Hepatic: decreased tacrolimus clearance with serum bilirubin >2 mg/dL -> lower dose may be considered
Renal: decrease dose
Oliguric Renal Transplant: start tacrolimus between 6-24 hrs post-transplant (although may be delayed until graft function recovers)
Hemodialysis: tacrolimus is not cleared by hemodialysis, no dose adjustment is necessary
Peritoneal Dialysis: unlikely to affect tacrolimus clearance
Drug Interactions
Interaction with Mycophenolate Mofetil (Cellcept) (see Mycophenolate Mofetil, [[Mycophenolate Mofetil]])
Tacrolimus Does Not Interfere with the Enterohepatic Circulation of Mycophenolate (Like Cyclosporine A Does): therefore, crossover from cyclosporine A to tacrolimus (with concomitant mycophenolate mofetil administration) may result in higher mycophenolate mofetil concentrations
Drugs/Supplements/Foods Which Decrease Tacrolimus Level
Carbamazepine (Tegretol) (see Carbamazepine, [[Carbamazepine]]): induces CYP3A enzyme
Caspofungin (see Caspofungin, [[Caspofungin]]): induces CYP3A enzyme
Phenobarbital (see Phenobarbital, [[Phenobarbital]]): induces CYP3A enzyme
Phenytoin (Dilantin) (see Phenytoin, [[Phenytoin]]): induces CYP3A enzyme
Concomitant phenytoin and tacrolimus administration may also increase phenytoin levels
Rifampin (see Rifampin, [[Rifampin]]): induces CYP3A enzyme
St. John’s Wort (see St. John’s Wort, [[St Johns Wort]]): induces CYP3A enzyme
Drugs/Supplements/Foods Which Increase Tacrolimus Level
Epidemiology: has bee reported (particularly with high tacrolimus levels)
Diagnosis
Echocardiogram: concentric hypertrophy of left ventricular posterior wall and intraventricular septum
Treatment: reversible with discontinuation of tacrolimus
Q-T Prolongation/Torsade (see Torsade, [[Torsade]])
Epidemiology: with definite association with torsade
Endocrinologic Adverse Effects
Diabetes Mellitus (DM) (see Diabetes Mellitus, [[Diabetes Mellitus]])
Epidemiology: new-onset diabetes mellitus has been reported
Drug-Induced Hyporeninemic Hypoaldosteronism (see Hypoaldosteronism, [[Hypoaldosteronism]])
Physiology: drug-induced hypoaldosteronism
Decreased renin release -> decreased secretion of aldosterone (i.e. hyporeninemic hypoaldosteronism) -> inhibition of potassium secretion in the renal collecting duct
Decreased responsiveness to aldosterone (likely due to decreased mineralocorticoid receptor expression) -> inhibition of potassium secretion in the renal collecting duct
Epidemiology: all cases had risk factors including parvovirus B19 infection, underlying disease, or concomitant medications which have been associated with pure red cell aplasia
Infectious Adverse Effects
Cytomegalovirus (CMV) (see Cytomegalovirus, [[Cytomegalovirus]])
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Polyomaviruses
BK Virus (BK Polyomavirus) (see BK Virus, [[BK Virus]])
Polyomavirus-Associated Nephropathy (PVAN)
JC Virus (JC Polyomavirus) (see JC Virus, [[JC Virus]])
Physiology: drug-induced hypoaldosteronism (see above)
Other Adverse Effects
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References
Frequency of hyperkalemia in recipients of simultaneous pancreas and kidney transplants with bladder drainage. Transplantation 1996;62: 1174-5 [MEDLINE]
Cyclosporine a and FK506 inhibit transcriptional activity of the human mineralocorticoid receptor: a cell-based model to investigate partial aldosterone resistance in kidney transplantation. Endocrinology. 2002 May;143(5):1932-41 [MEDLINE]
Hyponatremia and hyperkalemia are more frequent in renal transplant recipients treated with tacrolimus than with cyclosporin. Nephrol Dial Transplant. 2004 Feb;19(2):444-50 [MEDLINE]
Delayed effect of grapefruit juice on pharmacokinetics and pharmacodynamics of tacrolimus in a living-donor liver transplant recipient. Drug Metab Pharmacokinet. 2006 Apr;21(2):122-5 [MEDLINE]
Fludrocortisone is effective in the management of tacrolimus-induced hyperkalemia in liver transplant recipients. Transplant Proc. 2011 Sep;43(7):2664-8. doi: 10.1016/j.transproceed.2011.07.006 [MEDLINE]
Calcineurin inhibitor nephrotoxicity: a review and perspective of the evidence. Am J Nephrol. 2013;37(6):602-12. doi: 10.1159/000351648. Epub 2013 Jun 18 [MEDLINE]
Role of fludrocortisone in the management of tacrolimus-induced hyperkalemia in a renal transplant recipient. Saudi J Kidney Dis Transpl. 2014 Jan;25(1):149-51 [MEDLINE]
Drug-induced thrombotic microangiopathy: a systematic review of published reports. Blood. 2015 Jan 22;125(4):616-8. doi: 10.1182/blood-2014-11-611335. Epub 2014 Nov 20 [MEDLINE]