Interaction Between Omeprazole and Tacrolimus in Renal Allograft Recipients: A Clinical-Analytical Study

Pascual, Julio; Marcén, R.; Orea, O.E.; Navarro, M; Alarcón, María; Ocaña, Javier; Villafruela, J.J.; Burgos, Francisco; Ortuño, J

doi:10.1016/j.transproceed.2005.09.126

Cited by 19 publications

(11 citation statements)

References 6 publications

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“…18 Effects on gastrointestinal pH appear unlikely because there is no obvious influence of proton pump inhibitors. 19,20 Effects on bile flow appear unlikely because bile flow did not affect tacrolimus absorption in liver transplant patients. 21,22 A change in splanchnic blood flow is not expected to affect low-extraction drugs.…”

Section: Discussionmentioning

confidence: 99%

Differential Effect of a Continental Breakfast on Tacrolimus Formulations With Different Release Characteristics

Huppertz

Bollmann

Behnisch

et al. 2021

Clinical Pharm in Drug Dev

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Food reduces tacrolimus bioavailability after immediate-release tacrolimus (IR-Tac) and after a new prolonged-release tacrolimus formulation (PR-Tac), when using a high-fat breakfast, but the effects of a continental breakfast on PR-Tac are unknown. In an open-label, 4-phase, randomized, 2-sequence, crossover pharmacokinetic trial, 36 healthy volunteers (18 females) received single 5-mg tacrolimus doses as PR-Tac and as IR-Tac fasted or with a standardized continental breakfast. Tacrolimus pharmacokinetics were analyzed using noncompartmental methods and mixed-model analysis of variance.The continental breakfast significantly decreased average tacrolimus exposure (area under the plasma concentration-time curve) with both preparations (IR-Tac, 67%; 90% confidence interval [CI], 59%-75%; P < .01; and PR-Tac, 79%; 90%CI, 70%-89%; P < .01) with a nonsignificant difference between both preparations (P = .10). The maximum concentration (C max ) and the time to maximum concentration (t max ) were significantly affected only after IR-Tac (C max IR-Tac, 39%; 90%CI, 34%-45%; P < .01; and PR-Tac, 87%; 90%CI, 76%-101%; P = .11; t max IR-Tac, 212%, 90%CI, 179%-252%; P < .01; and PR-Tac, 101%; 90%CI, 86%-120%; P = .89), which was significantly different between both preparations (P < .01). Considering switching from IR-Tac to PR-Tac, predicted dose requirements differed according to the timing of drug intake in relation to food. In conclusion, a continental breakfast decreased average tacrolimus exposure of both preparations to a similar extent. C max and t max were affected only after IR-Tac. The effect of a standardized continental breakfast on PR-Tac was considerably smaller than previously reported effects of a high-fat breakfast on PR-Tac.

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Section: Discussionmentioning

confidence: 99%

Differential Effect of a Continental Breakfast on Tacrolimus Formulations With Different Release Characteristics

Huppertz

Bollmann

Behnisch

et al. 2021

Clinical Pharm in Drug Dev

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“…However, Pascual et al estimated the potential interaction between omeprazole and TAC in renal transplant recipients and concluded to absence of important drug interaction between omeprazole and TAC in the general transplant population 10. Although other PPIs have fewer documented drug interactions than omeprazole, recently Takahashi et al showed important interactions between lansoprazole and TAC 22…”

Section: Discussionmentioning

confidence: 99%

“…The presence of clinically relevant pharmacokinetic drug interaction between omeprazole and TAC remains a matter of controversy 2,3,7–10. Omeprazole is metabolized into its major primary metabolites by CYP2C19 with a minor contribution of CYP3A4 2,3.…”

Section: Introductionmentioning

confidence: 99%

Investigation of clinical interaction between omeprazole and tacrolimus in CYP3A5 non-expressors, renal transplant recipients

Katsakiori¹

2010

TCRM

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Background:As proton pump inhibitors share CYP3A4 enzyme with tacrolimus for their hepatic elimination, they potentially affect its pharmacokinetics, most prominently in patients with CYP2C19 or CYP3A5 gene mutations. Our aim was to investigate the impact of omeprazole on tacrolimus pharmacokinetics in CYP3A5 non-expressors, kidney transplant recipients.Methods:Twelve patients (five males/seven females) were observed for 175 ± 92.05 days. Omeprazole (20 mg pos) was administrated for 75.83 ± 45.17 days. Immunosuppressant regimen consisted of tacrolimus (n = 12), methylprednisolone (n = 10), mycophenolate mofetil (n = 11), azathioprine (n = 1), and everolimus (n = 2). Patient’s body weight, coadministered drugs, and tacrolimus trough levels were monitored. Aspartate and alanine aminotransferase, γ-glutamyltransferase, and bilirubin were used for evaluating hepatic function. Tacrolimus kinetics were estimated with daily dose, concentration, dose adjusted concentration, and volume of distribution with and without coadministration of omeprazole. CYP3A5 genotyping was performed with PCR followed by restriction fragment length polymorphism analysis. Statistical analysis was performed with Prism 4 software (GraphPad Software, Inc).Results:No statistically significant difference was observed in tacrolimus kinetics and hepatic function during coadministration of omeprazole.Conclusion:Our results let us propose that there is no need for more frequent therapeutic drug monitoring of tacrolimus when coadministrated with omeprazole in CYP3A5 nonexpressors, though prospective studies with more patients and longer observation period are needed to confirm these findings.

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“…Varying results have been noted in case reports and case-control studies evaluating the interaction between omeprazole and tacrolimus. Some have suggested that concurrent use has no effect on tacrolimus levels, whereas others have noted a continued rise in levels despite a continuous or decreased dose of PPI [54]. We recommend using omeprazole 20 mg daily and following tacrolimus levels closely.…”

Section: Tacrolimusmentioning

confidence: 93%

Important Drug Interactions in Hematopoietic Stem Cell Transplantation: What Every Physician Should Know

Glotzbecker

Duncan

Alyea

et al. 2012

Biology of Blood and Marrow Transplantation

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Morbidity is increased in patients undergoing hematopoietic stem cell transplantation when drug-drug interactions lead to unexpected outcomes. These interactions occur as a result of exposure to complicated medical regimens with drugs with narrow therapeutic windows and high toxicity profiles. In this report, we review the available evidence and possible mechanisms of the most clinically relevant drug interactions, including those involving inhibitors and inducers of the P450 isoenzyme system. We identify key interactions that should be familiar to any physician caring for patients after hematopoietic stem cell transplantation. We discuss drug metabolism in children and in the elderly and examine how age-related differences in metabolism make complicate drug regimens in these populations. A better understanding of these interactions and the responsible mechanisms will promote efficient delivery of the safest medical regimens to patients undergoing hematopoietic stem cell transplantation.

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Interaction Between Omeprazole and Tacrolimus in Renal Allograft Recipients: A Clinical-Analytical Study

Cited by 19 publications

References 6 publications

Differential Effect of a Continental Breakfast on Tacrolimus Formulations With Different Release Characteristics

Differential Effect of a Continental Breakfast on Tacrolimus Formulations With Different Release Characteristics

Investigation of clinical interaction between omeprazole and tacrolimus in CYP3A5 non-expressors, renal transplant recipients

Important Drug Interactions in Hematopoietic Stem Cell Transplantation: What Every Physician Should Know

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