Methemoglobinemia dapsone

Dapsone is oxidized by CYP2E1 with high affinity both in vitro and in vivo, and also by CYP3A4 (Scheme 11.20). The major side effects of dapsone (methemoglobinemia, agranulocytosis) are linked to its N-oxidation (25, 26). 

The combination of primaquine with clindamycin is used as second choice in the treatment or prevention of P. jiroveci pneumonia. If the patient has been treated immediately beforehand with dapsone, methemoglobinemia can result, especially in patients infected with HIV (SEDA-21, 296). 

Dapsone is a sulfone that, like sulfonamides, inhibits dihydrofolate synthesis (p. 272). It is bactericidal against susceptible strains of M. leprae. Dapsone is given orally. The most frequent adverse effect is methemoglobinemia with accelerated erythrocyte degradation (hemolysis). 

Although dapsone (Avlosulfon) was once used in the treatment and prophylaxis of chloroquine-resistant P. falciparum malaria, the toxicities associated with its administration (e.g., agranulocytosis, methemoglobinemia, hemolytic anemia) have severely reduced its use. 

Dapsone Supportive treatment for the adverse effects of dapsone may be initiated with stomach wash and activated charcoal. Methylene blue could be given to treat methemoglobinemia, but this is not effective in patients with glucose-6-phosphate dehydrogenase deficiency. Infusion of human erythrocytes can be... 

Methemoglobin reductase deficiency Acetaminophen, anesthetics, topical, benzocaine, chloroquine, dapsone, nitrites, primaquine, sulfonamides Methemoglobinemia... 

The adverse effects of dapsone have been comprehensively reviewed (8). The most common untoward effect is hemolysis of varying degree it is usually mild, except in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Methemoglobinemia and Heinz... 

A patient who had been taking dapsone inappropriately instead of an antispasmodic that had been prescribed for a spinal condition, because of incorrect labeling in a pharmacy, developed methemoglobinemia (24). Methylene bine was given intravenously and may have contribnted to the severe hemolysis that followed. 

TrUlo RA Jr, Aukburg S. Dapsone-induced methemoglobinemia and pulse oximetry. Anesthesiology 1992 77(3) 594-6. 

Dapsone (alone or in combination with pyrimethamine) can cause methemoglobinemia and hemolytic anemia. These complications tend to be dose-related and are more often encountered in G6PD-deficient subjects (SEDA-18, 287). 

Methemoglobinemia toxicity is caused by several aromatic amines, including aniline and dapsone. and is a re.sult oftlie bioconversion of the aromatic amine to its A/-hydroxy... 

Dapsone overdose (see also p 179) administer methyiene biue (p 466) for symptomatic methemoglobinemia. 

Dapsone 10-50h As little as 100 mg in an 18-month-old Methemoglobinemia, sulfhemoglobinemia, hemolysis metabolic acidosis hallucinations, confusion hepatitis (see p 179). 

A. Dapsone metabolites oxidize the ferrous iron hemoglobin complex to the ferric state, resulting in methemoglobinemia. 

Falkenhahn M et al Unexplained acute severe methaemoglobinaemia in a young adult. Br J Anaesth 2001 Feb 86(2) 278-280. [PMID 11573675] (A young woman developed methemoglobinemia [47%] due to dapsone.)... 

MacDonald RD, McGuigan MA Acute dapsone intoxication a pediatric case report. Pediatr Emerg Care 1997 13(2) 127-129. [PMID 9127424] (Ingestion of 37.5 mg/kg by a 3-year-old resulted in a methemoglobln level of 44%. Treatment with methylene blue was successful, but methemoglobinemia recurred 64 hours after ingestion.)... 

B. Usually, mild methemoglobinemia (less than 15-20%) is well tolerated and will resolve spontaneously. Continued metabolism of oxidant compounds from a long-acting parent compound (eg, dapsone) may lead to prolonged effects (2-3 days). 

Hematologic In a retrospective study of 34 patients with hematological malignancies who took dapsone, 18 had co-oximetry studies done and 13 had methemoglobinemia, with symptoms in 4 8 required intensive care support [9 ]. The mean onset was at 12 (range 4-18) days and all were anemic. 

Dapsone-induced methemoglobinemia reportedly relapsed 10 days after drug withdrawal in a 25-year-old woman with systemic lupus erythematosus [10 ]. The authors suggested, without evidence, that the prolonged action of dapsone may have been due to a polymorphism of the CYP2E1 gene. 

Figure 1 The FIDOS and DoTS descriptions of hemolytic anemia and methemoglobinemia due to dapsone.

The most common hematological adverse effects of dapsone are hemolytic anemia and methemoglobinemia. Agranulocytosis [45, 46 ] can also occur, as can rarely sulfhemo-globinemia [47", 48 ], aplastic anemia [49 ], and pure red cell aplasia [5(1 ]. 

Pathogenesis Dapsone is metabolized either by acetylation to non-toxic acetyldapsone or by N-hydroxylation by multiple CYP isoenzymes to toxic hydroxylamines [51 ]. The latter are thought to be responsible for methemoglobinemia and hemolysis. 

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