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 insoluble 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.

Dermatitis Herpetiformis: (D.H.)

Leprosy: All forms of leprosy except for cases of proven Dapsone resistance.

The dosage should be individually titrated starting in adults with 50 mg daily and correspondingly smaller doses in children. If full control is not achieved within the range of 50-300 mg daily, higher doses may be tried. Dosage should be reduced to a minimum maintenance level as soon as possible. In responsive patients there is a prompt reduction in pruritus followed by clearance of skin lesions. There is no effect on the gastrointestinal component of the disease.

Dapsone levels are influenced by acetylation rates. Patients with high acetylation rates, or who are receiving treatment affecting acetylation may require an adjustment in dosage.

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 order to reduce secondary Dapsone resistance, the WHO Expert Committee on Leprosy and the USPHS at Carville, LA, recommended that Dapsone should be commenced in combination with one or more anti-leprosy drugs. In the multidrug program Dapsone should be maintained at the full dosage of 100 mg daily without interruption (with corresponding smaller doses for children) and provided to all patients who have sensitive organisms with new or recrudescent disease or who have not yet completed a two year course of Dapsone monotherapy. For advice and other drugs, the USPHS at Carville, LA (1-800-642-2477) should be contacted. Before using other drugs consult appropriate product labeling.

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 coadministration 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.

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 always 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, antileprosy treatment is continued. Analgesics, steroids, and other agents available from USPHS, Carville, LA, are used to suppress the reaction.

Dapsone 25 mg, round white scored tablet, debossed "25" aboveand "102" below the score and on the obverse "Jacobus" in light and child-resistant bottles of 100, NDC 49938-102-01.

Dapsone 100 mg, round white scored tablet, debossed "100" above and "101" below the score and on the obverse "Jacobus" in light and child-resistant bottles of 100, NDC 49938-101-01.

Storage: Store at controlled room temperature, 20°-25°C (68°-77°F). Protect from light.

CAUTION: Federal law prohibits dispensing without prescription.

Dispense this product in a well-closed child-resistant container.

In addition to the warnings listed above, the following syndromes and serious reactions have been reported in patients on Dapsone.

Hematologic Effects

Dose-related hemolysis is the most common adverse effect and is seen in patients with or without G6PD deficiency. Almost all patients demonstrate the inter-related changes of a loss of 1-2 g of hemoglobin, an increase in the reticulocytes (2-12%), a shortened red cell life span and a rise in methemoglobin. G6PD deficient patients have greater responses.

Nervous System Effects

Peripheral neuropathy is a definite but unusual complication of Dapsone therapy in non-leprosy patients. Motor loss is predominant. If muscle weakness appears, Dapsone should be withdrawn. Recovery on withdrawal is usually substantially complete. The mechanism of recovery is reported by axonal regeneration. Some recovered patients have tolerated retreatment at reduced dosage. In leprosy this complication may be difficult to distinguish from a leprosy reactional state.

Body As A Whole

In addition to the warnings and adverse effects reported above, additional adverse reactions include: nausea, vomiting, abdominal pains, pancreatitis, vertigo, blurred vision, tinnitus, insomnia, fever, headache, psychosis, phototoxicity, pulmonary eosinophilia, tachycardia, albuminuria, the nephrotic syndrome, hypoalbuminemia without proteinuria, renal papillary necrosis, male infertility, drug-induced Lupus erythematosus and an infectious mononucleosis-like syndrome. In general, with the exception of the complications of severe anoxia from overdosage (retinal and optic nerve damage, etc.) these adverse reactions have regressed off drug.

Rifampin lowers Dapsone levels 7 to 10-fold by accelerating plasma clearance; in leprosy this reduction has not required a change in dosage.

Folic acid antagonists such as pyrimethamine may increase the likelihood of hematologic reactions.

A modest interaction has been reported for patients receiving 100 mg Dapsone od in combination with trimethoprim 5 mg/kg q6h. On Day 7, the serum Dapsone levels averaged 2.1 ± 1.0 mg/mL in comparison to 1.5 ± 0.5 mg/mL for Dapsone alone. On Day 7, trimethoprim levels averaged 18.4 ± 5.2 mg/mL in comparison to 12.4 ± 4.5 mg/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.

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 hemopolesis 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.

General

Hemolysis and Heinz body formation may be exaggerated in individuals with a glucose-6-phosphate dehydrogenase (G6PD) deficiency, or methemoglobin reductase deficiency, or hemoglobin M. This reaction is frequently dose-related. Dapsone should be given with caution to these patients or if the patient is exposed to other agents or conditions such as infection or diabetic ketosis capable of producing hemolysis. Drugs or chemicals which have produced significant hemolysis in G6PD or methemoglobin reductase deficient patients include Dapsone, sulfanilamide, nitrite, aniline, phenylhydrazine, napthalene, niridazole, nitro-furantoin and 8-amino-antimalarials such as primaquine.

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

See DRUG INTERACTIONS section.

Carcinogenesis, Mutagenesis

Dapsone has been found carcinogenic (sarcomagenic) for male rats and female mice causing mesenchymal tumors in the spleen and peritoneum, and thyroid carcinoma in female rats. Dapsone is not mutagenic with or without microsomal activation in S. typhimurium tester strains 1535, 1537, 1538, 98, or 100.

Pregnancy Category C

Animal reproduction studies have not been conducted with Dapsone. Extensive, but uncontrolled experience and two published surveys on the use of Dapsone in pregnant women have not shown that Dapsone increases the risk of fetal abnormalities if administered during all trimesters of pregnancy or can affect reproduction capacity. Because of the lack of animal studies or controlled human experience, Dapsone should be given to a pregnant woman only if clearly needed. In general, for leprosy, USPHS at Carville recommends maintenance of Dapsone. Dapsone has been important for the management of some pregnant D.H. patients.

Nursing Mothers

Dapsone is excreted in breast milk in substantial amounts. Hemolytic reactions can occur in neonates. See section on hemolysis. Because of the potential for tumorgenicity shown for Dapsone in animal studies a decision should be made whether to discontinue nursing or discontinue the drug taking into account the importance of drug to the mother.

Pediatric Use

Children are treated on the same schedule as adults but with correspondingly smaller doses. Dapsone is generally not considered to have an effect on the later growth, development and functional development of the child.

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.

Hypersensitivity to Dapsone and/or its derivatives.

Actions

The mechanism of action in Dermatitis herpetiformis has not been established. By the kinetic method in mice, Dapsone is bactericidal as well as bacteriostatic against Mycobacterium leprae.

Absorption and Excretion

Dapsone, when given orally, is rapidly and almost completely absorbed. About 85 percent of the daily intake is recoverable from the urine mainly in the form of water-soluble metabolites. Excretion of the drug is slow and a constant blood level can be maintained with the usual dosage.

Blood Levels

Detected a few minutes after ingestion, the drug reaches peak concentration in 4-8 hours. Daily administration for at least eight days is necessary to achieve a plateau level. With doses of 200 mg daily, this level averaged 2.3 mg/ml with a range of 0.1-7.0 mg/ml. The half-life in the plasma in different individuals varies from ten hours to fifty hours and averages twenty-eight hours. Repeat tests in the same individual are constant. Daily administration (50 - 100 mg) in leprosy patients will provide blood levels in excess of the usual minimum inhibitory concentration even for patients with a short Dapsone half-life.

See WARNINGS, PRECAUTIONS and CONTRAINDICATIONS.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

DAPSONE - ORAL

(DAP-sown)

USES: This medication is used to treat a certain type of skin disorder (dermatitis herpetiformis). It is also used with other drugs to treat Hansen's disease. Dapsone belongs to a class of drugs known as sulfones. It works by decreasing swelling (inflammation) and stopping the growth of bacteria.

This medication will not work for viral infections (e.g., common cold, flu). Unnecessary use or misuse of any antibiotic can lead to its decreased effectiveness.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This drug may also be used to treat or prevent a certain lung infection due to HIV (pneumocystis pneumonia), to prevent a certain brain infection due to HIV (toxoplasmosis), and to treat skin conditions in certain immune system disorders (e.g., systemic lupus erythematosus-SLE).

HOW TO USE: Take this medication by mouth with or without food, usually once daily or as directed by your doctor.

Medications for heartburn/reducing stomach acid (e.g., large amounts of antacids, ranitidine, famotidine), or didanosine may prevent full absorption of dapsone into your bloodstream, possibly reducing its effectiveness. Therefore, separate your dose of dapsone from your doses of any of these products by at least 2 hours. Ask your doctor or pharmacist for more details.

If you are taking dapsone for a skin disorder, your doctor may start you on a low dose of dapsone and gradually adjust your dose to control your disease. If you are taking this medication to treat Hansen's disease or to prevent infections due to HIV, the drug is usually taken for years or for life.

Dosage is based on your medical condition and response to treatment. In children, the dosage is also based on age and weight.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day.

Tell your doctor if your condition worsens.

SIDE EFFECTS: Nausea, vomiting, loss of appetite, dizziness, or blurred vision may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: unusually fast heartbeat, unusually fast breathing, bluish lips/skin, chest pain, mental/mood changes, muscle weakness, difficulty urinating.

This drug may rarely cause very serious low blood counts (bone marrow suppression) or liver disease. Seek immediate medical attention if you develop signs of an infection (e.g., fever, chills, persistent sore throat), easy bruising/bleeding, unusual tiredness, pale skin, yellowing eyes/skin, dark urine, stomach/abdominal pain.

Dapsone can commonly cause a rash that is usually not serious. However, you may not be able to tell it apart from a rare rash that could be a sign of a severe reaction. Therefore, seek immediate medical attention if you develop any rash.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking dapsone, tell your doctor or pharmacist if you are allergic to it; or to similar drugs such as sulfoxone; or if you have any other allergies.

This medication should not be used if you have a certain medical condition. Before using this medicine, consult your doctor or pharmacist if you have: severe anemia.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: certain blood disorders (e.g., G6PD deficiency, methemoglobin reductase deficiency), liver disease, severe heart disease, severe lung disease, serious infection, very high blood sugar (diabetic ketosis).

If using this drug to treat Hansen's disease, note that as your immune system helps fight the infection, you may notice skin sores worsening, and numbness/pain/tingling or muscle weakness. This may require special treatment, so tell your doctor immediately if these symptoms occur.

This drug may make you dizzy. Use caution while driving, using machinery, or doing any activity that requires alertness. Limit alcoholic beverages.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

Dapsone passes into breast milk and could have undesirable effects on a nursing infant (e.g., anemia). Therefore, breast-feeding is not recommended while using this drug. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: folic acid antagonists (such as pyrimethamine), nitrofurantoin, primaquine.

This medication may decrease the effectiveness of combination-type birth control pills. This can result in pregnancy. You may need to use an additional form of reliable birth control while using this medication. Consult your doctor or pharmacist for details.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: seizures, bluish skin (cyanosis), sudden vision changes, sudden loss of vision.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., complete blood counts/platelets, liver function tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

Iron, folic acid, and vitamin C might reduce the risk of developing a certain serious side effect (anemia). Ask your doctor for more details.

If you are using dapsone for dermatitis herpetiformis, a gluten-free diet may improve the condition. Consult your doctor for more information.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.