Tacrolimus dosage

MYCOPHENOLATE CORTICOSTEROIDS L plasma concentrations of mycophenolate and risk of transplant rejection Corticosteroids induce UGT enzymes and multidrug resistance associated protein 2, involved in disposition of mycophenolate Intervention to prevent rejection is mandatory, t tacrolimus dosage to maintain therapeutic blood levels (see below). As important is to monitor levels following steroid withdrawal to prevent adverse outcomes... 

A 38-year-old woman was switched from ciclosporin to tacrolimus 44 days after kidney and pancreas transplantation and 17 days later had sudden hearing loss with tinnitus. Her tacrolimus blood concentration 3 days later was 28 ng/ml and peaked at 35 ng/ml 8 days later. Audiograms showed bilateral hearing loss—80% for speech perception and mild to moderate sensorineural hearing loss. Her hearing improved on tacrolimus dosage reduction and after the tacrohmus blood concentration reached 15 ng/ml. 

There were higher than expected serum tacrohmus concentrations in most patients, and the highest concentrations were detected 1.6 days before the peak serum creatinine. However, renal histological lesions were independent of tacrolimus dosage or blood concentrations (77). 

A 10-fold increase in tacrolimus dosage was required in a 61-year-old patient with a renal transplant who took concomitant rifampicin (111). 

The interaction between tacrolimus and fluconazole is established, clinically important and can develop rapidly (within 3 days). The authors of one of the reports say that up to 200 mg of oral fluconazole daily can be used safely and effectively provided that the tacrolimus dosage is reduced by half One study specifically examining dose adjustments suggests that fluconazole can be safely used if 60% of the original tacrolimus dose is given. If tacrolimus is given intravenously, no clinically important interaction appears to occur. ... 

A 1-year retrospective study of two groups of liver transplant patients found that in the 22 patients taking nifedipine 30 or 60 mg daily there was a 55% increase in the tacrolimus blood levels after 1 month. By 6 months the tacrolimus dosage had been reduced by a total of 25.5% in the nifedipine group and by 12 months by 31.4% when compared with the group not taking nifedipine. The nifedipine group also had improved renal function (lowered serum creatinine). ... 

These appear to be the only reports of this interaction, but it is consistent with the known metabolic characteristics of both drugs and therefore it is expected to be an interaction of general importance. Monitor the outcome closely if systemic chloramphenicol is given to any patient taking tacrolimus, being alert for the need to reduce the tacrolimus dosage. It seems... 

Direct information seems to be limited to these case reports. However, it would be prudent to closely monitor the effects of adding clarithromycin or erythromycin in any patient, being alert for the need to reduce the tacrolimus dosage to avoid nephrotoxicity. The manufaeturers prediet that josamycin and troleandomycin will internet similarly and so the same precautions would also be appropriate. The manufaeturers of telithromy-cin also recommend close monitoring of tacrolimus levels and reducing the tacrolimus dose as required. Most other maerolides would also be expected to interact although they do not all behave identically. 

A number of liver transplant patients have needed markedly increased tacrolimus dosages when rifampicin (rifampin) was added. A pharmacokinetic study has shown that rifampicin increases the clearance and decreases the bioavailability of intravenous and oral tacrolimus. Rifabutin is unlikely to interact to the same extent, but given the magnitude of the interaction with rifampicin, caution is still warranted. 

Direct information about rifabutin seems to be lacking, but any interaction with tacrolimus is likely to be much less marked than with rifampicin because its enzyme-inducing effects are considerably less. Nevertheless until the situation is clear it would be prudent to closely monitor concurrent use with any rifamycin, being alert for the need to raise the tacrolimus dosage. 

Tacrolimus The co-prescription of posaconazole with tacrolimus has been evaluated in 14 lung transplant recipients with cystic fibrosis. Posaconazole inhibited CYP3A4-mediated tacrolimus metabolism, resulting in a threefold reduction in tacrolimus dosage requirements f4T]. 

Carbamazepine In a pharmacokinetic investigation in a woman in her 40s, tacrolimus trough concentrations fell within 7 days of treatment with carbamazepine 200 mg/day, and a 30-40% increase in tacrolimus dosage was required to maintain... 

HRT (Estreva 0.1%) comprising estradiol 0.5 mg/day (one-third of the recommended dose). The serum creatinine fell and eGFR rose to 44 ml/minute/m 2 weeks after a progressive 60% reduction in tacrolimus dosage (trough concentration 6.4 ng/ml). 

Chen SY, Li JL, Meng FH, Wang XD, Liu T, li J, et al. Individualization of tacrolimus dosage basing on cytochrome P4503A5 polymorphism -a prospective, randomized, controlled study. Clin Transplant 2013 May-Jun 27(3) E272-81. PubMed PMID 23432535. Epub 2013/02/26. eng. 

---