-
Seminars in Arthritis and Rheumatism Jun 1996Dapsone, a synthetic sulfone with chemical similarities to sulfapyridine, has been used for a number of years to treat leprosy and dermatitis herpetiformis. Recently, a... (Review)
Review
Dapsone, a synthetic sulfone with chemical similarities to sulfapyridine, has been used for a number of years to treat leprosy and dermatitis herpetiformis. Recently, a number of prospective, randomized, double-blind trials have shown their success in the management of rheumatoid arthritis, with dapsone being superior to placebo and comparable to chloroquine and hydroxychloroquine. Its mode of anti-inflammatory actions in rheumatoid arthritis is not clearly understood, but modulation of neutrophil activity or inhibition of neutrophil inflammatory product formation or release appear to play a role. The major limiting side effect is hemolytic anemia, which may be mitigated through careful patient selection, conservative drug dosing, close monitoring, and possibly, concurrent administration of antioxidants or cytochrome P450 inhibitors. Methemoglobinemia is another common finding among patients receiving dapsone therapy, but rarely does it result in prominent symptoms other than transient pallor. Less common adverse events to dapsone include the idiosyncratic reactions of leukopenia and agranulocytosis, cutaneous eruptions, peripheral neuropathy, psychosis, toxic hepatitis, cholestatic jaundice, nephrotic syndrome, renal papillary necrosis, severe hypoalbuminemia without proteinuria, an infectious mononucleosis-like syndrome, and minor neurological and gastrointestinal complaints. In this report, two patients with advanced rheumatoid arthritis, who were safely and effectively treated with dapsone after failure with other second-line agents, are described and the literature is reviewed. We suggest that dapsone is an effective second-line agent in the treatment of rheumatoid arthritis.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Clinical Trials as Topic; Dapsone; Female; Humans; Male; Middle Aged; Prednisone
PubMed: 8792511
DOI: 10.1016/s0049-0172(96)80004-7 -
General Pharmacology Nov 19951. Dapsone is a potent anti-inflammatory and anti-parasitic compound, which is metabolised by cytochrome P-450 to hydroxylamines, which in turn cause methaemoglobinaemia... (Review)
Review
1. Dapsone is a potent anti-inflammatory and anti-parasitic compound, which is metabolised by cytochrome P-450 to hydroxylamines, which in turn cause methaemoglobinaemia and haemolysis. However, during the process of methaemoglobin formation, erythrocytes are capable of detoxifying the hydroxylamine to the parent drug, which may either reach the tissues to exert a therapeutic effect or return to the liver and be re-oxidised in a form of systemic cycling. This glutathione-dependent effect, combined with the un-ionised state of the drug at physiological pH, may contribute to its efficacy. 2. Paradoxically, other aspects of the glutathione-dependent cycling of the hydroxylamine metabolite may contribute to the major adverse reaction of the drug, agranulocytosis. Erythrocytes exposed to the metabolite and repeatedly washed may still release the hydroxylamine in sufficient concentration to kill mononuclear leucocytes in vitro. Thus, erythrocytes may be a conduit for the hydroxylamine to reach the bone marrow to covalently bind to granulocyte precursors, which may trigger an immune response in certain individuals and may lead to the potentially fatal eradication of granulocytes from the circulation. 3. Attempts to increase patient tolerance to dapsone have been most successful using a metabolic inhibitor to reduce hepatic oxidation of the drug to the hydroxylamine. Methaemoglobin formation in the presence of cimetidine was maintained at 30% below control levels for almost 3 mo, and patients' reported side effects such as headache and lethargy were significantly reduced. 4. As clinical application of new and safer dapsone analogues is years away, the use of cimetidine provides an immediate route to increasing patient compliance during dapsone therapy, especially in those maintained on dapsone dosages in excess of 200 mg/day.
Topics: Agranulocytosis; Anti-Infective Agents; Dapsone; Humans; Liver; Methemoglobinemia
PubMed: 8690232
DOI: 10.1016/0306-3623(95)00029-1 -
Immunology and Allergy Clinics of North... May 2012Dapsone is used in the treatment of autoimmune bullous diseases (AIBD), a group of disorders resulting from autoimmunity directed against basement membrane and/or... (Review)
Review
Dapsone is used in the treatment of autoimmune bullous diseases (AIBD), a group of disorders resulting from autoimmunity directed against basement membrane and/or intercellular adhesion molecules on cutaneous and mucosal surfaces. This review summarizes the limited published data evaluating dapsone as a therapy for AIBD.
Topics: Agranulocytosis; Animals; Autoimmune Diseases; Dapsone; Disease Management; Drug Hypersensitivity; Humans; Leprostatic Agents; Methemoglobinemia; Neutrophil Activation; Neutrophils; Skin Diseases, Vesiculobullous
PubMed: 22560144
DOI: 10.1016/j.iac.2012.04.011 -
Clinics in Dermatology 2000
Review
Topics: Anti-Inflammatory Agents; Dapsone; Dermatologic Agents; Drug Approval; Drug Utilization; Humans; Immunosuppressive Agents; Skin Diseases; United States; United States Food and Drug Administration
PubMed: 10701085
DOI: 10.1016/s0738-081x(99)00093-0 -
Clinical Pharmacokinetics 1986Dapsone (DDS) has for about 4 decades been the most important antileprosy drug. Concentrations of dapsone and its monoacetyl metabolite, MADDS, can be determined in... (Review)
Review
Dapsone (DDS) has for about 4 decades been the most important antileprosy drug. Concentrations of dapsone and its monoacetyl metabolite, MADDS, can be determined in biological media by high-performance liquid chromatography. After oral administration, the drug is slowly absorbed, the maximum concentration in plasma being reached at about 4 hours, with an absorption half-life of about 1.1 hours. However, the extent of absorption has not been adequately determined. The elimination half-life of dapsone is about 30 hours. The drug shows linear pharmacokinetics within the therapeutic range and the time-course after oral administration fits a 2-compartment model. The concentration-time profile of dapsone after parenteral administration is reviewed. Of clinical importance is the development of a new long acting injection, which permits monthly supervised administration as recommended by the World Health Organization. Following dapsone injection in gluteal subcutaneous adipose tissue, a sufficiently sustained absorption for this purpose has been reported. Dapsone is about 70 to 90% protein bound and its monoacetylated metabolite (MADDS) is almost completely protein bound. The volume of distribution of dapsone is estimated to be 1.5 L/kg. It is distributed in most tissues, but M. leprae living in the Schwann cells of the nerves might be unaffected. Dapsone crosses the placenta and is excreted in breast milk and saliva. Dapsone is extensively metabolised. Dapsone, some MADDS and their hydroxylated metabolites are found in urine, partly conjugated as N-glucuronides and N-sulphates. The acetylation ratio (MADDS:dapsone) shows a genetically determined bimodal distribution and allows the definition of 'slow' and 'rapid' acetylators. As enterohepatic circulation occurs, the elimination half-life of dapsone is markedly decreased after oral administration of activated charcoal. This permits successful treatment in cases of intoxication. The daily dose of dapsone in leprosy is 50 to 100mg, but varies from 50 to 400mg in the treatment of other dermatological disorders. In malaria prophylaxis, a weekly dose of 100mg is used in combination with pyrimethamine. Side effects are mostly not serious below a daily dose of 100mg and are mainly haematological effects. The dapsone therapeutic serum concentration range can be defined as 0.5 to 5 mg/L. Alcoholic liver disease decreases the protein binding of dapsone; coeliac disease and dermatitis herpetiformis may delay its oral absorption and severe leprosy has been reported to affect the extent of absorption.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Dapsone; Humans; Kinetics
PubMed: 3530584
DOI: 10.2165/00003088-198611040-00003 -
IARC Monographs on the Evaluation of... 1980
Review
Topics: Animals; Chemical Phenomena; Chemistry; Cocarcinogenesis; Dapsone; Female; Humans; Male; Mice; Mutagenicity Tests; Neoplasms, Experimental; Rats; Terminology as Topic
PubMed: 7009401
DOI: No ID Found -
The Journal of Emergency Medicine 1994Two patients with dapsone intoxication, an adult and a 16-month-old child, are reported. Both developed symptomatic methemoglobin concentrations, of 35% and 37%,... (Review)
Review
Two patients with dapsone intoxication, an adult and a 16-month-old child, are reported. Both developed symptomatic methemoglobin concentrations, of 35% and 37%, respectively, and improved with intravenous methylene blue. Methemoglobin levels subsequently rose in both cases to 25% at 24 and 37 hours, respectively. The recurrence of elevated methemoglobin levels resulted from either continued absorption of dapsone or its toxic metabolite from the gastrointestinal tract. Both patients were begun on serial oral activated charcoal and the child received a second methylene blue treatment. During the intoxication, serum hemoglobin concentrations dropped 2 gm with an increase in the reticulocyte count. Review of 20 cases of dapsone overdose from the literature showed that the major toxic manifestations are methemoglobinemia and hemolysis. Delayed sulfhemoglobinemia, reported in only one case, resolved spontaneously. The treatment of dapsone intoxication is intravenous methylene blue for symptomatic methemoglobinemia, gastric decontamination, and early administration of serial oral activated charcoal. Hemolysis is mild but transfusions may be required for patients with a glucose-6-phosphate dehydrogenase deficiency.
Topics: Adolescent; Charcoal; Dapsone; Emergencies; Female; Humans; Infant; Methemoglobinemia; Methylene Blue
PubMed: 8040592
DOI: 10.1016/0736-4679(94)90277-1 -
Journal of the American Academy of... Sep 2001In their 60-year history, dapsone and the sulfones have been used as both antibacterial and anti-inflammatory agents. Dapsone has been used successfully to treat a range... (Review)
Review
In their 60-year history, dapsone and the sulfones have been used as both antibacterial and anti-inflammatory agents. Dapsone has been used successfully to treat a range of dermatologic disorders, most successfully those characterized by abnormal neutrophil and eosinophil accumulation. This article reviews and updates the chemistry, pharmacokinetics, clinical application, mechanism of action, adverse effects, and drug interactions of dapsone and the sulfones in dermatology.
Topics: Anti-Infective Agents; Dapsone; Drug Interactions; Humans; Skin Diseases; Sulfones
PubMed: 11511841
DOI: 10.1067/mjd.2001.114733 -
The British Journal of Dermatology Nov 1993Dapsone is useful in the treatment of a number of inflammatory conditions which are characterized by neutrophil infiltration. It is the drug of choice for suppression of... (Review)
Review
Dapsone is useful in the treatment of a number of inflammatory conditions which are characterized by neutrophil infiltration. It is the drug of choice for suppression of the symptoms of dermatitis herpetiformis, as it inhibits the process by which neutrophils leave the circulation and migrate to lesional sites. It also prevents the tissue destruction normally caused by the neutrophils' respiratory burst. Although dapsone can cause a number of serious idiosyncratic reactions, such as agranulocytosis, tolerance of the drug at higher doses is more usually determined by its haematological side-effects of methaemoglobinaemia and haemolysis. These effects are due entirely to the hepatic N-hydroxylation of dapsone to a hydroxylamine metabolite, some of which escapes from the liver and rapidly enters red cells. Attempts have been made to counteract the haemotoxic effects of the metabolite by the use of antioxidants such as vitamins E and C. Recently, the co-administration of a metabolic inhibitor such as cimetidine has been shown to reduce significantly dapsone-dependent methaemoglobinaemia, without any change in drug efficacy. It remains to be seen if this approach will be adopted clinically, to improve patient tolerance of high dapsone dosage.
Topics: Dapsone; Erythrocytes; Humans; Leukocytes; Liver; Neutrophils
PubMed: 8251346
DOI: 10.1111/j.1365-2133.1993.tb00476.x -
Clinical Infectious Diseases : An... Jul 1998Dapsone, with or without trimethoprim or pyrimethamine, has strong anti-Pneumocystis carinii activity, as demonstrated by in vitro methods, animal studies, and clinical... (Review)
Review
Dapsone, with or without trimethoprim or pyrimethamine, has strong anti-Pneumocystis carinii activity, as demonstrated by in vitro methods, animal studies, and clinical trials. The drug blocks folic acid synthesis of P. carinii by inhibition of dihydropteroate synthetase activity. Dapsone is efficiently absorbed (70%-80%) from the gastrointestinal tract, reaches peak serum concentration in 2-6 hours, and is adequately distributed to the fluid of the alveolar spaces. Synergistic effects against P. carinii are noted when trimethoprim is combined with dapsone. This combination is recommended for therapeutic use for P. carinii pneumonia (PCP) as an alternative for patients who cannot take trimethoprim-sulfamethoxazole (TMP-SMZ). Evidence from more than 40 studies of dapsone as prophylaxis for PCP in AIDS patients shows that dapsone, either alone or in combination with pyrimethamine, is as effective as aerosolized pentamidine or atovaquone but slightly less effective than TMP-SMZ. Adverse effects include rash, anemia, methemoglobinemia, agranulocytosis, and hepatic dysfunction. Desensitization can be accomplished with many cases. Dapsone is the most cost-effective prophylaxis currently available for PCP.
Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotic Prophylaxis; Clinical Trials as Topic; Dapsone; Disease Models, Animal; Drug Therapy, Combination; Evaluation Studies as Topic; Humans; Pneumonia, Pneumocystis
PubMed: 9675476
DOI: 10.1086/514626