Drug interactions between Nexium and tacrolimus
Interactions between your drugs
tacrolimus ↔ esomeprazole
Applies to:tacrolimus and Nexium (esomeprazole)
Consumer information for this interaction is not currently available.
MONITOR CLOSELY: Coadministration with some proton pump inhibitors (PPIs) may significantly increase the whole blood concentrations of tacrolimus, particularly in patients with CYP450 2C19 mutant alleles. The interaction has been reported primarily with lansoprazole and omeprazole, but may occur with other PPIs that have a similar metabolic profile such as dexlansoprazole and esomeprazole. The proposed mechanism is competitive inhibition of tacrolimus metabolism via intestinal and hepatic CYP450 3A4. Although these PPIs are primarily metabolized by CYP450 2C19, CYP450 3A4 is the major metabolic pathway in individuals who are CYP450 2C19-deficient (i.e., CYP450 2C19 poor metabolizers), thereby increasing the risk of CYP450 3A4-mediated interactions. In a study of healthy volunteers, administration of a single 2 mg dose of tacrolimus in combination with lansoprazole (30 mg daily for 4 days) increased the tacrolimus systemic exposure (AUC) by 81% in subjects with CYP450 2C19 mutant alleles and by 29% in subjects without (i.e., CYP450 2C19 extensive metabolizers), whereas administration with rabeprazole (10 mg daily for 4 days) had minimal effect in either group. There have also been various case reports of patients with such mutations who developed significant increases in tacrolimus trough levels within several days after the addition of a PPI, usually lansoprazole or omeprazole. Their levels normalized only after tacrolimus dosage was reduced and the PPI was discontinued or replaced with either famotidine or rabeprazole. Studies have indicated that the interaction does not occur with rabeprazole, presumably because it is metabolized by a nonenzymatic pathway in addition to the CYP450 pathways. Available data also suggest that pantoprazole does not significantly interact with tacrolimus, although the reason is unclear, since pantoprazole is similarly metabolized as the other PPIs.
MANAGEMENT: Approximately 16% to 25% of Caucasians and 36% to 47% of Asians have gene mutations that result in varying degrees of reduced CYP450 2C19 enzyme activity. It has been further estimated that approximately 3% to 5% of Caucasians and individuals of African descent and 17% to 23% of Asians are poor metabolizers with minimal CYP450 2C19 functional capacity. Since 2C19 genotype information is not frequently available for patients, caution is advised whenever tacrolimus is coadministered with PPIs. Pharmacologic response to tacrolimus and blood concentrations should be monitored more closely whenever the PPI is added to or withdrawn from therapy, and the tacrolimus dosage adjusted as necessary to prevent concentration-dependent adverse effects such as nephrotoxicity, neurotoxicity, posttransplant diabetes mellitus, infections, and myocardial hypertrophy. Clinicians should bear in mind that CYP450 2C19 deficiency can also be pharmacologically induced by drugs such as cimetidine, delavirdine, efavirenz, felbamate, fluconazole, fluoxetine, fluvoxamine, oxcarbazepine, ticlopidine, and voriconazole. To minimize the risk of interaction, alternatives such as famotidine, nizatidine, ranitidine, or rabeprazole should be considered for acid suppression therapy in patients treated with tacrolimus.
MONITOR CLOSELY: Chronic use of proton pump inhibitors (PPIs) may induce hypomagnesemia, and the risk may be increased during concomitant use of other agents that can cause magnesium loss such as tacrolimus. The mechanism via which hypomagnesemia may occur during long-term PPI use is unknown, although changes in intestinal absorption of magnesium may be involved. Hypomagnesemia has been reported rarely in patients treated with PPIs for at least three months, but in most cases, after a year or more. Serious adverse events include tetany, seizures, tremor, carpopedal spasm, atrial fibrillation, supraventricular tachycardia, and abnormal QT interval; however, patients do not always exhibit these symptoms. Hypomagnesemia can also cause impaired parathyroid hormone secretion, which may lead to hypocalcemia. In approximately 25% of the cases of PPI-associated hypomagnesemia reviewed by the U.S. Food and Drug Administration, the condition did not resolve with magnesium supplementation alone but also required discontinuation of the PPI. Both positive dechallenge as well as positive rechallenge (i.e., resolution of hypomagnesemia with PPI cessation and recurrence with PPI resumption) were reported in some cases. After discontinuing the PPI, the median time required for magnesium levels to normalize was one week. After restarting the PPI, the median time for hypomagnesemia to recur was two weeks.
MANAGEMENT: Monitoring of serum magnesium levels is recommended prior to initiation of therapy and periodically thereafter if prolonged treatment with a PPI is anticipated or when combined with other agents that can cause hypomagnesemia such as tacrolimus. Patients should be advised to seek immediate medical attention if they develop potential signs and symptoms of hypomagnesemia such as palpitations, arrhythmia, muscle spasm, tremor, or convulsions. In children, abnormal heart rates may cause fatigue, upset stomach, dizziness, and lightheadedness. Magnesium replacement as well as discontinuation of the PPI may be required in some patients.
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- Itagaki F, Homma M, Yuzawa K, et al "Effect of lansoprazole and rabeprazole on tacrolimus pharmacokinetics in healthy volunteers with CYP2C19 mutations." J Pharm Pharmacol 56 (2004): 1055-9
- Miura M, Inoue K, Kagaya H, et al. "Influence of rabeprazole and lansoprazole on the pharmacokinetics of tacrolimus in relation to CYP2C19, CYP3A5 and MDR1 polymorphisms in renal transplant recipients." Biopharm Drug Dispos 28 (2007): 167-75
- Cerner Multum, Inc. "Australian Product Information." O 0
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- "Product Information. Protonix (pantoprazole)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
- Pascual J, Marcen R, Orea OE, et al. "Interaction Between Omeprazole and Tacrolimus in Renal Allograft Recipients: A Clinical-Analytical Study." Transplant Proc 37 (2005): 3752-3753
- Takahashi K, Motohashi H, Yonezawa A, et al "Lansoprazole-tacrolimus interaction in Japanese transplant recipient with CYP2C19 polymorphism." Ann Pharmacother 38 (2004): 791-4
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- "Product Information. Prograf (tacrolimus)." Fujisawa, Deerfield, IL.
- "Product Information. Aciphex (rabeprazole)" Janssen Pharmaceuticals, Titusville, NJ.
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- "Product Information. Prilosec (omeprazole)." Merck & Co, Inc, West Point, PA.
- "Product Information. Prevacid (lansoprazole)." TAP Pharmaceuticals Inc, Deerfield, IL.
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- "Product Information. Dexilant (dexlansoprazole)." Takeda Pharmaceuticals America, Lincolnshire, IL.
- "Product Information. Nexium (esomeprazole)" Astra-Zeneca Pharmaceuticals, Wilmington, DE.
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- FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of proton pump inhibitor drugs (PPIs). Available from: URL: http://www.fda.gov/Drugs/DrugSafety/ucm245011.htm." ([2011 Mar 2]):
Drug and food interactions
Applies to: tacrolimus
Tacrolimus should be taken on a consistent schedule before or after you eat at the same times each day. Grapefruit and grapefruit juice may increase the amount of tacrolimus in your body. This can lead to potentially dangerous side effects and should be avoided. If you are already consuming grapefruit products, do not increase or decrease the amount of these products in your diet without first talking to your doctor.
Applies to: Nexium (esomeprazole)
Food may interfere with the absorption of esomeprazole. Esomeprazole should be taken at least one hour before meals and at the same time every day. When esomeprazole is given to patients receiving continuous enteral nutrition (tube feedings), the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of esomeprazole. This will make it easier for your body to absorb the medication. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.
Therapeutic duplication warnings
No therapeutic duplications were found for your selected drugs.
Drug Interaction Classification
|Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.|
|Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.|
|Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.|
|No information available.|
Do not stop taking any medications without consulting your healthcare provider.
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