Omeprazole with Mycophenolate Mofetil Interaction Details

Brand Names Associated with Omeprazole

Brand Names Associated with Mycophenolate Mofetil

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 05, 2023

Interaction Effect

Reduced mycophenolic acid exposure

Interaction Summary

Coadministration of proton pump inhibitors in single doses to healthy volunteers and multiple doses to transplant patients receiving mycophenolate mofetil has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA). An approximate reduction of 30% to 70% in the Cmax and 25% to 35% in the AUC of MPA has been observed, possibly due to a decrease in MPA solubility at an increased gastric pH. Obtaining MPA plasma levels before and after the initiation or discontinuation of concomitant medications may be necessary to ensure MPA levels remain stable. If coadministration of mycophenolate mofetil and a PPI is necessary, the dose of mycophenolate mofetil may need to be increased to reach equal immunosuppressive effects . Monitor patients for alterations in efficacy when coadministration with a PPI is required . Use omeprazole with caution in transplant patients receiving mycophenolate mofetil .

Severity

Major

Onset

Rapid

Evidence

Established

How To Manage Interaction

Concomitant use of mycophenolate mofetil with a proton pump inhibitor (PPI) may decrease exposure to the active metabolite mycophenolic acid (MPA), leading to decreased efficacy of mycophenolate mofetil. Monitor patients for alterations in efficacy when coadministration with a PPI is required. Obtaining MPA plasma levels before and after the initiation or discontinuation of concomitant medications may be necessary to ensure MPA levels remain stable. Enteric-coated mycophenolate sodium exposure was not affected by coadministration with PPIs . The dose of mycophenolate mofetil may need to be increased to reach equal immunosuppressive effects . Use omeprazole with caution in transplant patients receiving mycophenolate mofetil .

Mechanism Of Interaction

Incomplete dissolution and decreased absorption of mycophenolate mofetil when the gastric pH is increased

Literature Reports

A) Administration of omeprazole 20 mg twice daily for 4 days and a single 1000 mg dose of mycophenolate mofetil approximately one hour after the last dose of omeprazole to 12 healthy subjects in a crossover study resulted in a 52% reduction in the Cmax and 23% reduction in the AUC of MPA .

B) Reduced exposure of mycophenolate mofetil (CellCept(R)), but not enteric-coated mycophenolate sodium (Myfortic(R)), was reported in healthy subjects when coadministered with omeprazole in 2 randomized, crossover design with a 1-week washout period pharmacokinetic studies (N=12 each). Mycophenolic acid (MPA) levels were compared following a single oral dose of mycophenolate mofetil 1000 mg or enteric-coated mycophenolate sodium 720 mg as monotherapy, or in combination with omeprazole 20 mg twice daily (started 4 days prior). All medications were administered in fasted state with 240 mL of water. Mean Cmax of MPA was 21.7 +/- 9.9 mg/L when mycophenolate mofetil was administered alone, compared with 10.5 +/- 3.6 mg/mL when administered in the presence of omeprazole (p less than 0.01). Mean AUC (0 to 12 hours) of MPA was 33.3 +/- 11.5 mg x hr/L when mycophenolate mofetil was administered alone, compared with 25.8 +/- 6.4 mg x hr/L when administered in the presence of omeprazole (p less than 0.05). In contrast, mean Cmax and AUC of MPA following administration of enteric-coated mycophenolate sodium were unaffected when administered alone (21.6 +/-6.5 and 31.8 +/- 7.7 mg/L, respectively) or in the presence of omeprazole (23.7 +/- 8 and 33.2 +/-6.5 mg/L, respectively) .

C) In a prospective, case-controlled pharmacokinetic study, coadministration of pantoprazole 40 mg with mycophenolate mofetil (1000 mg twice daily) and tacrolimus (dose adjusted to reach target trough levels 5 to 14 nanograms/mL) resulted in reduced mycophenolic acid concentrations in 22 heart transplant recipients. Coadministration with pantoprazole resulted in significant decreases in mycophenolic acid concentrations at 30 minutes (8.3 mg/L vs 18.3 mg/L (0.0259 mmol/L vs 0.0571 mmol/L)) and 1 hour (10 mg/L vs 15.8 mg/L (0.03 mmol/L vs 0.0493 mmol/L)), but not at 2 hours. Pantoprazole also significantly reduced mycophenolic acid AUC (51.2 mg x hr/L vs 68.7 mg x hr/L) and Cmax (12.2 mg/L vs 20.6 mg/L (0.038 mmol/L vs 0.0643 mmol/L)) and increased the time to reach Cmax (Tmax; 60 +/- 27.8 minutes vs 46.4 +/- 22.2 minutes) .

D) Coadministration of pantoprazole with mycophenolate mofetil significantly decreased mean serum concentrations of the active metabolite, mycophenolate acid (MPA), at 30 and 60 minutes postdose compared with subjects not receiving pantoprazole. Concomitant administration also significantly decreased Cmax and AUC and increased Tmax of MPA compared with subjects not receiving pantoprazole. Eligible subjects were receiving mycophenolate mofetil 1 to 2 g/day for autoimmune diseases (23 receiving concomitant pantoprazole 40 mg/day and 13 not receiving proton pump inhibitors (non-PPI)). Mean MPA plasma levels at 30 and 60 minutes postdose were significantly decreased in the pantoprazole-treated subjects compared with the non-PPI treated subjects ( 9.2 mg/L vs 30.3 mg/L (0.0287 mmol/L vs 0.0945 mmol/L) at 30 minutes and 11 mg/L vs 18.3 mg/L (0.034 mmol/L vs 0.0571 mmol/L) at 60 minutes). Cmax was significantly lowered in the pantoprazole-treated subjects compared with non-PPI subjects, (14.2 mg/L vs 35.4 mg/L (0.0443 mmol/L vs 0.1105 mmol/L)) and Tmax was significantly delayed (61.6 minutes vs 36.4 minutes, respectively). From 90 minutes to 12 hours postdose, MPA plasma concentrations did not differ significantly between groups. In the pantoprazole group, 5 patients experienced increased disease activity compared with 1 patient in the non-PPI group .

E) In a randomized crossover study of stable renal transplant patients (N=20), there was no significant difference in mycophenolic acid exposure when mycophenolate mofetil or enteric-coated mycophenolate sodium were administered with or without pantoprazole .

Omeprazole Overview

• Prescription omeprazole is used alone or with other medications to treat the symptoms of gastroesophageal reflux disease (GERD), a condition in which backward flow of acid from the stomach causes heartburn and possible injury of the esophagus (the tube between the throat and stomach) in adults and children 1 year of age and older. Prescription omeprazole is used to treat damage from GERD in adults and children 1 month of age and older. Prescription omeprazole is used to allow the esophagus to heal and prevent further damage to the esophagus in adults and children 1 year of age and older with GERD. Prescription omeprazole is also used to treat conditions in which the stomach produces too much acid such as Zollinger-Ellison syndrome in adults. Prescription omeprazole is also used to treat ulcers (sores in the lining of the stomach or intestine) and it is also used with other medications to treat and prevent the return of ulcers caused by a certain type of bacteria (H. pylori) in adults. Nonprescription (over-the-counter) omeprazole is used to treat frequent heartburn (heartburn that occurs at least 2 or more days a week) in adults. Omeprazole is in a class of medications called proton-pump inhibitors. It works by decreasing the amount of acid made in the stomach.

Mycophenolate Mofetil Overview

• Mycophenolate (CellCept) is used with other medications to help prevent transplant organ rejection (attack of the transplanted organ by the immune system of the person receiving the organ) in adults and children 3 months of age and older who have received kidney, heart, or liver transplants. Mycophenolate (Myfortic) is used with other medications to help prevent the body from rejecting kidney transplants in adults and children 5 years of age and older. Mycophenolate is in a class of medications called immunosuppressive agents. It works by weakening the body's immune system so it will not attack and reject the transplanted organ.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.