Dapsone (DDS)

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Chapter: Essential pharmacology : Antileprotic Drugs

It is diamino diphenyl sulfone (DDS), the simplest, oldest, cheapest, most active and most commonly used member of its class. All other sulfones are converted in the body to DDS; many have been used, but none is superior.


DAPSONE (DDS)

 

It is diamino diphenyl sulfone (DDS), the simplest, oldest, cheapest, most active and most commonly used member of its class. All other sulfones are converted in the body to DDS; many have been used, but none is superior.

 


 

Activity And Mechanism

 

Dapsone is chemically related to sulfonamides and has the same mechanism of action, i.e. inhibition of PABA incorporation into folic acid; its antibacterial action is antagonized by PABA. It is leprostatic at low concentrations, and at relatively higher concentrations arrests the growth of many other bacteria sensitive to sulfonamides. Specificity for M. leprae may be due to difference in the affinity of its folate synthase. Doses of dapsone needed for the treatment of acute infections are too toxic, so not used.

 

Dapsone-resistance among M. leprae, first noted in 1964, has spread, and has necessitated the use of multidrug therapy (MDT). It may be primary—in untreated patients, i.e. they have acquired infection from a patient harbouring resistant bacilli, or secondary—which develops during therapy in an individual patient with a single drug. The incidence of primary dapsone resistance reported from different parts of the world, from time-to-time, has varied from 2.5% to 40%; whereas secondary dapsone resistance occurred in about 20% patients treated with monotherapy. The mechanism of secondary resistance appears to be the same as for M. tuberculosis . However, the peak serum concentration of dapsone after 100 mg/day dose exceeds MIC for M. leprae by nearly 500 times; it continues to be active against low to moderately resistant bacilli.

 

Pharmacokinetics

 

Dapsone is completely absorbed after oral administration and is widely distributed in the body, though penetration in CSF is poor. It is 70% plasma protein bound, but more importantly concentrated in skin (especially lepromatous skin), muscle, liver and kidney.

 

Dapsone is acetylated as well as glucuronide and sulfate conjugated in liver. Metabolites are excreted in bile and reabsorbed from intestine, so that ultimate excretion occurs mostly in urine. The plasma t½ of dapsone is variable, though often > 24 hrs. The drug is cumulative due to retention in tissues and enterohepatic circulation. Elimination takes 1–2 weeks or longer.

 

DAPSONE 25, 50, 100 mg tab.

 

Adverse Effects

 

Dapsone is generally well tolerated at doses 100 mg/day or less.

 

Mild haemolytic anaemia is common. It is a dose-related toxicity—reflects oxidising property of the drug. Patients with G6PD deficiency are more susceptible; doses > 50 mg/day produce haemolysis in them.

 

Gastric intolerance—nausea and anorexia are frequent in the beginning, decrease later.

 

Other side effects are methaemoglobinaemia, headache, paresthesias, mental symptoms and drug fever.

 

Cutaneous reactions include allergic rashes, fixed drug eruption, hypermelanosis, phototoxicity and rarely exfoliative dermatitis.

 

Hepatitis and agranulocytosis are other rare complications.

 

Lepra reaction and sulfone syndrome (see below).

 

Contraindications Dapsone should not be used in patients with severe anaemia with Hb < 7g%, G6PD deficiency and in those showing hypersensitivity reactions.

 

Other Use In combination with pyrimethamine, dapsone can be used for chloroquineresistant malaria.

 

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