RESUMO
Tacrolimus, an immunosuppressor indicated in solid organ transplantation, has a large inter- and intra-individual variability, a narrow therapeutic index and numerous drug interactions. It is metabolized in the enterocytes and the liver by CYP3A4. Association to enzymatic inhibitors like azole antifungals increase its blood levels and may increase its toxicity directly related to an increase of its blood concentration. We describe in this study four cases of drug interaction between tacrolimus and azole antifungals. These patients were renal transplanted in 2009 and treated with tacrolimus. For fungal infections, azole antifungals were added in these cases. Three were treated by fluconazole and one with voriconazole. By the risk of drug interaction occurrence, tacrolimus doses were decreased by two thirds in one case and by the third in the second case. This association leaded to an increase in tacrolimus concentration (1.33 to 2.45 times the initial concentration) in all patients. Side effects observed in our patients were liver toxicity in two cases, an increase in serum creatinin and an hyperglycemia were notified in all patients. An increase in tacrolimus concentration with about 1.33 times was observed in the case receiving fluconazole intravenously at the dose of 100mg one day out of two and with a tacrolimus doses decrease by two thirds. The patient had impaired renal function before fluconazole introduction. This suggests that in the presence of renal function alteration even low doses of fluconazole with an inhibition of only liver CYPA3A4 (without inhibition of intestinal CYP3A4 and P-gp) leads to an increase on tacrolimus concentration and occurrence of adverse effects related to tacrolimus toxicity. With the co-administration of azole antifugals, it is recommended to adjust tacrolimus dosage on the basis of therapeutic tacrolimus blood monitoring in order to maintain tacrolimus concentration in therapeutic range and to avoid adverse toxic effects.
RESUMO
OBJECTIVES: Actinomycosis is a rare little known granulomatous suppurative disease, more common in women, aided by the use of contraceptive purposes intrauterine device (IUD). Pelvic location is the rarest with an extension to adjacent organs making preoperative diagnosis difficult and misleading clinical presentation. Early diagnosis of this affection determines the therapeutic strategy and avoids mutilating interventions especially in young women. METHODS: We reviewed the record of women who consulted the department of obstetrics and gynecology at Ben Arous hospital (Tunisia) between January 2003 and December 2013 for a pelvic pain syndrome and in whom diagnosis of actinomycosis was suspected by clinical and imaging and confirmed by pathology. RESULTS: Eight cases of gynecologic abdominopelvic actinomycosis were diagnosed during the study period. Seven patients were carriers of an intrauterine device, with an average duration of 5 years wearing. Functional signs were essentially pelvic pain and fever. Physical examination of patients mainly showed two clinical presentations: a pelvic tumor syndrome or abdominopelvic and an array of pelvic abscess or pelvic inflammatory disease. Radiological investigations were allowed to suspect the diagnosis of actinomycosis only in one patient, in whom percutaneous biopsy confirmed the histological diagnosis without resorting to a surgical procedure. Operative procedures performed were varied as appropriate. The diagnosis of actinomycosis was made by pathology without any cases of bacterial isolation. All patients received antibiotic treatment with penicillin. The subsequent evolution was favorable. CONCLUSION: The diagnosis of actinomycosis should be considered in any invasive abdominal mass of neoplastic appearance and in case of table of genital infection especially in patients bearing IUD for 5 years or more.