What Medications Make Colitis Worse?

October 8, 2025 •

4 min read

Globally, nearly 7 million people have Inflammatory Bowel Disease (IBD), a condition that can be aggravated by certain drugs [1.5.7]. For those managing colitis, understanding what medications make colitis worse is crucial for preventing symptom flare-ups and maintaining remission [1.3.2].

Quick Summary

Managing colitis involves knowing which drugs can trigger flares. Key medications to avoid or use with caution include NSAIDs like ibuprofen, certain antibiotics that disrupt gut flora, and other specific drugs known to exacerbate IBD symptoms.

Key Points

NSAIDs are a primary trigger: Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen can cause colitis flare-ups and should be avoided [1.3.2, 1.3.3].
Antibiotics disrupt gut flora: Certain antibiotics can alter the gut microbiome, potentially leading to worsened symptoms or C. diff infection [1.3.4, 1.5.5].
Acetaminophen is a safer pain reliever: For mild pain and fever, acetaminophen (Tylenol) is the recommended alternative to NSAIDs for people with colitis [1.3.5].
Isotretinoin has a controversial link: The acne medication isotretinoin has a debated association with ulcerative colitis, with some studies showing a transient increased risk [1.6.6].
Consult your doctor: Always talk to your healthcare provider, especially your gastroenterologist, before taking any new over-the-counter or prescription medication [1.2.1, 1.3.3].
Other drugs can be culprits: Medications like oral contraceptives, some immunomodulators, and proton pump inhibitors have also been linked to colitis issues [1.2.2, 1.2.5, 1.7.4].
Broad-spectrum antibiotics pose a higher risk: Antibiotics that target a wide range of bacteria are more likely to cause gut dysbiosis and trigger IBD symptoms [1.5.1, 1.5.7].

Understanding Colitis and Medication Sensitivity

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by inflammation and ulceration of the colon's lining [1.2.1]. This inflammation leads to symptoms like diarrhea, abdominal pain, and rectal bleeding [1.3.2]. A critical part of managing UC involves not only prescribed treatments but also avoiding triggers that can cause a flare-up. While food and stress are well-known triggers, certain medications—both over-the-counter and prescription—can also significantly worsen colitis symptoms [1.3.7].

Drug-induced colitis occurs when a medication either initiates or exacerbates inflammation in the colon [1.2.7]. The mechanisms vary, from direct irritation of the gut lining to altering the delicate balance of the gut microbiome [1.4.6, 1.5.4]. Therefore, individuals with colitis must be vigilant about any new medication they take and maintain open communication with their healthcare providers [1.3.3].

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): The Primary Culprits

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common medications that people with colitis are advised to avoid [1.3.2]. These drugs, frequently used for pain and fever, can trigger flare-ups and worsen inflammation [1.2.3, 1.3.3]. NSAIDs work by blocking COX enzymes; while this reduces pain, it can also inhibit the production of prostaglandins that protect the gut lining, potentially leading to irritation, ulcers, and bleeding [1.4.6, 1.4.7].

Common NSAIDs to avoid include:

Ibuprofen (Advil, Motrin, Brufen) [1.2.1, 1.3.6]
Naproxen (Aleve) [1.2.1, 1.3.6]
Aspirin: The evidence on aspirin is mixed. Some sources state it can worsen symptoms, while a 2023 study suggested long-term use might be associated with lower in-hospital mortality for UC patients. It is crucial to consult a doctor before using aspirin [1.2.1].
Diclofenac (Voltaren) [1.3.5]

For mild pain or fever, acetaminophen (Tylenol) is generally considered a safer alternative as it does not typically cause the same gastrointestinal side effects [1.3.5, 1.3.6].

The Complex Role of Antibiotics

The relationship between antibiotics and colitis is complex. While certain antibiotics like metronidazole and ciprofloxacin may be prescribed to treat specific IBD-related complications like abscesses or pouchitis, their use can also be problematic [1.5.3, 1.5.6]. Antibiotics can disrupt the gut microbiome, the fragile ecosystem of bacteria in your intestines [1.3.4]. This disruption, known as dysbiosis, can kill beneficial bacteria, allowing harmful ones like Clostridioides difficile (C. diff) to overgrow, potentially leading to a flare-up or a new form of colitis called pseudomembranous colitis [1.5.4, 1.5.5].

Research suggests that just one course of antibiotics can increase the risk of developing IBD, and multiple courses elevate that risk further [1.5.4]. Broad-spectrum antibiotics, which target a wide range of bacteria, are particularly associated with an increased risk [1.5.1, 1.5.7].

Antibiotics that may pose a higher risk include:

Fluoroquinolones (e.g., Ciprofloxacin) [1.5.4]
Penicillin and Ampicillin [1.5.4]
Clindamycin [1.5.4]
Cephalosporins [1.5.4]
Nitroimidazoles (e.g., Metronidazole) [1.2.8]

If an antibiotic is necessary for an unrelated infection, patients should always inform their gastroenterologist [1.3.4].

Other Medications of Concern

Beyond NSAIDs and antibiotics, several other medications have been linked to worsening colitis symptoms or inducing the condition.

Isotretinoin (formerly Accutane): Used for severe acne, the link between isotretinoin and IBD has been controversial. While some studies show no increased lifetime risk, others suggest it may be associated with a slight, transient increase in UC risk, particularly within the first six months of use [1.6.2, 1.6.6]. Case reports have documented UC flares after starting the medication [1.6.4].
Oral Contraceptives: Some studies suggest that oral contraceptives may slightly increase the chance of developing ulcerative colitis [1.2.5, 1.7.7].
Immune Checkpoint Inhibitors: Medications used in cancer therapy, such as ipilimumab and pembrolizumab, can cause drug-induced colitis [1.2.2, 1.7.5].
Mycophenolate Mofetil: An immunosuppressive agent that has been linked to drug-induced IBD [1.2.2].
Certain Proton Pump Inhibitors (PPIs): Drugs like lansoprazole and omeprazole have been associated with microscopic colitis [1.7.3, 1.7.4].

Comparison of Problematic Medications for Colitis


Medication Class	Examples	Mechanism of Worsening Colitis	Safer Alternatives/Considerations
NSAIDs	Ibuprofen, Naproxen, Aspirin [1.2.1]	Inhibit protective prostaglandins in the gut lining, causing irritation and inflammation [1.4.6].	Acetaminophen (Tylenol) is generally recommended for mild pain and fever [1.3.5].
Antibiotics	Ciprofloxacin, Amoxicillin, Clindamycin [1.5.4, 1.5.5]	Disrupt the gut microbiome, leading to dysbiosis and potential overgrowth of harmful bacteria like C. diff [1.3.4].	Use should be judicious. Inform gastroenterologist of any antibiotic prescriptions [1.3.3]. Narrow-spectrum antibiotics may be preferred [1.5.1].
Retinoids	Isotretinoin [1.6.4]	The exact mechanism is not fully understood but may involve impacting T-cell function and adaptive immunity [1.6.4]. Association is controversial but some studies show a transient risk [1.6.6].	Discuss risks and benefits with a dermatologist and gastroenterologist. Monitor for GI symptoms [1.6.4].
Oral Contraceptives	Various hormonal pills	May slightly increase the chance of developing UC [1.2.5].	Discuss family planning options and IBD risks with a healthcare provider.

Conclusion

Managing colitis effectively requires a comprehensive approach that includes careful consideration of all medications. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely recognized culprits for triggering flare-ups and should generally be avoided [1.3.2]. The role of antibiotics is nuanced; while necessary for certain infections, they can disturb the gut microbiome and should be used with caution and under medical supervision [1.5.5]. Other medications, from isotretinoin to oral contraceptives and specific immunotherapies, also carry potential risks [1.2.2, 1.2.5]. The most important step for any individual with colitis is to maintain an open dialogue with their healthcare team, ensuring that any new medication's benefits are weighed against the potential risks to their gastrointestinal health. Always consult a doctor before starting or stopping any medication [1.2.1].

For more information, you can visit the Crohn's & Colitis Foundation.

Frequently Asked Questions

For mild pain or fever, acetaminophen (Tylenol) is generally considered the safest pain reliever for people with ulcerative colitis, as it does not typically worsen symptoms like NSAIDs can [1.3.5, 1.3.6].

It is strongly recommended that people with ulcerative colitis avoid taking ibuprofen. Ibuprofen is an NSAID that can cause inflammation in the intestines, worsen symptoms, and trigger a flare-up [1.2.1, 1.3.3].

Not all antibiotics will make colitis worse, and some are used to treat IBD-related infections. However, many antibiotics, especially broad-spectrum ones, can disrupt the gut microbiome and potentially cause a flare-up. It's crucial to use them with caution and inform your gastroenterologist [1.3.3, 1.5.1].

The link is controversial. Some studies suggest a slight and temporary increase in the risk of developing ulcerative colitis, particularly in the first few months of use, while other studies have not found a significant long-term association. If you have IBD, discuss the risks with your doctor before starting isotretinoin [1.6.2, 1.6.6].

Some studies suggest that using oral contraceptives might slightly increase the risk of developing ulcerative colitis. If you have IBD or a family history of it, you should discuss contraceptive options with your doctor [1.2.5].

If a doctor prescribes a medication like an NSAID or a high-risk antibiotic, make sure they are aware you have ulcerative colitis. Discuss your concerns and ask if there are any safer alternatives available for your situation [1.2.1, 1.3.3].

Other medications linked to colitis issues include some immune checkpoint inhibitors used for cancer, certain immunosuppressants like mycophenolate mofetil, and proton pump inhibitors (PPIs) which have been associated with microscopic colitis [1.2.2, 1.7.1, 1.7.4].