Pantoprazole with Methotrexate Interaction Details
Brand Names Associated with Pantoprazole
- Pantoprazole
- Protonix®
Brand Names Associated with Methotrexate
- Amethopterin
- Methotrexate
- MTX
- Rheumatrex®
- Trexall®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 17, 2023
Interaction Effect
Increased concentration of methotrexate and its metabolite and an increased risk of methotrexate toxicity
Interaction Summary
Case reports, population pharmacokinetic studies, and a retrospective cohort study, suggest that concomitant use of methotrexate (primarily high doses) and proton pump inhibitors (pantoprazole, omeprazole, or esomeprazole) may result in delayed elimination of methotrexate and increased methotrexate and/or hydroxymethotrexate concentrations with potential for methotrexate toxicity. Although no pharmacokinetic studies have been performed with methotrexate and ranitidine, in 2 case reports delayed elimination of methotrexate was not observed when ranitidine was coadministered with methotrexate . If used concomitantly, monitor methotrexate plasma levels and monitor patients for symptoms of increased methotrexate toxicity, such as myalgia and bone pain. To avoid the potential for methotrexate toxicity, the proton pump inhibitor may have to be temporarily discontinued during methotrexate administration.
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Concomitant use of methotrexate and proton pump inhibitors (pantoprazole, omeprazole, or esomeprazole) may cause delayed elimination of methotrexate and its metabolite and subsequent methotrexate toxicity. If used concomitantly, monitor methotrexate plasma levels and monitor patients for symptoms of increased methotrexate toxicity, such as myalgia and bone pain. To avoid the potential for methotrexate toxicity, the proton pump inhibitor may have to be temporarily discontinued during methotrexate administration.
Mechanism Of Interaction
Decreased renal elimination of 7-hydroxymethotrexate by pantoprazole
Literature Reports
A) A retrospective, non-interventional cohort study (n=79) revealed a 6.7-fold increased risk of delayed methotrexate elimination with concomitant use of a proton pump inhibitor. Patients with various types of cancer (mean age, 48.8 years; range, 16 to 76 years) received cycles of high-dose IV methotrexate (greater than 1 g/m(2)). Cycles with avoidable causes for delayed methotrexate elimination were excluded from analysis. Delayed methotrexate elimination was defined as plasma methotrexate concentrations greater than 15, 1.5, and/or 0.15 mcmol/L at 24, 48, and 72 hours, respectively. Of 197 cycles, delayed methotrexate elimination was noted in 16% (32/197) of cycles. Of the cycles with delayed methotrexate elimination, concomitant use of a proton pump inhibitor (pantoprazole, lansoprazole, omeprazole, or esomeprazole) was significantly greater compared with cycles without delayed methotrexate elimination (53.1% vs 15%; p less than 0.001; odds ratio 6.66; 95% confidence interval, 3.13 to 14.17). Plasma methotrexate concentrations were significantly greater at each time point (24, 48, and 72 hours) in patients with delayed elimination compared with patients without delayed elimination (p less than 0.01) .
B) A case report described severe generalized myalgia and bone pain in a 59-year-old patient with folliculotropic cutaneous T cell lymphoma and Barrett's esophagus after methotrexate (15 mg intramuscularly once a week) was added to a regimen that included oral pantoprazole 20 mg/day. Symptoms led to partial immobility, which began 3 to 4 hours after the injection, continued for several days, and recurred over the 4 following methotrexate cycles. When pantoprazole was replaced with ranitidine, the myalgia and bone pain subsided and eventually disappeared. The patient was then rechallenged with pantoprazole, which was initiated 6 days prior to his weekly methotrexate dose. Serum concentrations of methotrexate and its metabolite, 7-hydroxymethotrexate, were taken after the dose. Methotrexate levels without concomitant pantoprazole were measured following a 6-week washout period. Upon rechallenge, symptoms recurred with concomitant pantoprazole but not with methotrexate alone. Although the methotrexate AUC was not impacted by pantoprazole, the 7-hydroxymethotrexate AUC (0 to 144 hours) was 70% higher in the presence of pantoprazole compared to methotrexate alone (1929 nanograms x hour/mL vs 1131 nanograms x hour/mL). Also, the half-life of 7-hydroxymethotrexate increased from 36.4 hours to 81.4 hours in the presence of pantoprazole, indicating a decrease in renal elimination of 7-hydroxymethotrexate as opposed to a metabolic interaction .
Pantoprazole Overview
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Pantoprazole is used to treat damage from 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 5 years of age and older. Pantoprazole is used to allow the esophagus to heal and prevent further damage to the esophagus in adults with GERD. It is also used to treat conditions where the stomach produces too much acid, such as Zollinger-Ellison syndrome in adults. Pantoprazole is in a class of medications called proton-pump inhibitors. It works by decreasing the amount of acid made in the stomach.
Methotrexate Overview
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Methotrexate is used to treat severe psoriasis (a skin disease in which red, scaly patches form on some areas of the body) that cannot be controlled by other treatments. Methotrexate is also used along with rest, physical therapy, and sometimes other medications to treat severe active rheumatoid arthritis (RA; a condition in which the body attacks its own joints, causing pain, swelling, and loss of function) that cannot be controlled by certain other medications. Methotrexate is also used to treat certain types of cancer including cancers that begin in the tissues that form around a fertilized egg in the uterus, breast cancer, lung cancer, certain cancers of the head and neck, certain types of lymphoma, and leukemia (cancer that begins in the white blood cells). Methotrexate is in a class of medications called antimetabolites. Methotrexate treats cancer by slowing the growth of cancer cells. Methotrexate treats psoriasis by slowing the growth of skin cells to stop scales from forming. Methotrexate may treat rheumatoid arthritis by decreasing the activity of the immune system.
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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:
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.