Dapsone dosage

Trimethoprim has been reported to decrease the therapeutic effect of cyclosporine with a concomitant increased risk of nephrotoxicity. Increased levels of dapsone, warfarin, methotrexate, zidovudine, and sul-fonylureas may occur when given together with trimethoprim dosages of these drugs should be modified and the patient monitored accordingly. 

Rifampin (see earlier discussion) in a dosage of 600 mg daily is highly effective in lepromatous leprosy. Because of the probable risk of emergence of rifampin-resistant M leprae, the drug is given in combination with dapsone or another antileprosy drug. A single monthly dose of 600 mg may be beneficial in combination therapy. 

Interactions. Rifampicin is a powerful enzyme inducer and speeds the metabolism of numerous drugs, including warfarin, steroid contraceptives, narcotic analgesics, oral antidiabetic agents, phenytoin and dapsone. Appropriate increase in dosage, and alternative methods of contraception, are required to compensate for increased drug metabolism (see also paracetamol overdose, p. 287). 

Dapsone is 4,4-diaminodiphenylsulfone (DDS, avlosul-fone, disulfone) (SEDA-17, 352). It is a bacteriostatic antileprosy drug with a sulfonamide-like structure. The dosage should be 50-100 mg/day in adults (1). In children aged 3-5 years, the dosage should be reduced according to weight to, for example, 25 mg/day (2). 

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. 

Neuropathy has not been reported in patients with leprosy taking the usually recommended dosage of 100 mg/day. Isolated cases of dapsone-induced peripheral neuropathy, including motor and minor sensory defects, have been published (15,16). The clinical characteristics include a motor neuropathy affecting the extremities with onset within 5 years after the start of dapsone therapy in doses of over 300 mg/day. Complete recovery from the neuropathy almost always occurs after the dose is reduced or the drug is withdrawn. 

Linear IgA dermatosis with erythema multiforme-Uke clinical features has been reported in a 19-year-old man several days after completion of a 5-day-course treatment with sulfadimethoxine (500 mg bd) for a flu-like syndrome (134). Treatment with methylprednisolone (150 mg) with gradnal dosage rednction was started. Slow improvement was followed by a flare-up after reduction to 80mg/day. Therapy was changed to dapsone 100 mg/day, and there was a dramatic improvement. 

It appears that dapsone is a safe drug when used in standard dosage. Perhaps, renal involvement should be watched for when administering dapsone to patients with G6PD deficiency that could develop hemolytic complications [207] and in patients that present with dapsone hypersensitivity syndrome. 

The interaction between dapsone and rifampicin is established but of uncertain clinical importance. Concurrent use should be well monitored to confirm that treatment is effective. It may be necessary to raise the dosage of dapsone. It has been pointed out that there is the risk of treatment failures for Pneumocystis pneumonia as well as for leprosy. Also be alert for any evidence of methaemoglobinaemia. 

Although there is less information, rifabutin appears to interact similarly to rifampicin. When dapsone is given with rifabutin, the dosage of dapsone may need to be increased, but this may increase exposure to the potentially toxic hydroxylamine metabolite. ... 

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