Understanding the Link: Can Pentasa Cause Diarrhea?

October 8, 2025 •

4 min read

According to clinical trials, diarrhea is one of the most common side effects of Pentasa, affecting approximately 3.4% of patients [1.3.5]. While used to treat inflammatory bowel conditions, many wonder, can Pentasa cause diarrhea or worsen existing symptoms?

Quick Summary

Pentasa, a brand name for mesalamine, can indeed cause diarrhea as a side effect. It can also paradoxically worsen colitis symptoms, a condition known as mesalamine intolerance.

Key Points

Diarrhea is a Common Side Effect: In clinical trials, diarrhea was one of the most frequently reported side effects of Pentasa, affecting about 3.4% of patients [1.3.5].
Paradoxical Worsening: Pentasa can cause a paradoxical reaction called mesalamine intolerance, leading to worsened symptoms like bloody diarrhea and severe cramps, which mimics a colitis flare [1.2.7, 1.7.1].
Distinguishing Symptoms: Mesalamine intolerance often occurs soon after starting the drug and may be accompanied by fever and a rash, helping to distinguish it from a typical IBD flare [1.2.7, 1.7.3].
Mechanism of Action: Pentasa (mesalamine) works as a topical anti-inflammatory agent within the gut to reduce the inflammation that causes ulcerative colitis symptoms [1.5.3].
Consult a Doctor: If you experience severe or worsening diarrhea, especially with blood, fever, or severe cramps, you should stop taking Pentasa and contact your healthcare provider immediately [1.4.7].
Management Strategies: Mild diarrhea may be managed with hydration and dietary changes, such as avoiding dairy and high-fiber foods, but any changes should be discussed with a doctor [1.4.2, 1.4.5].
Alternative Medications Exist: If Pentasa is not tolerated, other 5-ASA drugs (like Balsalazide), corticosteroids, and biologics are available as alternative treatments for IBD [1.6.1, 1.6.4].

What is Pentasa and How Does It Work?

Pentasa is a brand name for the medication mesalamine, also known as 5-aminosalicylic acid (5-ASA) [1.5.4]. It is a first-line anti-inflammatory drug used to treat and manage mild to moderate ulcerative colitis (UC), a type of inflammatory bowel disease (IBD) [1.5.5, 1.6.1]. The exact mechanism of action is not completely understood, but it is believed to work topically on the cells lining the colon [1.5.3]. Pentasa helps to reduce inflammation by inhibiting the production of various inflammatory mediators, such as prostaglandins and leukotrienes, in the gut [1.5.1, 1.5.2].

What distinguishes Pentasa from other mesalamine formulations is its unique controlled-release system. The active ingredient is contained within ethylcellulose-coated microgranules, which are designed to release mesalamine gradually throughout the gastrointestinal tract, from the small intestine down to the colon [1.8.1, 1.5.3]. This makes it effective for inflammation in different parts of the digestive system [1.8.1].

Can Pentasa Cause Diarrhea?

Yes, diarrhea is a recognized side effect of Pentasa and other mesalamine products [1.2.1, 1.2.4]. In clinical trials, diarrhea was reported as one of the most common adverse events, occurring in about 3.4% of patients using Pentasa [1.3.5]. Some studies have noted this side effect in up to 5% of patients [1.3.3].

For most individuals, these side effects are mild and may lessen or resolve after a few weeks of treatment [1.2.7]. However, it is crucial for patients to communicate with their healthcare provider if diarrhea persists or becomes bothersome [1.2.1, 1.2.3].

Mesalamine Intolerance: When the Treatment Worsens Symptoms

A more complex issue is a condition known as mesalamine intolerance or mesalamine-induced paradoxical worsening of colitis. In some patients, instead of alleviating symptoms, Pentasa can paradoxically cause an exacerbation of colitis symptoms, including severe abdominal pain, cramps, and bloody diarrhea [1.7.1, 1.7.6].

This intolerance syndrome can be difficult to distinguish from a natural flare-up of the underlying ulcerative colitis because the symptoms are so similar [1.2.7]. It is reported to occur in about 3% of patients in clinical trials [1.2.7]. Key indicators that might suggest intolerance rather than a disease flare include:

The onset of worsening symptoms shortly after starting the medication, often within the first few weeks [1.3.4].
The presence of other symptoms like fever, headache, and a rash alongside the gastrointestinal distress [1.2.7, 1.7.6].
Symptoms resolving upon discontinuation of the drug and returning if the drug is re-administered [1.7.1].

If you experience worsening bloody diarrhea, severe stomach cramps, or fever after starting Pentasa, it is essential to stop taking the medication and contact your doctor immediately [1.4.7].

Managing Diarrhea While Taking Pentasa

If you experience mild diarrhea as a side effect, your doctor might recommend several strategies before considering a change in medication. Lifestyle and dietary adjustments can be effective:

Stay Hydrated: Drink plenty of fluids, with water being the best choice. Avoid alcohol and caffeine, which can stimulate the intestines [1.4.2, 1.4.5].
Dietary Modifications: Limiting dairy products, high-fiber foods (like nuts, seeds, and raw vegetables), and spicy or greasy foods can help reduce symptoms [1.4.4, 1.4.5].
Eat Small, Frequent Meals: Some people find that eating five or six small meals a day is easier on their digestive system than two or three large ones [1.4.2].

For more severe diarrhea, a healthcare provider might suggest over-the-counter antidiarrheal medicines like loperamide (Imodium), but this should only be used with great caution and after consulting your doctor, as it can increase the risk of complications in IBD patients [1.4.2, 1.4.6].

Comparison of Pentasa and Alternatives

Pentasa is one of several 5-ASA medications available. The main difference between them lies in their delivery mechanisms, which affects where in the gut the drug is released [1.6.6].


Medication	Active Ingredient	Delivery Mechanism	Common Side Effects (including but not limited to)
Pentasa	Mesalamine	Controlled-release microgranules (pH-independent)	Diarrhea, headache, nausea, abdominal pain, rash [1.3.5].
Sulfasalazine	Sulfasalazine	Cleaved by colon bacteria into mesalamine & sulfapyridine	Headache, nausea, loss of appetite, rash. The sulfapyridine part causes more side effects [1.2.2, 1.8.3].
Balsalazide (Colazal)	Balsalazide	Prodrug converted to mesalamine in the colon	Headache, abdominal pain, nausea, diarrhea [1.6.1]. Often considered better tolerated [1.6.1].
Asacol/Lialda	Mesalamine	pH-dependent coating (releases at pH >7)	Abdominal pain, headache, flatulence, nausea [1.8.1].

If Pentasa is not effective or causes intolerable side effects, a doctor may suggest switching to another 5-ASA formulation, corticosteroids (like Budesonide), immunomodulators, or biologic therapies [1.6.1, 1.6.4]. The choice depends on the severity and location of the disease [1.6.1]. For example, for inflammation confined to the rectum (proctitis), rectal suppositories (Canasa) or enemas (Rowasa) might be preferred [1.6.1].

Conclusion

So, can Pentasa cause diarrhea? The answer is yes. Diarrhea is a known and relatively common side effect, which often subsides with time. However, it's also crucial to be aware of the possibility of mesalamine intolerance, where the medication paradoxically worsens symptoms like bloody diarrhea and cramping. Differentiating between a mild side effect, a drug intolerance reaction, and a flare-up of the underlying disease is critical for proper management. Always maintain open communication with your healthcare provider, report any new or worsening symptoms promptly, and never alter your medication dosage without medical advice [1.2.3].

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always consult with a qualified healthcare professional for any health concerns or before making any decisions related to your medication.

Find more information from the Crohn's & Colitis Foundation.

Frequently Asked Questions

Diarrhea is one of the most common side effects, reported in approximately 3.4% of patients during clinical trials for Pentasa [1.3.5].

Yes, in some cases, Pentasa can cause a paradoxical reaction known as mesalamine intolerance, which leads to a worsening of colitis symptoms like bloody diarrhea, severe abdominal pain, and fever [1.7.1, 1.7.6].

If you develop severe stomach pain, cramping, or bloody diarrhea (which may be accompanied by fever or a rash), you should stop using Pentasa and call your doctor at once [1.4.7].

For many people who experience mild diarrhea as a side effect, it often lessens or goes away after a few weeks of treatment as their body adjusts. Persistent or severe diarrhea should be discussed with a healthcare provider [1.2.7].

The primary difference is the delivery mechanism. Pentasa uses a time-dependent release system that works throughout the GI tract, while others like Lialda and Asacol have a pH-dependent coating designed to release the medication in the colon [1.8.1, 1.5.3].

You should use antidiarrheal medicines like loperamide (Imodium) with great caution and only after speaking with your healthcare team, as they can increase the risk of a serious complication called toxic megacolon in people with IBD [1.4.2].

Yes, alternatives include other 5-ASA medications (like balsalazide or sulfasalazine), rectal mesalamine formulations, corticosteroids, immunomodulators, and biologic drugs. Your doctor can recommend the best option based on your specific condition [1.6.1, 1.6.4].