Consumer medicine information

DAPSONE TABLETS

Dapsone

BRAND INFORMATION

Brand name

Dapsone

Active ingredient

Dapsone

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using DAPSONE TABLETS.

What is in this leaflet?

This leaflet answers some common questions about Dapsone. It does not contain all the available information. It does not take the place of talking to your doctor and pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Dapsone against the benefits they expect it will have for you.

Keep this leaflet with the medicine. You may need to read it again.

What Dapsone is used for?

Dapsone is used to treat leprosy (Hansen’s disease) and to help control a skin problem called dermatitis and a fungal disease called Actinomycotic mycetoma. When it is used to treat leprosy, Dapsone may be given with one or more other medicines.

Mechanism of action:
Dapsone (DAP-sone), a sulfone, belongs to the family of medicines called anti-infectives.

Dapsone works by killing the bacteria or fungi causing your infection or by stopping its growth.

Dapsone will not work against infections caused by viruses such as colds or the flu.

Dapsone is available only with a doctor's prescription.

There is no evidence that Dapsone is addictive.

Before taking Dapsone

When you must not take it?
When you must not be given it?

Do not take/use Dapsone if:
you have ever had an allergic reaction to Dapsone or any other sulpha drugs or any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include skin rash, which is always present, fever, jaundice, and eosinophilia.

Tampering and Expiry Date Warnings:

Do not use Dapsone if the packaging is torn or shows signs of tampering.

If you are not sure whether you should start taking Dapsone, contact your doctor.

Before you start to take it
Before you are given it

Tell your doctor if:

  1. you have any type of allergic reaction to sulpha drugs (sulfonamide medicines):
    You may have an increased chance of being allergic to Dapsone if you are allergic to sulpha drugs.
  2. you have any allergies to:
    any other medicines any other substances, such as foods, preservatives or dyes.
  3. Pregnancy and breastfeeding: you are pregnant, or intend to become pregnant. The use of Dapsone during pregnancy should be avoided.
    Dapsone may affect your developing baby if you take it during pregnancy.
  4. you are breastfeeding or intend to breastfeed.
    Dapsone passes into breast milk and may affect your baby. Dapsone may cause blood problems in nursing babies. Therefore, breast feeding may need to be stopped because of the risks to the baby.
  5. if you have or have had any medical conditions, including:
    anemia, or liver or kidney disease

If you have not told your doctor about any of the above, tell them before you take/are given dapsone.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines that you buy without a prescription from your pharmacy (over-the-counter products), supermarket or health food shop.

Some medicines may interfere with Dapsone. These include:

  • Amprenavir
  • Didanosin
  • Rifampicin
  • Clofazimine
  • Probenecid
  • Trimethoprim
  • Cimetidine
  • Pyrimethamine

These medicines may be affected by Dapsone, or may affect how well it works.

You may need to take different amounts of your medicine, or you may need to take different medicines. Your doctor will advise you.

When you are taking Dapsone, it is especially important that your healthcare professional knows if you are taking any of the above.

Talk to your doctor about the need for an additional method of contraception while taking Dapsone.

Some medicines may decrease the effectiveness of some birth control pills, although this has not been shown with Dapsone.

Your doctor and pharmacist may have more information on medicines to be careful with or avoid while taking Dapsone.

How to take Dapsone?

Take Dapsone with a full glass of water or another liquid, with or after food.

Tablets should be taken whole and small doses should be made up from 25 mg tablets. Do not split the tablet.

How long to take it?

Keep taking your Dapsone for as long as your doctor tells you to. Remember it may take a number of months for Dapsone to work.

Do not stop taking Dapsone even if you begin to feel better. For best effect Dapsone must be taken regularly.

Do not take a double dose to make up for the dose that you missed.

If you have trouble remembering to take your tablets, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (13 11 26) for advice or go to the Emergency Department at your nearest hospital, if you think that you or anyone else may have taken too much Dapsone. Do this even if there are no signs of discomfort or poisoning.

While you are using Dapsone

Things you must do

If the symptoms of your infection do not improve within 2 to 3 months, or if they become worse, tell your doctor.

If you become pregnant while you are taking Dapsone tell your doctor immediately.

If you are about to start taking any new medicine, tell your doctor and pharmacist that you are taking Dapsone.

Your doctor may give you a schedule for regular blood tests. This schedule should be carefully followed–

If you have to test your urine for sugar while you are using/being given Dapsone, make sure your doctor knows which type of test you use.

Dapsone may affect the results of some of these tests.

If you have to have any blood tests tell your doctor you are taking/using Dapsone.

Dapsone may affect the results of some blood tests.

Tell all the doctors, dentists and pharmacists who are treating you that you are taking Dapsone.

Things you must not do

Do not stop taking your tablets because you are feeling better, unless advised by your doctor.

If you do not complete the full course prescribed by your doctor, all of the bacteria/fungi causing your infection may not be killed. These bacteria may continue to grow and multiply so that your infection may not clear completely or it may return.

Do not give Dapsone to anyone else, even if they have the same condition as you.

Do not use Dapsone to treat any other complaints unless your doctor tells you to.

Things to be careful of

Dapsone may make you dizzy. Be careful when driving a car or using machinery.

Side effects

Check with your doctor as soon as possible if you have any problems while taking Dapsone, even if you do not think the problems are connected with the medicine or are not listed in this leaflet.

Like other medicines, Dapsone can cause some side effects. If they occur, most are likely to be minor and temporary. However, some may be serious and need medical attention.

While taking Dapsone

If any of the following happen, stop taking Dapsone and tell your doctor immediately. These are very serious side effects. You may need urgent medical attention or hospitalisation

  • Severe skin rash
  • Muscle weakness, unusual tiredness or weakness
  • Yellowing of skin or eyes
  • Bluish finger nails, lips or skin
  • Fever, sore throat and difficulty in breathing
  • Back, leg or stomach pains
  • Itching, dryness, redness, scaling or peeling of the skin
  • Loss of hair
  • Mood or other mental changes
  • Numbness, tingling, pain, burning or weakness in hands or feet;
  • Unusual bleeding or bruising

Tell your doctor if you notice any of the following and they worry you: These side effects are usually mild.

  • Nausea, vomiting;
  • Loss of appetite;
  • Headache;
  • Nervousness;
  • Dizziness

Other side effects not listed above may also occur in some patients. Tell your doctor if you notice any other effects.

Some people may get other side effects while taking/using/being given Dapsone.

Do not be alarmed by this list of possible side effects. You may not experience any of them after using Dapsone.

Storage

Keep your tablets in the original pack until it is time to take them. Keep the pack in a cool dry place. Do not leave it in the car on a hot day. Do not store medicine in the bathroom or near a sink. Heat and dampness can destroy some medicines.

Store all medicines out of the reach of children such as in a locked cupboard.

If your doctor tells you to stop taking Dapsone, ask your pharmacist what to do with any tablets that are left over.

Store below 25°C. Protect from light.

What it looks like?

Tablets, 25 mg and 100 mg (white, scored): 100’s

Ingredients

Active. Dapsone.

Inactive. Starch-maize, cellulose-microcrystalline, magnesium stearate, silicon dioxide.

Tablets do not contain alcohol, gluten, lactose, parabens, sugar, sulfite or tartrazine.

Manufacturer/Distributor/Supplier

Manufactured by:
Jacobus Pharmaceutical Co. Inc. (USA)

Supplied and distributed by:
Link Medical Products Pty Ltd
5 Apollo Street,
Warriewood, NSW 2102, Australia

Supplied and distributed in NZ by:
Link Pharmaceutical LTD
Auckland

25 mg Tablets AUST R 104482
100 mg Tablets AUST R 104483

Prepared on 11 August 2011

Published by MIMS April 2014

BRAND INFORMATION

Brand name

Dapsone

Active ingredient

Dapsone

Schedule

S4

 

1 Name of Medicine

Dapsone.

2 Qualitative and Quantitative Composition

Dapsone tablets are available in strengths of 25 mg and 100 mg round, white, scored tablets.
Dapsone tablets do not contain alcohol, gluten, lactose, parabens, sugar, sulfites or tartrazine.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Tablets.

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. Tablets should be taken whole and small doses should be made up from 25 mg tablets. Do not split the tablet.

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-amino-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.
(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.
 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.

Nonlepromatous 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

Maize starch, microcrystalline cellulose, magnesium stearate and silicon dioxide.

6.2 Incompatibilities

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

6.3 Shelf Life

5 years.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

Dapsone 25 mg, 100 tablets in a bottle with a child-resistant cap, available as round white scored tablets, debossed '25' above and '102' below the score line and 'JACOBUS' on the reverse. AUST R 104482.
Dapsone 100 mg, 100 tablets in a bottle with a child-resistant cap, available as round white scored tablets, debossed '100' above and '101' below the score line and 'JACOBUS' on the reverse. AUST R 104483.

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.
Molecular formula: C12H12N2O2S.
Molecular weight: 248.31.

Chemical structure.


CAS number.

80-08-0.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes