Non-steroidal anti-inflammatory drugs (NSAIDs)
ATC code: M01AB05 (Diclofenac)
Brand names
Voltaren
Non-selective cyclooxygenase inhibitor with greater COX-2 selectivity than ibuprofen. Potent anti-inflammatory effect through prostaglandin synthesis suppression and inhibition of leukocyte migration to the site of inflammation. Analgesic onset within 20-30 minutes of oral intake. Available as oral, rectal, intramuscular, and topical formulations.
First line
Diclofenac 50 mg 2-3 times daily or 75 mg twice daily is one of the most effective NSAIDs for pain of various origins. Maximum daily dose 150 mg. Surpasses ibuprofen in analgesic potency. Short course of 5-7 days is preferred. If prolonged use is needed, cardiovascular and gastrointestinal risk must be assessed.
First line
For osteoarthritis, OA 2022 recommends starting with topical NSAIDs – diclofenac gel applied to the affected joint 3-4 times daily. Topical form provides local effect with minimal systemic exposure. Oral diclofenac is used when topical therapy is insufficient. Due to high cardiovascular risk, short courses are preferred.
First line
Diclofenac is first-line for renal colic. Administered intramuscularly 75 mg or rectally 100 mg. Efficacy is comparable to opioid analgesics with less nausea and vomiting. A 2015 Cochrane review confirmed NSAIDs' advantage over antispasmodics in renal colic.
Adjunct
Diclofenac is used as symptomatic treatment in rheumatoid arthritis to reduce pain and stiffness. NSAIDs do not affect disease progression – disease-modifying therapy (methotrexate etc.) is mandatory. Prescribed at the lowest effective dose during flares.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID). It is prescribed for osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and acute pain (AEMPS Ficha Técnica). In anti-aging circles, diclofenac is promoted as an anti-aging drug to suppress low-grade inflammation in healthy adults, citing older work on inflammation and aging. Regular diclofenac use in people without a confirmed inflammatory disease is not justified: the Bhala 2013 meta-analysis (CNT collaboration, over 350,000 patients) showed that diclofenac increases cardiovascular events by 40% versus placebo, more than most other NSAIDs. Regular use also elevates the risk of gastrointestinal bleeding and acute kidney injury. If diclofenac was prescribed for chronic use against aging-related inflammation, consider seeking a second opinion.
15 pairs found. Sorted from critical to minor.
Mechanism
Ketorolac and diclofenac are both NSAIDs. Co-administration adds up the risks: gastrointestinal bleeding, acute kidney injury, raised blood pressure. Toradol Section 4.3 specifically lists other NSAIDs as contraindications.
Symptoms
Black or tarry stools (melena), vomiting blood or coffee-ground material, epigastric pain. Acute kidney injury and a rise in blood pressure are also possible. Risk of bleeding multiplies in patients over 65 and with prior peptic ulcer disease.
Management
The combination is not prescribed. For adequate analgesia, choose one NSAID as monotherapy (diclofenac or ketorolac short course with PPI cover such as pantoprazole). Alternative: paracetamol plus an opioid if pain is insufficiently controlled.
Sources
Mechanism
Diclofenac competitively inhibits platelet cyclooxygenase-1 and blocks aspirin's access for COX-1 acetylation. Co-administration loses aspirin's cardioprotective effect. Additive ulcerogenic effect of two NSAIDs.
Symptoms
Black or tarry stools (melena), vomiting blood or coffee-ground material, epigastric pain. Risk multiplies in older patients and with prior peptic ulcer disease.
Management
If the patient takes aspirin for cardioprotection, give aspirin 30 minutes before or 8 hours after diclofenac. Alternative analgesic without this issue: paracetamol or a selective COX-2 inhibitor (celecoxib).
Mechanism
Apixaban inhibits factor Xa; diclofenac injures the gastric mucosa and reduces platelet aggregation. Diclofenac additionally raises cardiovascular event risk, which matters in atrial fibrillation patients.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.
Management
Avoid where possible. If diclofenac is needed for a short course, use the minimum effective dose for no more than 5–7 days under pantoprazole cover. For chronic analgesia, choose paracetamol, celecoxib, or topical NSAIDs.
Symptoms
Reduced urine output, rising creatinine and potassium, oedema. Symptoms appear earlier in older patients and in chronic kidney disease.
Management
Avoid prolonged combination. If diclofenac is needed for a short course, use the minimum effective dose for 5–7 days with creatinine monitoring. For chronic analgesia: paracetamol or celecoxib.
Mechanism
Similar to naproxen + lithium. NSAIDs reduce renal lithium clearance via prostaglandin blockade.
Symptoms
Tremor, muscle twitching, nausea, diarrhoea, confusion, ataxia. Symptoms emerge when serum lithium exceeds 1.2 mmol/L.
Management
Avoid prolonged combination. If diclofenac is needed for a short course, reduce lithium by 25–30% and check level at 5–7 days. For chronic analgesia: paracetamol.
Mechanism
Diclofenac, like other NSAIDs, reduces methotrexate renal clearance. With high-dose methotrexate – fatal myelosuppression and nephrotoxicity. With low-dose methotrexate – higher risk of cytopenia and liver injury.
Symptoms
Same as with ibuprofen: mucositis, cytopenia, rising creatinine and transaminases.
Management
Same approach as methotrexate+ibuprofen. If a rheumatoid arthritis patient needs an NSAID, prefer paracetamol or a short ibuprofen course with lab monitoring.
Mechanism
Similar to ibuprofen – additive GI bleeding risk. Diclofenac has a higher ulcerogenic potential among NSAIDs.
Symptoms
Black or tarry stools (melena), vomiting blood or coffee-ground material, epigastric pain. Risk multiplies in older patients and with prior peptic ulcer disease.
Management
Avoid prolonged combination. If diclofenac is needed, use the minimum effective dose for 5–7 days with mandatory pantoprazole cover. For chronic analgesia: paracetamol or celecoxib.
Mechanism
Additive GI bleeding risk: anticoagulant (rivaroxaban) + ulcerogenic NSAID (diclofenac). Diclofenac additionally raises cardiovascular risk.
Symptoms
Black or tarry stools (melena), vomiting blood or coffee-ground material, epigastric pain. Risk multiplies in older patients and with prior peptic ulcer disease.
Management
Avoid prolonged combination. If diclofenac is needed for a short course, use the minimum effective dose for 5–7 days under pantoprazole cover. For chronic analgesia: paracetamol, celecoxib (less GI toxicity), or topical NSAIDs.
Mechanism
Diclofenac (NSAID) suppresses renal prostaglandin synthesis maintaining glomerular perfusion. Tacrolimus is nephrotoxic in its own right. Additive acute kidney injury risk in transplant patients.
Symptoms
Reduced urine output, rising creatinine, potassium accumulation. In kidney transplant patients: accelerated graft function decline.
Management
Avoid chronic diclofenac on tacrolimus. For analgesia post-transplant, use paracetamol (up to 2 g/day) or a short opioid course. For neuropathic pain, gabapentin or pregabalin.
Mechanism
Diclofenac (NSAID) inhibits platelet aggregation, injures the gastric mucosa, and weakly displaces warfarin from albumin binding. Additive GI bleeding risk independent of INR.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.
Management
Avoid chronic diclofenac on warfarin. For analgesia, choose paracetamol (up to 2 g/day for short courses). For chronic NSAID needs, use a selective COX-2 inhibitor (celecoxib) under pantoprazole cover.
Mechanism
No direct pharmacokinetic interaction. Additive bleeding risk in patients on concurrent warfarin or amiodarone (the latter enhances anticoagulation via CYP2C9 inhibition).
Symptoms
Epigastric pain, heartburn, black or tarry stools, gum bleeding, bruising. Higher risk in older patients and prior peptic ulcer disease.
Management
For short diclofenac courses (3–7 days), no specific adjustment needed. For long-term needs, consider paracetamol up to 2 g/day, topical NSAIDs, or physiotherapy. Avoid NSAIDs on a warfarin-amiodarone regimen.
Mechanism
NSAIDs weaken amlodipine's antihypertensive effect via prostaglandin suppression. Diclofenac additionally raises cardiovascular risk.
Symptoms
Gradual blood pressure rise 1–2 weeks after starting the NSAID. In chronic kidney disease: risk of fluid retention and oedema.
Management
Avoid prolonged diclofenac use. For acute pain: short course (5–7 days) with pantoprazole cover. For chronic analgesia: paracetamol, celecoxib, or topical NSAIDs.
Mechanism
NSAIDs weaken the antihypertensive effect of beta-blockers via renal prostaglandin suppression. Diclofenac is one of the most ulcerogenic NSAIDs with elevated cardiovascular risk.
Symptoms
Gradual blood pressure rise 1–2 weeks after starting the NSAID. In chronic kidney disease: risk of fluid retention and oedema.
Management
Avoid prolonged diclofenac use. For acute pain: short course (5–7 days) with pantoprazole cover. For chronic analgesia: paracetamol, celecoxib, or topical NSAIDs.
Mechanism
Glucocorticoid plus NSAID — additive GI ulcer and bleeding risk with systemic budesonide. Inhaled budesonide does not clinically affect risk.
Symptoms
Epigastric pain, heartburn, black or tarry stools, blood in vomit, bruising. Higher risk in older patients, prior peptic ulcer, and concurrent anticoagulants.
Management
On systemic budesonide, limit diclofenac to short courses (no more than 5–7 days) with pantoprazole 20 mg/day. For long-term analgesia: paracetamol up to 2 g/day or topical NSAIDs. Inhaled budesonide with diclofenac is safe. In older patients and prior peptic ulcer, risk outweighs benefit.
Mechanism
Additive nephrotoxicity. NSAIDs reduce renal blood flow by suppressing vasodilatory prostaglandin synthesis; contrast adds tubular osmotic load. Contrast-induced AKI risk rises 2–3-fold.
Symptoms
Decreased urine output, rising creatinine, oedema, nausea. Symptoms develop 24–72 hours after contrast.
Management
Stop diclofenac 24–48 hours before elective contrast imaging; restart 48 hours after the study once creatinine normalises. With creatinine clearance below 60 mL/min, give IV isotonic hydration 6–12 hours before and 6–12 hours after imaging. Analgesic alternative: paracetamol up to 3 g/day.
Sources
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FDA category C in the first and second trimesters. Contraindicated in the third trimester (category D) due to risk of premature ductus arteriosus closure and oligohydramnios. Avoid after 20 weeks.
Excreted in breast milk in small amounts. Short-term use is acceptable. If prolonged treatment is needed, ibuprofen is preferred.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Diclofenac is evaluated for the following indications with varying evidence strength: Rheumatoid arthritis (evidence tier A), Renal colic (evidence tier A), Mild to moderate pain in adults (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of Diclofenac (≥ 1 in 100): Dyspepsia, epigastric pain, nausea, Headache, dizziness, Elevated liver transaminases, Fluid retention, edema. See the Safety section for uncommon and serious reactions.
FDA category C. FDA category C in the first and second trimesters. Contraindicated in the third trimester (category D) due to risk of premature ductus arteriosus closure and oligohydramnios. Avoid after 20 weeks.
Excreted in breast milk in small amounts. Short-term use is acceptable. If prolonged treatment is needed, ibuprofen is preferred.
Diclofenac is contraindicated in: Established coronary artery disease, prior MI or stroke; Heart failure (NYHA II-IV); Uncontrolled arterial hypertension; Active peptic ulcer disease or GI bleeding; Severe renal impairment (eGFR below 30). Full list in the Safety section.