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  • CLASSES

    Drugs For The Treatment of Leprosy
    Other Topical Anti-Acne Products

    DEA CLASS

    Rx

    DESCRIPTION

    Synthetic sulfone chemically similar to sulfonamides
    Has antiinfective and immunosuppressive properties
    Agent of choice for all forms of leprosy; used for PCP prophylaxis; used in combination with pyrimethamine for prevention of toxoplasmosis in AIDS patients; used for various dermatologic disorders and topically for acne.

    COMMON BRAND NAMES

    Aczone

    HOW SUPPLIED

    Aczone/Dapsone Topical Gel: 5%, 7.5%
    Dapsone Oral Tab: 25mg, 100mg

    DOSAGE & INDICATIONS

    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 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 acne vulgaris.
    Topical dosage (Aczone 5% gel)
    Adults, Adolescents, and Children 12 years and older

    Apply a thin layer topically to acne affected areas twice daily; if no improvement after 12 weeks, reassess appropriateness of dapsone therapy.

    Topical dosage (Aczone 7.5% gel)
    Adults, Adolescents, and Children 12 years and older

    Apply a thin layer topically to the entire face once daily. In addition, a thin layer may be applied topically to other acne affected areas once daily. Reassess appropriateness of dapsone therapy if no improvement after 12 weeks.

    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.

    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.

    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 thrombocytopenia/idiopathic thrombocytopenic purpura (ITP)†.
    Oral dosage
    Adults

    A dosage of 75 to 100 mg PO per day has been recommended.

    For the treatment of polychondritis†.
    Oral dosage
    Adults

    A dose of 100 mg PO once daily or twice daily has been used.

    For the treatment of mild to moderate Pneumocystis pneumonia (PCP)†.
    Oral dosage
    Adults and Adolescents

    100 mg PO once daily in combination with trimethoprim for 21 days, has been recommended in the HIV guidelines.

    Infants and Children

    Optimal dosage has not been established. The HIV guidelines recommend 2 mg/kg PO daily (Max: 100 mg/day) plus trimethoprim for 21 days, then chronic suppressive therapy.

    For Pneumocystis pneumonia (PCP) prophylaxis†.
    For primary PCP prophylaxis† in HIV-infected patients.
    Oral dosage
    Adults and Adolescents

    As an alternative to first-line regimens, HIV guidelines recommend 50 mg PO twice daily or 100 mg PO once daily. Alternatively, 50 mg PO once daily can be given with weekly pyrimethamine (50 mg PO) plus leucovorin (25 mg PO) or a once weekly regimen of 200 mg PO can be given with pyrimethamine (75 mg PO) plus leucovorin (25 mg PO). Prophylaxis is recommend for patients with CD4 counts < 200 cells/mm3 , CD4% < 14% or a history of AIDS-defining illness such as oropharyngeal candidiasis, > 200 but < 250 CD4 cells/mm3 if CD4 count monitoring every 1—3 months is not possible. Primary prophylaxis for PCP may be discontinued if the CD4 count is > 200 cells/mm3 for > 3 months. Prophylaxis should be restarted if CD4 count is < 200 cells/mm3.

    Infants and Children

    As an alternative to first-line regimens, HIV guidelines recommend 2 mg/kg/dose PO once daily (maximum of 100 mg/day) or 4 mg/kg/dose PO once weekly (maximum of 200 mg) in HIV-infected or HIV-indeterminate infants 1—12 months of age; in HIV-infected children 1—5 years of age with a CD4 count < 500 cells/mm3 or CD4 percentage < 15%; or in HIV-infected children 6—12 years of age with a CD4 count < 200 cells/mm3 or CD4 percentage < 15%. Discontinue prophylaxis in children who are subsequently HIV-negative. HIV-infected infants and infants whose infection status remains unknown should continue to receive prophylaxis for the first year of life. For children 1—5 years of age, primary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy with a CD4 count > 500 cells/mm3 or a CD4+ percentage is > 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 is > 200 cells/mm3 or a CD4 percentage is > 15% for more than 3 consecutive months.

    For secondary PCP prophylaxis† in HIV-infected patients after PCP treatment.
    Oral dosage
    Adults and Adolescents

    As alternatives to first-line regimens, the HIV treatment guidelines recommend dapsone 100 mg PO once daily. Alternatively, dapsone 50 mg PO once daily can be given in combination with weekly pyrimethamine (50 mg PO) plus leucovorin (25 mg PO) OR as a weekly regimen of 200 mg PO plus pyrimethamine (75 mg PO) and leucovorin (25 mg PO).  Secondary prophylaxis can be discontinued for those patients whose CD4 count is > 200 cells/micro-liter for at least 3 months in response to highly active antiretroviral therapy. Prophylaxis should be restarted if the CD4 count decreases to < 200 cells/mm3 or if PCP has returned at a CD4 count > 200 cells/mm3. If PCP is diagnosed or recurs at a CD4 count > 200 cells/mm3, prophylaxis should be lifelong.

    Infants >= 1 month and Children

    As an alternative to first-line regimens, the HIV guidelines recommend 2 mg/kg/dose (maximum of 100 mg) PO once daily or 4 mg/kg/dose (maximum of 200 mg) PO once weekly. For children 1—5 years of age, secondary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy and with a CD4 count is > 500 cells/mm3 or a CD4 percentage is > 15% for more than 3 consecutive months. For children at least 6 years of age, secondary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy and with a CD4 count is > 200 cells/mm3 or a CD4 percentage is > 15% for more than 3 consecutive months.

    For primary toxoplasmosis prophylaxis† in HIV-infected patients, specifically prevention of toxoplasmic encephalitis (TE)† due to Toxoplasmosis gondii.
    Oral dosage
    Adults and Adolescents

    As alternative regimens, the HIV guidelines recommend dapsone 50 mg PO once daily in combination with weekly pyrimethamine plus leucovorin OR 200 mg PO weekly with weekly pyrimethamine plus leucovorin in Toxoplasma-seropositive patients with < 100 CD4 cells/mm3. Primary prophylaxis for TE may be discontinued in patients who have responded to highly active antiretroviral treatment with an increase in CD4 counts to > 200 cells/mm3 for at least 3 months. Prophylaxis should be reintroduced if the CD4 counts decrease to < 100—200 cells/mm3.

    Infants and Children

    As an alternative regimen, the HIV guidelines recommend 2 mg/kg or 15 mg/m2 (Max: 25 mg) PO once daily in combination with pyrimethamine plus leucovorin in Toxoplasma-seropositive HIV-infected patients with severe immunosuppression (i.e., children < 6 years of age with a CD4 percentage < 15% or children > 6 years of age with a CD4 count < 100 cells/mm3). HIV-infected infants and infants whose infection status remains unknown should continue to receive prophylaxis for the first year of life. For children 1—5 years of age, primary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy and with a CD4 percentage is > 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 is > 100—200 cells/mm3 or a CD4 percentage is > 15% 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.

    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.

    †Indicates off-label use

    MAXIMUM DOSAGE

    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

    Maximum dosage information not established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    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.

    Renal Impairment

    No dosage adjustment needed.

    ADMINISTRATION

    Oral Administration

    Dapsone may be administered orally without regard to meals.

    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.

    STORAGE

    Generic:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Aczone:
    - Protect from freezing
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Anemia, G6PD deficiency, methemoglobin reductase deficiency

    Dapsone should be used with caution in cases of severe anemia, G6PD deficiency (glucose 6-phosphate dehydrogenase deficiency) or methemoglobin reductase deficiency because hemolytic anemia can occur. The safety of dapsone topical gel (Ac zone) was evaluated in a randomized, double-blind, cross-over study of 64 patients with G6PD deficiency and acne vulgaris. After 2 weeks, a mean decline of 0.32 g/dL in hemoglobin was noted in patients treated with Aczone gel; however, by week 12, hemoglobin levels generally returned to baseline levels. Decreases in hemoglobin of > 1g/dL were noted in a similar proportion of patients in the Aczone gel group and the vehicle group (Aczone: 8 out of 58, vehicle: 7 out of 56). The study found no evidence of clinically significant hemolytic anemia following application of dapsone topical gel. Laboratory changes suggestive of mild hemolysis were noted in some subjects. Glucose 6-phosphate dehydrogenase levels should be obtained in all patients before using systemically administered dapsone. Baseline complete blood counts, including a reticulocyte count, should be obtained in patients who are G6PD deficient or with a history of anemia. Routine follow-up for complete blood count and reticulocyte count should be implemented for patients at risk.

    Hepatic disease

    Toxic hepatitis, cholestatic jaundice, and hyperbilirubinemia have been reported during the initial stages of systemic dapsone treatment. Periodic monitoring of liver-function tests is recommended. Dapsone should be used cautiously in patients with preexisting hepatic disease.

    Pregnancy

    Dapsone is classified as pregnancy category C. Uncontrolled studies in pregnant women have not demonstrated fetal risk. 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.

    Breast-feeding

    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.

    Children, infants, neonates

    Oral dapsone can be used safely in children and adolescents; however, the safe and effective use of dapsone topical gel in neonates, infants, and children < 12 years of age has not been established. Clinical studies of topical dapsone gel did include adolescents age 12 to 17 years.

    Sulfonamide hypersensitivity

    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.

    ADVERSE REACTIONS

    Severe

    erythema nodosum / Delayed / 0-1.0
    toxic epidermal necrolysis / Delayed / 0-1.0
    erythema multiforme / Delayed / 0-1.0
    exfoliative dermatitis / Delayed / 0-1.0
    methemoglobinemia / Early / 10.0
    vasculitis / Delayed / 10.0
    pancytopenia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    nephrotic syndrome / Delayed / Incidence not known
    renal papillary necrosis / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    eosinophilic pneumonia / Delayed / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known

    Moderate

    erythema / Early / 13.0-13.0
    bullous rash / Early / 0-1.0
    peripheral neuropathy / Delayed / 0-1.0
    hemolysis / Early / 10.0
    anemia / Delayed / 10.0
    depression / Delayed / 10.0
    neuritis / Delayed / 10.0
    iritis / Delayed / 10.0
    leukopenia / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    psychosis / Early / Incidence not known
    blurred vision / Early / Incidence not known
    hypoalbuminemia / Delayed / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    infertility / Delayed / Incidence not known

    Mild

    xerosis / Delayed / 0-16.0
    pharyngitis / Delayed / 2.0-5.0
    headache / Early / 4.0-4.0
    infection / Delayed / 3.0-3.0
    cough / Delayed / 2.0-2.0
    sinusitis / Delayed / 2.0-2.0
    pruritus / Rapid / 1.0-1.0
    urticaria / Rapid / 0-1.0
    weakness / Early / 0-1.0
    influenza / Delayed / 1.0-1.0
    epistaxis / Delayed / 10.0
    malaise / Early / 10.0
    fever / Early / 10.0
    photosensitivity / Delayed / Incidence not known
    vomiting / Early / Incidence not known
    nausea / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    insomnia / Early / Incidence not known
    vertigo / Early / Incidence not known
    tinnitus / Delayed / Incidence not known

    DRUG INTERACTIONS

    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.
    Adapalene; Benzoyl Peroxide: (Minor) Coadministration of topical benzoyl peroxide-containing products, such as benzoyl peroxide; clindamycin, with topical sulfone products, such as dapsone, may cause skin and facial hair to temporarily change color to a yellow/orange color.
    Alogliptin; Pioglitazone: (Minor) The metabolism of dapsone may be accelerated when administered concurrently with pioglitazone, 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.
    Amprenavir: (Minor) Amprenavir may inhibit the metabolism of other medications that are metabolized via cytochrome P450 3A4 including dapsone. Although drug interaction studies have not been conducted, the serum concentrations of dapsone may be increased with concomitant administration of amprenavir.
    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.
    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.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with phenobarbital, 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.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with phenobarbital, 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.
    Benzoyl Peroxide: (Minor) Coadministration of topical benzoyl peroxide-containing products, such as benzoyl peroxide; clindamycin, 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, such as benzoyl peroxide; clindamycin, 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, such as benzoyl peroxide; clindamycin, 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, such as benzoyl peroxide; clindamycin, with topical sulfone products, such as dapsone, may cause skin and facial hair to temporarily change color to a yellow/orange color.
    Bexarotene: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with bexarotene, 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.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering dapsone with boceprevir due to an increased potential for dapsone-related adverse events. If dapsone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dapsone. Dapsone is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated dapsone plasma concentrations.
    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) If these drugs are used together, closely monitor for a reduction in dapsone efficacy and signs or symptoms of hemolytic anemia. The metabolism of dapsone may be accelerated when administered concurrently with bosentan, 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).
    Carbamazepine: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with carbamazepine, 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.
    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.
    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.
    Clobazam: (Minor) The metabolism of dapsone may be accelerated when administered concurrently with clobazam, 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.
    Clofazimine: (Moderate) Clofazimine is often administered with dapsone as a combination therapy that is most effective in treating leprosy. The two drugs have opposing effects on neutrophil motility and lymphocyte transformation, so dapsone can oppose the antiinflammatory effects of clofazimine, reducing its efficacy in erythema nodosum leprosum.
    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.
    Cobicistat; Elvitegravir; 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.
    Cobicistat; Elvitegravir; 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.
    Conivaptan: (Major) According to the manufacturer, concomitant use of conivaptan, a strong CYP3A4 inhibitor, and CYP3A substrates, such as dapsone, should be avoided. Coadministration of conivaptan with other CYP3A substrates (midazolam, simvastatin, amlodipine) has resulted in increased mean AUC values (2 to 3 times). Theoretically, similar pharmacokinetic effects could be seen with dapsone. Treatment with dapsone may be initiated no sooner than 1 week after completion of conivaptan therapy.
    Dabrafenib: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with dabrafenib, 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.
    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.
    Dasabuvir; Ombitasvir; Paritaprevir; 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.
    Dasatinib: (Moderate) Dasatinib inhibits CYP3A4. Therefore, caution is warranted when drugs that are metabolized by this enzyme, such as dapsone, are administered concurrently with dasatinib as increased adverse reactions may occur.
    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.
    Dexamethasone: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with dexamethasone, 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) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as dapsone.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as dapsone.
    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.
    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) The metabolism of dapsone may be accelerated when administered concurrently with eslicarbazepine, 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.
    Etravirine: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with etravirine, 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.
    Felbamate: (Minor) The metabolism of dapsone may be accelerated when administered concurrently with felbamate, 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.
    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) The metabolism of dapsone may be accelerated when administered concurrently with fosphenytoin, 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.
    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.
    Glimepiride; Pioglitazone: (Minor) The metabolism of dapsone may be accelerated when administered concurrently with pioglitazone, 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.
    Griseofulvin: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with griseofulvin, 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.
    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) Rifampin, a known hepatic enzyme inducer, decreases plasma concentrations of dapsone if given concurrently. The clinical significance of this pharmacokinetic interaction is unclear.
    Isoniazid, INH; Rifampin: (Moderate) Rifampin, a known hepatic enzyme inducer, decreases plasma concentrations of dapsone if given concurrently. The clinical significance of this pharmacokinetic interaction is unclear.
    Ivacaftor: (Moderate) Use caution when administering ivacaftor and dapsone concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as dapsone, can increase dapsone exposure leading to increased or prolonged therapeutic effects and adverse events.
    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.
    Lesinurad: (Minor) The metabolism of dapsone may be accelerated when administered concurrently with lesinurad, 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.
    Lesinurad; Allopurinol: (Minor) The metabolism of dapsone may be accelerated when administered concurrently with lesinurad, 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.
    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.
    Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may decrease the systemic exposure of dapsone; if used together, monitor for therapeutic efficacy. Dapsone is a CYP3A4 substrate. Lumacaftor is a strong CYP3A inducer. Rifampin, another strong CYP3A inducer, decreases dapsone concentrations 7- to 10-fold by accelerating plasma clearance; in the treatment of leprosy, this reduction has not required a change in dapsone dosage.
    Lumacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and dapsone concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as dapsone, can increase dapsone exposure leading to increased or prolonged therapeutic effects and adverse events.
    Metformin; Pioglitazone: (Minor) The metabolism of dapsone may be accelerated when administered concurrently with pioglitazone, 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.
    Methotrexate: (Major) Drugs with similar pharmacologic activity, such as dapsone, may lead to additive antifolate effects and bone marrow suppression when used with methotrexate.
    Metyrapone: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with metyrapone, 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.
    Mitotane: (Major) Use caution if mitotane and dapsone are used concomitantly, and monitor for decreased efficacy of dapsone and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and dapsone is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of dapsone.
    Modafinil: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with modafinil, 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.
    Nafcillin: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with nafcillin, 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.
    Nevirapine: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with nevirapine, 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.
    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.
    Ombitasvir; Paritaprevir; 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.
    Oritavancin: (Moderate) Dapsone is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of dapsone may be reduced if these drugs are administered concurrently.
    Oxcarbazepine: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with oxcarbazepine, 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.
    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.
    Phenobarbital: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with phenobarbital, 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.
    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) The metabolism of dapsone may be accelerated when administered concurrently with phenytoin, 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.
    Pioglitazone: (Minor) The metabolism of dapsone may be accelerated when administered concurrently with pioglitazone, 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.
    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: (Minor) Patients treated with prilocaine who are receiving other drugs that can cause methemoglobin formation, such as dapsone, are at greater risk for developing methemoglobinemia.
    Prilocaine; Epinephrine: (Minor) Patients treated with prilocaine who are receiving other drugs that can cause methemoglobin formation, such as dapsone, are at greater risk for developing methemoglobinemia.
    Primidone: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with primidone, 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.
    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.
    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.
    Pyrimethamine; Sulfadoxine: (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.
    Ribociclib: (Moderate) Use caution if coadministration of ribociclib with dapsone is necessary, as the systemic exposure of dapsone may be increased resulting in an increase in treatment-related adverse reactions. Ribociclib is a moderate CYP3A4 inhibitor and dapsone is a CYP3A4 substrate.
    Ribociclib; Letrozole: (Moderate) Use caution if coadministration of ribociclib with dapsone is necessary, as the systemic exposure of dapsone may be increased resulting in an increase in treatment-related adverse reactions. Ribociclib is a moderate CYP3A4 inhibitor and dapsone is a CYP3A4 substrate.
    Rifabutin: (Moderate) The metabolism of dapsone is accelerated when administered concurrently with rifabutin, a known inducer of CYP3A4. Coadministration decreases the plasma concentration of dapsone and increases 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%. If these drugs must be administered together, closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia.
    Rifampin: (Moderate) Rifampin, a known hepatic enzyme inducer, decreases plasma concentrations of dapsone if given concurrently. The clinical significance of this pharmacokinetic interaction is unclear.
    Rifapentine: (Moderate) Rifapentine induces hepatic isoenzyme CYP3A4. Drugs metabolized by CYP3A4, such as dapsone, may require dosage adjustments when administered concurrently with rifapentine.
    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.
    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: (Severe) According to the manufacturer, concurrent administration of dapsone and saquinavir boosted with ritonavir is contraindicated due to the risk of life threatening cardiac arrhythmias. Saquinavir prolongs the QT and PR intervals in a dose-dependent fashion, which may increase the risk for serious cardiac arrhythmias such as torsades de pointes (TdP). In addition, 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. Due to elevated plasma dapsone concentrations, there is a potential for excessive dapsone-related side effects, including hemolytic anemia, methemoglobinemia, or peripheral neuropathy.
    Simeprevir: (Minor) Simeprevir, a mild intestinal CYP3A4 inhibitor, may increase the side effects of dapsone, which is a CYP3A4 substrate. Monitor patients for adverse effects of dapsone, such as peripheral neuropathy or hematologic changes.
    St. John's Wort, Hypericum perforatum: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with St. John's Wort, 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.
    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.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering dapsone with telaprevir due to an increased potential for dapsone-related adverse events. If dapsone dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of dapsone. Dapsone is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated dapsone plasma concentrations.
    Telithromycin: (Minor) Concentrations of dapsone may be increased with concomitant use of telithromycin. Dapsone is a CYP3A4 substrate and telithromycin is a strong CYP3A4 inhibitor. Patients should be monitored for increased side effects.
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and dapsone is necessary, as the systemic exposure of dapsone may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of dapsone; consider increasing the dose of dapsone if necessary. Dapsone is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate.
    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.
    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.
    Trimetrexate: (Major) Additive antifolate effects may be seen with concomitant treatment with trimetrexate and dapsone.
    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.
    Zalcitabine, ddC: (Minor) Coadministration of zalcitabine, ddC with drugs associated with peripheral neuropathy, such as dapsone, should be avoided when possible.
    Zidovudine, ZDV: (Minor) Zidovudine, ZDV should be given with caution to patients also receiving dapsone due to the risk of additive hematologic toxicity.

    PREGNANCY AND LACTATION

    Pregnancy

    Dapsone is classified as pregnancy category C. Uncontrolled studies in pregnant women have not demonstrated fetal risk. 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.

    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.

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    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

    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.