How to treat diarrhea from methotrexate?

October 13, 2025 •

4 min read

Gastrointestinal issues, including diarrhea, are among the most common side effects for individuals taking low-dose methotrexate. Learning how to treat diarrhea from methotrexate is crucial for managing symptoms and maintaining your treatment plan. This guide outlines effective strategies and necessary precautions for addressing this frequent side effect.

Quick Summary

Management strategies for methotrexate-induced diarrhea include dietary adjustments, ensuring adequate hydration, and collaborating with a healthcare provider. Options may involve adjusting folic acid supplementation, changing the medication's administration route, or modifying the dosage to alleviate symptoms.

Key Points

Consult Your Doctor: Always inform your healthcare provider about new or persistent diarrhea while on methotrexate to rule out serious issues and discuss safe management options.
Increase Folic Acid: Your doctor will likely increase your folic acid supplementation, which helps protect healthy cells and can reduce GI side effects like diarrhea.
Switch Administration Route: For persistent GI issues, switching from oral to subcutaneous methotrexate injections can significantly reduce diarrhea risk by improving drug absorption.
Stay Hydrated: Drink plenty of clear fluids like water and broth to combat dehydration caused by diarrhea.
Adopt a Bland Diet: Follow a low-fiber, bland diet like the BRAT diet (bananas, rice, applesauce, toast) during a diarrhea flare-up to ease digestive stress.
Avoid Trigger Foods: Temporarily cut out high-fat, dairy, spicy, and caffeinated items, as these can exacerbate diarrhea symptoms.
Report Severe Symptoms: Contact your doctor immediately if you experience severe symptoms like fever, bloody stools, or persistent abdominal pain alongside diarrhea.

Understanding Methotrexate-Induced Diarrhea

Methotrexate (MTX) is a powerful medication used to treat conditions like rheumatoid arthritis, psoriasis, and certain cancers. While effective, it can cause gastrointestinal (GI) side effects, with diarrhea being a common complaint. The medication works by interfering with cell growth, which can, in turn, affect the rapidly dividing cells lining the gastrointestinal tract, leading to inflammation and irritation.

GI issues most frequently occur in the first one to two years of treatment and are often dose-dependent. However, even low, weekly doses can induce these problems. Factors such as a patient's age, renal function, or other co-existing medical conditions can also increase the risk. Understanding this mechanism is the first step toward effective management.

Medical Management: The Cornerstone of Treatment

Any persistent or severe diarrhea while on methotrexate requires immediate medical consultation. Self-treating with over-the-counter (OTC) anti-diarrheal medications without a doctor's supervision is not recommended, as it could mask a more serious issue or interact with other medications. A healthcare provider can assess the severity and determine the most appropriate course of action, which may involve one or more of the following strategies.

Folic Acid and Folinic Acid Supplementation

One of the most effective strategies to mitigate GI side effects is taking a folic acid supplement. Methotrexate inhibits the body's use of folate (Vitamin B9), and supplementation helps protect healthy cells without compromising the drug's effectiveness against the targeted disease.

Your doctor will determine the correct dosage and timing for your supplement. A typical regimen might involve a 5mg tablet taken once a week, ideally the day after your methotrexate dose. For persistent issues, the dose may be increased or switched to a more potent form, such as folinic acid (leucovorin).

Adjusting the Medication Route

For many patients, especially those with rheumatoid arthritis, switching from oral tablets to subcutaneous injections can significantly reduce or even eliminate GI side effects. Subcutaneous administration has higher bioavailability and bypasses some of the direct irritation to the gastrointestinal tract caused by oral intake. This adjustment allows patients to maintain their therapeutic dose while improving their quality of life.

Modifying Dosage or Timing

Your doctor may also suggest adjusting your dosage or the timing of your methotrexate. Taking the oral dose with food or splitting the weekly dose into two smaller doses taken 12 hours apart can sometimes help reduce stomach upset. Never make these changes without your doctor's guidance, as improper dosing can affect the treatment's efficacy.

Lifestyle and At-Home Management

While medical intervention is critical, several at-home strategies can help manage the symptoms of diarrhea and prevent complications like dehydration.

Hydration is Key

Diarrhea leads to a significant loss of fluids and electrolytes. It is critical to stay well-hydrated by drinking plenty of clear fluids throughout the day.

Water
Clear broths
Oral rehydration solutions
Juice (avoid those with high sugar content, as they can worsen diarrhea)

The BRAT Diet

During a flare-up of diarrhea, a bland diet can be easier on your digestive system. The BRAT diet (bananas, rice, applesauce, and toast) is a classic example of foods that are easy to digest and can help firm up stools.

Bananas: High in potassium, which is lost during diarrhea.
Rice: Provides carbohydrates without upsetting the stomach.
Applesauce: Contains pectin, a fiber that can help absorb water.
Toast: Simple carbohydrates that are easy to digest.

Foods to Avoid

When experiencing diarrhea, it is best to avoid certain foods that can aggravate symptoms. These include:

Dairy products
High-fat and greasy foods
Caffeinated and alcoholic beverages
Spicy foods
High-fiber foods (temporarily, as they can increase bowel movements)

Methotrexate Administration Routes: Oral vs. Subcutaneous


Feature	Oral Methotrexate	Subcutaneous Methotrexate
Diarrhea Risk	Higher risk of gastrointestinal side effects, including diarrhea.	Significantly lower risk of GI side effects.
Bioavailability	Lower absorption rates, which can vary between individuals.	Higher and more consistent absorption, leading to fewer side effects.
Patient Convenience	Easy to take as a pill; no injections required.	Requires self-injection, which can be an adjustment for some patients.
Effectiveness	Highly effective for many patients, but side effects can lead to non-adherence.	Maintains or improves therapeutic efficacy while reducing GI toxicity.

Conclusion

While diarrhea from methotrexate can be a challenging side effect, effective management strategies are available. The most important step is to communicate openly with your healthcare provider about your symptoms. They can help you implement key strategies, including adjusting folic acid intake, changing the drug's administration route from oral to subcutaneous, and modifying the dosage. Combining these medical interventions with careful dietary management and vigilant hydration can significantly improve your comfort and adherence to your treatment plan. Remember, managing side effects is a collaborative effort between you and your care team, so never hesitate to report new or worsening symptoms.

For more information on methotrexate and managing its side effects, consult MedlinePlus, a service of the National Library of Medicine: MedlinePlus Methotrexate Information.

Frequently Asked Questions

Methotrexate is a folate antagonist that targets rapidly dividing cells. The cells lining the gastrointestinal tract are fast-dividing and can be damaged by the drug, leading to inflammation, irritation, and diarrhea as a side effect.

You should not take over-the-counter anti-diarrheal drugs like loperamide without consulting your doctor. They need to evaluate the severity of your condition and ensure there are no interactions with your other medications.

Folic acid is a synthetic version of vitamin B9. Methotrexate can cause a functional folic acid deficiency. Taking a folic acid supplement helps protect healthy cells from the drug's effects, which can reduce side effects such as nausea and diarrhea.

Folinic acid (leucovorin) is a more potent form of folic acid. It is sometimes prescribed as a 'rescue' treatment for more severe methotrexate toxicity, while a regular folic acid supplement is typically used for less severe side effects.

Focus on a bland diet, such as the BRAT diet (bananas, rice, applesauce, toast), and ensure you are drinking plenty of clear fluids. Avoid foods that are difficult to digest, like spicy, high-fat, or high-fiber foods, and stay away from caffeine and alcohol.

For many, diarrhea is a temporary side effect that occurs on or shortly after taking the weekly dose and resolves within 1-2 days. If it persists or worsens, you must contact your doctor for further evaluation.

Call your doctor immediately if you experience persistent, severe diarrhea, a fever of 100.4°F or higher, bloody or black stools, severe stomach pain, or signs of dehydration like dizziness.