DAPSONE TABLETS

Indications

• Multibacillary leprosy
• Paucibacillary leprosy
• Prophylaxis against Pneumocystis jirovecii pneumonia
• Treatment of mild to moderate Pneumocystis jirovecii pneumonia
• Dermatitis herpetiformis
• Lyme disease

Dosage

Adults: 100 mg three times a day for one month, subsequent dose

Mechanism of action

Dapsone acts by inhibiting the synthesis of dihydrofolic acid, competing with para-amino-benzoate for the active site of dihydropteroate synthetase. This action disrupts the folate pathway in bacteria and protozoa. Additionally, dapsone has anti-inflammatory properties, which are believed to be mediated through inhibition of neutrophil activity, including myeloperoxidase and lysosomal enzymes, and reducing tissue damage caused by neutrophils.

Pharmacodynamics

Dapsone has broad-spectrum activity, being effective against various bacteria and protozoa. It is particularly effective in treating leprosy as part of a multidrug regimen recommended by the World Health Organization. Its anti-inflammatory effects may help in conditions like dermatitis herpetiformis. Dapsone is rapidly absorbed, reaching peak plasma concentrations within hours, and is known to have a long duration of action due to its retention in tissues.

Pharmacokinetics

Dapsone is well absorbed from the gastrointestinal tract and is widely distributed in body tissues, with significant accumulation in the liver, kidney, skin, and muscle. The drug has a half-life of approximately 24 hours, allowing for once-daily dosing. It undergoes hepatic metabolism and is excreted primarily in urine, with traces remaining in the body for weeks after cessation of therapy.

Contra-indications

• Known hypersensitivity to dapsone or any of its components
• Severe glucose-6-phosphate dehydrogenase (G6PD) deficiency

Adverse effects

• Abdominal pain
• Anorexia
• Dry eye
• Fatigue
• Gastrointestinal disorders
• Headache
• Lymphadenopathy
• Nausea
• Photosensitivity reaction
• Skin discoloration
• Visual impairment
• Vomiting
• Weight loss
• Haemolytic anaemia
• Dapsone syndrome (rash with fever and eosinophilia)

Interactions

• Increased risk of methaemoglobinaemia with topical prilocaine
• Increased risk of methaemoglobinaemia with local anaesthetics
• Increased risk of methaemoglobinaemia with aminosalicylic acid
• Increased risk of methaemoglobinaemia with antiepileptics (fosphenytoin, phenobarbital, phenytoin, primidone)
• Increased risk of methaemoglobinaemia with nitrates
• Increased risk of methaemoglobinaemia with nitrofurantoin
• Increased risk of methaemoglobinaemia with nitroprusside
• Increased risk of methaemoglobinaemia with paracetamol
• Increased risk of methaemoglobinaemia with sulfonamides

Precautions

• Use with caution in hepatic impairment
• Use with caution in renal impairment
• Monitor blood disorders during long-term treatment
• Avoid use in patients with persistent abdominal pain and diarrhea

Pregnancy

Use with caution. Folic acid may be given to mother throughout pregnancy; higher doses recommended in third trimester due to risk of hemolysis and methaemoglobinaemia.

Breast-feeding

May alter color of milk; risk to infant very small unless infant is G6PD deficient.

Storage

Store in a cool, dry place, protected from light. Keep out of reach of children.

Formulations

• Dapsone 50 mg

Mechanism of action

Dapsone acts against bacteria and protozoa in the same way as sulphonamides, that is by inhibiting the synthesis of dihydrofolic acid through competition with para-amino-benzoate for the active site of dihydropteroate synthetase. The anti-inflammatory action of the drug is unrelated to its antibacterial action and is still not fully understood. Dapsone is a structural analog of para-aminobenzoic acid (PABA) and a competitive inhibitor of dihydropteroate synthase (folP1P2) in the folate pathway ... The effect on this evolutionarily conserved pathway also explains why dapsone is a broad-spectrum agent with antibacterial, anti-protozoal, and antifungal effects. The anti-inflammatory effects of dapsone occur via inhibition of tissue damage by neutrophils. First, dapsone inhibits neutrophil myeloperoxidase activity and respiratory burst. Second, it inhibits activity of neutrophil lysosomal enzymes. Third, it may also act as a free radical scavenger, counteracting the effect of free radicals generated by neutrophils. Fourth, dapsone may also inhibit migration of neutrophils to inflammatory lesions. 1-30 Ug/mL dapsone interfered with myeloperoxidase-H2O2-halide-mediated cytotoxic system in polymorphonuclear leukocytes. Kinetic studies revealed competitive inhibition of myeloperoxidase. Its action in dermatitis herpetiformis may be explained by effect on this system.

Pharmacodynamics

Dapsone is a sulfone with anti-inflammatory immunosuppressive properties as well as antibacterial and antibiotic properties. Dapsone is the principal drug in a multidrug regimen recommended by the World Health Organization for the treatment of leprosy. As an anti-infective agent, it is also used for treating malaria and, recently, for Pneumocystic carinii pneumonia in AIDS patients. Dapsone is absorbed rapidly and nearly completely from the gastrointestinal tract. Dapsone is distributed throughout total body water and is present in all tissues. However, it tends to be retained in skin and muscle and especially in the liver and kidney: traces of the drug are present in these organs up to 3 weeks after therapy cessation.