Dapsone Information
Dapsone () Description
Dapsone () -USP, 4,4'-diaminodiphenylsulfone (DDS), is a primary treatment for Dermatitis herpetiformis. It is an antibacterial drug for susceptible cases of leprosy. It is a white, odorless crystalline powder, practically in-soluble in water and insoluble in fixed and vegetable oils.
Dapsone () is issued on prescription in tablets of 25 and 100 mg for oral use.
Inactive Ingredients: Colloidal silicone dioxide, magnesium stearate, microcrystalline cellulose and corn starch.
Dapsone () Clinical Pharmacology
Actions:
Mycobacterium leprae.
Absorption and Excretion:
Blood Levels:
Dapsone () Indications And Usage
Dermatitis herpetiformis: (D.H.)
Leprosy: All forms of leprosy except for cases of proven Dapsone () resistance.
Dapsone () Contraindication
Hypersensitivity to Dapsone () and/or its derivatives.
Dapsone () Warnings
The patient should be warned to respond to the presence of clinical signs such as sore throat, fever, pallor, purpura or jaundice. Deaths associated with the administration of Dapsone () have been reported from agranulocytosis, aplastic anemia and other blood dyscrasias. Complete blood counts should be done frequently in patients receiving Dapsone () . The FDA Dermatology Advisory Committee recommended that, when feasible, counts should be done weekly for the first month, monthly for six months and semi-annually thereafter. If a significant reduction in leucocytes, platelets or hemopoiesis is noted, Dapsone () should be discontinued and the patient followed intensively. Folic acid antagonists have similar effects and may increase the incidence of hematologic reactions; if co-administered with Dapsone () the patient should be monitored more frequently. Patients on weekly pyrimethamine and Dapsone () have developed agranulocytosis during the second and third month of therapy.
Severe anemia should be treated prior to initiation of therapy and hemoglobin monitored. Hemolysis and methemoglobin may be poorly tolerated by patients with severe cardiopulmonary disease.
Cutaneous reactions, especially bullous, include exfoliative dermatitis and are probably one of the most serious, though rare, complications of sulfone therapy. They are directly due to drug sensitization. Such reactions include toxic erythema, erythema multiforme, toxic epidermal necrolysis, morbilliform and scarlatiniform reactions, urticaria and erythema nodosum. If new or toxic dermatologic reactions occur, sulfone therapy must be promptly discontinued and appropriate therapy instituted. Leprosy reactional states, including cutaneous, are not hypersensitivity reactions to Dapsone () and do not require discontinuation. See special section.
Dapsone () Precautions
General:
Toxic hepatitis and cholestatic jaundice have been reported early in therapy. Hyperbilirubinemia may occur more often in G6PD deficient patients. When feasible, baseline and subsequent monitoring of liver function is recommended; if abnormal, Dapsone () should be discontinued until the source of the abnormality is established.
Drug Interactions:
A modest interaction has been reported for patients receiving 100 mg Dapsone () daily in combination with trimethoprim 5 mg/kg q6h. On Day 7, the serum Dapsone () levels averaged 2.1 ± 1.0 μg/mL in comparison to 1.5 ± 0.5 μg/mL for Dapsone () alone. On Day 7, trimethoprim levels averaged 18.4 ± 5.2 μg/mL in comparison to 12.4 ± 4.5 μg/mL for patients not receiving Dapsone () . Thus, there is a mutual interaction between Dapsone () and trimethoprim in which each raises the level of the other about 1.5 times.
A crossover study designed to assess the potential of a drug interaction between Dapsone () , 100 mg/day and trimethoprim, 200 mg every 12 hours, in eight asymptomatic HIV positive volunteers (average CD4 count 524 cells/mm) demonstrated that there was not a significant drug intreraction between Dapsone () and trimethoprim. However, an earlier report also by Lee et al, in 78 HIV infected patients with acute pneumonia, receiving Dapsone () , 100 mg/day and higher trimethoprim dose, 20 mg/kg/day, demonstrated that the serum levels of Dapsone () were increased by 40% and trimethoprim levels were increased by 48% when the drugs were administered concurrently.
Carcinogenesis, mutagenesis:
S. typhimurium
Pregnancy: Teratogenic Effects. Pregnancy Category C:
Nursing Mothers:
Pediatric Use:
Dapsone () Adverse Reactions
In addition to the warnings listed above, the following syndromes and serious reactions have been reported in patients on Dapsone () .
Hematologic Effects:
Nervous System Effects:
Body As A Whole:
Dapsone () Overdosage
Nausea, vomiting, hyperexcitability can appear a few minutes up to 24 hours after ingestion of an overdosage. Methemoglobin induced depression, convulsions or severe cyanosis requires prompt treatment. In normal and methemoglobin reductase deficient patients, methylene blue, 1-2 mg/kg of body weight, given slowly intravenously, is the treatment of choice. The effect is complete in 30 minutes, but may have to be repeated if methemoglobin reaccumulates. For non-emergencies, if treatment is needed, methylene blue may be given orally in doses of 3-5 mg/kg every 4-6 hours. Methylene blue reduction depends on G6PD and should not be given to fully expressed G6PD deficient patients.
Dapsone () Dosage And Administration
Dermatitis herpetiformis:
A strict gluten free diet is an option for the patient to elect, permitting many to reduce or eliminate the need for Dapsone () ; the average time for dosage reduction is 8 months with a range of 4 months to 2 1/2 years and for dosage elimination 29 months with a range of 6 months to 9 years.
Leprosy:
In bacteriologically negative tuberculoid and indeterminate disease, the recommendation is the coadministration of Dapsone () 100 mg daily with six months of Rifampin 600 mg daily. Under WHO, daily Rifampin may be replaced by 600 mg Rifampin monthly, if supervised. The Dapsone () is continued until all signs of clinical activity are controlled - usually after an additional six months. Then Dapsone () should be continued for an additional three years for tuberculoid and indeterminate patients and for five years for borderline tuberculoid patients.
In lepromatous and borderline lepromatous patients, the recommendation is the co-administration of Dapsone () 100 mg daily with two years of Rifampin 600 mg daily. Under WHO daily Rifampin may be replaced by 600 mg Rifampin monthly, if supervised. One may elect the concurrent administration of a third anti-leprosy drug, usually either Clofazamine 50-100 mg daily or Ethionamide 250-500 mg daily. Dapsone () 100 mg daily is continued 3-10 years until all signs of clinical activity are controlled with skin scrapings and biopsies negative for one year. Dapsone () should then be continued for an additional 10 years for borderline patients and for life for lepromatous patients.
Secondary Dapsone () resistance should be suspected whenever a lepromatous or borderline lepromatous patient receiving Dapsone () treatment relapses clinically and bacteriologically, solid staining bacilli being found in the smears taken from the new active lesions. If such cases show no response to regular and supervised Dapsone () therapy within three to six months or good compliance for the past 3-6 months can be assured, Dapsone () resistance should be considered confirmed clinically. Determination of drug sensitivity using the mouse footpad method is recommended and, after prior arrangement, is available without charge from the USPHS, Carville, LA. Patients with proven Dapsone () resistance should be treated with other drugs.
Dapsone () Leprosy Reactional States
Abrupt changes in clinical activity occur in leprosy with any effective treatment and are known as reactional states. The majority can be classified into two groups. The “Reversal” reaction (Type 1) may occur in borderline or tuberculoid leprosy patients often soon after chemotherapy is started. The mechanism is presumed to result from a reduction in the antigenic load: the patient is able to mount an enhanced delayed hypersensitivity response to residual infection leading to swelling (“Reversal”) of existing skin and nerve lesions. If severe, or if neuritis is present, large doses of steroids should be used. If severe, the patient should be hospitalized. In general anti-leprosy treatment is continued and therapy to suppress the reaction is indicated such as analgesics, steroids, or surgical decompression of swollen nerve trunks. USPHS at Carville, LA should be contacted for advice in management.
Erythema nodosum leprosum (ENL) (lepromatous reaction) (Type 2 reaction) occurs mainly in lepromatous patients and small numbers of borderline patients. Approximately 50% of treated patients show this reaction in the first year. The principal clinical features are fever and tender erythematous skin nodules sometimes associated with malaise, neuritis, orchitis, albuminuria, joint swelling, iritis, epistaxis or depression. Skin lesions can become pustular and/or ulcerate. Histologically there is a vasculitis with an intense polymorphonuclear infiltrate. Elevated circulating immune complexes are considered to be the mechanism of reaction. If severe, patients should be hospitalized. In general, anti-leprosy treatment is continued. Analgesics, steroids, and other agents available from USPHS, Carville, LA, are used to suppress the reaction.
Dapsone () How Supplied
Dapsone () Tablets USP, 25 mg are available as round white scored tablets, debossed “25” above and “102” below the score and on the obverse “JACOBUS” in a Unit of Use carton of 30 tablets (2 x 15). The blisters are light and child-resistant. NDC 49938-102-30.
Dapsone () Tablets USP, 100 mg are available as round white scored tablets, debossed “100” above and “101” below the score and on the obverse “JACOBUS” in a Unit of Use carton of 30 tablets (2 x 15).The blisters are light and child-resistant. NDC 49938-101-30.
Dapsone () Tablets USP, 25 mg are available as round white scored tablets, debossed “25” above and “102” below the score and on the obverse “JACOBUS” in a Unit of Use carton of 28 tablets (2 x 14). The blisters are light and child-resistant. NDC 49938-102-28.
Dapsone () Tablets USP, 100 mg are available as round white scored tablets, debossed“100" above and “101” below the score and on the obverse “JACOBUS” in a Unit of Use carton of 28 tablets (2 x 14). The blisters are light and child-resistant. NDC 49938-101-28.
Dapsone () References
Store at 20°- 25° C (68°- 77°F). [see USP Controlled Room Temperature]. Protect from light.
Rx only. Keep this and all medication out of the reach of children.
JACOBUS PHARMACEUTICAL CO., INC.P.O. Box 5290Princeton, NJ 08540
Revised August 2009
0826A09
Dapsone ()
Dapsone ()
