Dapsone

Dapsone (4,4’-diaminodiphenylsulfone) is sulfon

1. interference with the Sulfone; prevents normal bacterial utilization of para-aminobenzoic acid (PABA)
for the synthesis of folic acid by acting as a competitive antagonist of PABA; it is bactericidal and
bacteriostatic against Mycobacterium.
2.its anti-inflammatory effect, the mechanisms of which are still incompletely not known
3.inhibits migration of neutrophilsto areas of inflammation by inhibiting neutrophil chemotaxis to the
chemoattractant signals F-metleu-phe1,2 and leukotriene B4 (LTB4)
inhibits the adherence of neutrophils to skin-localized IgA6 and endothelium..
4.inhibit the release of inflammatory mediators including interleukin-8 (IL-8),8 PGD2, and tumonecrosis
factor-α (TNF-α).
5.inhibit the myeloperoxidase H2O2-halide mediated cytotoxic system, by inhibiting the
calcium flux necessary for these events.

PHARMACOLOGY
Absorbed from the gut peak levels 2–6 hours .
Half life 30 hours
doses from 25 mg to 400 mg
activated charcoal in reducing drug levels during accidental or intentional over dose.
cross-reactions occur in only 7%–22% of sulfa-allergic patients.
Sulfapyridine is thought to have similar mechanisms of action although with a reduced activity level
and lower incidence of toxicity

Transmitted through human milk.

classified as pregnancy category C.

metabolized in the liver. The two major metabolic pathways involve acetylation and N-hydroxylation

Cimetidine and omeprazole, which block N-hydroxylation of dapsone, have been used to mitigate some
of the side effects of dapsone.
Cimetidine dosed 400 mg three times a day has reduced methemoglobin levels

Metabolism

Hepatic P450 enzymes CYP2E1, CYP3A4

Elimination

Half-life: 28 hr

Excretion: Urine (85%) as metabolites

Within erythrocytes, dapsone hydroxylamine generates reactive oxygen species which

oxidize oxyhemoglobin into methemoglobin. The oxidizedhemoglobin becomes microscopically visible
asHeinz bodies. These Heinz bodies and hydroxylatedmetabolite/cellular protein adducts may label the
red blood cells as senescent, targeting them for removal by the spleen.
Patients with preexisting iron or B12/ folate deficiency may not be able to mount appropriate
erythropoesis and are at greater risk for symptomatic drops in hemoglobin.
higher rate of hemolysis may be due to the greater frequency of renal insufficiency
If dapsone therapy is efficacious but hemolysis is limiting therapy coadministration of darbepoetin
may allow continuation of drug at therapeutic doses.
Methemoglobinemia
due to dapsone hydroxylamine’s generation of reactive oxygen species
Pulse oximetry is a reasonable screening test for methemoglobinemia
Lipoic acid, a dietary supplement with antioxidant properties, as also been shown in vitro to decrease
methemoglobin formation and 90 mg daily of lipoic acid daily has been suggested for dapsone-treated
patients.

Treatment
activated charcoal reduces drug levels by removing drug from the gut.
Intravenous methylene blue, 1% solution given 1–2 mg/ kg slowly IV, can be used to decrease the degree
of methemoglobinemia. Methylene blue is a cofactorfor methemoglobin reductase after first being
reduced by cellular stores of NADPH to leukomethylene blue.
G6PD-deficient patients should not be given methyleneblue, as they may have insufficient NADPH and
unreduced methylene blue is its own direct hemolytic agent. Ascorbic acid 1,000 mg intravenously every
twelve hours has also been used in a case of overdose and certainly could be used until G6PD status is
reviewed so that methylene blue can be administered.Ascorbic acid’s effect is due to its ability to increase
methemoglobin reductase activity.

Sulfone syndrome
sulfone syndrome is a drug-induced hypersensitivity syndrome like those seen with someanticonvulsants
and other medications. These syndromes are postulated to be due to drug-allergyinduced
immunosuppression leading to reactivation of human herpesvirus 6 (HHV6) or other latent viruses such
as CMV and EBV. They develop between 2 and 7 weeks after initiating the medication and inevitably
include the triad of fever, rash, and hepatitis

Treatment
Treatment of the sulfone syndrome involves prompt discontinuation of dapsone. Corticosteroids have
proved helpful but doses up to 1g/day of methylprednisolone for 3 days may be required, followed
by a prednisone taper over 4–6 weeks. It is the reactivation of HHV6 that is thought to cause the late
flaring of rash, fever, and hepatitis that is Characteristically Seen In this class of drug reactions, necessitating such
as long steroid taper
endorgan damage must be managed supportively (dialysisfor renal failure,165 diuretics for
myocarditis,163 etc.) Plasma exchange has also been successfully used in a case where tapering of
steroids led to recrudescence of symptoms.

MONITORING OF DAPSONE THERAPY

history and physical examination to screen for significant preexisting cardiopulmonary disease
cbc e Retic count
(weekly for the first month
twice a month during the next 2 months
HB
WBC e differntial
G6PD
LFT
RFT