Dapsone 100mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Dapsone 100mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Dapsone BP 100mg
3 PHARMACEUTICAL FORM
Dapsone tablets are presented as a white normal convex tablet with a breakline scored on one side.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
1) As part of a multi-drug regimen in the treatment of all forms of leprosy.
2) Treatment of dermatitis herpetiformis and other dermatoses.
3) Prophylaxis of malaria in combination with pyrimethamine.
4) Prophylaxis of Pneumocystis carinii pneumonia in immunodeficient subjects, especially AIDS patients.
4.2 Posology and method of administration
Posology
Adults and children over 12 years:
Multibacillary leprosy (3-drug regimen): 100mg daily for at least two years. Paucibacillary leprosy (2-drug regimen): 100mg daily for at least six months.
Malaria prophylaxis: 100mg weekly with 12.5mg pyrimethamine.
Dermatitis herpetiformis: Initially 50mg daily, gradually increased to 300mg daily if required. Once lesions have begun to subside, the dose should be reduced to a minimum as soon as possible, usually 25-50mg daily, which may be continued for a number of years. Maintenance dosage can often be reduced in patients receiving a gluten-free diet.
Pneumocystis carinii pneumonia: In combination with trimethoprim, 50100mg daily; 100mg twice weekly or 200mg once weekly.
Children 6-12 years:
Multibacillary leprosy (3-drug regimen): 50mg daily for at least two years. Paucibacillary leprosy (2-drug regimen): 50mg daily for at least six months.
Elderly:
Dosage should be reduced in the elderly where there is an impairment of hepatic function.
Method of Administration
For oral administration.
4.3 Contraindications
Hypersensitivity to Dapsone. Known hypersensitivity to sulphonamides, sulphones, or any of the excipients. Patients intolerant of frusemide, thiazide diuretics, sulphonylureas or carbonic anhydrase inhibitors may also be intolerant of this medication. Severe anaemia. Acute porphyria, severe glucose-6-phosphate dehydrogenase deficiency.
4.4 Special warnings and precautions for use
Caution should be exercised in the following conditions.
• Cardiac or pulmonary disease.
• Anaemia (severe anaemia should be treated before starting chemotherapy. Regular
blood counts should be performed during treatment).
• G6PD-deficiency (including breast feeding of affected children)
• Patients with methaemoglobin reductose and with haemoglobin m deficiency are
also more susceptible to its haemolytic effects.
4.5 Interaction with other medicinal products and other forms of interaction
When probenecid is used concurrently with Dapsone the excretion of the latter is reduced. Concurrent use of rifampicin with Dapsone may decrease the effects of Dapsone because of stimulation of hepatic microsomes enzyme activity, resulting in decreased Dapsone concentrations by 7-10 fold. However, dosage adjustments are not required during concurrent rifampicin therapy for leprosy, although they may be required in the treatment of other diseases. Concurrent use of haemolytics with Dapsone may increase the potential for toxic side effects.
Concurrent use of Dapsone with bone marrow depressants may increase the leucopenic and/or thrombocytopenic effects: if concurrent use is required, close observation for mylotoxic effects should be considered.
Concurrent use of aminobenzoates in the treatment of leprosy is not recommended since aminobenzoates may be absorbed by bacteria preferentially over sulphones; however aminobenzoates do not antagonize the effects of Dapsone in the treatment of dermatitis herpetiformis.
Increased dapsone and trimethoprim concentrations have been reported following concurrent administration in AIDS patients.
4.6 Fertility, Pregnancy and lactation
It is now generally considered that the benefits of dapsone in the treatment of leprosy outweigh any potential risk to the pregnant patient. Some leprologists recommend 5mg folic acid daily for leprosy patients receiving dapsone during pregnancy.
Dapsone diffuses into breast milk and there has been a report of haemolytic anaemia in a breast fed infant. While some feel that dapsone should not be used in lactating mothers, in general treatment for leprosy is continued in such patients.
4.7 Effects on ability to drive and use machines
None.
4.8 Undesirable effects
Most adverse effects caused by Dapsone are dose related and are uncommon at low doses of up to 100mg daily which are usually employed in the treatment of leprosy. Adverse effects include anorexia, nausea, vomiting, headache, dizziness, tachycardia, insomnia, anaemia, hemolytic anemia, rash, photosensitivity, Pruritus, hepatitis, agranulocytosis and psychosis. Peripheral neuropathy has been seen in patients on Dapsone for skin conditions.
Hypersensitivity reactions have rarely been reported and tend to occur during the first six weeks of therapy.
A Dapsone (or sulphone) syndrome, a form of hypersensivity reaction, has been rarely reported and may occur during the first 6 weeks therapy. Its most common features are jaundice with hepatitis (most prominent), fever and rash, examthematous skin eruptions which may progress to exfoliative dermatitis, toxic epidermal necrolysis or Stevens-Johnson syndrome. Other manifestations include hepatosplenomegaly, lymphadenopathy, eosinophilia, mononucleosis, leucopenia, haemolysis, peripheral neuropathy, hypoalbuminaemia, renal papillary necrosis and arthralgias. Patients usually improve upon Dapsone withdrawal but steroid treatment may be needed. Fatalities have been reported.
Varying degrees of dose-related haemolysis and methaemoglobinaemia are the most frequently reported adverse effects of dapsone and occur in most subjects given more than 200mg daily; doses of up to 100mg daily do not cause significant haemolysis but subjects deficient in glucose-6-phosphate dehydrogenase are affected by doses above about 50mg daily.
Although agranulocytosis has been reported rarely with dapsone when used alone, reports have been more common when Dapsone has been used with other agents in the prophylaxis of malaria.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme (Tel: Freephone 0808 100 3352 or Website: www.mhra.gov.uk/yellowcard).
4.9 Overdose
Unabsorbed Dapsone should be removed from the stomach by gastric aspiration and lavage.
Activated charcoal by mouth enhances elimination of Dapsone and its monoacetyl metabolite.
Methaemoglobinemia has been treated with slow intravenous injection of methylene blue 1-2mg/kg body weight repeated after one hour if necessary. Ascorbic acid 0.5-2.0g may be administered orally or by intravenous injection. It should not normally be used alone because of its slow speed of action, but may be used in patients deficient in glucose-6-phosphate dehydrogenase in whom methylene blue will be ineffective.
Haemolysis is treated by infusion of concentrated human red blood cells to replace the damaged cells.
Supportive therapy includes administration of oxygen to alleviate hypoxia and fluids to maintain renal blood flow and promote the elimination of Dapsone.
5.1 Pharmacodynamic properties
Dapsone is a sulphone with a bacteriostatic action. The mechanism of action is similar to that of sulphonamides. Both have a similar range of antibacterial activity and are antagonised by aminobenzoates (PABA). Dapsone may also act as a dihydrofolate reductase inhibitor. When used in dermatitis herpetiforms, the mechanism of action is not known but it is not due to its bacteriostatic effect. Dapsone may act as an enzyme inhibitor or oxidising agent. In addition, Dapsone has numerous immunologic effects (e.g. immunosuppression) which is most likely to account for its suppression of dermatitis herpetiformis.
5.2 Pharmacokinetic properties
Dapsone is rapidly and almost completely absorbed from the gastrointestinal tract. Approximately 50-80% of Dapsone in the circulation is bound to plasma proteins and nearly 100% of its monoacetylated metabolite is bound.
The plasma half life varies, ranging from 10-15 hours with an average of 28 hours.
It is well distributed throughout total body water and is found in all tissues especially liver, muscle, kidneys, skin and is subject to enterohepatic recycling. It is also found in the CSF, placenta and breast milk.
Dapsone is metabolised in the liver by acetylation and N-oxidation, together with glucuronic acid and sulphate conjunction; acetylation exhibits genetic polymorphism and slow, intermediate and rapid acetylators have been identified. Approximately 70-85% of the dose is excreted in the urine of which about 20% is unchanged drug. Small amounts are eliminated in the faeces. It is excreted in breast milk in clinically significant amounts and it may be detected in the serum of breast-fed infants.
5.3 Preclinical safety data
Not applicable
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Maize starch BP Povidone BP Isopropyl alcohol BP Potable water HSE Sodium lauryl sulphate BP Magnesium stearate BP
Maize starch BP
6.2 Incompatibilities
None
6.3 Shelf life
3 years
6.4 Special precautions for storage
Protect from heat, light and moisture.
Keep out of the reach of children.
6.5 Nature and contents of container
Dapsone tablets are packed in the following containers and closures;
• Opaque plastic containers fitted with snap-on plastic closures for all pack sizes (9, 10, 14, 15, 20, 21, 28, 30, 50, 56, 84, 100, 250, 500 and 1000 tablets).
• Opaque plastic containers composed of either high density polypropylene or high density polyethylene with a tamper evident or child resistant tamper evident closure, composed of high density polyethylene for all pack sizes ( 9, 10, 14, 15, 20, 21, 28, 30, 50, 56, 84, 100, 250, 500 and 1000 tablets).
• aluminium/opaque PVC blister packs of 9, 10, 14, 15, 20, 21, 28, 30, 56
and 84 tablets.
6.6 Special precautions for disposal and other handling
No special instructions for use/handling
7 MARKETING AUTHORISATION HOLDER
YJB PORT LIMITED
Unit 32 Stadium Business Centre,
North End Road,
Wembley,
Middlesex,
HA9 0AT,
UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 34793/0005
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
08/01/2009
10 DATE OF REVISION OF THE TEXT
08/11/2016