Mesalamine XR Side Effects: What to Expect and When to Call Your Doctor

Mesalamine XR is generally well-tolerated, and serious side effects are uncommon. Most people who take it for ulcerative colitis do so for years without significant problems. But like all medications, it carries potential side effects — and a few of them require prompt medical attention. Here's what to watch for.

Common Side Effects of Mesalamine XR

In clinical trials, the most commonly reported side effects of mesalamine extended-release capsules (occurring in at least 1–3% of patients) include:

Headache: One of the most frequently reported side effects. Usually mild and manageable with OTC pain relievers (check with your doctor).

Nausea and vomiting: Most common when starting treatment; taking capsules with food or splitting doses may help.

Diarrhea: Can occur even in patients taking mesalamine to treat diarrhea from UC — distinguish this from a disease flare.

Abdominal pain or cramping: Mild and usually temporary; worsening pain warrants medical evaluation.

Nasopharyngitis and upper respiratory symptoms: Cold-like symptoms have been reported in clinical trials.

Flu-like illness: General malaise, fever, and aches that resemble flu can occur in some patients.

Sun sensitivity: Mesalamine can make your skin more sensitive to sunlight. Use sunscreen and protective clothing when outdoors.

Serious Side Effects: When to Call Your Doctor Immediately

While uncommon, several serious side effects can occur with Mesalamine XR. Contact your doctor right away or seek emergency care if you experience any of the following:

Mesalamine-Induced Acute Intolerance Syndrome (AIS)

This is one of the most confusing potential side effects because its symptoms look just like a UC flare: cramping, acute abdominal pain, bloody diarrhea, and sometimes fever, headache, and rash. The key difference is that AIS worsens when you take mesalamine and improves when you stop. It has occurred in about 3% of patients in clinical trials. If you suspect AIS, stop taking Mesalamine XR and call your doctor immediately.

Kidney Problems (Nephrotoxicity)

Mesalamine is excreted primarily through the kidneys, and prolonged use can sometimes cause kidney damage — including interstitial nephritis, minimal change disease, and, rarely, renal failure. Your doctor should check your kidney function before starting Mesalamine XR and periodically during treatment. Call your doctor if you notice: changes in urination frequency, swelling in your legs or feet, unexplained weight gain, or lower back pain.

Heart Inflammation (Myocarditis and Pericarditis)

Rare but serious, mesalamine-induced myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the lining around the heart) have been reported. Symptoms include chest pain, shortness of breath, and heart palpitations. Seek emergency care immediately if these occur.

Blood Disorders

Agranulocytosis, aplastic anemia, and leukopenia have been reported with mesalamine, particularly in older adults and in patients also taking azathioprine or 6-mercaptopurine. Symptoms include unexplained fever, unusual bruising or bleeding, or repeated infections. Your doctor may monitor your blood counts periodically.

Liver Problems

Hepatotoxicity, including hepatitis and, in rare cases, liver failure, has been reported with mesalamine. Warning signs include yellowing of the skin or eyes (jaundice), dark urine, clay-colored stools, or unexplained fatigue with right-side abdominal pain.

Allergic Reactions

Because mesalamine is related to aspirin (salicylates), patients with aspirin allergy or sulfasalazine sensitivity may react to mesalamine. Symptoms of a serious allergic reaction include hives, difficulty breathing, or swelling of the face, lips, tongue, or throat. Seek emergency care immediately.

A Note About Empty Capsule Shells in Stool

Many patients who take Mesalamine XR capsules notice empty or partially empty capsule shells in their stool. This is completely normal — the polymer coating releases the medication as it passes through the GI tract, and the empty shell is left behind. However, if you see a whole, apparently intact capsule (as if no drug was released), let your doctor know — it may indicate the medication isn't being absorbed properly.

Monitoring While on Mesalamine XR

Your doctor should check your kidney function (BMP or CMP) before starting Mesalamine XR and at regular intervals during long-term use. For patients at higher risk of blood disorders, periodic CBC monitoring may be recommended. For more on drug interactions that can affect mesalamine's safety, see: Mesalamine XR drug interactions: what to avoid.