Dapsone is a versatile drug. It is a synthetic sulfone and is chemically similar to sulfonamides, but cross-sensitivity has not been substantiated. It is used as an antiinfective (for leprosy, Pneumocystis pneumonia (PCP), and prophylaxis of malaria) and as an immunosuppressive agent (for relapsing polychondritis and systemic lupus erythematosus). Dapsone also has been used to treat various dermatologic disorders such as actinomycotic mycetoma, dermatitis herpetiformis, pemphigoid, subcorneal pustular dermatosis, granuloma annulare, and pyoderma gangrenosum. In addition, dapsone is commonly used to treat Loxosceles reclusa (e.g., brown recluse spider) bites; however, both human and animal data to support its routine use are conflicting. A few case reports and small case series indicate efficacy in humans, but prospective human trials supporting its use are not available. Furthermore, in addition to the lack of evidence to support its use, dapsone can cause serious, life-threatening toxicities (e.g., hemolytic anemia, hepatitis, methemoglobinemia). A prospective epidemiologic study found that patients treated with dapsone for suspected loxoscelism experienced a nonsignificant increase in healing time and scarring. The benefits of administering dapsone for the treatment of loxoscelism should be carefully balanced against the risks; supportive therapy and wound care are the treatment modalities of choice in patients presenting with loxoscelism. Dapsone is currently the agent of choice in the treatment of all forms of leprosy, unless the organism exhibits dapsone resistance. Dapsone can be used for prophylaxis of PCP either as a single agent or in combination with pyrimethamine. In combination with trimethoprim, dapsone is effective for treatment of PCP. In combination with pyrimethamine, dapsone is effective for prevention of toxoplasmosis in patients with AIDS. Acedapsone is a long-acting repository form. In Canada, a commonly used brand name of oral dapsone is Avlosulfon. Dapsone was originally approved by the FDA in 1955. A topical dapsone gel (Aczone) was approved in a 5% strength for the treatment of acne vulgaris in July 2005, and in a 7.5% strength in February 2016.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Dapsone may be administered orally without regard to meals.
Oral Liquid Formulations
-Extemporaneous oral suspension: Shake well before administering. Measure dosage with calibrated measuring device.
Extemporaneous Compounding-Oral
NOTE: Extemporaneously compounded oral dapsone suspension is not FDA-approved.
Extemporaneous preparation of 2 mg/mL dapsone oral suspension
-Using a mortar and pestle, grind sixteen 25-mg dapsone tablets to a fine powder.
-Add a small amount of vehicle (1:1 mixture of Ora-Plus and Ora-Sweet) and mix to a uniform paste.
-Add geometric proportions of vehicle to almost desired volume while continuing to mix then transfer to graduated cylinder.
-Rinse mortar and pestle with vehicle and transfer to graduated cylinder.
-Add enough vehicle to bring the final volume to 200 mL.
-Storage: The oral suspension is stable for 90 days when stored at room temperature or refrigerated.
Topical Administration
-Before applying topical formulations of dapsone, gently cleanse affected area with a mild soap and pat skin dry.
Other Topical Formulations
Gel Formulation:
-Apply a thin layer to the acne affected area as directed. Rub the gel into the skin gently and completely. Aczone gel is gritty with visible drug substance particles present. Wash hands immediately after applying.
Dose-related hemolysis is the most common adverse effect reported with oral dapsone and is noted in persons with or without glucose 6-phosphate dehydrogenase (G6PD) deficiency. Almost all persons experience hemoglobin decreases of 1 to 2 g/dL, reticulocyte count increases of 2% to 12%, shortened red cell life span, and methemoglobinemia. Persons with G6PD deficiency, methemoglobin reductase deficiency, or hemoglobin M may experience more pronounced adverse hematologic effects, such as hemolytic anemia, Heinz body formation, and/or methemoglobinemia. Potentially fatal agranulocytosis, aplastic anemia, and other blood dyscrasias have been documented. Monitor blood counts frequently in persons receiving oral dapsone; when feasible, monitor blood counts weekly for the first month, monthly for 6 months, and then semi-annually thereafter. Discontinue dapsone for significant reductions in leukocytes, platelets, or hemopoiesis. Studies with topical dapsone have found no evidence of clinically significant hemolytic anemia; however, laboratory changes suggestive of hemolysis have been reported. Discontinue topical dapsone if signs or symptoms suggestive of hemolytic anemia occur.
Severe dermatologic reactions develop rarely during therapy with dapsone and are frequently the result of sensitization to the drug. Cutaneous effects that have been reported during oral therapy include bullous rash, exfoliative dermatitis, toxic erythema, erythema multiforme, morbilliform and scarlatiniform reactions, urticaria, toxic epidermal necrolysis, and erythema nodosum leprosum in patients being treated for leprosy. These reactions have not been observed during clinical trials with the topical formulation; however, rash (including erythematous rash) and swelling of the face (including lip and eye swelling) have been noted in postmarketing reports with the topical product. Photosensitivity has also been observed during oral dapsone therapy. Application site reactions have been reported with the use of topical dapsone and include unspecified reactions (18%), dryness or xerosis (up to 16%), erythema (13%), burning (1%), pruritus (1%), and oiliness or peeling (up to 13%).
Adverse gastrointestinal effects that can occur during therapy with oral dapsone include nausea, vomiting, and abdominal pain.
In rare cases, peripheral neuropathy has occurred in patients receiving oral dapsone for non-leprosy purposes. This complication, which is characterized by motor loss and muscle weakness, usually resolves following discontinuance of the drug. In leprosy patients, this complication may be difficult to distinguish from a leprosy reactional state. No cases of peripheral neuropathy were reported during clinical trials with topical dapsone.
Toxic hepatitis and cholestatic jaundice have occurred, particularly during the initial stages of therapy with oral dapsone. These complications can manifest as elevated hepatic enzymes, specifically elevations in alkaline phosphatase, SGOT, bilirubin, and LDH. Hyperbilirubinemia may occur more often in G6PD deficient patients.
Adverse renal effects observed during therapy with oral dapsone include albuminuria, nephrotic syndrome, and renal papillary necrosis.
Abrupt changes in the patient's clinical status during effective treatment with dapsone for leprosy can cause leprosy reactional states. These reactional states can be divided into two categories: reversal reactions (type I) and lepromatous lepra reactions (type II). Type I reactions occur primarily in borderline or tuberculoid leprosy patients. Patients can exhibit an enhanced delayed hypersensitivity reaction to the infection, which can manifest as swelling of the skin and nerve lesions, ulceration of lesions, acute neuritis, and loss of nerve function. Type II reactions occur primarily in patients with lepromatous or borderline leprosy. Approximately 50% of patients experience this complication within the first year of treatment. These reactions are the result of increased immune complexes on sensitized tissues. Primary manifestations include fever and erythematous skin lesions, sometimes in conjunction with joint swelling, epistaxis, neuritis, orchitis, albuminuria, malaise, iritis, or depression. Histologically, there is a vasculitis with an intense polymorphonuclear infiltrate. Fever has also been associated with 1% of patients receiving the topical gel.
Headache has been reported with the use of oral and topical (4%) dapsone. Insomnia and psychosis have been noted in patients treated with oral dapsone.
Nasopharyngitis (5%), unspecified upper respiratory tract infection (3%), sinusitis (2%), influenza (1%), pharyngitis (2%), and cough (2%) have been reported with the use of topical dapsone in clinical trials. An infectious mononucleosis-like syndrome has been reported with the use of oral dapsone.
Vertigo, blurred vision, and tinnitus have been reported with the use of oral dapsone.
Pancreatitis has been reported with the use of oral dapsone.
Pulmonary eosinophilia (eosinophilic pneumonia) and hypoalbuminemia without proteinuria have been reported with the use of oral dapsone.
Sinus tachycardia has been reported with the use of oral dapsone.
Male infertility has been reported with the use of oral dapsone.
A drug-induced Lupus erythematosus (lupus-like symptoms) has been reported with the use of oral dapsone.
Perform testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to dapsone therapy. Use oral dapsone with caution in persons with G6PD deficiency, methemoglobin reductase deficiency, or hemoglobin M because hemolysis, Heinz body formation, and/or methemoglobinemia may be exaggerated in persons with these conditions. Additional guidance recommends avoiding oral dapsone in persons with G6PD deficiency due to high risk of hemolytic anemia. Use oral dapsone with caution with other medications or conditions, such as diabetic ketoacidosis or infection, capable of producing hemolysis. Monitor blood counts frequently in persons receiving oral dapsone; when feasible, monitor blood counts weekly for the first month, monthly for 6 months, and then semi-annually thereafter. Studies with topical dapsone found no evidence of clinically significant hemolytic anemia; however, laboratory changes suggestive of hemolysis have been reported. Treat severe anemia prior to the initiation of oral dapsone and monitor hemoglobin. Hyperbilirubinemia may also occur more often in G6PD deficient persons receiving oral dapsone. When possible, baseline and subsequent monitoring of liver function is recommended; if abnormal, discontinue oral dapsone until the source of the abnormality is established.
Uncontrolled studies of systemic dapsone use in pregnant women have not demonstrated fetal risk during any trimester of pregnancy nor did use affect reproduction capacity. Although further study is needed, it has been recommended by some authorities that dapsone therapy be maintained during pregnancy in cases of leprosy or dermatitis herpetiformis. Information on the use of topical dapsone in pregnant patients is not available; however, systemic exposure of the topical gel is low compared to oral dapsone administration (approximately 100 times less).
Dapsone is distributed into breast milk in large quantities after oral dosing and can cause hemolytic anemia in nursing infants with G6PD deficiency. However, the American Academy of Pediatrics (AAP) states that dapsone is usually compatible with breast-feeding. Absorption after topical administration is minimal relative to oral dapsone administration. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Administer dapsone, a synthetic sulfone, with caution in patients with sulfonamide hypersensitivity. It may be prudent to monitor patients for allergic-type reactions when initiating dapsone. Although structurally it contains an aromatic amine known to trigger adverse reactions at position N4, dapsone does not contain the N1-moiety that is present in sulfonamide antibiotics and thought to be responsible for hypersensitivity-type adverse reactions. The risk of cross-sensitivity in patients taking a nonantibiotic sulfonamide that have a history of sulfonamide hypersensitivity is low and has been confirmed by observational studies. In general, patients with a history of hypersensitivity to any drug are predisposed for subsequent hypersensitivity reactions to other drugs. Because of this, patients with a history of sulfonamide hypersensitivity should be monitored for hypersensitivity reactions to other drugs, including dapsone; however, treatment with a nonantibiotic sulfonamide may not need to be withheld in patients with a sulfonamide allergy as long as patients are monitored appropriately, especially if alternative therapies are not available.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Cutibacterium acnes, Mycobacterium leprae
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
This drug may also have activity against the following microorganisms: Actinomadura madurae, Mycobacterium tuberculosis, Nocardia sp., Plasmodium falciparum, Pneumocystis jirovecii (formerly Pneumocystis carinii), Streptomyces somaliensis, Toxoplasma gondii
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.
For the treatment of actinomycotic mycetoma*:
-for actinomycotic mycetoma* caused by Actinomadura madurae* or Streptomyces somaliensis*:
Oral dosage:
Adults: 100 mg PO or 1.5 mg/kg PO twice daily (i.e., morning and evening) for several months following resolution of symptoms in combination with streptomycin.
Children: Safety and efficacy have not been established.
-for actinomycotic mycetoma* caused by Nocardia sp.*:
Oral dosage:
Adults: 100 mg PO or 1.5 mg/kg PO twice daily (i.e., morning and evening) for several months following resolution of symptoms in combination with co-trimoxazole.
Children: Safety and efficacy have not been established.
For the treatment of dermatitis herpetiformis:
Oral dosage:
Adults: 50 mg PO once daily initially. Maintenance dosage is usually 25 to 300 mg daily. The lowest effective dose should be used as soon as possible.
Children: 2 mg/kg PO daily initially. The dose may be increased if the symptoms are not completely controlled.
For the treatment of granuloma annulare*:
Oral dosage:
Adults: A dose of 100 mg PO once daily has been used.
For the treatment of chronic immune thrombocytopenic purpura (ITP)*:
Oral dosage:
Adults: A dosage of 75 to 100 mg PO per day has been recommended.
For the treatment leprosy (Hansen's disease):
-for multibacillary leprosy:
Oral dosage:
Adults and Adolescents >= 15 years: 100 mg PO once daily in combination with clofazimine and rifampin for at least 12 months.
Children 10 to 14 years: 50 mg PO once daily in combination with clofazimine and rifampin for at least 12 months.
Children younger than 10 years: 2 mg/kg PO once daily in combination with clofazimine and rifampin for at least 12 months.
-for paucibacillary leprosy:
Oral dosage:
Adults and Adolescents aged 15 years and older: 100 mg PO once daily in combination with rifampin for at least 6 months.
Children 10 to 14 years: 50 mg PO once daily in combination with rifampin for at least 6 months.
Children younger than 10 years: 2 mg/kg PO once daily in combination with rifampin for at least 6 months.
For the treatment of polychondritis*:
Oral dosage:
Adults: A dose of 100 mg PO once daily or twice daily has been used.
Children: Safety and efficacy have not been established.
For the treatment of Pneumocystis pneumonia (PCP)*:
-for the treatment of PCP in HIV-infected patients*:
Oral dosage:
Adults: 100 mg PO once daily in combination with trimethoprim for 21 days as alternative therapy for mild to moderate infection then chronic suppressive therapy.
Adolescents: 100 mg PO once daily in combination with trimethoprim for 21 days as alternative therapy for mild to moderate infection then chronic suppressive therapy.
Infants and Children: 2 mg/kg/dose (Max: 100 mg/dose) PO once daily in combination with trimethoprim for 21 days as alternative therapy for mild to moderate infection then chronic suppressive therapy.
-for the treatment of PCP in patients with hematological malignancies, cancer, or autoimmune/inflammatory disease* or solid organ transplant recipients*:
Oral dosage:
Adults: 100 mg PO once daily in combination with trimethoprim for 14 to 21 days as alternative therapy for mild to moderate infection.
Adolescents: 100 mg PO once daily in combination with trimethoprim for 14 to 21 days as alternative therapy for mild to moderate infection.
Infants and Children: 2 mg/kg/dose (Max: 100 mg/dose) PO once daily in combination with trimethoprim for 14 to 21 days as alternative therapy for mild to moderate infection.
For Pneumocystis pneumonia (PCP) prophylaxis*:
-for primary PCP prophylaxis in HIV-infected patients*:
Oral dosage:
Adults: 50 mg PO twice daily; 100 mg PO once daily; or 50 mg PO once daily or 200 mg PO once weekly in combination with weekly pyrimethamine plus leucovorin as alternative therapy. Recommended for patients with CD4 count less than 200 cells/mm3, CD4 less than 14%, or CD4 count of 200 to 250 cells/mm3 if antiretroviral therapy (ART) initiation must be delayed and if CD4 count monitoring every 3 months is not possible. May discontinue if the CD4 count is 200 cells/mm3 or more for more than 3 months in response to ART or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit.
Adolescents: 50 mg PO twice daily; 100 mg PO once daily; or 50 mg PO once daily or 200 mg PO once weekly in combination with weekly pyrimethamine plus leucovorin as alternative therapy. Recommended for patients with CD4 count less than 200 cells/mm3, CD4 less than 14%, or CD4 count of 200 to 250 cells/mm3 if antiretroviral therapy (ART) initiation must be delayed and if CD4 count monitoring every 3 months is not possible. May discontinue if the CD4 count is 200 cells/mm3 or more for more than 3 months in response to ART or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit.
Children 6 to 12 years: 2 mg/kg/dose (Max: 100 mg/dose) PO once daily or 4 mg/kg/dose (Max: 200 mg/dose) PO once weekly as alternative therapy. Recommended for patients with CD4 count less than 200 cells/mm3 or CD4 less than 15%. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 200 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 200 cells/mm3 or CD4 is less than 15%.
Children 1 to 5 years: 2 mg/kg/dose PO once daily or 4 mg/kg/dose PO once weekly as alternative therapy. Recommended for patients with CD4 count less than 500 cells/mm3 or CD4 less than 15%. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 500 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 500 cells/mm3 or CD4 is less than 15%.
Infants: 2 mg/kg/dose PO once daily or 4 mg/kg/dose PO once weekly as alternative therapy. Recommended for all HIV-infected or HIV-indeterminate infants younger than 12 months regardless of CD4 count or percentage. Consider prophylaxis for infants born to HIV-infected mothers beginning at 4 to 6 weeks. Discontinue prophylaxis in infants with indeterminate HIV infection status when they are determined to be definitively ore presumptively HIV-uninfected. Do not discontinue prophylaxis in HIV-infected infants younger than 12 months.
-for secondary PCP prophylaxis (i.e., long-term suppressive therapy) in HIV-infected patients*:
Oral dosage:
Adults: 50 mg PO twice daily; 100 mg PO once daily; or 50 mg PO once daily or 200 mg PO once weekly in combination with weekly pyrimethamine plus leucovorin as alternative therapy. May discontinue if the CD4 count is more than 200 cells/mm3 for more than 3 months in response to antiretroviral therapy (ART) or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit. If PCP is diagnosed or recurs at a CD4 count of more than 200 cells/mm3, lifelong prophylaxis is necessary.
Adolescents: 50 mg PO twice daily; 100 mg PO once daily; or 50 mg PO once daily or 200 mg PO once weekly in combination with weekly pyrimethamine plus leucovorin as alternative therapy. May discontinue if the CD4 count is more than 200 cells/mm3 for more than 3 months in response to antiretroviral therapy (ART) or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit. If PCP is diagnosed or recurs at a CD4 count of more than 200 cells/mm3, lifelong prophylaxis is necessary.
Children 6 to 12 years: 2 mg/kg/dose (Max: 100 mg/dose) PO once daily or 4 mg/kg/dose (Max: 200 mg/dose) PO once weekly as alternative therapy. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 200 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 200 cells/mm3 or CD4 is less than 15%.
Children 1 to 5 years: 2 mg/kg/dose PO once daily or 4 mg/kg/dose PO once weekly as alternative therapy. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 500 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 500 cells/mm3 or CD4 is less than 15%.
Infants: 2 mg/kg/dose PO once daily or 4 mg/kg/dose PO once weekly as alternative therapy. Do not discontinue prophylaxis in HIV-infected infants younger than 12 months.
-for PCP prophylaxis in solid organ transplant recipients*:
Oral dosage:
Adults: 50 or 100 mg PO once daily for 3 to 6 months after kidney transplant, for at least 6 to 12 months after other transplants, as well as for at least 6 weeks during and after antirejection therapy in kidney transplant recipients, as alternative therapy. Lifelong prophylaxis is recommended for lung and small bowel transplant recipients, as well as patients with a history of prior PCP or chronic cytomegalovirus disease.
Adolescents: 50 or 100 mg PO once daily for 3 to 6 months after kidney transplant, for at least 6 to 12 months after other transplants, as well as for at least 6 weeks during and after antirejection therapy in kidney transplant recipients, as alternative therapy. Lifelong prophylaxis is recommended for lung and small bowel transplant recipients, as well as patients with a history of prior PCP or chronic cytomegalovirus disease.
Infants and Children: 2 mg/kg/dose (Max: 100 mg/dose) PO once daily or 4 mg/kg/dose (Max: 200 mg/dose) PO once weekly for 3 to 6 months after kidney transplant, for at least 6 to 12 months after other transplants, as well as for at least 6 weeks during and after antirejection therapy in kidney transplant recipients, as alternative therapy. Lifelong prophylaxis is recommended for lung and small bowel transplant recipients, as well as patients with a history of prior PCP or chronic cytomegalovirus disease.
-for primary PCP prophylaxis in hematopoietic stem cell transplant (HSCT) recipients*:
Oral dosage:
Adults: 50 mg PO twice daily or 100 mg PO once daily starting at engraftment or 1 to 2 weeks before HSCT and continuing for at least 6 months after HSCT as alternative therapy. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs. Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease.
Adolescents: 50 mg PO twice daily or 100 mg PO once daily starting at engraftment or 1 to 2 weeks before HSCT and continuing for at least 6 months after HSCT as alternative therapy. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs. Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease.
Infants and Children: 2 to 4 mg/kg/dose (Max: 100 mg/dose) PO once daily starting at engraftment or 1 to 2 weeks before HSCT and continuing for at least 6 months after HSCT as alternative therapy. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs. Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease.
-for primary PCP prophylaxis in patients with cancer-related immunosuppression and hematological malignancies*:
Oral dosage:
Adults: 50 mg PO twice daily as alternative therapy. Recommended for patients receiving alemtuzumab, fludarabine/cyclophosphamide/rituximab, corticosteroids at doses equivalent to more than 20 mg/day of prednisone for 4 weeks, nucleoside or purine analogs, radiotherapy for brain tumors/metastasis plus high-dose steroids as well as for patients with acute lymphoblastic leukemia (ALL) and lymphoma treated with R-CHOP14 or escalated BEACOPP. Duration of prophylaxis for ALL is from induction to the end of maintenance. Prophylaxis for alemtuzumab-associated treatment and fludarabine/cyclophosphamide/rituximab treatment is suggested for at least 6 months after treatment completion.
Infants, Children, and Adolescents: 2 to 4 mg/kg/dose (Max: 100 mg/dose) PO once daily as alternative therapy. Recommended for patients receiving alemtuzumab or corticosteroids at doses equivalent to more than 0.4 mg/kg/day or 16 mg/day of prednisone for 1 month or more as well as patients with acute lymphoblastic leukemia (ALL), severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome (WAS), X-linked agammaglobulinemia, human leukocyte antigen (HLA) II combined immunodeficiency, acute myeloid leukemia (AML), and solid tumors. Duration of prophylaxis for ALL is from induction to the end of maintenance. Patients receiving corticosteroids or with SCID, WAS, X-linked agammaglobulinemia, or HLA II combined immunodeficiency require lifelong prophylaxis or until restoration of the underlying defect. Prophylaxis is recommended for patients with AML and solid tumors for the duration of chemotherapy.
-for primary PCP prophylaxis in dermatology and rheumatology patients receiving corticosteroids*:
Oral dosage:
Adults: 100 mg PO once daily as alternative therapy. Recommended for patients receiving corticosteroids at doses equivalent to 20 mg/day or more of prednisone for 4 weeks or more, particularly if an additional risk factor is present.
For primary toxoplasmosis prophylaxis* in persons with HIV, specifically prevention of toxoplasmic encephalitis (TE)* due to Toxoplasmosis gondii:
Oral dosage:
Adults: 50 mg PO once daily in combination with weekly pyrimethamine plus leucovorin OR 200 mg PO once weekly with weekly pyrimethamine plus leucovorin in Toxoplasma-seropositive patients with CD4 count less than 100 cells/mm3 as an alternative regimen. Primary prophylaxis for TE may be discontinued in patients who have responded to highly active antiretroviral treatment with an increase in CD4 count to more than 200 cells/mm3 for at least 3 months. Prophylaxis should be reintroduced if the CD4 count decreases to less than 100 to 200 cells/mm3.
Adolescents: 50 mg PO once daily in combination with weekly pyrimethamine plus leucovorin OR 200 mg PO once weekly with weekly pyrimethamine plus leucovorin in Toxoplasma-seropositive patients with CD4 count less than 100 cells/mm3 as an alternative regimen. Primary prophylaxis for TE may be discontinued in patients who have responded to highly active antiretroviral treatment with an increase in CD4 count to more than 200 cells/mm3 for at least 3 months. Prophylaxis should be reintroduced if the CD4 count decreases to less than 100 to 200 cells/mm3.
Infants and Children: 2 mg/kg/dose or 15 mg/m2/dose (Max: 25 mg/dose) PO once daily in combination with pyrimethamine plus leucovorin as an alternative regimen in Toxoplasma-seropositive patients with severe immunosuppression (i.e., children younger than 6 years of age with a CD4 percentage less than 15% or children 6 years and older with a CD4 count less than 100 cells/mm3). Infants and infants whose infection status remains unknown should continue to receive prophylaxis for the first year of life. For children 1 to 5 years, primary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy and with a CD4 percentage of at least 15% for more than 3 consecutive months. For children at least 6 years of age, primary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy and with a CD4 count more than 200 cells/mm3 for more than 3 consecutive months.
For the treatment of pyoderma gangrenosum*:
Oral dosage:
Adults: A dose of 50 to 100 mg PO once daily, in combination with other agents has been used.
Children: Safety and efficacy have not been established.
For the treatment of subcorneal pustular dermatosis*:
Oral dosage:
Adults: A dose of 100 mg PO once daily, increasing the dose by 50 mg every 1 to 2 weeks until remission occurs has been used. Subsequently, reduce dosage to lowest effective maintenance dose.
Children: Safety and efficacy have not been established.
For the treatment of acne vulgaris:
Topical dosage (5% gel):
Adults: Apply a thin layer topically to the affected skin area(s) twice daily. If no improvement is observed after 12 weeks, reassess appropriateness of dapsone therapy.
Children and Adolescents 12 to 17 years: Apply a thin layer topically to the affected skin area(s) twice daily. If no improvement is observed after 12 weeks, reassess appropriateness of dapsone therapy.
Topical dosage (7.5% gel):
Adults: Apply a thin layer topically to the affected skin area(s) once daily. If no improvement is observed after 12 weeks, reassess appropriateness of dapsone therapy.
Children and Adolescents 9 to 17 years: Apply a thin layer topically to the affected skin area(s) once daily. If no improvement is observed after 12 weeks, reassess appropriateness of dapsone therapy.
Maximum Dosage Limits:
-Adults
Leprosy, up to 100 mg/day PO; dermatitis herpetiformis, up to 300 mg/day PO; relapsing polychondritis, up to 200 mg/day PO; for acne topical use, 5% gel 2 applications/day topically or 7.5% gel 1 application/day topically.
-Geriatric
Leprosy, up to 100 mg/day PO; dermatitis herpetiformis, up to 300 mg/day PO; relapsing polychondritis, up to 200 mg/day PO; for acne topical use, 5% gel 2 applications/day topically or 7.5% gel 1 application/day topically.
-Adolescents
Leprosy, up to 100 mg/day PO; dermatitis herpetiformis, up to 300 mg/day PO; relapsing polychondritis, up to 200 mg/day PO; for acne topical use, 5% gel 2 applications/day topically or 7.5% gel 1 application/day topically.
-Children
12 years: Maximum oral dosage information not established; for acne topical use, 5% gel 2 applications/day topically or 7.5% gel 1 application/day topically.
9 to 11 years: Maximum oral dosage information not established; for acne topical use, 7.5% gel 1 application/day topically, safety and efficacy of 5% gel not established.
1 to 8 years: Maximum oral dosage information not established; safety and efficacy of topical gel not established.
-Infants
Maximum oral dosage information not established; safety and efficacy of topical gel not established.
-Neonates
Safety and efficacy not established.
Patients with Hepatic Impairment Dosing
Dapsone can cause toxic hepatitis and cholestatic jaundice, however, specific dosage adjustment guidelines in patients with hepatic impairment are not available. Hepatic function should be monitored before and during treatment with dapsone.
Patients with Renal Impairment Dosing
No dosage adjustment needed.
*non-FDA-approved indication
Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Minor) Zidovudine, ZDV should be given with caution to patients also receiving dapsone due to the risk of additive hematologic toxicity.
Acetaminophen: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Aspirin: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Caffeine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Chlorpheniramine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Codeine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Dextromethorphan: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Diphenhydramine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Hydrocodone: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Ibuprofen: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Oxycodone: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Phenylephrine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Acetaminophen; Pseudoephedrine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Adapalene; Benzoyl Peroxide: (Minor) Coadministration of topical benzoyl peroxide-containing products with topical sulfone products, such as dapsone, may cause skin and facial hair to temporarily change color to a yellow/orange color.
Apalutamide: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with apalutamide is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and apalutamide is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with another strong CYP3A4 inducer decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage.
Aprepitant, Fosaprepitant: (Moderate) Use caution if dapsone and aprepitant, fosaprepitant are used concurrently and monitor for an increase in dapsone-related adverse effects for several days after administration of a multi-day aprepitant regimen. Dapsone is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of dapsone. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Armodafinil: (Minor) The metabolism of dapsone may be accelerated when administered concurrently with armodafinil, a known inducer of CYP3A4. Coadministration is expected to decrease the plasma concentration of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis). If these drugs must be administered together, closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia.
Articaine; Epinephrine: (Moderate) Coadministration of dapsone with articaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Atazanavir; Cobicistat: (Minor) Plasma concentrations of dapsone may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hemolytic anemia, methemoglobinemia, or peripheral neuropathy, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while dapsone is a CYP3A4 substrate.
Benzalkonium Chloride; Benzocaine: (Moderate) Coadministration of dapsone with benzocaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Benzhydrocodone; Acetaminophen: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Benzocaine: (Moderate) Coadministration of dapsone with benzocaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Benzocaine; Butamben; Tetracaine: (Moderate) Coadministration of dapsone with benzocaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Benzoyl Peroxide: (Minor) Coadministration of topical benzoyl peroxide-containing products with topical sulfone products, such as dapsone, may cause skin and facial hair to temporarily change color to a yellow/orange color.
Benzoyl Peroxide; Clindamycin: (Minor) Coadministration of topical benzoyl peroxide-containing products with topical sulfone products, such as dapsone, may cause skin and facial hair to temporarily change color to a yellow/orange color.
Benzoyl Peroxide; Erythromycin: (Minor) Coadministration of topical benzoyl peroxide-containing products with topical sulfone products, such as dapsone, may cause skin and facial hair to temporarily change color to a yellow/orange color.
Benzoyl Peroxide; Sulfur: (Minor) Coadministration of topical benzoyl peroxide-containing products with topical sulfone products, such as dapsone, may cause skin and facial hair to temporarily change color to a yellow/orange color.
Bexarotene: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with bexarotene is necessary. Dapsone is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like dapsone; the risk of peripheral neuropathy may be additive.
Bosentan: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with bosentan is necessary. Dapsone is a CYP3A4 substrate and bosentan is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Bupivacaine Liposomal: (Moderate) Coadministration of dapsone with bupivacaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Bupivacaine: (Moderate) Coadministration of dapsone with bupivacaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Bupivacaine; Epinephrine: (Moderate) Coadministration of dapsone with bupivacaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Bupivacaine; Lidocaine: (Moderate) Coadministration of dapsone with bupivacaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia. (Moderate) Coadministration of dapsone with lidocaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Bupivacaine; Meloxicam: (Moderate) Coadministration of dapsone with bupivacaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Butalbital; Acetaminophen: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Butalbital; Acetaminophen; Caffeine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Carbamazepine: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with carbamazepine is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and carbamazepine is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with another strong CYP3A4 inducer decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage.
Cenobamate: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with cenobamate is necessary. Dapsone is a CYP3A4 substrate and cenobamate is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Charcoal: (Moderate) Patients who ingest activated charcoal as a dietary supplement for flatulence or other purposes should be aware that the effectiveness of other regularly taken medications (e.g., dapsone) may be decreased. In some drug overdoses, such as dapsone overdose, multiple-doses of charcoal slurries are an effective therapeutic adjunct. Repeat doses may decrease the entero-hepatic recycling of some of these agents.
Chloroprocaine: (Moderate) Coadministration of dapsone with chloroprocaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Chloroquine: (Moderate) Coadministration of dapsone with chloroquine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Ciprofloxacin: (Moderate) Clinical monitoring for adverse effects, such as hemolytic anemia, methemoglobinemia, or peripheral neuropathy, is recommended during coadministration of dapsone and ciprofloxacin. Plasma concentrations of dapsone may be elevated when administered concurrently with ciprofloxacin. Ciprofloxacin is a CYP3A4 inhibitor, while dapsone is a CYP3A4 substrate.
Clindamycin; Adapalene; Benzoyl Peroxide: (Minor) Coadministration of topical benzoyl peroxide-containing products with topical sulfone products, such as dapsone, may cause skin and facial hair to temporarily change color to a yellow/orange color.
Cobicistat: (Minor) Plasma concentrations of dapsone may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hemolytic anemia, methemoglobinemia, or peripheral neuropathy, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while dapsone is a CYP3A4 substrate.
Dabrafenib: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with dabrafenib is necessary. Dapsone is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Darunavir: (Minor) The plasma concentrations of dapsone may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as hemolytic anemia, methemoglobinemia, or peripheral neuropathy, is recommended during coadministration. Darunavir is a CYP3A4 inhibitor, while dapsone is a CYP3A4 substrate.
Darunavir; Cobicistat: (Minor) Plasma concentrations of dapsone may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hemolytic anemia, methemoglobinemia, or peripheral neuropathy, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while dapsone is a CYP3A4 substrate. (Minor) The plasma concentrations of dapsone may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as hemolytic anemia, methemoglobinemia, or peripheral neuropathy, is recommended during coadministration. Darunavir is a CYP3A4 inhibitor, while dapsone is a CYP3A4 substrate.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Minor) Plasma concentrations of dapsone may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hemolytic anemia, methemoglobinemia, or peripheral neuropathy, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while dapsone is a CYP3A4 substrate. (Minor) The plasma concentrations of dapsone may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as hemolytic anemia, methemoglobinemia, or peripheral neuropathy, is recommended during coadministration. Darunavir is a CYP3A4 inhibitor, while dapsone is a CYP3A4 substrate.
Deferasirox: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with deferasirox, a known inducer of CYP3A4. Coadministration is expected to decrease the plasma concentration of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis). If these drugs must be administered together, closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia.
Didanosine, ddI: (Moderate) Dapsone clinical failures have been noted when dapsone was administered with didanosine. Despite a lack of a documented pharmacokinetic interaction, clinicians should be wary of possible dapsone clinical failure when dapsone is used with didanosine since this has been reported previously.
Dronedarone: (Moderate) Dronedarone is metabolized by and is an inhibitor of CYP3A. Dapsone is a substrate for CYP3A4. The concomitant administration of dronedarone and CYP3A substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution.
Efavirenz: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with efavirenz is necessary. Dapsone is a CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with efavirenz is necessary. Dapsone is a CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with efavirenz is necessary. Dapsone is a CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Elbasvir; Grazoprevir: (Minor) Administering dapsone with grazoprevir may result in elevated dapsone plasma concentrations. Dapsone is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Elexacaftor; tezacaftor; ivacaftor: (Major) If dapsone and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Ivacaftor is a CYP3A substrate and dapsone is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Minor) Plasma concentrations of dapsone may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hemolytic anemia, methemoglobinemia, or peripheral neuropathy, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while dapsone is a CYP3A4 substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) Plasma concentrations of dapsone may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hemolytic anemia, methemoglobinemia, or peripheral neuropathy, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while dapsone is a CYP3A4 substrate.
Encorafenib: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with encorafenib is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A metabolite and encorafenib is a strong CYP3A inducer. Strong CYP3A inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with another strong CYP3A inducer decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage.
Enzalutamide: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with enzalutamide is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and enzalutamide is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with another strong CYP3A4 inducer decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage.
Eslicarbazepine: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with eslicarbazepine is necessary. Dapsone is a CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Etravirine: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with etravirine is necessary. Dapsone is a CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Fluorouracil, 5-FU: (Major) Agranulocytosis has been reported in the second to third month of weekly concomitant treatment with dapsone and other hemolytic agents such as fluorouracil. These combinations increase the likelihood of adverse hematologic events.
Flutamide: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with flutamide, a known inducer of CYP3A4. Coadministration is expected to decrease the plasma concentration of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis). If these drugs must be administered together, closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia.
Fosamprenavir: (Minor) Fosamprenavir may inhibit the metabolism of other medications that are metabolized via cytochrome P450 3A4. Although drug interaction studies have not been conducted, the serum concentrations of dapsone may be increased with concomitant administration of fosamprenavir.
Fosphenytoin: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with fosphenytoin is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and fosphenytoin is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with another strong CYP3A4 inducer decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage. Also, coadministration of dapsone with fosphenytoin may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Ganciclovir: (Moderate) Use ganciclovir and dapsone together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Coadministration of dapsone with nitrates may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dapsone, a CYP3A substrate, as dapsone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Imatinib: (Minor) Imatinib, STI-571 may inhibit the metabolism of dapsone and leading to increased levels and potential toxicity. Monitor patients closely who receive concurrent therapy.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with dapsone may result in increased serum concentrations of dapsone. Dapsone is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with rifampin is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and rifampin is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with rifampin decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage.
Isoniazid, INH; Rifampin: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with rifampin is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and rifampin is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with rifampin decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage.
Isosorbide Dinitrate, ISDN: (Moderate) Coadministration of dapsone with nitrates may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Isosorbide Mononitrate: (Moderate) Coadministration of dapsone with nitrates may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Ivacaftor: (Major) If dapsone and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Ivacaftor is a CYP3A substrate and dapsone is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Lamivudine, 3TC; Zidovudine, ZDV: (Minor) Zidovudine, ZDV should be given with caution to patients also receiving dapsone due to the risk of additive hematologic toxicity.
Letermovir: (Moderate) A clinically relevant increase in the plasma concentration of dapsone may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Dapsone is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Lidocaine: (Moderate) Coadministration of dapsone with lidocaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Lidocaine; Epinephrine: (Moderate) Coadministration of dapsone with lidocaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Lidocaine; Prilocaine: (Moderate) Coadministration of dapsone with lidocaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia. (Moderate) Coadministration of dapsone with prilocaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Lopinavir; Ritonavir: (Moderate) Concurrent administration of dapsone with ritonavir may result in elevated dapsone plasma concentrations. Dapsone is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
Lorlatinib: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with lorlatinib is necessary. Dapsone is a CYP3A4 substrate and lorlatinib is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Lumacaftor; Ivacaftor: (Major) If dapsone and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Ivacaftor is a CYP3A substrate and dapsone is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold. (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with lumacaftor; ivacaftor is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and lumacaftor; ivacaftor is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with another strong CYP3A4 inducer decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage.
Lumacaftor; Ivacaftor: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with lumacaftor; ivacaftor is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and lumacaftor; ivacaftor is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with another strong CYP3A4 inducer decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage.
Mafenide: (Moderate) Coadministration of dapsone with sulfonamides may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Mavacamten: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with mavacamten is necessary. Dapsone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Mepivacaine: (Moderate) Coadministration of dapsone with mepivacaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Methotrexate: (Major) Drugs with similar pharmacologic activity, such as dapsone, may lead to additive antifolate effects and bone marrow suppression when used with methotrexate.
Mitotane: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with mitotane is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and mitotane is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with another strong CYP3A4 inducer decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage.
Modafinil: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with modafinil is necessary. Dapsone is a CYP3A4 substrate and modafinil is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Nafcillin: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with nafcillin is necessary. Dapsone is a CYP3A4 substrate and nafcillin is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Nilotinib: (Moderate) Concomitant use of nilotinib, a moderate CYP3A4 inhibitor, and dapsone, a CYP3A4 substrate, may result in increased dapsone levels. A dapsone dose reduction may be necessary if these drugs are used together.
Nirmatrelvir; Ritonavir: (Moderate) Concurrent administration of dapsone with ritonavir may result in elevated dapsone plasma concentrations. Dapsone is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
Nitrates: (Moderate) Coadministration of dapsone with nitrates may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Nitrofurantoin: (Moderate) Coadministration of dapsone with nitrofurantoin may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Nitroglycerin: (Moderate) Coadministration of dapsone with nitrates may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Nitroprusside: (Moderate) Coadministration of dapsone with sodium nitroprusside may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with rifabutin is necessary. Dapsone is a CYP3A4 substrate and rifabutin is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis). In a study of 16 HIV-infected patients, rifabutin decreased dapsone exposure by 27% to 40%.
Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and dapsone, a CYP3A4 substrate, may cause an increase in systemic concentrations of dapsone. Use caution when administering these drugs concomitantly.
Penicillin G Benzathine; Penicillin G Procaine: (Moderate) Coadministration of dapsone with penicillin G procaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Penicillin G Procaine: (Moderate) Coadministration of dapsone with penicillin G procaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Pexidartinib: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with pexidartinib is necessary. Dapsone is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Phenobarbital: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with phenobarbital is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and phenobarbital is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with another strong CYP3A4 inducer decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage. Also, coadministration of dapsone with phenobarbital may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with phenobarbital is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and phenobarbital is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with another strong CYP3A4 inducer decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage. Also, coadministration of dapsone with phenobarbital may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Phentermine; Topiramate: (Minor) The metabolism of dapsone may be accelerated when administered concurrently with topiramate, a known inducer of CYP3A4. Coadministration is expected to decrease the plasma concentration of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis). If these drugs must be administered together, closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia.
Phenytoin: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with phenytoin is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and phenytoin is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with another strong CYP3A4 inducer decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage. Also, coadministration of dapsone with phenytoin may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Posaconazole: (Moderate) Posaconazole and dapsone should be coadministered with caution due to an increased potential for dapsone-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of dapsone. These drugs used in combination may result in elevated dapsone plasma concentrations, causing an increased risk for dapsone-related adverse events.
Prilocaine: (Moderate) Coadministration of dapsone with prilocaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Prilocaine; Epinephrine: (Moderate) Coadministration of dapsone with prilocaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Primaquine: (Moderate) Coadministration of dapsone with primaquine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Primidone: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with primidone is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and primidone is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with another strong CYP3A4 inducer decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage. Also, coadministration of dapsone with primidone may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Probenecid: (Minor) Current evidence suggests that probenecid can inhibit the renal excretion of dapsone, resulting in elevated plasma concentrations. Dapsone toxicity as a result of this interaction has not been studied, so patients receiving these agents concurrently should be monitored for hemolytic anemia, methemoglobinemia, and/or peripheral neuropathy with muscle weakness. This interaction may, however, be beneficial in treating organisms that are resistant to dapsone.
Probenecid; Colchicine: (Minor) Current evidence suggests that probenecid can inhibit the renal excretion of dapsone, resulting in elevated plasma concentrations. Dapsone toxicity as a result of this interaction has not been studied, so patients receiving these agents concurrently should be monitored for hemolytic anemia, methemoglobinemia, and/or peripheral neuropathy with muscle weakness. This interaction may, however, be beneficial in treating organisms that are resistant to dapsone.
Pyrimethamine: (Major) Agranulocytosis has been reported in the second to third month of weekly concomitant treatment with dapsone and other hemolytic agents, such as pyrimethamine. This combination can increase the likelihood of adverse hematologic events.
Quinine: (Moderate) Coadministration of dapsone with quinine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Repotrectinib: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with repotrectinib is necessary. Dapsone is a CYP3A substrate and repotrectinib is a moderate CYP3A inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Rifabutin: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with rifabutin is necessary. Dapsone is a CYP3A4 substrate and rifabutin is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis). In a study of 16 HIV-infected patients, rifabutin decreased dapsone exposure by 27% to 40%.
Rifampin: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with rifampin is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and rifampin is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with rifampin decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage.
Rifapentine: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with rifapentine is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and rifapentine is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with another strong CYP3A4 inducer decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage.
Ritonavir: (Moderate) Concurrent administration of dapsone with ritonavir may result in elevated dapsone plasma concentrations. Dapsone is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
Ropivacaine: (Moderate) Coadministration of dapsone with ropivacaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Rufinamide: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as dapsone, may occur during concurrent use with rufinamide.
Saquinavir: (Major) Concurrent administration of oral dapsone and saquinavir boosted with ritonavir is not recommended, due to the potential for elevated dapsone concentrations and risk of dapsone-related side effects (i.e., hemolytic anemia, methemoglobinemia, or peripheral neuropathy). The metabolism of dapsone is mediated by CYP3A4, coadministration of drugs that inhibit CYP3A4, such as saquinavir boosted with ritonavir, may cause decreased clearance of dapsone.
Sotorasib: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with sotorasib is necessary. Dapsone is a CYP3A4 substrate and sotorasib is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
St. John's Wort, Hypericum perforatum: (Moderate) Monitor for an increase in hemolysis if coadministration of dapsone with St. John's Wort is necessary; dapsone efficacy may also be compromised. Dapsone is a CYP3A4 metabolite and St. John's Wort is a strong CYP3A4 inducer. Strong CYP3A4 inducers may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Coadministration with another strong CYP3A4 inducer decreased dapsone levels by 7-fold to 10-fold; in leprosy, this reduction has not required a change in dosage.
Sulfadiazine: (Moderate) Coadministration of dapsone with sulfonamides may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) Agranulocytosis has been reported in the second to third month of weekly concomitant treatment with dapsone and other hemolytic agents such as folic acid antagonists (e.g., trimethoprim, sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole). These combinations increase the likelihood of adverse hematologic events. Concurrent administration of dapsone with trimethoprim increases the plasma concentrations of both drugs. The efficacy of dapsone is increased, which may provide a therapeutic advantage in the treatment of Pneumocystis pneumonia; however, an increase in the frequency and severity of dapsone toxicity (methemoglobinemia, hemolytic anemia) also has been noted. (Moderate) Coadministration of dapsone with sulfonamides may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Sulfasalazine: (Moderate) Coadministration of dapsone with sulfonamides may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Sulfonamides: (Moderate) Coadministration of dapsone with sulfonamides may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Tetracaine: (Moderate) Coadministration of dapsone with tetracaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Tezacaftor; Ivacaftor: (Major) If dapsone and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Ivacaftor is a CYP3A substrate and dapsone is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Topiramate: (Minor) The metabolism of dapsone may be accelerated when administered concurrently with topiramate, a known inducer of CYP3A4. Coadministration is expected to decrease the plasma concentration of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis). If these drugs must be administered together, closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia.
Tramadol; Acetaminophen: (Moderate) Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Tretinoin; Benzoyl Peroxide: (Minor) Coadministration of topical benzoyl peroxide-containing products with topical sulfone products, such as dapsone, may cause skin and facial hair to temporarily change color to a yellow/orange color.
Trimethoprim: (Major) Agranulocytosis has been reported in the second to third month of weekly concomitant treatment with dapsone and other hemolytic agents such as folic acid antagonists (e.g., trimethoprim, sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole). These combinations increase the likelihood of adverse hematologic events. Concurrent administration of dapsone with trimethoprim increases the plasma concentrations of both drugs. The efficacy of dapsone is increased, which may provide a therapeutic advantage in the treatment of Pneumocystis pneumonia; however, an increase in the frequency and severity of dapsone toxicity (methemoglobinemia, hemolytic anemia) also has been noted.
Valganciclovir: (Moderate) Use valganciclovir and dapsone together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
Vemurafenib: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with vemurafenib, a known inducer of CYP3A4. Coadministration is expected to decrease the plasma concentration of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis). If these drugs must be administered together, closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia.
Voriconazole: (Minor) Voriconazole is known inhibitor of isoenzyme CYP2C9 and theoretically may lead to increased concentrations of drugs that are substrates for this enzyme, including dapsone.
Zidovudine, ZDV: (Minor) Zidovudine, ZDV should be given with caution to patients also receiving dapsone due to the risk of additive hematologic toxicity.
Similar to sulfonamides, dapsone inhibits dihyropteroate synthase in susceptible organisms. Other proposed mechanisms for dapsone include inhibition of the neutrophilic-cytotoxic system and interference with the alternate pathway of the complement system. Although the mechanism of dapsone in dermatologic disorders is unknown, it has been suggested that it may act as an immunomodulator.
For many years, dapsone was the main therapy for leprosy (Mycobacterium leprae). Unfortunately, years of monotherapy has lead to significant resistance in this organism. Resistance to M. leprae develops in 2-10% of patients after prolonged administration. Nevertheless, dapsone remains a component of combination therapy for leprosy.
Dapsone is administered orally or topically. It is widely distributed and is retained in the skin, muscles, kidneys, and liver. It also crosses the placenta and is distributed into breast milk.
Dapsone and its primary acetylated metabolite, monoacetyldapsone (MADDS), undergo enterohepatic recirculation. Acetylation is accomplished via N-acetyltransferase. Unlike with other acetylated compounds, slow and fast acetylators have exhibited no differences in pharmacokinetics, side effects, or therapeutic response. Minor metabolites include diacetyl derivatives and hydroxylamine dapsone (NOH-DDS). The latter metabolite appears to be associated with methemoglobinemia and hemolysis, which have been reported during therapy. The hydroxylamine metabolite is primarily produced by N-hydroxylation via CYP3A and CYP2C9 enzymes. The average half-life of both dapsone and MADDS is 30 hours. About 20% of a dose is excreted unchanged in the urine, while 70-85% is excreted as metabolites. A small amount can be detected in the feces.
Affected cytochrome P450 isoenzymes: CYP3A, CYP2C9
-Route-Specific Pharmacokinetics
Oral Route
Dapsone is almost completely absorbed from the GI tract following oral administration. Peak serum levels are reached in 2-8 hours.
Topical Route
Following topical application, dapsone is absorbed into systemic circulation; however, systemic drug exposures are only 1% of those observed with the 100 mg oral dose. Steady state concentrations are achieved within 7 days of dosing.