7 Common Crohn’s Disease Medication Side Effects and How to Cope With Them

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On September 18, 2025

Medications for Crohn’s disease can reduce inflammation, ease Crohn’s symptoms, and prevent flares, but some come with side effects that can be difficult to handle. There are several types of Crohn’s medications, such as 5-aminosalicylates (5-ASAs), steroids, biologics, and janus kinase (JAK) inhibitors, and each carry a risk of different side effects.

If you’re having side effects, it’s important to let your doctor know, especially if they persist. Don’t stop taking your medication without talking to your doctor first. “We screen, monitor, and adjust treatment to catch problems early, whether that means splitting a dose, protecting bone health, or switching medications,” says Ritu Nahar, MD, a gastroenterologist with Allied Digestive Health in New Brunswick, New Jersey. “The goal is always the same: control inflammation while keeping patients feeling their best.”

Here are seven of the most common Crohn’s disease medication side effects and how you can manage them.

1. Nausea and Vomiting

Several drugs sometimes used for Crohn’s, such as antibiotics, mesalamines, and methotrexate, a drug that suppresses the immune system, can cause nausea and vomiting.

These drugs typically irritate the gastrointestinal (GI) tract, which can lead to stomach upset, says Shubha Bhat, PharmD, a clinical pharmacy specialist in IBD at the Digestive Disease Institute at Cleveland Clinic in Ohio.

How to manage it: To lessen nausea and vomiting, try to eat small meals and snacks throughout the day and rinse your mouth afterward to avoid an unpleasant aftertaste. Avoid alcohol and spicy, fatty, or very sweet foods.

You can try ginger lozenges or tea between meals to ease the feeling of nausea.

“Taking them with food, splitting the dose, or switching to an injection form can often help,” says Dr. Nahar.

In severe cases, your healthcare provider may prescribe an anti-nausea medication, says Dr. Bhat.

2. Headaches

Headaches can happen with any Crohn’s disease medication, says Tanvi Dhere, MD, a gastroenterologist and an associate professor with the division of digestive diseases at Emory University School of Medicine in Atlanta.

“Steroids may raise blood pressure, which can trigger headaches, and some patients experience headaches when tapering or discontinuing [them],” she says

Biologic drugs, like infliximab (Remicade), vedolizumab (Entyvio), and ustekinumab (Stelara), can also cause headaches while your body is getting used to treatment, but this side effect often improves over time, says Bhat.

How to manage it: For headaches, Dr. Dhere recommends acetaminophen (Tylenol) for relief. “[But] if headaches persist, it is important to evaluate for other potential causes, such as dehydration or nutritional deficiencies,” she says. Bhat also suggests hydrating before infusion of biologics to minimize the risk of dehydration.

3. Fatigue

Crohn’s disease causes fatigue, and certain medications used to treat Crohn’s can make fatigue worse.

“Steroids may cause sleep disturbances and mood changes, which can contribute to fatigue,” says Dhere.

Some also experience fatigue when starting a biologic agent or JAK inhibitors like upadacitinib (Rinvoq), though this often improves over time, she says.

How to manage it: If you’re feeling fatigued from Crohn’s medications, Bhat recommends getting plenty of rest, especially after an infusion of biologics.

You can also combat Crohn’s fatigue with lifestyle changes. Good sleep habits, like keeping a consistent sleep schedule and limiting screen time before bed, can lessen daytime sleepiness. Daily exercise can help with stress management, another common cause of fatigue.

4. Injection Site Reactions

Biologic medications are typically injected, either through an IV catheter or into the skin with a small needle.
“Some people can have reactions where the medicine is given, either during an infusion or at the injection site,” says Dhere. “In some cases, these reactions can be severe enough that the medication needs to be stopped, especially if the body develops antibodies against infliximab (Remicade) or adalimumab (Humira).”

How to manage it: Skin reactions are usually managed by taking antihistamines beforehand, slowing the infusion, or switching your medication to another class, says Nahar. For those taking injections, rotating injection sites and allowing the medication to come to room temperature before injecting can help ease reactions, says Dhere.

5. Skin Problems

Several Crohn’s medications can cause skin problems like acne, rashes, and thinning skin.
“[For example,] anti-TNF alpha agents, such as infliximab (Remicade) and adalimumab (Humira), can occasionally cause skin reactions like psoriasis,” says Dhere.

JAK inhibitors like upadacitinib (Rinvoq) and tofacitinib (Xeljanz) can change the skin’s microbiome and cause or worsen acne, says Bhat.
5-ASAs like mesalamine can cause rashes and itching, and steroids change the skin by slowing the production of collagen (which gives your skin elasticity) leading to thinning and fragile skin.

How to manage it: The best way to manage skin changes from Crohn’s medications is to see a dermatology provider, who can manage side effects with topical treatments, says Dhere. “In more severe cases, switching to another medication — such as ustekinumab (Stelara) or risankizumab (Skyrizi) — may be considered, as these agents can treat both Crohn’s disease and psoriasis,” she says.

6. Greater Risk of Infection

Since so many Crohn’s medications suppress the immune system, many could increase your risk of infections, says Nahar.
For example, research suggests some JAK inhibitors increase the risk of shingles infection.

“Biologic agents such as infliximab (Remicade), vedolizumab (Entyvio), and ustekinumab (Stelara), as well as oral immune-suppressing medications, can increase the risk of infections, though the risk of serious infection is generally low,” says Dhere.

How to manage it: To help prevent infection, Bhat recommends practicing good preventive care: Wash your hands often, avoid touching your face, get enough sleep, and follow a nutritious diet.

“Several vaccines can [also] help prevent these infections, including the flu vaccine, shingles vaccine, and COVID-19 vaccine,” says Dhere, who recommends the shingles vaccine for people on immunosuppressive therapy.

“[It] is especially important for those taking upadacitinib (Rinvoq), as this medication carries a higher risk of shingles,” she says. You can work with your healthcare provider to stay current on all recommended vaccines.

7. Heart Problems and Blood Clots

In various ways, Crohn’s medications can affect how well your heart and blood vessels function. For example, people who take JAK inhibitors can have a higher risk of blood clots, which researchers believe may happen because of blocked immune system messengers called cytokines.
That said, Crohn’s disease itself can cause an increase in blood clots, and medication treatment may help reduce the overall risk of blood clots.

How to manage it: You can lessen your risk of heart complications by following a heart-healthy lifestyle: Get your blood pressure and cholesterol checked regularly, maintain a healthy weight, exercise regularly, do your best to manage stress, quit smoking, and get enough sleep.

A heart-healthy diet is also important. This means eating plenty of fruits and vegetables, and limiting or avoiding saturated fats, salt, and processed foods as much as possible.
Be sure to check in with your provider regularly so they can monitor your heart health and recommend further treatments if needed.

The Takeaway

Medications for Crohn’s disease can help manage symptoms, but they can also cause certain unwanted side effects.
Upset stomach, headaches, fatigue, injection site reactions, skin changes, infection, and heart issues are common side effects of Crohn’s medication.
You can manage all these side effects by working with your provider to adjust your medications or change your lifestyle habits to feel your best.
Don’t stop taking your Crohn’s medication without talking to your doctor first.