Medications for ulcerative colitis (UC) can treat and prevent flares, but they can also come with some uncomfortable side effects. For example, immunomodulators like azathioprine (Azasan) decrease UC inflammation by suppressing the immune system, but this effect is linked to an increased risk of infections.
Other UC medications like aminosalicylates (5-ASAs), steroids, and biologics may also come with unwanted side effects that can vary in severity.
Some side effects may be temporary and go away with time. But if uncomfortable side effects persist, it’s important to let your doctor know. They may tweak your medication regimen or suggest other ways to manage the side effects.
Here are seven of the most common UC medication side effects and tips for dealing with them.
1. Upset Stomach
UC medications can cause an upset stomach because they affect the lining of your gastrointestinal (GI) tract, says Adam Pont, MD, a gastroenterologist in private practice in New York City. “Essentially all UC meds have nausea, vomiting, and upset stomach as potential side effects,” he says.
But these symptoms may happen most often with medications like methotrexate or 5-ASAs like mesalamine, says Shubha Bhat, PharmD, a clinical pharmacy specialist in IBD at the digestive disease institute at Cleveland Clinic in Ohio.
How to manage it: If you experience an upset stomach after taking your UC medications, tell your healthcare provider, who can adjust your dose if needed, says Dr. Pont. “Make sure you are taking it correctly,” he says. Pont also sometimes recommends anti-nausea or acid-reducing medication and suggests eating small, more frequent meals and staying well-hydrated to alleviate this side effect.
2. Tiredness
Tiredness or fatigue, a common symptom of UC itself, can also be a side effect of steroids, 5-ASAs, and biologics for the condition.
“Steroids may cause sleep disturbances and mood changes, which can contribute to fatigue,” says Tanvi Dhere, MD, a gastroenterologist and an associate professor with the division of digestive diseases at Emory University School of Medicine in Atlanta. Some people feel extra tired when starting a biologic agent or oral medication, though this often improves over time, Dr. Dhere says.
How to manage it: If you have fatigue, your provider may check for low iron or vitamin levels, which can contribute to tiredness, or change your medication dose if needed. But you can also improve your energy by exercising regularly, doing your best to manage stress, practicing mindfulness, and getting a good night’s sleep every night. For better sleep, limit caffeine before bed, keep the same daily sleep schedule, and make your bedroom cool, dark, and comfy.
3. Headache
Headaches can happen as a side effect of any medication for UC, says Dhere. “Steroids may raise blood pressure, which can trigger headaches, and some people experience [them] when tapering or stopping steroids,” she says.
Other UC meds, like aminosalicylates, biologics, immunomodulators, and synthetic small molecules, can provoke headaches in those who are sensitive to their ingredients or because of general effects on the immune system, says Pont.
How to manage it: Pont recommends staying hydrated and taking acetaminophen (Tylenol) for headache pain, but urges anyone with persistent headaches after taking UC medications to tell their provider.
“If headaches persist, it’s important to check for other possible causes, such as dehydration or nutritional deficiencies,” says Dhere.
4. Skin Problems
Certain UC medications can cause skin problems as a side effect. For example, steroids can cause the skin to lose elasticity and get thinner over time with long-term use, and other medications can lead to rashes. “Anti-TNF alpha agents such as infliximab (Remicade) and adalimumab (Humira) have been linked to certain skin reactions such as psoriasis,” says Dhere.
Janus kinase (JAK) inhibitors can lead to acne breakouts, says Dr. Bhat. In addition, some people may experience injection site reactions — like bruising, itching, and rashes — with IV or injected biologic treatments, Bhat says.
How to manage it: If you’re having persistent skin problems, you may want to see a dermatologist, who can prescribe skin ointments to help manage medication reactions or assess if your skin condition is related to your underlying UC, says Dhere. “Sometimes switching to another agent such as ustekinumab (Stelara) or risankizumab (Skyrizi) is needed to manage psoriasis if it is severe, as these agents can treat both ulcerative colitis and psoriasis,” she says.
For infusion or injection site reactions, Pont recommends rotating the injection site with each dose to lessen irritation. “You can pretreat the injection site with a cooling alcohol spray, or apply a cold pack after injection,” he says.
If IV infusions prompt a skin reaction, your provider may slow or stop it. If the reaction stays mild, they may recommend taking acetaminophen (Tylenol) and diphenhydramine (Benadryl), an antihistamine, before your next dose to minimize side effects, says Dhere.
5. Increased Risk of Infection
Many UC medications lower intestinal inflammation by suppressing the immune system, but this can increase your risk of infections. For example, JAK inhibitors can increase the likelihood you’ll contract the shingles virus, says Bhat.
“Biologic agents such as infliximab (Remicade), vedolizumab (Entyvio), and ustekinumab (Stelara) as well as oral medication that can suppress the immune system, such as prednisone and upadacitinib (Rinvoq), can increase the risk of infections, says Dhere, although the rate of serious infections is quite low.
How to manage it: To lessen your infection risk, Pont recommends getting any vaccines you may need, wearing a surgical face mask in public, and avoiding crowds during peak flu season.
“There are several vaccines available to help prevent some of these infections, including flu, pneumonia, shingles, and COVID,” says Dhere. “It is important to work with your healthcare provider to ensure you are up-to-date with all your vaccines,” says Dhere.
6. Mental Health Concerns
Steroids suppress the immune system and decrease UC inflammation, but if they’re taken for too long, they can also cause mental health issues like irritability, anxiety, and depression. Side effects like these are why steroids are typically only prescribed for short periods.
No other UC medications are known to have this effect. In fact, one study review of JAK inhibitors for rheumatoid arthritis found these drugs may actually improve mental health.
How to manage it: If you notice new mental health symptoms after starting a UC medication, tell your provider right away. They can help you monitor these side effects and adjust your meds if needed.
7. Cardiovascular Concerns
Steroids can contribute to high blood pressure and cholesterol, and research suggests that long-term use of steroids or multiple courses can increase the risk of heart attack, cardiac arrhythmia, and heart failure. JAK inhibitors like tofacitinib (Xeljanz) and baricitinib (Olumiant) have also been linked to cardiac events (like heart attacks) and blood clots.
How to manage it: Your provider will screen you for heart problems during your visits and may recommend medications, like statins for high cholesterol, to help manage any issues. Along with any medication your doctor prescribes, you can improve your heart health by eating foods low in salt and saturated fats, exercising regularly, maintaining a healthy weight, and not smoking.
The Takeaway
Medications used to treat ulcerative colitis (UC) can cause some unpleasant side effects that vary in severity.
UC medication side effects can include upset stomach, headaches, tiredness, skin changes, infection, mental health challenges, and heart issues.
You can manage these side effects by working with your provider to adjust medications or make certain lifestyle changes.
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Shamail GM et al. Association Between Janus Kinase Inhibitors Therapy and Mental Health Outcome in Rheumatoid Arthritis: A Systematic Review and Meta-analysis. Rheumatology and Therapy. 2021.
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Yuying Luo, MD, is an assistant professor of medicine at Mount Sinai West and Morningside in New York City. She aims to deliver evidence-based, patient-centered, and holistic care for her patients.
Her clinical and research focus includes patients with disorders of gut-brain interaction such as irritable bowel syndrome and functional dyspepsia; patients with lower gastrointestinal motility (constipation) disorders and defecatory and anorectal disorders (such as dyssynergic defecation); and women’s gastrointestinal health.
She graduated from Harvard with a bachelor's degree in molecular and cellular biology and received her MD from the NYU Grossman School of Medicine. She completed her residency in internal medicine at the Icahn School of Medicine at Mount Sinai, where she was also chief resident. She completed her gastroenterology fellowship at Mount Sinai Hospital and was also chief fellow.
Abby McCoy is an experienced registered nurse who has worked with adults and pediatric patients encompassing trauma, orthopedics, home care, transplant, and case management. She is a married mother of four and loves the circus — that is her home! She has family all over the world, and loves to travel as much as possible.
McCoy has written for publications like Remedy Health Media, Sleepopolis, and Expectful. She is passionate about health education and loves using her experience and knowledge in her writing.
