DAPSOMED

MIMS Revision Date: 01 April 2025

Notes

Distributed by Medsurge Healthcare Pty Ltd

1 Name of Medicine

Dapsone.

2 Qualitative and Quantitative Composition

Dapsomed tablets contain either 50 mg or 100 mg of dapsone as the active ingredient.
Excipient with known effect. Lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Dapsomed 50 mg tablets are white or slight yellowish, round, biconvex tablets, debossed with "50" on one side, with a score line on the other side.
Dapsomed 100 mg tablets are white or slight yellowish, round, biconvex tablets, debossed with "D" on one side, with a score line on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

Dermatitis herpetiformis. Leprosy. Actinomycotic mycetoma.

4.2 Dose and Method of Administration

To be taken with or after food. For ease of swallowing, 50 mg tablets can be broken in half.
Do not use half a 50 mg tablet when a 25 mg dose is required, and do not use half a 100 mg tablet when a 50 mg dose is required.
Dermatitis herpetiformis. Adults. The usual maintenance dosage is 50 to 100 mg daily, but as little as 50 mg weekly may be adequate. Dosages of up to 300 mg daily may be considered, but efforts should be made to reduce this to the minimal maintenance dosage as soon as possible.
Leprosy. Adults. The standard dose is 100 mg daily (1 to 2 mg/kg bodyweight).
Children. Dosage should be adjusted according to bodyweight.
The modern treatment of leprosy involves the use of multiple drug regimens to avoid the development of resistant strains. The World Health Organization has made the following recommendations for standard adult treatment regimens (with dosage adjustments according to bodyweight).
Multibacillary leprosy. Rifampicin 600 mg once monthly supervised; dapsone 100 mg daily, self-administered; clofazimine 300 mg once monthly, supervised; and 50 mg daily self-administered.
Paucibacillary leprosy. Rifampicin 600 mg once monthly for 6 months, supervised; dapsone 100 mg daily for 6 months, self-administered.
Actinomycotic mycetoma. Adults. Published reports suggest that a dose of 100 mg should be given twice daily and continued for some months after the clinical symptoms have disappeared. Streptomycin at 14 mg/kg daily for the first month and alternate days thereafter (or the equivalent) should always be used in combination with dapsone. Streptomycin, sulfamethoxazole and trimethoprim is an alternative therapy.

4.3 Contraindications

Hypersensitivity to dapsone and/or its derivatives.

4.4 Special Warnings and Precautions for Use

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 anaemia 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 haemopoiesis is noted, dapsone should be discontinued and the patient followed intensively. Folic acid antagonists have similar effects and may increase the incidence of haematologic reactions; if co-administered with dapsone the patients should be monitored more frequently. Patients on weekly pyrimethamine and dapsone have developed agranulocytosis during the second and third month of therapy.
Severe anaemia should be treated prior to initiation of therapy and haemoglobin monitored. Haemolysis and methaemoglobin 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 sensitisation. 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, (abrupt changes in clinical activity occur in leprosy with any effective treatment and are known as reactional states, see Section 4.8 Adverse Effects (Undesirable Effects), Leprosy reactional states) including cutaneous, are not hypersensitivity reactions to dapsone and do not require discontinuation.
Haemolysis and Heinz body formation may be exaggerated in individuals with a glucose-6-phosphate dehydrogenase (G6PD) deficiency, or methaemoglobin reductase deficiency, or haemoglobin 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 haemolysis. Drugs or chemicals which have produced significant haemolysis in G6PD or methaemoglobin reductase deficient patients include dapsone, sulfanilamide, nitrite, aniline, phenylhydrazine, naphthalene, niridazole, nitrofurantoin and 8-aminoquinolone-antimalarials such as primaquine.
Toxic hepatitis and cholestatic jaundice have been reported early in therapy. Hyperbilirubinaemia 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.
Use in patients with cardiac, pulmonary, renal and hepatic conditions. Dapsone should be used with caution in patients with cardiac, pulmonary, hepatic or renal diseases.
Use in the elderly. No data available.
Paediatric 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.
Effects on laboratory tests. No data available.
Use in porphyria patients. Dapsone has been associated with acute attacks of porphyria and is considered unsafe in porphyric patients.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Amprenavir. Possible increase in plasma levels of dapsone.
Didanosine (buffered formulations). Dapsone bioavailability reduced.
Rifampicin. Rifampicin reduces serum concentrations of dapsone to a level that may compromise efficacy in infections other than leprosy. Increased risk of methaemoglobinaemia from metabolite. Rifampicin concentrations are generally unaffected.
Clofazimine. Dapsone may antagonise the anti-inflammatory activity of clofazimine.
Probenecid. Serum concentrations of dapsone are increased with a consequent increased risk of adverse effects when given with probenecid, probably as a result of reduced renal excretion of dapsone.
Trimethoprim. Increased dapsone and trimethoprim concentrations have also been reported in patients receiving both drugs and such patients may be at increased risk of dapsone toxicity.
Cimetidine. Cimetidine has been reported to increase the area under the curve for dapsone, but to decrease the area under the curve for the metabolite dapsone hydroxylamine. Haemotoxicity is thought to be related to production of this metabolite. (See Section 4.8 Adverse Effects (Undesirable Effects), Blood disorders.)
Pyrimethamine. Folic acid antagonists such as pyrimethamine may increase the likelihood of haematologic reactions.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility. No data available.
Use in pregnancy. (Category B2)
The sulfone drugs are generally contraindicated in pregnancy and therefore the use of dapsone during pregnancy should be avoided unless, in the judgment of the doctor, potential benefit outweighs the risk. Animal reproduction studies have not been conducted with dapsone. Dapsone in high doses has been reported to be carcinogenic in rats and mice, but negative in Salmonella mutagenicity assays. The relevance of this finding to human exposure is unclear. Dapsone is excreted in breast milk in therapeutic amounts. Sulfones may cause haemolytic anaemia in glucose-6-phosphate deficient neonates.
Use in lactation. Dapsone is excreted in breast milk in substantial amounts. Haemolytic reactions can occur in neonates. (See Section 4.8 Adverse Effects (Undesirable Effects), Blood disorders.) Because of the potential for tumourgenicity 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 the drug to the mother.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

The following convention has been used for the classification of adverse reactions in terms of frequency: very common ≥ 10%; common (frequent) ≥ 1% and < 10%; uncommon ≥ 0.1% and < 1%; rare ≥ 0.01% and < 0.1%; very rare < 0.01%.
Blood disorders. Rare: agranulocytosis has occurred rarely following dapsone use in leprosy and skin disease. More cases have been observed when used for malaria prophylaxis.
Very rare: aplastic anaemia. Thrombocytosis was reported in a patient with HIV/AIDS receiving dapsone prophylactically.
Dose-related haemolysis is the most common adverse effect and is seen in patients with or without G6PD deficiency. Almost all patients demonstrate the interrelated changes of a loss of 1-2 g of haemoglobin, an increase in the reticulocytes (2-12%), a shortened red cell life span and a rise in methaemoglobin. G6PD deficient patients have greater responses.
Liver disorders. Toxic hepatitis and cholestatic jaundice have been reported. Jaundice may also form part of the dapsone reaction (see Section 4.8 Adverse Effects (Undesirable Effects), Hypersensitivity reactions). Deterioration in liver function tests during dapsone treatment has been noted in a patient with dermatitis herpetiformis and primary sclerosing cholangitis.
Nervous system disorders. Peripheral neuropathy, motor loss, muscle weakness and some patients experienced sensory impairment, most recovered within several months of discontinuing dapsone.
Hypersensitivity reactions. Dapsone syndrome is a rare hypersensitivity reaction, although it has been suggested that the incidence has increased since the introduction of multidrug therapy for leprosy. It occurs in the first 6 weeks of therapy and symptoms include rash, which is always present, fever, jaundice and eosinophilia.
If dapsone is not stopped immediately, the syndrome may progress to exfoliative dermatitis, hepatitis, albuminuria and psychosis. Deaths have been recorded. Most patients require steroid therapy for several weeks, possibly due to the prolonged elimination time of the drug.
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, nephrotic syndrome, hypoalbuminaemia 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.
Leprosy reactional states. Leprosy patients receiving effective chemotherapy may suffer episodes of acute or chronic inflammation, which are called reactions. Generally, anti-leprosy chemotherapy should be continued unchanged but these reactions must be adequately treated since they may result in crippling deformity.
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 hospitalised. 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.
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 hospitalised. In general, anti-leprosy treatment is continued. Analgesics, steroids, and other agents are used to suppress the reaction.
Non-lepromatous lepra or "reversal" reactions. Complications may include severe peripheral neuritis with accompanying cutaneous sensory loss and paralysis and may require surgical decompression. In the management of acute neuritis, corticosteroids should always be used.
Lepromatous lepra or erythema nodosum lepromatous (ENL) reactions. Complications may include neuritis, an increase in muscle weakness, lymphadenitis, iridocyclitis, orchitis and, more rarely, nephritis and large joint arthritis. In the management of these reactions, corticosteroids and agents to modify the autoimmune reaction are used.
Reporting suspected adverse effects. Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

There is no specific antidote and therefore treatment should be symptomatic, e.g. intravenous methylene blue 1 to 2 mg/kg bodyweight, intravenous ascorbic acid 0.5 to 1 g and oxygen for the methaemoglobinaemia plus general supportive measures. The repeated administration of activated charcoal has been reported to increase the elimination rate of dapsone and its metabolite following overdosage.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action. Dapsone is a sulfone active against a wide range of bacteria, but it is mainly used for its action against Mycobacterium leprae. Its mechanism of action is probably similar to that of the sulfonamides, which involves inhibition of folic acid synthesis in susceptible organisms. It is usually considered to be bacteriostatic against M. leprae although it may also possess weak bactericidal activity. It is also active against Plasmodium and Pneumocystis carinii. As with the sulfonamides, antibacterial activity is inhibited by p-aminobenzoic acid.
Secondary (acquired) dapsone resistance of Mycobacterium leprae is mainly associated with dapsone being used on its own. Primary dapsone resistance has also been reported with increasing frequency in areas with secondary resistance. Resistance of M. leprae to dapsone should be suspected whenever a patient relapses clinically and bacteriologically.
Clinical trials. No data available.

5.2 Pharmacokinetic Properties

Absorption. Dapsone is almost completely absorbed from the gastrointestinal tract with peak plasma concentrations occurring 2 to 8 hours after a dose. Steady-state concentrations are not attained until after at least 8 days of daily administration, doses of 100 mg daily provide trough concentrations of 0.5 microgram/mL, which are well in excess of the MIC for M. leprae. About 50 to 80% of dapsone in the circulation is bound to plasma proteins and nearly 100% of its monoacetylated metabolite is bound.
Distribution. Dapsone undergoes enterohepatic recycling. It is widely distributed; it is present in saliva and breast milk and crosses the placenta. The half-life ranges from 10 to 80 hours.
Metabolism. Dapsone is acetylated to monacetyldapsone, the major metabolite, and to other mono and diacetyl derivatives. Acetylation exhibits genetic polymorphism. Hydroxylation is the other major metabolic pathway resulting in hydroxylamine dapsone, which may be responsible for dapsone-associated methaemoglobinaemia haemolysis.
Excretion. Dapsone is mainly excreted in the urine, only 20% of a dose as unchanged drug.

5.3 Preclinical Safety Data

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

6 Pharmaceutical Particulars

6.1 List of Excipients

Lactose monohydrate, sodium lauryl sulfate, maize starch, magnesium stearate and colloidal anhydrous silica.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Dapsomed tablets are packaged in PVC/Al blister packs containing 100 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

The chemical name for dapsone is 4,4'-sulfonylbisbenzenamine.
Chemical structure.

Molecular formula: C₁₂H₁₂N₂O₂S.
Molecular weight: 248.31.
CAS number. 80-08-0.

7 Medicine Schedule (Poisons Standard)

Schedule 4 (S4) - Prescription Only Medicine.

Date of First Approval

02 December 2024

Summary Table of Changes