Which Medicines Cause Stomach Pain?

Medication-related stomach pain or upset is a common complaint. For some people, certain prescription or over-the-counter (OTC) medications may have this side effect.

If you have inflammatory bowel disease (IBD), avoiding medications that could lead to these types of stomach problems is important. This is especially true if you already have a history of medications causing gastrointestinal irritation.

This article discusses some of the prescription and over-the-counter drugs that are most likely to cause stomach pain and upset. It also provides some tips on how to prevent this side effect and when you should talk to your healthcare provider.

A woman with stomach ache sitting up in bed
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Pain Relievers + Fever Reducers

Certain types of pain medications are well known to cause stomach irritation if taken frequently or at high dosages.


Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for everyday pain and can be purchased over the counter. Their availability and popularity are likely reasons why they are also the most common medication-related cause of stomach irritation.

NSAIDs affect the lining of the stomach, called the mucosa. They reduce pain and inflammation by helping suppress the creation of compounds called prostaglandins.

Prostaglandins are involved in the inflammatory process. Without them, levels of pain and inflammation decrease. However, prostaglandins are also key to another important process that goes on in the stomach: the creation and upkeep of the protective mucosa.

The mucosa contains cells that produce mucus, a stringy yellowish-white substance that coats the stomach and protects it from digestive juices. NSAIDs disrupt the production of mucus, which leads to a weakness in the mucosa layer.

This thinning of the mucosa layer causes normal digestive enzymes to irritate or inflame the lining of the stomach. When there is inflammation in the stomach lining, it is called gastritis. When the inflammation progresses it can lead to bleeding, ulcers (sores in the stomach lining), or rarely, a perforation (a hole in the stomach).

Some people are more at risk of developing stomach irritation after taking NSAIDs. This includes older people or those who already have a history of stomach problems. Older individuals who take NSAIDs on a regular basis for pain and inflammation from arthritis or other conditions are at risk for stomach irritation.

A history of peptic ulcers or gastritis is also associated with a greater risk of complications after taking NSAIDs. In some cases, medications may be prescribed that can help protect the stomach lining from the negative effect of NSAIDs.


Tylenol (acetaminophen) is an alternative OTC pain medication. It is not an NSAID, so it is less likely to cause stomach irritation. However, some research has found that people taking higher doses of Tylenol may also experience stomach problems.

Importantly, high doses of Tylenol have also been associated with liver toxicity. For these reasons, you should always take the lowest effective dose of Tylenol, and never exceed the dose indicated on the packaging.


Symptoms of stomach irritation from NSAIDs can include: 

Seek emergency care at once if you're taking Tylenol and you experience any of the following symptoms:

  • Pain in the upper right part of the abdomen
  • Nausea and vomiting
  • Fatigue
  • Paleness and sweating


Antibiotics can upset the natural balance of bacteria in your stomach. All antibiotics can potentially cause stomach problems like nausea and pain. Most of the time, these symptoms are temporary.

The use of certain antibiotics, especially penicillins and cephalosporins, can cause an overgrowth of Clostridioides difficile bacteria (C. diff). The risk is especially high if you are over 65 or you are immunocompromised.


Typical side effects of antibiotics include nausea and diarrhea. If your diarrhea is severe, it may be a sign of C. diff infection. Other symptoms of C. diff can include:

  • Stomach pain
  • Nausea
  • Fever
  • Loss of appetite


Some antacids contain aluminum hydroxide as one of the main active ingredients. Antacids work for a short period of time, 30 to 60 minutes. There is a potential for rebound effect after it wears off, where more stomach acid is produced. Medications containing this drug could also lead to constipation when used long-term. 

Antacids can also cause delayed gastric emptying. Delayed gastric emptying means that the muscles in the stomach slow down and food isn't moved out of the stomach at the rate that it should. For people with gastroparesis, a disorder that causes the stomach to delay emptying, drugs that increase this slowdown effect can cause significant problems.


Some common stomach-related side effects of aluminium hydroxide include:

  • Nausea and vomiting
  • Stomach pain
  • Constipation
  • Loss of appetite

Iron Supplements

Iron supplements are best absorbed when taken on an empty stomach. This can lead to stomach problems in some people, however. 

Iron pill-induced gastritis is a rare but potentially serious complication of taking an iron supplement. It's thought that iron supplements can oxidize in the body, causing damage to the stomach and esophagus.


Side effects you might experience after taking iron supplements include:

  • Constipation
  • Nausea
  • Stomach pain
  • Dark stools


Antidiarrheal medications include over-the-counter preparations containing bismuth subsalicylate such as Pepto Bismol, Maalox, and Kaopectate. Other types of medications that may be used to treat diarrhea include:

  • Metamucil (psyllium)
  • Imodium (loperamide)
  • Imodium Multi-Symptom Relief (simethicone)


Antidiarrheals can cause:

  • Constipation
  • Loss of appetite
  • Abdominal pain
  • Nausea and vomiting

Anticholinergic Drugs

Anticholinergic medications are used to treat depression, sleep disorders, and incontinence. Some of the drugs included in this class are tricyclic antidepressants, barbiturates, muscle relaxants, and benzodiazepines. This category also includes the common OTC antihistamine Benadryl (diphenhydramine).


Like antacids, anticholinergics can cause delayed gastric emptying. This can lead to side effects such as:

  • Nausea and vomiting
  • Stomach pain
  • Constipation 
  • Loss of appetite

H2 Blockers

H2 receptor antagonists are used to treat gastroesophageal reflux disease (GERD). Some of these drugs may delay food emptying from the stomach. However, other H2 receptor antagonists may have the opposite effect and increase the rate that food empties from the stomach. The exact effects of individual drugs in this class are still under study.


H2 blockers may cause the following stomach-related side effects:

  • Nausea and vomiting
  • Diarrhea
  • Loss of appetite

Tips for Prevention

Check the medication label before you take any new medication. Some medications that cause stomach upset will include instructions for how they should be taken in order to reduce this side effect. You can also discuss this with your pharmacist when picking up a new prescription.

Generally speaking, many medication-related stomach problems can be reduced with the following precautions:

  • Take medications with food or with a full glass of water.
  • Take no more than the prescribed dose or the dose recommended on the packaging.
  • Choose coated tablets, if available.
  • Avoid drinking alcohol while taking these medications.
  • For medications that cause constipation, discuss the temporary use of laxatives or stool softeners with your healthcare provider.
  • After taking antibiotics, eat yogurt or other foods high in Lactobacillus to help restore the normal flora in your stomach.

When to Talk to Your Healthcare Provider

Check with your healthcare provider any time you have a medication side effect that concerns you. Most medication side effects are minor and will go away on their own, but some can be a sign of a serious problem. 

Seek emergency care if you have any side effects that seem serious, such as abdominal pain or diarrhea that persists or is severe.


One of the most common side effects of prescription and over-the-counter medication is stomach upset and/or stomach pain. Symptoms may include abdominal cramps, diarrhea, constipation, or nausea and vomiting. Some of these side effects are common, while others may be a sign of a more serious problem.

To reduce the uncomfortable side effects, check the label for instructions on the best way to take your medication. These effects can often be reduced with simple precautions, such as taking the medication with food. Always be sure to consult your healthcare provider if you have concerns, and seek emergency medical attention if your side effects seem severe.

A Word From Verywell

There can be risks with any medication, even those that are available over the counter. This is why it's important to let your healthcare provider know all the medications you're taking, even those that seem benign, such as an OTC pain reliever.

For most people, NSAIDs and drugs for heartburn aren't going to cause major issues, but when stomach problems crop up, regular use of these drugs could be a clue as to what might be causing the symptoms.

7 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  4. Centers for Disease Control and Prevention. What is C. diff?

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By Amber J. Tresca
Amber J. Tresca is a freelance writer and speaker who covers digestive conditions, including IBD. She was diagnosed with ulcerative colitis at age 16.