Diclofenac Side Effects: What to Expect and When to Call Your Doctor

Diclofenac is an effective NSAID for managing pain and inflammation, but like all medications in this class, it carries real risks that patients should understand. The FDA has issued boxed warnings — the most serious type — for cardiovascular and gastrointestinal side effects. Knowing what to watch for helps you stay safe while benefiting from the medication.

FDA Boxed Warnings for Diclofenac

Diclofenac carries two FDA boxed warnings — the agency's highest-level safety alert:

Cardiovascular risk: NSAIDs including Diclofenac can increase the risk of serious cardiovascular events such as heart attack and stroke, which can be fatal. This risk may be higher with longer use and higher doses. Diclofenac should not be used in patients who have just had heart bypass surgery (CABG).

Gastrointestinal risk: NSAIDs can cause serious GI events including bleeding, ulceration, and perforation of the stomach or intestines. These can occur at any time without warning symptoms and can be fatal. Elderly patients are at greater risk.

Common Side Effects of Diclofenac

Most people who take Diclofenac experience mild side effects that improve as their body adjusts. Common side effects include:

Nausea or stomach upset

Heartburn or indigestion

Stomach pain or cramping

Diarrhea or constipation

Headache or dizziness

Mild elevation in liver enzymes (typically detected on blood tests)

Fluid retention or ankle swelling

For topical Diclofenac (gel or patch), local skin reactions at the application site — redness, itching, dryness — are the most common complaints. Systemic side effects are much less common with topical forms.

Serious Side Effects: Call Your Doctor or Seek Emergency Care

The following are warning signs of serious side effects. Seek immediate medical attention if you experience any of these:

Cardiovascular emergency: Chest pain, shortness of breath, weakness on one side of the body, or slurred speech — call 911 immediately.

GI bleeding: Black, tarry stools; vomiting blood or material that looks like coffee grounds; severe stomach pain — seek emergency care.

Liver toxicity signs: Yellowing of skin or eyes (jaundice), nausea with right upper abdominal pain, dark urine, or extreme fatigue — call your doctor right away.

Kidney problems: Sudden decrease in urination, severe swelling of hands/feet/face, or unexplained weight gain — contact your doctor.

Severe allergic reaction: Hives, facial swelling, difficulty breathing — call 911. Anaphylaxis is rare but can occur.

DRESS syndrome: Drug Reaction with Eosinophilia and Systemic Symptoms — a rare but potentially life-threatening allergic response with rash, fever, and organ involvement. Stop the drug and seek care immediately.

Diclofenac and Liver Health: A Special Note

Diclofenac has a somewhat higher risk of hepatotoxicity (liver toxicity) compared to other NSAIDs. Meaningful elevations in liver enzymes (AST/ALT) occur in about 2–4% of patients during treatment. Rarely, severe hepatic reactions including liver failure have been reported. Because of this:

Your doctor may order liver function tests 4–8 weeks after starting Diclofenac and periodically during treatment.

Avoid alcohol while taking Diclofenac — it increases both GI bleeding and liver toxicity risk.

Tell your doctor if you have a history of liver disease before starting Diclofenac.

How to Reduce Your Risk of Side Effects

Take the lowest effective dose for the shortest time necessary

Take oral Diclofenac with food or milk to reduce stomach irritation (exception: capsule forms should be taken on an empty stomach per label)

Avoid taking Diclofenac with other NSAIDs (ibuprofen, naproxen, aspirin)

Ask your doctor about a stomach-protecting medication (proton pump inhibitor) if you're at GI risk

Attend scheduled follow-up appointments for liver and kidney function monitoring

For information on which other drugs interact with Diclofenac and can increase side effect risk, see our guide on Diclofenac drug interactions.