Clinical management of Tacrolimus drug interactions in renal transplant patients

Effect of micafungin on cytochrome P450 3A4 and multidrug resistance protein 1 activities, and its comparison with azole antifungal drugs

“…In this study, we found that ketoconazole, itraconazole and, possibly, miconazole had inhibitory effects on both CYP3A4 metabolic activity and MDR1 transport activity; fluconazole and micafungin had only slight effects on CYP3A4, and amphotericin B had no effect. The pharmacokinetic profiles of two widely used immunosuppressants, ciclosporin and tacrolimus, were reported to be altered by co-administration of ketoconazole in transplant patients (Foradori et al 1998;McLachlan & Tett 1998;Moreno et al 1999). These interactions were discussed in terms of the inhibition of CYP3A4 metabolic activity, but the blocking of MDR1 transport activity would also be a factor, since ciclosporin and tacrolimus are also substrates for MDR1.…”

Decreased Tacrolimus Levels after Administration of Rifampin to a Patient with Renal Transplant

“…Therapeutic tacrolimus levels were achieved shortly after the switch. Moreno and others 15 described a similar case of subtherapeutic tacrolimus levels despite a 2-fold dose increase following initiation of rifampin treatment. Therapeutic tacrolimus levels were achieved 6 days after the rifampin was discontinued and replaced with pyrazinamide.…”

“…Five of the 6 published cases involved patients who had undergone renal transplant. 12,13,[15][16][17] The time between transplant and occurrence of the tacrolimus-rifampin interaction ranged from 4 days to 7 years. As expected, larger baseline doses of tacrolimus were required to meet higher target tacrolimus trough levels in patients whose transplant surgery had occurred more recently.…”

“…15,16 López-Montes and others 16 described a nearly 4-fold increase in the tacrolimus dose following initiation of antituberculosis treatment with rifampin in a Hispanic patient who had undergone renal transplant. Despite the increased dosage, tacrolimus trough levels remained subtherapeutic (3.7-5.5 ng/mL; target range 10-15 ng/mL).…”

“…7 Rifampin is known to affect the metabolism of tacrolimus through induction of CYP3A4 8 and, to a far lesser extent, CYP3A5. 9,10 Although the interaction between these drugs is in theory well recognized, its clinical significance in adults has been reported for only 4 Asian patients, [11][12][13][14] 2 Hispanic patients, 15,16 and one Kuwaiti patient. 17 To our knowledge, this interaction has not been described previously for adult white patients, the population with the lowest frequency of CYP3A5*1 allele carriers.…”