Understanding the Risks: What Organ Does Diclofenac Affect?

October 9, 2025 •

4 min read

As many as 15% of patients taking oral diclofenac chronically may experience mild elevations in liver enzymes, signaling a potential impact on the liver. This is just one example of what organ does diclofenac affect, alongside significant risks to the gastrointestinal and cardiovascular systems.

Quick Summary

Diclofenac is an NSAID that can impact several internal organs, particularly the gastrointestinal tract, cardiovascular system, kidneys, and liver. Potential side effects include ulcers, bleeding, heart attack, stroke, and organ damage. Risks are heightened with higher doses and prolonged use.

Key Points

Gastrointestinal Tract: Diclofenac commonly affects the stomach and intestines, posing a risk for ulcers, bleeding, and perforation due to reduced protective prostaglandins.
Cardiovascular System: The medication carries an FDA boxed warning for serious and potentially fatal cardiovascular events, including heart attack and stroke, especially with high doses or long-term use.
Kidneys: Diclofenac can cause kidney damage by reducing renal blood flow and is not recommended for patients with pre-existing kidney dysfunction.
Liver: The liver can also be affected, with mild elevations in liver enzymes being relatively common, and rare but serious cases of acute liver disease or failure documented.
Oral vs. Topical Risks: Topical formulations of diclofenac carry a much lower risk of systemic organ damage compared to oral forms, though local skin reactions are possible.
Risk Mitigation: The lowest effective dose for the shortest duration, along with avoiding alcohol and using gastroprotective agents when advised, can help minimize organ-related risks.

Diclofenac is a widely prescribed non-steroidal anti-inflammatory drug (NSAID) used to manage pain and inflammation in conditions like arthritis. While effective, its pharmacological action, which involves inhibiting cyclooxygenase (COX) enzymes, can have systemic effects that impact multiple organs throughout the body. A comprehensive understanding of the potential adverse effects is crucial for patients and healthcare providers to ensure safe usage.

The Primary Organs Affected by Diclofenac

Gastrointestinal (GI) Tract

The gastrointestinal tract is one of the most commonly and seriously affected organ systems. The inhibition of COX-1, an enzyme responsible for producing protective prostaglandins that maintain the stomach lining, makes the GI tract vulnerable. This can lead to a range of issues, from mild upset stomach to life-threatening complications.

Common side effects: Nausea, vomiting, heartburn, diarrhea, constipation, and abdominal pain.
Serious complications: Gastric ulcers, intestinal bleeding, and perforation (a tear in the stomach or intestinal wall). The FDA has issued a boxed warning for these risks, noting they can occur at any time, with or without warning symptoms.

Cardiovascular System

Diclofenac and other NSAIDs carry a risk of serious cardiovascular thrombotic events, such as heart attack and stroke. The risk is associated with the drug's inhibition of COX-2, which affects the balance of pro- and anti-thrombotic prostaglandins. This risk can increase with higher doses and longer duration of use, even in patients without pre-existing heart disease.

Increased risks: Heart attack, stroke, blood clots, and heart failure.
FDA boxed warning: A boxed warning emphasizes the increased risk of potentially fatal cardiovascular events.
Contraindications: Diclofenac is generally contraindicated in patients with established cardiovascular disease, including ischemic heart disease, peripheral arterial disease, cerebrovascular disease, and moderate-to-severe heart failure.

Kidneys

The kidneys are particularly susceptible to damage from NSAIDs. The inhibition of prostaglandins, which are vital for maintaining proper blood flow to the kidneys, is the main mechanism of harm. This reduction in renal blood flow can cause acute kidney injury, particularly in at-risk individuals.

Potential issues: Decreased renal blood flow, fluid retention (edema), high potassium levels (hyperkalemia), and acute or worsening kidney injury.
Risk factors: Pre-existing kidney disease, concomitant use of diuretics or certain blood pressure medications (ACE inhibitors, ARBs), and dehydration increase the risk of kidney problems.
FDA warnings: The drug label explicitly warns that long-term use can cause renal papillary necrosis and other kidney injury.

Liver

While less common than GI or cardiovascular issues, diclofenac can cause liver damage (hepatotoxicity). This can range from mild, asymptomatic elevations in liver enzymes to rare cases of severe hepatitis and acute liver failure. The liver is central to metabolizing the drug, and genetic factors may play a role in susceptibility to injury.

Common effects: Mild and transient elevations of liver enzymes in some patients.
Severe complications: In rare instances, clinically apparent liver disease with jaundice can occur, and in very rare cases, this can lead to liver failure.
Risk factors: Pre-existing liver disease or taking other potentially hepatotoxic drugs can increase the risk.

Comparing Risks: Oral vs. Topical Diclofenac


Feature	Oral Diclofenac	Topical Diclofenac (e.g., gel)
Systemic Absorption	High absorption into the bloodstream, distributing throughout the body.	Much lower absorption into the bloodstream, with most effect being localized.
Gastrointestinal Risk	Significant risk of GI side effects, including ulcers, bleeding, and perforation. Black box warning in place.	Minimal risk of serious GI side effects because less drug reaches the stomach.
Cardiovascular Risk	Increased risk of heart attack, stroke, and blood clots. Black box warning in place. Risk increases with dose and duration.	Minimal systemic risk due to low absorption. Less likely to cause cardiovascular events.
Kidney Risk	Notable risk of causing or worsening kidney injury, especially with long-term, high-dose use and comorbidities.	Minimal risk to kidneys due to low systemic exposure.
Liver Risk	Potential for liver enzyme elevation and, rarely, severe hepatotoxicity.	Extremely low risk of clinically apparent liver injury.
Application Site Reactions	Not applicable.	Common side effect is skin irritation at the application site, such as rash or itching.

How to Minimize the Risks of Diclofenac

To safely use diclofenac, it is essential to follow a healthcare professional's guidance and adopt strategies to reduce potential harm to your organs.

Use the lowest effective dose for the shortest duration possible. This is the most important rule for all NSAIDs, including diclofenac, to minimize the risk of side effects.
Take with food or milk. This can help reduce the risk of mild stomach upset.
Avoid alcohol. The combination of diclofenac and alcohol significantly increases the risk of GI bleeding and ulcers.
Consider gastroprotective medication. For high-risk individuals or those on long-term treatment, a healthcare provider may co-prescribe a proton pump inhibitor (PPI) or H2 blocker to protect the stomach.
Stay hydrated. Adequate fluid intake is especially important to help protect the kidneys.
Monitor for symptoms. Be vigilant for any signs of adverse effects, such as black stools, yellowing skin, or chest pain, and seek medical attention immediately if they occur.
Inform your doctor. Disclose all health conditions, including history of heart, kidney, or liver disease, and all other medications you are taking, as drug interactions can increase risks.

Conclusion

Diclofenac is a powerful and useful medication for pain and inflammation, but its use comes with risks to several vital organs, including the stomach, intestines, heart, kidneys, and liver. Its mechanism of action, involving COX enzyme inhibition, is responsible for both its therapeutic effects and its potential for harm. The risks are typically dose-dependent and heightened with prolonged treatment. By using diclofenac cautiously, at the lowest effective dose, and for the shortest duration necessary, patients can help mitigate these risks. Anyone considering diclofenac, especially those with pre-existing conditions, should have a thorough discussion with their doctor to weigh the benefits against the potential side effects.

For more detailed prescribing information and boxed warnings, consult authoritative drug safety websites.

Frequently Asked Questions

The most serious organ-related side effects of diclofenac, based on FDA boxed warnings, are serious cardiovascular events like heart attack and stroke, and severe gastrointestinal problems, including bleeding, ulcers, and perforation.

Yes, diclofenac can cause kidney damage, ranging from temporary reduced function to acute kidney injury or, in rare cases, kidney failure, particularly with long-term use or in high-risk patients.

Yes, diclofenac can affect the liver. It is known to cause elevations in liver enzymes, and in rare instances, it can lead to serious liver disease or even acute liver failure.

People with a history of heart, kidney, or liver disease are at higher risk. Other risk factors include advanced age, heavy alcohol consumption, smoking, and using diclofenac for a long duration or at high doses.

Yes, topical diclofenac formulations (gels, patches) are absorbed less systemically than oral forms and thus carry a significantly lower risk of serious GI, cardiovascular, and renal side effects.

Warning signs of internal GI bleeding include black, tarry stools; vomiting blood or material that looks like coffee grounds; and persistent or severe stomach pain.

To protect your stomach, take diclofenac with food, use the lowest effective dose for the shortest time, avoid alcohol, and discuss with your doctor whether a gastroprotective medication (like a PPI) is necessary.

Diclofenac harms organs by inhibiting cyclooxygenase (COX) enzymes, particularly COX-1 and COX-2. This action blocks the production of prostaglandins, which are protective in the stomach and kidneys, and disrupts the balance of substances affecting blood clot formation.

No, you should not take other NSAIDs, such as ibuprofen or aspirin, with diclofenac unless directed by a doctor, as this significantly increases the risk of serious GI side effects and bleeding.

If you suspect organ damage (e.g., chest pain, difficulty breathing, yellowing skin, severe stomach pain), stop taking the medication and seek immediate medical attention. Your doctor will perform tests and evaluate your condition.