Omeprazole Impairs the Absorption of Mycophenolate Mofetil But Not of Enteric‐Coated Mycophenolate Sodium in Healthy Volunteers

Kees, Martin G.; Steinke, Thomas; Moritz, Stefan; Rupprecht, Korbinian; Paulus, Eva‐Maria; Kees, Frieder; Bucher, Michael; Faerber, Lothar

doi:10.1177/0091270011412968

Cited by 49 publications

(39 citation statements)

References 33 publications

(81 reference statements)

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“…Kees et al demonstrated in vitro that MMF tablets dissolved completely at pH G4.0, but only 47% and 13% of the tablet were dissolved at pH 5 and 7, respectively, after 4 days of omeprazole 20 mg twice daily (27). Although all PPIs have been shown to increase the gastric pH levels to above 4.0, the exact pH achieved and time maintained at pH 94.0 vary widely by patient, PPI used, PPI dose, and PPI frequency (28).…”

Section: Discussionmentioning

confidence: 99%

“…Although data to support conversion from MMF to EC-MPS for gastrointestinal adverse events are limited to open-label, crossover studies, pharmacokinetic studies have shown that MPA exposure in patients given EC-MPS is not adversely effected by PPI (19,25,27). Because a generic is not available, EC-MPS remains a more expensive but potential alternative to MMF in patients requiring a PPI who are at high risk for rejection.…”

Section: Discussionmentioning

confidence: 99%

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Concomitant Proton Pump Inhibitors With Mycophenolate Mofetil and the Risk of Rejection in Kidney Transplant Recipients

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Concomitant Proton Pump Inhibitors With Mycophenolate Mofetil and the Risk of Rejection in Kidney Transplant Recipients

et al. 2014

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“…Following administration of MMF, higher ph-levels reduce peak concentrations (C max ) and the AUCs in healthy volunteers diminished significantly. 79 In contrast, C max and AUC were not impacted by the acid-resistant ECMPS formulation. 80 …”

Section: Introductionmentioning

confidence: 95%

A Rationale for Age-Adapted Immunosuppression in Organ Transplantation

et al. 2015

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Demographic changes are associated with a steady increase of older patients with end-stage organ failure in need for transplantation. As a result, the majority of transplant recipients are currently older >50 years and organs from elderly donors are more frequently utilized. Nevertheless, the benefit of transplantation in older patients is well recognized whereas the most frequent causes of death among older recipients are potentially linked to side effects of their immunosuppressants. Immunosenescence is a physiological part of aging linked to higher rates of diabetes, bacterial infections and malignancies representing the major causes of death in older patients. These age-related changes impact older transplant candidates and may have significant implications for an age-adapted immunosuppression. For instance, immunosenescence is linked to lower rates of acute rejections in older recipients while the engraftment of older organs has been associated with higher rejection rates. Moreover, new-onset diabetes mellitus following transplantation is more frequent in the elderly, potentially related to corticosteroids, calcineurin inhibitors and mTOR inhibitors. This review presents current knowledge for an age-adapted immunosuppression based on both, experimental and clinical studies in and beyond transplantation. Recommendations of maintenance and induction therapy may help to improve graft function and to design future clinical trials in the elderly.

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“…Omeprazole impairs the absorption of MMF, but not enteric-coated mycophenolate sodium (a formulation therapeutically equivalent to MMF), in healthy volunteers, indicating that impaired absorption of MMF with concomitant PPI is a result of incomplete dissolution of MMF in the stomach at elevated pH 53. Therefore, enteric-coated mycophenolate sodium may be an alternative to immunosuppressant treatment.…”

Section: Circumstance 1: Omeprazole Is Comedicated As a Precipitant Drugmentioning

confidence: 99%

Pharmacokinetic drug interaction profile of omeprazole with adverse consequences and clinical risk management

Li¹,

Zeng²,

Yu³

et al. 2013

TCRM

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BackgroundOmeprazole, a proton pump inhibitor (PPI), is widely used for the treatment of dyspepsia, peptic ulcer, gastroesophageal reflux disease, and functional dyspepsia. Polypharmacy is common in patients receiving omeprazole. Drug toxicity and treatment failure resulting from inappropriate combination therapy with omeprazole have been reported sporadically. Systematic review has not been available to address the pharmacokinetic drug-drug interaction (DDI) profile of omeprazole with adverse consequences, the factors determining the degree of DDI between omeprazole and comedication, and the corresponding clinical risk management.MethodsLiterature was identified by performing a PubMed search covering the period from January 1988 to March 2013. The full text of each article was critically reviewed, and data interpretation was performed.ResultsOmeprazole has actual adverse influences on the pharmacokinetics of medications such as diazepam, carbamazepine, clozapine, indinavir, nelfinavir, atazanavir, rilpivirine, methotrexate, tacrolimus, mycophenolate mofetil, clopidogrel, digoxin, itraconazole, posaconazole, and oral iron supplementation. Meanwhile, low efficacy of omeprazole treatment would be anticipated, as omeprazole elimination could be significantly induced by comedicated efavirenz and herb medicines such as St John’s wort, Ginkgo biloba, and yin zhi huang. The mechanism for DDI involves induction or inhibition of cytochrome P450, inhibition of P-glycoprotein or breast cancer resistance protein-mediated drug transport, and inhibition of oral absorption by gastric acid suppression. Sometimes, DDIs of omeprazole do not exhibit a PPI class effect. Other suitable PPIs or histamine 2 antagonists may be therapeutic alternatives that can be used to avoid adverse consequences. The degree of DDIs associated with omeprazole and clinical outcomes depend on factors such as genotype status of CYP2C19 and CYP1A2, ethnicity, dose and treatment course of precipitant omeprazole, pharmaceutical formulation of object drug (eg, mycophenolate mofetil versus enteric-coated mycophenolate sodium), other concomitant medication (eg, omeprazole-indinavir versus omeprazole–indinavir–ritonavir), and administration schedule (eg, intensified dosing of mycophenolate mofetil versus standard dosing).ConclusionDespite the fact that omeprazole is one of the most widely prescribed drugs internationally, clinical professionals should enhance clinical risk management on adverse DDIs associated with omeprazole and ensure safe combination use of omeprazole by rationally prescribing alternatives, checking the appropriateness of physician orders before dispensing, and performing therapeutic drug monitoring.

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Omeprazole Impairs the Absorption of Mycophenolate Mofetil But Not of Enteric‐Coated Mycophenolate Sodium in Healthy Volunteers

Cited by 49 publications

References 33 publications

Concomitant Proton Pump Inhibitors With Mycophenolate Mofetil and the Risk of Rejection in Kidney Transplant Recipients

Concomitant Proton Pump Inhibitors With Mycophenolate Mofetil and the Risk of Rejection in Kidney Transplant Recipients

A Rationale for Age-Adapted Immunosuppression in Organ Transplantation

Pharmacokinetic drug interaction profile of omeprazole with adverse consequences and clinical risk management

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