02a","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/tools"]},{"id":"clm-042","text":"In responsive dermatitis herpetiformis patients, oral dapsone produces a prompt reduction in pruritus followed by clearance of skin lesions; it has no effect on the gastrointestinal (celiac) component of the disease. Dosing starts at 50 mg daily in adults, titrated within 50 to 300 mg daily.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=13002250-b4c5-5890-e063-6394a90a2036","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies","https://dapsonerx.com/faq"]},{"id":"clm-043","text":"A strict gluten-free diet lets many dermatitis herpetiformis patients reduce or eliminate dapsone: per the label, average time to dose reduction is 8 months (range 4 months to 2.5 years) and to elimination 29 months (range 6 months to 9 years).","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=13002250-b4c5-5890-e063-6394a90a2036","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/faq"]},{"id":"clm-044","text":"No randomized controlled trial of dapsone efficacy in dermatitis herpetiformis has ever been published: dapsone's first-line status rests on seven decades of clinical experience dating to 1955 Lancet reports, label recognition as primary treatment, and consensus guidelines. The only DH randomized studies PubMed indexes under dapsone are small NSAID-interaction experiments.","source_url":"https://pubmed.ncbi.nlm.nih.gov/?term=dermatitis+herpetiformis%5Bti%5D+AND+dapsone%5Btiab%5D+AND+randomized+controlled+trial%5Bpt%5D","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies","https://dapsonerx.com"]},{"id":"clm-045","text":"The 2021 European S2k consensus guideline for dermatitis herpetiformis, produced by 26 specialists under EADV with the European Dermatology Forum, summarizes evidence-based and expert-based (S2-level) recommendations for managing the disease, which it defines as a chronic, pruritic, gluten-induced skin disorder with granular IgA deposition and variable enteropathy identical to celiac disease.","source_url":"https://europepmc.org/article/MED/34004067","grade":"review","grade_label":"Review or guideline","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies"]},{"id":"clm-046","text":"WHO-recommended leprosy treatment is multidrug therapy combining dapsone, rifampicin and clofazimine, supplied free of cost through WHO; the oral label directs that dapsone be commenced in combination with other anti-leprosy drugs at 100 mg daily to reduce secondary resistance.","source_url":"https://www.who.int/news-room/fact-sheets/detail/leprosy","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies","https://dapsonerx.com/faq"]},{"id":"clm-047","text":"Multidrug therapy including dapsone is effective: WHO-recommended courses run 6 months for paucibacillary and 12 months for multibacillary leprosy, annual new case detection plateaued around 200,000 before the COVID-19 pandemic, and a 2025 meta-analysis of 26 studies (71,385 participants) put pooled relapse prevalence after regular MDT at about 4% (95% CI 2 to 5%).","source_url":"https://europepmc.org/article/MED/39609422","grade":"meta-analysis","grade_label":"Meta-analysis","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies"]},{"id":"clm-048","text":"Therapeutic resistance to dapsone has been reported for Mycobacterium leprae when patients were treated with oral dapsone, which is why monotherapy was abandoned; no resistance studies were conducted in the acne gel trials, so effects on Propionibacterium acnes susceptibility are unknown.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=22058b7d-a578-4eaa-a476-ac982337f02a","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/comparisons"]},{"id":"clm-049","text":"In the ACTG randomized trial of 843 HIV patients with fewer than 200 CD4 cells, dapsone prophylaxis had an estimated 36-month Pneumocystis pneumonia risk of 17%, versus 18% for trimethoprim-sulfamethoxazole and 21% for aerosolized pentamidine; among patients under 100 CD4 cells, TMP-SMX (19%) and dapsone (22%) beat pentamidine (33%), and 100 mg dapsone failed less often than 50 mg.","source_url":"https://europepmc.org/article/MED/7854375","grade":"human-rct","grade_label":"Human RCT","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies"]},{"id":"clm-050","text":"Dapsone's history in inflammatory dermatology spans 60-plus years: it has been used most successfully in disorders characterized by abnormal neutrophil and eosinophil accumulation.","source_url":"https://europepmc.org/article/MED/11511841","grade":"review","grade_label":"Review or guideline","used_on":["https://dapsonerx.com/monograph"]},{"id":"clm-051","text":"Both gel labels state plainly: the mechanism of action of dapsone gel in treating acne vulgaris is not known.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=22058b7d-a578-4eaa-a476-ac982337f02a","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/faq","https://dapsonerx.com"]},{"id":"clm-052","text":"In vitro, at concentrations comparable to therapeutic blood levels (1 to 30 mcg/mL), dapsone interferes primarily with the myeloperoxidase-H2O2-halide cytotoxic system of neutrophils, a competitive inhibition, without affecting chemotaxis, phagocytic ingestion, oxidative metabolism, or lysosomal enzyme release: a proposed mechanism for its dermatitis herpetiformis effect.","source_url":"https://europepmc.org/article/MED/207742","grade":"in-vitro","grade_label":"In vitro","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies"]},{"id":"clm-053","text":"Against Mycobacterium leprae, dapsone is bactericidal as well as bacteriostatic by the kinetic method in mice; in dermatitis herpetiformis the label itself says the mechanism has not been established.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=13002250-b4c5-5890-e063-6394a90a2036","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph"]},{"id":"clm-054","text":"Using benzoyl peroxide at the same time as dapsone gel can temporarily turn skin and facial hair yellow or orange at the application site. This is a label-documented interaction of the topical route.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=22058b7d-a578-4eaa-a476-ac982337f02a","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/comparisons","https://dapsonerx.com/faq","https://dapsonerx.com/tools"]},{"id":"clm-055","text":"Trimethoprim/sulfamethoxazole raises systemic dapsone levels (topical and oral routes both carry the interaction); with oral dapsone, trimethoprim and dapsone each raise the other's level about 1.5 times, and rifampin lowers dapsone levels 7 to 10-fold by accelerating plasma clearance. Folic acid antagonists such as pyrimethamine may increase hematologic reactions.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=13002250-b4c5-5890-e063-6394a90a2036","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/tools"]},{"id":"clm-056","text":"The gel label lists drugs that induce methemoglobinemia and may compound risk when combined with topical dapsone, including sulfonamides, acetaminophen, benzocaine, chloroquine, nitrates and nitrites, nitrofurantoin, nitroglycerin, phenytoin, primaquine and quinine.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=22058b7d-a578-4eaa-a476-ac982337f02a","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/tools"]},{"id":"clm-057","text":"Cimetidine co-administration reduced dapsone-induced methemoglobinemia in small human studies: in 8 patients on chronic dapsone, methemoglobin fell from 5.5% to 3.9% over 3 months while plasma dapsone rose about 30% and disease control was unchanged; in 6 dermatitis herpetiformis patients, methemoglobinemia fell about 27% in the first two weeks.","source_url":"https://europepmc.org/article/MED/7888363","grade":"human-trial","grade_label":"Human trial","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies"]},{"id":"clm-058","text":"There are no data on dapsone gel use in pregnant women; the label leans on the low systemic absorption relative to oral dapsone and on animal studies where embryocidal effects occurred only at oral exposures more than 400 times the maximum topical human exposure.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=22058b7d-a578-4eaa-a476-ac982337f02a","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/faq","https://dapsonerx.com/studies"]},{"id":"clm-059","text":"Oral dapsone in pregnancy is Category C under the older labeling system: extensive but uncontrolled experience and two published surveys have not shown increased fetal abnormalities, and the label notes dapsone has been important for managing some pregnant dermatitis herpetiformis patients and that leprosy authorities recommend maintaining it. Dapsone is excreted in breast milk in substantial amounts and hemolytic reactions can occur in neonates.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=13002250-b4c5-5890-e063-6394a90a2036","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/faq"]},{"id":"clm-060","text":"Rat and rabbit reproduction studies of oral dapsone showed embryocidal effects at 75 and 150 mg/kg/day respectively (roughly 1407 and 425 times the human topical exposure), with increased stillbirths and decreased pup weight at high exposures; the effects were judged probably secondary to maternal toxicity.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=22058b7d-a578-4eaa-a476-ac982337f02a","grade":"animal","grade_label":"Animal","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/studies"]},{"id":"clm-061","text":"Peripheral neuropathy (motor loss and muscle weakness) and severe skin reactions including toxic epidermal necrolysis and erythema multiforme have been reported with oral dapsone; none of these were observed in the topical gel clinical trials. The gel labels carry the oral experience anyway, as class information.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=22058b7d-a578-4eaa-a476-ac982337f02a","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/comparisons"]},{"id":"clm-062","text":"The topical gel labels list no contraindications at all (Contraindications: None), while the oral label contraindicates use in hypersensitivity to dapsone or its derivatives. Toxic hepatitis and cholestatic jaundice have been reported early in oral therapy.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=22058b7d-a578-4eaa-a476-ac982337f02a","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/comparisons"]},{"id":"clm-063","text":"Dapsone is a sulfone, not a sulfonamide: a 2010 review of topical dapsone safety states that despite some structural similarities, cross-reaction with sulfonamides has not been demonstrated, and that topical dapsone gel showed no risk of hemolytic anemia including in G6PD-deficient patients.","source_url":"https://europepmc.org/article/MED/20480797","grade":"review","grade_label":"Review or guideline","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/faq"]},{"id":"clm-064","text":"Dapsone gel 7.5% is applied once daily as approximately a pea-sized amount in a thin layer to the entire face, plus a thin layer to other affected areas; the 5% gel is applied twice daily as a pea-sized amount in a thin layer to acne-affected areas. Both labels direct reassessment if there is no improvement after 12 weeks.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=22058b7d-a578-4eaa-a476-ac982337f02a","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/tools","https://dapsonerx.com/faq"]},{"id":"clm-065","text":"Aczone gel 7.5% is supplied in 30, 60 and 90 gram airless pumps; Aczone gel 5% is supplied in 30, 60 and 90 gram laminate tubes. Both store at controlled room temperature, 20 to 25 C, protected from freezing.","source_url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=22058b7d-a578-4eaa-a476-ac982337f02a","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://dapsonerx.com/monograph","https://dapsonerx.com/tools"]},{"id":"clm-066","text":"The fingertip unit (FTU) is the standard dermatology quantity measure: the amount of ointment expressed from a 5 mm nozzle from the distal skin-crease to the tip of the index finger. Face and neck take 2.5 FTU per application in the defining study; one FTU covers about 286 square centimeters.","source_url":"https://europepmc.org/article/MED/1806320","grade":"human-trial","grade_label":"Human trial","used_on":["https://dapsonerx.com/tools","https://dapsonerx.com/monograph"]},{"id":"clm-067","text":"One fingertip unit of a semisolid preparation weighs approximately 0.5 g in the standard convention used across this fleet's topical references, so a 2.5 FTU face-and-neck application is about 1.25 g.","source_url":"https://europepmc.org/article/MED/1806320","grade":"analytical","grade_label":"Analytical study","used_on":["https://dapsonerx.com/tools"]},{"id":"clm-068","text":"Azelaic acid 15% gel matched benzoyl peroxide 5% in a randomized blinded comparative trial of 351 patients over 4 months (median inflamed-lesion reduction 70%), with distinctly less burning and irritation than benzoyl peroxide. This is the same trial the azelaic acid sister site reports, stated with the same numbers.","source_url":"https://europepmc.org/article/MED/16281587","grade":"human-rct","grade_label":"Human RCT","used_on":["https://dapsonerx.com/comparisons"]},{"id":"clm-100","text":"This monograph's study table contains 26 rows: 24 human, 1 in vitro, 1 animal (label reproduction studies). Every row carries a species label and a route label.","source_url":"https://dapsonerx.com","grade":"internal-measurement","grade_label":"Internal measurement","used_on":["https://dapsonerx.com","https://dapsonerx.com/monograph"]},{"id":"clm-101","text":"This site cites 44 unique fetch-verified sources; 100.0% are peer-reviewed journals or government sources (31 peer-reviewed, 13 government).","source_url":"https://dapsonerx.com","grade":"internal-measurement","grade_label":"Internal measurement","used_on":["https://dapsonerx.com","https://dapsonerx.com/monograph"]},{"id":"clm-102","text":"Of the study table's 24 human rows, 11 are topical-route evidence, 11 are oral or systemic-route evidence, and 1 is the crossover study that measured both routes at once; the route column renders on every row so the two lives of the molecule never blur.","source_url":"https://dapsonerx.com","grade":"internal-measurement","grade_label":"Internal measurement","used_on":["https://dapsonerx.com","https://dapsonerx.com/monograph"]}]}