Dapsone adverse effects

The documentation is very limited. It is likely that the probenecid will raise the serum levels of dapsone given long-term. The importance of this is uncertain, but the extent of the rise and the evidence that the haematological toxicity of dapsone may be related to dapsone levels suggests that it may well have some clinical importance. It would therefore seem prudent to monitor for dapsone adverse effects if probenecid is also given. 

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). 

Dapsone (Avlosulfon) is a member of a class of chemical agents known as the sulfones. Dapsone is especially effective against M. leprae and is used with rifampin as the primary method of treating leprosy. Dapsone appears to exert its antibacterial effects in a manner similar to that of the sulfonamide drugs that is, dapsone impairs folic acid synthesis by competing with PABA in bacterial cells. Primary adverse effects associated with dapsone include peripheral motor weakness, hypersensitivity reactions (skin rashes, itching), fever, and blood dyscrasias, such as hemolytic anemia. 

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... 

DAPSONE ANTIVIRALS-ZIDOVUDINE Possible t adverse effects when co administered with zidovudine Uncertain possible T bioavailability of zidovudine Use with caution monitor for peripheral neuropathy... 

The sulfone acedapsone (rINN) (4,4 -diacetyldiaminodi-phenylsulfone, DADDS) is the diacetyl derivative of dapsone with a long half-life (7). However, its plasma concentrations are much lower than those of dapsone and it could enhance the emergence of resistant strains of Mycobacterium leprae. Its adverse effects are similar to those of dapsone, which it can replace if gastrointestinal symptoms become severe. It is available in an enteric-coated formulation, given in a dosage of 330 mg/day. 

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... 

In France, dapsone is available in combination with ferrous oxalate as Disulone (Aventis), and in 1983-98, 249 adverse reactions were reported to French pharma-covigilance centers, mainly blood dyscrasias (often neutropenia and agranulocytosis, rarely hemolysis and anemia) (11). Five patients died three of them had septicemia secondary to agranulocytosis. There were 29 cases of dapsone syndrome, 39 skin reactions, 27 cases of hver damage, and 27 cases of neurological and psychiatric adverse effects. Patients taking dapsone need to be under close medical supervision for early recognition of adverse reactions. 

Janndice and hepatitis can occnr as part of the sulfone syndrome with dapsone (26). Previons liver damage can predispose to serions hepatic or other adverse effects. 

Dapsone passes into the breast milk, with a milk to plasma AUC ratio of 0.22 0.45 (36). Assuming a daily milk ingestion of 1 liter by the infant, the maximum percentage of the maternal dose in milk was 14% over 9 days. Usually no adverse effects are noted in the newborn, unless there is G6PD deficiency. 

Previous liver damage predisposes to adverse effects during dapsone therapy (41). 

Levamisole has been used experimentally in leprosy, particularly in combination with dapsone. This combination was used in a documented series of Indian patients, some currently lepromatous and others in the course of a leprosy reaction (1). When using doses sufficient to provide as good an effect as that obtained with clofazimine + dapsone in a comparison group, adverse effects were limited to gastrointestinal intolerance (which was usually mild), affecting only five of the 30 patients treated an incidental case developed pyrexia. 

Zidovudine is rapidly absorbed from the G1 tract with peak serum concentrations occurring within 30 to 90 minutes. It binds to plasma proteins to the extent of 35 to 40%. Zidovudine is rapidly metabolized in the liver to the inactive 3 -azido-3 -deoxy-5 -0-beta-D-glucopyranuronosylthymi-dine (GAZT), which has an apparent elimination half-life of 1 hour. Zidovudine undergoes glomerular filtration and active tubular secretion. Coadministration of zidovudine with agents such as dapsone, pentamidine, amphotericin B, flucytosine, vincristine, vinblastine, adriamycin, and interferon with potential to cause nephrotoxicity or cytotoxicity to hematopoietic elements, enhance its risk of adverse effects. Probenecid will inhibit the renal excretion of zidovudine. 

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 ]. 

Management Cimetidine The use of cimeti-dine to reduce dapsone-dependent hematological adverse effects in a patient with mucous membrane pemphigoid has been reported [58 ]. 

Rifampicin toxicity is becoming of greater importance in the treatment of leprosy. Several studies have recently been reported in which rifampicin was used in combination with Isoprodian, a combination of dapsone, isoniazid and prothionamide. The commonest adverse effects observed on this combination are gastrointestinal disturbances and mild hepatitis, manifested either as abnormalities in biochemical parameters or clinically by jaundice. One case of exfoliative dermatitis was reported from a trial carried out in South India (35 ). 

Two cases of alopecia due to ethionamide administration were reported from India (44 ). In both cases gradual recovery followed withdrawal of the compound. Two reports from Germany (45, 46 ) referred to the use of isoprodian, a combination of isoniazid, prothionamide and dapsone, in the treatment of pulmonary tuberculosis. In both cases the adverse effects were stated to be minimal, and although in one series a transient faU in haemoglobin level and erythrocyte count was noted, values returned to normal with continued therapy. If this work is substantiated it seems likely that this particular combination wiU be more widely used, especially as, in combination with... 

There has been some overlap in recent publications relating to adverse effects of drugs used in leprosy and tuberculosis because of the increasing use in leprosy of rifampicin and isoprodian which contains isoniazid, prothionamide and dapsone. Publications relating to adverse effects produced by a combination of rifampicin and isoprodian have already been referred to in the section dealing with drugs used in tuberculosis. 

A useful review of the adverse effects of Dapsone by Graham (55 ) considered its potential for producing haemolytic anaemia and methaemogjobinaemia in some detail. Particular attention was paid to the role played by G6PD deficiency. 

The adverse CNS effects of cycloserine are increased by isoniazid. Dapsone + Clofozimine... 

Dapsone 100 mg daily had no effect on the pharmacokinetics of a single 200-mg dose of zidovudine in 8 TUV-positive subjects. In a further study, which considered the safety of dapsone in combination with zidovudine, dapsone was shown to increase the risk of zidovudine-related blood dys-crasias. Therefore it would seem that dapsone and zidovudine can be given concurrently, but monitoring for an increase in adverse events would seem advisable. 

Observational studies In a retrospective study of the effects of dapsone 100 mg/day for at least 30 days in 52 adults with immune thrombocytopenic purpura, in whom first-line therapy with glucocorticoids had failed [43 ]. Dapsone resulted in a sustained increase in platelet count in 23 patients after a median follow-up of 21 months and none of those who responded required splenectomy compared with 20 of the other 29. Dapsone-related adverse events were mild and were promptly reversed by withdrawal. 

---