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Current Drug Safety

Author(s): Mouna B. Sassi, Emna Gaies, Issam Salouage, Sameh Trabelsi, Mohamed Lakhal and Anis Klouz

DOI: 10.2174/1574886310666150512105459

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Involvement of CYP 3A5 In the Interaction Between Tacrolimus and Nicardipine: A Case Report

Page: [254 - 256] Pages: 3

  • * (Excluding Mailing and Handling)

Abstract

Tacrolimus is a calcineurin inhibitor primarily metabolized by CYP3A4 and secondarily by CYP3A5. Several drugs can modify tacrolimus blood levels as calcium channel blockers (CCBs). Interaction with nicardipine was reported in some cases.

A man with a history of malignant arterial hypertension treated with nicardipine, underwent kidney transplantation. After transplantation, he was treated with tacrolimus, mycophenolate mofetil and corticoids. Therapeutic drug monitoring of tacrolimus was done regularly showing a mean trough concentration (C0) of 24.39 ng/mL with some concentrations reaching 52 ng/mL. After changing nicardipine by prazosine, the first tacrolimus C0 after stopping nicardipine was 3.2 ng/mL.

Increase of tacrolimus trough concentrations is due to the inhibition of CYP3A4. Very high levels of tacrolimus suggest the non expression of CYP3A5. Thus, because of the possible lack of the secondary pathway, therapeutic drug monitoring of tacrolimus is highly recommended at the introduction of CCBs and also at its stopping.

Keywords: CYP 3A5, drug interaction, nicardipine, renal transplantation, tacrolimus, therapeutic drug monitoring.

[1]
Catic-Djordjevic A, Velickovic-Radovanovic R, Stefanovic N, Tatjana Cvetkovic T. Interactions between Tacrolimus and Metronidazole in a renal transplant patient. Cent Eur J Med 2012; 7(5): 587-90.
[2]
Brunet M, Torregrosa JV, Oppenheimer F, Corbella J. Therapeutic Drug Monitoring of Tacrolimus in Kidney Transplantation: 9-Month Follow–Up. Transplant Proc 1998; 30: 4068-9.
[3]
Mignat C. Clinically Significant Drug Interactions with New Immunosuppressive Agents. Drug Saf 1997; 16: 267-78.
[4]
Seifeldin RA, Marcos-Alvarez A, Gordon FD, Jenkins RL. Nifedipine interaction with tacrolimus in liver transplant recipients. Ann Pharmacother 1997; 31: 571-5.
[5]
Kuypers DR, Neumayer HH, Fritsche L, Budde K, Rodicio JL, Vanrenterghem Y. Calcium channel blockade and preservation of renal graft function in cyclosporine-treated recipients: a prospective randomized placebo-controlled 2-year study. Transplantation 2004; 78: 1204-11.
[6]
Xue W, Song Y, Tian P, et al. The effects of diltiazem in renal transplantation patients treated with cyclosporine A. J Biomed Res 2010; 24: 317-23.
[7]
Seifeldin R, Marcos-Alvarez A, Lewis D, et al. Effect of Nifedipine on Renal Function in Liver Transplant Recipients Receiving Tacrolimus. Clinic Therap 1996; 18: 491-6.
[8]
Hooper DK, Carle AC, Schuchter J, Goebel J. Interaction between tacrolimus and intravenous nicardipine in the treatment of post-kidney transplant hypertension at pediatric hospitals. Pediatr Transplant 2011; 15: 88-95.
[9]
Hooper D, Fukuda T, Gardiner R, et al. Risk of Tacrolimus Toxicity in CYP3A5 Nonexpressors Treated With Intravenous Nicardipine After Kidney Transplantation. Transplantation 2012; 93: 806-12.
[10]
Anglicheau D, Flamant M, Schlageter MH, et al. Pharmacokinetic interaction between corticosteroids and tacrolimus after renal transplantation. Nephrol Dial Transplant 2003; 18: 2409-14.