Can nicorandil cause diarrhea? Understanding the Risks and Side Effects

October 8, 2025 •

4 min read

While nicorandil is generally well-tolerated, gastrointestinal disorders, including diarrhea, are recognized side effects. For some individuals, however, persistent or severe diarrhea may not be a simple stomach upset but a symptom of a more serious underlying condition, such as gastrointestinal ulceration.

Quick Summary

Nicorandil is a medication used for angina, and mild diarrhea is a common adverse effect. However, severe or chronic diarrhea may indicate gastrointestinal ulceration, a rare but serious side effect that requires immediate medical attention. Management depends on the cause, with ulcers typically resolving only after discontinuing the drug under a doctor's supervision.

Key Points

Diarrhea is a reported side effect: Mild diarrhea can be a common side effect of nicorandil, often occurring early in treatment and potentially resolving over time.
Severe diarrhea can signal ulceration: Persistent, severe, or bloody diarrhea may indicate the development of gastrointestinal ulcers, a more serious but rarer side effect.
Ulceration affects the whole GI tract: Nicorandil-induced ulcers can appear anywhere from the mouth to the colon and anus, causing significant pain and symptoms like severe diarrhea.
Ulcers are refractory to normal treatment: Unlike typical ulcers, those caused by nicorandil often do not heal with standard medication and require discontinuation of nicorandil.
Management requires medical supervision: Patients experiencing persistent or severe GI symptoms must contact their doctor. Stopping the drug should only happen under the careful guidance of a cardiologist.
Awareness is critical: Both patients and healthcare providers should be aware of the link between nicorandil and GI ulceration to ensure timely diagnosis and appropriate treatment.

Nicorandil and its Common Gastrointestinal Effects

Nicorandil is a potassium channel activator and nitrate-like compound used to prevent and treat angina pectoris, a type of chest pain caused by reduced blood flow to the heart. By relaxing and widening blood vessels, it improves blood and oxygen supply to the heart muscle. Like all medications, nicorandil can cause side effects. Among the common, non-serious side effects, transient gastrointestinal complaints such as nausea, vomiting, and mild diarrhea have been reported, especially during the initial stages of treatment. These symptoms are often mild and may resolve on their own as the body adjusts to the medication.

Distinguishing Common vs. Severe Diarrhea

For most people, experiencing occasional or mild diarrhea is a temporary inconvenience. It might be managed with dietary adjustments or by taking the medication with food, as suggested for general gastrointestinal upset. However, it is crucial to recognize that persistent, severe, or bloody diarrhea while taking nicorandil can be a red flag for a more serious complication.

The Dangerous Link Between Nicorandil and Gastrointestinal Ulceration

A less common, but potentially severe, side effect of nicorandil is the development of painful ulcerations throughout the gastrointestinal (GI) tract. These ulcers can manifest in various locations, including the mouth, stomach, intestines, colon, and perianal region. When these ulcers occur in the intestinal or colonic areas, severe, bloody, and chronic diarrhea becomes a prominent symptom.

Case reports highlight the seriousness of this complication, with some patients enduring debilitating symptoms for years before the link to nicorandil was identified. A key feature of nicorandil-induced ulcers is that they are often refractory, meaning they do not respond to standard ulcer treatments and only begin to heal upon discontinuation of the drug.

Potential Mechanisms Behind Ulceration

The exact reason nicorandil causes ulceration is not fully understood, but several theories have been proposed. It may involve a direct toxic effect of the drug or one of its metabolites on the gastrointestinal mucosa. Another hypothesis is the "vascular steal phenomenon," where the drug's vasodilatory effects cause blood to be diverted from certain areas of the intestine, leading to localized ischemia and subsequent ulcer formation. The risk of ulceration may also be dose-dependent, with higher doses increasing the risk, though cases have been reported at lower doses as well.

Common vs. Serious Gastrointestinal Side Effects of Nicorandil

This list highlights the range of GI side effects, from common and mild to rare and serious, associated with nicorandil use.

Common (mild to moderate)

Nausea
Vomiting
Indigestion
Diarrhea (mild)
Abdominal pain

Serious (requiring immediate medical attention)

Severe or chronic diarrhea
Gastrointestinal ulcerations (oral, gastric, intestinal, colonic, anal)
Gastrointestinal bleeding
Gastrointestinal perforation
Fistula formation
Weight loss associated with GI symptoms

Nicorandil vs. Other Anti-Angina Medications


Feature	Nicorandil	Long-Acting Nitrates (e.g., Isosorbide mononitrate)	Beta-blockers (e.g., Atenolol)
Mechanism of Action	Dual (K-ATP channel opener & NO donor)	NO donor only	Blocks beta-adrenergic receptors
Most Common Side Effect	Headache	Headache	Fatigue, dizziness
Common GI Effects	Nausea, vomiting, mild diarrhea	Nausea, vomiting	Nausea, vomiting, diarrhea
Risk of GI Ulceration	Rare but serious risk throughout GI tract	No significant risk reported	No significant risk reported
GI Ulcer Management	Discontinuation of the drug	Not applicable	Not applicable

What to Do If You Experience Persistent Diarrhea

If you are taking nicorandil and experience persistent, worsening, or severe diarrhea, it is vital to contact your healthcare provider immediately. Do not stop taking the medication on your own without professional medical advice, as this could be dangerous for your heart condition. Your doctor may need to perform a thorough investigation, possibly including an endoscopy or colonoscopy, to rule out nicorandil-induced ulceration. If a link is confirmed, the only effective treatment is to cease taking nicorandil, a process that must be managed by a cardiologist to ensure your heart condition remains stable. Prompt recognition can prevent the condition from worsening and avoid the need for unnecessary surgical interventions.

Conclusion

Diarrhea can be a side effect of nicorandil, but it is important to understand the context. While mild, transient diarrhea may occur, severe or persistent diarrhea can be a sign of a more serious, rare complication: gastrointestinal ulceration. Because these ulcers are refractory to standard treatments and typically only heal upon nicorandil withdrawal, prompt communication with your healthcare provider is crucial. Raising awareness of this serious side effect among patients and clinicians is key to ensuring early diagnosis and appropriate management, potentially preventing irreversible harm.

For more information on the safety of medications, consult the European Medicines Agency (EMA) or other national regulatory bodies. For instance, the European Medicines Agency (EMA) has provided safety updates regarding nicorandil.

Frequently Asked Questions

No, mild and temporary diarrhea is a known common side effect. However, if diarrhea becomes severe, persistent, bloody, or is accompanied by severe abdominal pain, it could be a sign of a serious complication, such as gastrointestinal ulceration.

Besides diarrhea, other reported GI side effects include nausea, vomiting, abdominal pain, indigestion, constipation, and in more serious cases, ulcerations in the mouth, stomach, or intestines.

You should contact your doctor immediately. Persistent diarrhea may indicate a more serious issue like ulceration. Do not stop taking the medication without consulting your doctor, as this could pose a risk to your heart condition.

The onset of ulcers varies widely. They can develop within a few months of starting the drug, or in some cases, several years later.

No, nicorandil-induced ulcers are typically refractory to treatment and will only heal upon discontinuation of the drug. Management requires a cardiologist's supervision to ensure continued cardiac care.

Your doctor will take a thorough medical history and may recommend diagnostic procedures like an endoscopy or colonoscopy to check for ulcerations. If ulcers are found and other causes are ruled out, nicorandil will be considered the likely cause.

Some evidence suggests that a higher dose of nicorandil may increase the risk of ulceration, but cases have been reported even at lower doses. It is important to be vigilant regardless of your prescribed dosage.