Dozens of commonly prescribed and over-the-counter medications can cause bowel problems, ranging from mild constipation or diarrhea to serious complications like intestinal bleeding. The most frequent culprits include opioid painkillers, antibiotics, anti-inflammatory drugs like ibuprofen, iron supplements, diabetes medications, and acid-reducing drugs. Understanding which medications carry these risks can help you recognize what’s behind a sudden change in your bowel habits.
Opioid Painkillers
Opioids are among the most reliable triggers of constipation. Estimates of opioid-induced constipation range from 15% to as high as 81% of people taking these drugs, depending on the dose and duration. This isn’t a side effect that fades with time the way drowsiness might. Opioids bind to receptors throughout the gut, slowing the muscular contractions that push stool forward. The longer you take them, the more likely constipation becomes, and it rarely resolves on its own without intervention.
Medications in this category include oxycodone, hydrocodone, morphine, codeine, and tramadol. Even codeine-containing cough syrups can slow things down. If you’re prescribed an opioid for more than a few days, your provider will often recommend starting a stool softener or laxative at the same time rather than waiting for constipation to develop.
Antibiotics
Antibiotics are one of the most common causes of drug-related diarrhea. They work by killing bacteria, but they can’t distinguish between the harmful bacteria causing your infection and the helpful bacteria in your gut. When that balance gets disrupted, the result is often loose or watery stools that start within days of beginning the medication.
In more serious cases, wiping out protective bacteria allows a harmful species called Clostridioides difficile (C. diff) to multiply unchecked. C. diff produces toxins that damage the lining of the large intestine, causing severe diarrhea, cramping, and sometimes fever. Broad-spectrum antibiotics, those designed to target a wide range of bacteria, carry the highest risk. Older adults and people who’ve recently been hospitalized are especially vulnerable to C. diff infection.
NSAIDs: Ibuprofen, Naproxen, and Aspirin
Nonsteroidal anti-inflammatory drugs are so widely used that their gut effects often go underappreciated. These medications block an enzyme that helps produce protective compounds lining the stomach and intestines. Without that protective layer, the tissue becomes vulnerable to damage from stomach acid and digestive enzymes. The result can be erosions, ulcers, and bleeding anywhere from the stomach to the lower intestine.
NSAIDs can also directly increase the permeability of the intestinal lining, making the barrier less stable. This doesn’t always cause obvious symptoms. Some people develop slow, chronic blood loss they don’t notice until it causes anemia. Others experience nausea, stomach pain, or visible blood in their stool. The risk climbs with higher doses, longer use, and age over 65.
Anticholinergic Medications
A large family of drugs shares a common mechanism that slows gut motility: blocking a chemical messenger called acetylcholine. This messenger controls the involuntary muscle contractions that move food through your digestive tract. When it’s blocked, transit time slows dramatically, leading to constipation, bloating, and sometimes nausea.
You might not realize how many medications have this effect. The list includes certain antihistamines (like diphenhydramine), bladder control drugs (like solifenacin), older antidepressants (tricyclics like amitriptyline), some antipsychotics, and anti-nausea medications. Many older adults take several of these at once, compounding the effect. If you’re dealing with unexplained constipation and take multiple medications, anticholinergic side effects are worth investigating.
Antidepressants
Both older and newer antidepressants can affect bowel function, though in different ways. Tricyclic antidepressants have strong anticholinergic properties, making constipation their primary gut side effect. Newer antidepressants in the SSRI and SNRI classes more commonly cause diarrhea or nausea, especially in the first few weeks. Duloxetine, an SNRI, appears frequently in adverse event reports for constipation as well, so the picture varies by specific drug.
These side effects often improve after the first month as your body adjusts. Starting at a lower dose and increasing gradually can reduce the initial impact on your gut.
Iron Supplements
Iron supplements are notorious for causing bowel trouble in both directions. Constipation is the most common complaint, but some people experience diarrhea, stomach cramps, or nausea instead. Higher doses tend to cause worse symptoms. One harmless but alarming change: iron turns stool black, which is completely normal and not a sign of bleeding.
Taking iron with food, splitting the dose into smaller amounts throughout the day, or switching to a different formulation can reduce symptoms. Some forms of supplemental iron are gentler on the stomach than others, so if one type causes problems, an alternative may work better.
Metformin
Metformin, the most widely prescribed medication for type 2 diabetes, is well known for causing diarrhea, nausea, gas, and abdominal discomfort. Diarrhea and nausea are the most frequent complaints, and they’re a leading reason people stop taking the drug. The symptoms tend to be worst when first starting the medication or after a dose increase.
Starting at a low dose and increasing slowly over several weeks helps many people tolerate it. An extended-release version of metformin releases the drug more gradually and causes fewer gut symptoms for most people. Still, some individuals can’t tolerate metformin at all, and convincing someone to try it again after a bad initial experience can be difficult.
Proton Pump Inhibitors
Acid-reducing drugs like omeprazole, esomeprazole, and lansoprazole are designed to help the stomach, but they can create problems further down the digestive tract. By suppressing stomach acid, they reduce one of the body’s natural defenses against bacterial overgrowth in the small intestine.
A meta-analysis found that about 37% of people on PPIs had small intestinal bacterial overgrowth (SIBO), compared to roughly 20% of people not taking them. The risk increased with duration: people taking PPIs for more than six months had roughly four times the odds of developing SIBO compared to non-users. Each additional month of PPI therapy was associated with a 4.3 percentage point increase in SIBO prevalence. SIBO typically causes bloating, gas, diarrhea, and abdominal discomfort, symptoms that are easy to mistake for other conditions.
PPIs can also cause diarrhea directly in some people, though this is less common.
Chemotherapy Drugs
Cancer treatments frequently cause both diarrhea and constipation, sometimes alternating between the two. Chemotherapy targets rapidly dividing cells, and the cells lining your intestine are among the fastest-dividing in your body. The resulting damage to the intestinal lining can cause watery diarrhea, cramping, and poor nutrient absorption. Anti-nausea medications given alongside chemotherapy often have anticholinergic properties, adding constipation risk on top.
Other Common Offenders
Several other medications deserve mention:
- Calcium channel blockers used for blood pressure can slow gut contractions and cause constipation.
- Magnesium-containing antacids draw water into the intestine and commonly cause or worsen diarrhea.
- Bisphosphonates like alendronate, used for osteoporosis, can irritate the upper digestive tract and are associated with constipation.
- Immunosuppressants such as mycophenolate frequently cause diarrhea as a side effect.
- Herbal teas containing senna or other natural laxative compounds can cause diarrhea that people don’t always connect to something they’re drinking.
Recognizing Serious Warning Signs
Most medication-related bowel changes are uncomfortable but manageable. However, certain symptoms signal something more serious. Nausea and vomiting combined with bloating, belly swelling, or abdominal pain can indicate a bowel obstruction or severe constipation that needs medical attention. Blood in your stool, whether bright red or dark and tarry (and you’re not taking iron), warrants prompt evaluation. Severe or persistent diarrhea, especially after antibiotics, could point to a C. diff infection that requires specific treatment. Unexplained weight loss alongside bowel changes also needs investigation, since it may not be the medication at all.
If your bowel habits changed shortly after starting a new medication, that timing is valuable information for your provider. In many cases, adjusting the dose, switching to a different formulation, or adding a targeted remedy can resolve the problem without giving up a medication you need.