Diclofenac, a widely used anti-inflammatory painkiller, can cause side effects ranging from mild stomach upset to serious cardiovascular events. The most common problems are gastrointestinal: heartburn, nausea, stomach pain, and diarrhea affect a significant number of users. But diclofenac also carries an FDA black box warning for increased risk of heart attack and stroke, making it important to understand both the everyday and the serious risks before taking it.
Stomach and Digestive Side Effects
The digestive system takes the biggest hit from oral diclofenac. Common complaints include heartburn, indigestion, stomach cramps, bloating, nausea, constipation, and diarrhea. These are the side effects most people notice first, and they’re the reason many people stop taking the drug. In one clinical comparison, 28.2% of people taking oral diclofenac reported side effects, most of them gastrointestinal.
More concerning digestive effects are also possible. Diclofenac can cause bleeding in the stomach or intestines, sometimes without warning pain beforehand. Signs to watch for include black or tarry stools, vomiting blood or material that looks like coffee grounds, and blood in your urine. These symptoms point to internal bleeding and need immediate medical attention. The risk goes up the longer you take the drug and at higher doses, and it’s greater in older adults.
Heart Attack and Stroke Risk
Diclofenac carries a boxed warning from the FDA, the most serious type of safety alert. Clinical trials of NSAIDs lasting up to three years have shown an increased risk of heart attack and stroke, both of which can be fatal. This risk can appear as early as the first weeks of treatment and tends to climb with higher doses and longer use.
People who already have heart disease face the greatest absolute danger. Data from the Danish National Registry found that among patients who had already had a heart attack, those who then took NSAIDs had a death rate of 20 per 100 person-years in the first year, compared to 12 per 100 person-years among those not taking NSAIDs. That elevated risk persisted for at least four years. Diclofenac is also specifically contraindicated right before or after coronary artery bypass graft surgery, where trials showed clear increases in heart attack and stroke.
Kidney and Liver Effects
Diclofenac, like other NSAIDs, can impair kidney function through two main pathways. The first is a reduction in blood flow to the kidneys. NSAIDs block the production of certain protective compounds that help keep the kidneys’ blood vessels dilated, so when those compounds drop, the kidneys receive less blood and can’t filter as efficiently. The second pathway is an immune-mediated reaction in which the kidney tissue itself becomes inflamed.
People who are dehydrated, elderly, or already have reduced kidney function are most vulnerable. If you notice swelling in your ankles, a significant decrease in how much you urinate, or unexplained weight gain while taking diclofenac, those can be signs your kidneys are struggling. Liver problems are less common but possible. Symptoms like clay-colored stools, dark urine, or yellowing of the skin or eyes suggest the liver is affected.
Nervous System and Energy
Headache, dizziness, and unusual tiredness are among the more common neurological side effects. These are generally mild and often improve as your body adjusts to the medication.
Less frequently, diclofenac can cause numbness or tingling in the hands and feet, confusion, difficulty concentrating, trouble sleeping, or a spinning sensation. Some people experience lightheadedness when standing up quickly. Drowsiness is also reported, which is worth knowing if you drive or operate machinery.
Skin Reactions and Sun Sensitivity
Mild skin reactions like itching and rash are relatively common. Diclofenac is also a known photosensitizing drug, meaning it can make your skin more reactive to sunlight. This happens through two mechanisms: a direct toxic reaction where the drug in your skin absorbs UV light and damages cells, and an allergic reaction where sunlight triggers an immune response. If you’re taking diclofenac and notice an unusual sunburn or rash on sun-exposed areas, the medication is likely involved.
Rare but serious skin reactions are also possible. Blistering, peeling skin, or red lesions with purple centers are warning signs that need prompt medical evaluation. These can indicate severe allergic reactions affecting the skin.
Topical Diclofenac Has Fewer Risks
If you use diclofenac as a gel or cream applied to the skin rather than taking it as a pill, the side effect profile changes dramatically. A crossover study in healthy volunteers found that oral diclofenac produced blood levels 14 to 27 times higher than the topical gel, depending on whether the gel was applied to one joint or two. Peak drug concentrations were 87 to 161 times higher with the oral form.
This difference shows up clearly in side effect rates. Only 2.6% of people using topical diclofenac reported drug-related side effects (mostly a mild burning sensation at the application site), compared to 28.2% of those taking the oral tablets. If your pain is localized to a joint like a knee or hand, the topical form delivers the drug where you need it while keeping very little in your bloodstream.
Drug Interactions That Raise Risk
Several common medications interact with diclofenac in ways that amplify side effects. Blood thinners like warfarin combined with diclofenac significantly increase the chance of bleeding, since both drugs interfere with clotting through different mechanisms. Blood pressure medications, including ACE inhibitors, can become less effective when you take diclofenac, because the drug promotes fluid retention that works against the blood pressure medication’s purpose. Diuretics (water pills) pose a double problem: diclofenac can reduce their effectiveness while the combination puts extra stress on the kidneys.
If you take any of these medications regularly, the interaction matters more than the diclofenac side effects alone. The combination can create risks that neither drug would cause on its own.
What Affects Your Risk Level
Not everyone faces the same odds of side effects. Several factors push the risk higher:
- Dose and duration: Higher doses and longer courses consistently increase both cardiovascular and gastrointestinal risks.
- Age: Older adults are more susceptible to stomach bleeding and kidney problems.
- Existing heart disease: People with a history of heart attack, stroke, or heart failure face the highest absolute cardiovascular risk.
- Kidney function: If your kidneys are already compromised, even short courses can cause further decline.
- Dehydration: Being dehydrated while taking diclofenac magnifies the kidney effects, because your kidneys are already working with reduced blood flow.
For short-term use at the lowest effective dose, most people tolerate diclofenac well. The serious risks become more relevant with chronic use, higher doses, and preexisting health conditions.