indication

For the treatment and management of leprosy and dermatitis herpetiformis.

pharmacology

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.

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.

toxicity

Overdosage might be expected to produce nasal congestion, syncope, or hallucinations. Measures to support blood pressure should be taken if necessary.

biotransformation

Hepatic, mostly CYP2E1-mediated.

absorption

Bioavailability is 70 to 80% following oral administration.

half life

28 hours (range 10-50 hours)

route of elimination

Renal

drug interactions

Aluminium: Formation of non-absorbable complexes

Calcium: Formation of non-absorbable complexes

Lumefantrine: Concomitant therapy may increase the risk of adverse hemolytic reactions. Monitor patients closely for symptoms of hemolytic reactions during concomitant therapy. Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, methoglobulin reductase deficiency or hemoglobin M are at higher risk of experiencing hemolytic reactions.

Magnesium: Formation of non-absorbable complexes

Magnesium oxide: Formation of non-absorbable complexes

Rifabutin: Decreased levels of dapsone

Rifampin: Decreased levels of dapsone

Telithromycin: Telithromycin may reduce clearance of Dapsone. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Dapsone if Telithromycin is initiated, discontinued or dose changed.

Tolbutamide: Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Dapsone. Consider alternate therapy or monitor for changes in Dapsone therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.

Trimethoprim: Increased toxicity of both products

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of dapsone by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of dapsone if voriconazole is initiated, discontinued or dose changed.