Dozens of commonly prescribed medications can cause bowel problems, ranging from constipation and diarrhea to more serious complications like intestinal inflammation and bacterial infections. Pain relievers, antibiotics, blood pressure drugs, diabetes medications, and even over-the-counter supplements are frequent culprits. In many cases, the bowel symptoms are predictable side effects that can be managed once you know what’s causing them.
Opioid Pain Medications
Opioid painkillers are one of the most reliable causes of constipation. Drugs like oxycodone, hydrocodone, morphine, and codeine activate receptors throughout the gut that slow muscle contractions, reduce fluid secretion into the intestines, and tighten the anal sphincter. The result is hard, infrequent stools that can persist for the entire time you take the medication. Unlike many drug side effects, opioid-induced constipation doesn’t improve as your body adjusts to the drug. If you’re prescribed an opioid for more than a few days, your doctor will often recommend a stool softener or laxative from the start.
NSAIDs and Over-the-Counter Pain Relievers
Ibuprofen, naproxen, aspirin, and other nonsteroidal anti-inflammatory drugs are best known for causing stomach ulcers, but they can damage the entire length of the digestive tract. In the small intestine, NSAIDs strip away the protective mucus lining and increase permeability, which allows bacteria and digestive enzymes to irritate the tissue underneath. This can lead to inflammation, bleeding, and ulceration that you might notice as cramping, loose stools, or dark tarry stool.
Small bowel damage is especially common with NSAIDs that recirculate through the liver and back into the intestines. Long-term or high-dose use raises the risk significantly. Even occasional use can trigger nausea or diarrhea in some people.
Antibiotics
Antibiotics kill bacteria indiscriminately, wiping out beneficial gut flora along with the infection you’re treating. This disruption often causes loose stools or outright diarrhea that can start within days of beginning a course and sometimes linger for weeks after finishing it. Broad-spectrum antibiotics, which target a wide range of bacteria, are the worst offenders.
The more serious concern is a gut infection caused by Clostridioides difficile (C. diff), a bacterium that thrives when antibiotics have cleared out its competition. C. diff releases toxins that damage the intestinal lining, causing watery diarrhea, fever, and abdominal pain. Hospitalized patients are at highest risk because the organism survives on surfaces like bed rails, doorknobs, and countertops in healthcare settings. But community-acquired C. diff infections can also develop, sometimes even without recent antibiotic use.
Acid-Suppressing Medications (PPIs)
Proton pump inhibitors like omeprazole, pantoprazole, and lansoprazole reduce stomach acid to treat heartburn and ulcers, but stomach acid also serves as a barrier against swallowed bacteria. Suppressing it long-term can allow bacteria to survive the stomach and colonize the small intestine, a condition called small intestinal bacterial overgrowth (SIBO). Symptoms include bloating, gas, diarrhea, and abdominal discomfort.
PPIs also increase susceptibility to enteric infections, including C. diff, for the same reason. If you’ve been on a PPI for months and develop persistent bloating or changes in bowel habits, the medication itself may be contributing.
Metformin for Diabetes
Metformin is the most widely prescribed diabetes medication in the world, and digestive side effects are its most common drawback. Roughly 7% of patients develop diarrhea, and smaller numbers experience nausea or vomiting. These symptoms tend to be worst in the first few weeks of treatment and when the dose increases. Starting at a low dose and increasing gradually helps many people tolerate it. An extended-release formulation also causes fewer gut symptoms than standard metformin because the drug is absorbed more slowly.
GLP-1 Weight Loss and Diabetes Drugs
Semaglutide (Ozempic, Wegovy) and liraglutide (Saxenda) belong to a class of drugs that mimic a gut hormone called GLP-1. They work partly by slowing stomach emptying, which helps you feel full longer. But that same mechanism can cause nausea, vomiting, and constipation, particularly in the first weeks of treatment.
More concerning are rarer complications. A retrospective study comparing GLP-1 users to people taking another weight-loss drug found that GLP-1 users had roughly four times the risk of gastroparesis (severely delayed stomach emptying) and a similarly elevated risk of bowel obstruction. These are uncommon outcomes, but they’re worth knowing about if you develop severe abdominal pain, persistent vomiting, or an inability to pass gas or stool while taking one of these medications.
Blood Pressure Medications
Among blood pressure drugs, calcium channel blockers are the ones most likely to affect your bowels. Verapamil is the biggest offender, with constipation reported in 12% to 42% of users, and most estimates landing above 30%. The drug relaxes smooth muscle throughout the body, including the muscles that move stool through the colon. Diltiazem, another calcium channel blocker, causes fewer digestive side effects. The dihydropyridine types like amlodipine and nifedipine are less likely to cause constipation but can occasionally cause nausea or loose stools.
Iron Supplements
Iron tablets are notorious for causing constipation, and they also turn stool dark or black. The color change is harmless (it’s just unabsorbed iron reacting with digestive enzymes), but it can be alarming if you aren’t expecting it, since dark stool can also signal intestinal bleeding. If you know you’re taking iron, the color change alone isn’t a concern.
The constipation is more of a practical problem. Taking iron with food, splitting the dose, or switching to a different formulation (like iron bisglycinate instead of ferrous sulfate) can reduce symptoms, though it may also slightly reduce absorption.
Chemotherapy Drugs
Cancer chemotherapy is one of the harshest categories for bowel side effects. The lining of the intestines replaces itself every few days, making it one of the fastest-dividing tissues in the body. Chemotherapy drugs that target rapidly dividing cells inevitably damage the gut lining along with tumor cells. This causes a condition called intestinal mucositis: inflammation, ulceration, and breakdown of the intestinal wall that leads to pain, diarrhea, and sometimes dangerous infections as bacteria cross from the gut into the bloodstream.
Depending on the drug and dosing regimen, intestinal mucositis affects 40% to 100% of patients receiving chemotherapy. Drugs like 5-fluorouracil, methotrexate, irinotecan, and doxorubicin are among the most commonly implicated. The damage typically begins within days of a treatment cycle and peaks before the gut lining regenerates.
Antidepressants and Psychiatric Medications
SSRIs like sertraline and fluoxetine increase serotonin levels, and since about 90% of the body’s serotonin is produced in the gut, this can speed up intestinal motility and cause diarrhea, nausea, or cramping. These effects often ease after the first few weeks. Tricyclic antidepressants have the opposite problem: their anticholinergic properties slow the gut and frequently cause constipation. Antipsychotic medications, particularly older ones, share this anticholinergic effect and can cause significant constipation with long-term use.
What to Do if You Suspect a Medication
If bowel problems started around the same time as a new medication or dose change, the connection is worth investigating. Keep a simple log of your symptoms and when they occur relative to taking the drug. Don’t stop a prescribed medication on your own, but do bring it up with your prescriber. In many cases, the fix is straightforward: adjusting the dose, switching to an extended-release version, taking the drug with food, or trying a different medication in the same class. For drugs that reliably cause constipation, adding fiber, fluids, or an over-the-counter laxative may be enough to manage the problem without changing your prescription.