Fluconazole Dapsone

Drugs that may affect zidovudine include acetaminophen, atovaquone, bone marrow suppressive/cytotoxic agents (eg, adriamycin, dapsone), clarithromycin, doxorubicin, fluconazole, ganciclovir, methadone, nelfinavir/ritonavir, phenytoin, probenecid, ribavirin, rifamycins, stavudine, trimethoprim, and valproic acid. 

Figure 17.4 Compounds which are mentioned throughtout the chapter and numbered in the main text as follows (1) DMZ, (2) diclofenac, (3) flurbiprofen, (4) warfarin, (5) fluconazole, (6) coumarin, (7) dapsone, (8) retinoic acid, (9) arachidonic acid, (10) troglitazone, (11) fluvastatin, (12) cerivastatin, (13) taxol, (14) gemfibrozil, (15) verapamil, (16) amodiaquine, (17) amiodarone, (18) metyrapone, (19) progesterone, (20) testosterone, (21) erythromycin, (22) ketoconazole, (23) nicotine, (24) IV -Nitrosonor-nicotine, (25) 4-(Methylnitrosamino)-l-(3-pyridyl)-l-butanone...

When the CD4 count of this patient fell below 200/pL. prophylaxis against pneumocystis pneumonia was instituted. The currently recommended therapy is double-strength trimethoprim-sulfamethoxazole or dapsone. Alternative prophylactic regimens include aerosolic pentamidine, dapsone plus pyrimethamine, and atovaquone. Primary prophylaxis against toxoplasmosis is normally recommended with CD4 cell counts below 100/pL in AIDS patients who are IgG antibody-positive. Trimethoprim-sulfamethoxazole plus dapsone is also prophylactic against toxoplasmosis. With the continued decline in CD4 cells, exacerbation of candidal infection may occur despite use of clotrimazole troches, necessitating treatment with fluconazole or itraconazole. 

Winter TrqmeU CB, Slattery JT, Jacobson M, Greenspan DL, Hootai TM, Unadkat JD. The effect of claritiiFcniycin, fluconazole, and rifabutin on dapsone hydroxylamine formation in individuals with human immunodeficiency virus infection (AACTG 283). Clin Pharmacol 77 r (2004) 76,579-87. 

Fluconazole decreases the production of the toxic metabolite of dapsone, and might therefore reduce the incidence of adverse reactions to dapsone. 

Twelve HIV-positive patients were given dapsone 100 mg daily for 2 weeks and then in random order either fluconazole 200 mg daily, rifabutin 300 mg daily or fluconazole with rifabutin, each for 2 weeks. Dapsone pharmaeokineties were unaffected by fluconazole. However, fluconazole inhibited the production of the jV-hydroxylamine metabolite of dapsone (AUC, urinary recovery, and formation clearance reduced by about 50%). ... 

Hydroxylamine is assumed to be responsible for the haematological toxicity of dapsone (methaemoglobinaemia). The findings of this study suggest that the production of this metabolite is mediated via the cytochrome P450 isoenzyme CYP2C9, which fluconazole inhibits. 

On the basis of these results, fluconazole would not be expected to alter the efficacy of dapsone, but might reduce its toxicity. Further study is needed to assess this potential. 

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