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Drug Reference

diclofenac

nonsteroidal anti-inflammatory drug· Brands: Voltaren, Cataflam, VoltarolIMIVPOPRTOP

Mechanism of action
Diclofenac inhibits the cyclo-oxygenase (COX) enzymes, COX-1 and COX-2, thereby reducing the synthesis of prostaglandins. This results in anti-inflammatory, analgesic, and antipyretic effects. It is non-selective, and its actions on gastric mucosal prostaglandins account for gastrointestinal adverse effects.
Pharmacokinetics
Diclofenac is rapidly and completely absorbed from the gastrointestinal tract when taken orally. It undergoes extensive first-pass metabolism in the liver, with only about 50% of the dose reaching systemic circulation. It is highly bound to plasma proteins (>99%). Metabolism is mainly via CYP2C9, with a short elimination half-life of approximately 1 to 2 hours. It is excreted in urine and bile, both as unchanged drug and metabolites.
Indications & dosing

Osteoarthritis

Use lowest effective dose for shortest duration.

  • adult · PO: 50 mg 2-3 times daily · Use lowest effective dose for shortest duration.

Rheumatoid arthritis

Usually given as 50 mg two or three times daily or 75 mg twice daily as modified release.

  • adult · PO: 50 mg 2-3 times daily · Usually given as 50 mg two or three times daily or 75 mg twice daily as modified release.

Ankylosing spondylitis

May require up to 150 mg daily; use lowest effective dose.

  • adult · PO: 50 mg 2-3 times daily · May require up to 150 mg daily; use lowest effective dose.

Acute musculoskeletal pain

Short-term use for a few days; take with food.

  • adult · PO: 50 mg 2-3 times daily · Short-term use for a few days; take with food.

Primary dysmenorrhea

Start with 50 mg three times daily, usually for the first 1-2 days of menses.

  • adult · PO: 50 mg 3 times daily · Start with 50 mg three times daily, usually for the first 1-2 days of menses.

Acute gout

Use for short-term management of acute attacks; consider NSAID alternatives.

  • adult · PO: 50 mg 3 times daily · Use for short-term management of acute attacks; consider NSAID alternatives.

Acute severe pain

For short-term use; give by deep intragluteal injection.

  • adult · IM: 75 mg once or twice daily · For short-term use; give by deep intragluteal injection.
Contraindications & precautions
  • Hypersensitivity to diclofenac or any NSAID · Risk of anaphylaxis and severe skin reactions.
  • Active peptic ulcer or gastrointestinal bleeding · NSAIDs can exacerbate bleeding and perforation.
  • Severe heart failure (NYHA class III or IV) · NSAIDs increase risk of thrombotic events and fluid retention.
  • Third trimester of pregnancy · Risk of premature closure of ductus arteriosus and fetal renal impairment.
  • Perioperative period of coronary artery bypass graft surgery · Increased risk of myocardial infarction and stroke.
  • Severe hepatic impairment · Diclofenac can cause hepatic injury; avoid or use with caution.
  • Use the lowest effective dose for the shortest duration necessary.
  • Caution in patients with cardiovascular disease or cardiovascular risk factors.
  • Monitor blood pressure, renal function, and liver function during treatment.
  • Caution in the elderly, as they are at increased risk of GI bleeding and renal impairment.
  • Avoid concurrent use of other NSAIDs or anticoagulants due to additive risk of bleeding.
  • Caution in patients with asthma, as diclofenac may precipitate bronchospasm.
Adverse effects
  • Dyspepsia
  • Abdominal pain
  • Nausea
  • Gastrointestinal ulcer or bleedingserious
  • Cardiovascular thrombotic events (e.g. myocardial infarction, stroke)serious
  • Acute kidney injuryserious
  • Hepatotoxicity (elevated transaminases, hepatitis)serious
  • Bronchospasm in patients with aspirin-sensitive asthmaserious
Interactions
  • lisinoprilmajorMonitor blood pressure and renal function (serum creatinine and potassium) at baseline and within 1 to 2 weeks of starting or changing doses. Consider using a non-NSAID analgesic if possible. If an NSAID is necessary, use the lowest effective dose for the shortest duration. Avoid in patients with chronic kidney disease or dehydration. Adjust lisinopril dose as needed.
  • aspirinmajorAvoid concurrent use if possible. If combination is necessary, use the lowest effective dose of diclofenac for the shortest duration, consider gastroprotective therapy (e.g., PPI), and administer aspirin at least 30 minutes before diclofenac to minimise interference. Monitor for signs of GI bleeding and cardiovascular events.
  • methotrexatemajorAvoid co-prescription if possible. If necessary, use with extreme caution: monitor renal function, blood counts, and methotrexate levels frequently; consider a lower methotrexate dose and ensure adequate hydration and alkalinisation.
  • lithiummajorAvoid concurrent use if alternatives exist. If co-prescription is necessary, monitor serum lithium levels closely before and during therapy, and after stopping diclofenac. Adjust lithium dose based on levels. Monitor renal function and watch for signs of toxicity. Consider a non-NSAID analgesic such as paracetamol if appropriate. Advise patients to seek medical attention if symptoms develop.
  • warfarinmajorAvoid co-prescription where possible. If the combination is necessary, use the lowest effective dose of diclofenac for the shortest duration and consider gastroprotection with a proton pump inhibitor. Monitor INR closely (e.g., more frequently than usual) and watch for signs of bleeding. Consider alternative analgesics such as paracetamol or opioid-based analgesia.
  • rivaroxabanmajorAvoid concurrent use where possible, especially in patients with high bleeding risk. Consider alternative analgesic or anti-inflammatory therapy, such as paracetamol or a selective cyclo-oxygenase-2 inhibitor, after assessing cardiovascular risk. If co-administration is unavoidable, prescribe the lowest effective dose and shortest duration of diclofenac, and monitor closely for signs of bleeding (e.g., melaena, haematemesis, fall in haemoglobin). Consider gastroprotective therapy with a proton pump inhibitor.
  • perindoprilmajorAvoid the combination if possible; consider paracetamol or a non-NSAID analgesic. If diclofenac is necessary, use the lowest effective dose for the shortest duration, and monitor blood pressure, serum creatinine, and potassium within a few days of starting, and periodically thereafter.
  • ramiprilmajorAvoid co-prescription where possible, especially in patients at high risk (elderly, dehydration, diuretic use, pre-existing renal disease, heart failure). If combined use is unavoidable, use the lowest effective dose of diclofenac for the shortest duration, ensure adequate hydration, and monitor blood pressure and renal function (serum creatinine, potassium) at baseline and within 1 to 2 weeks after starting or changing therapy. Consider alternative analgesia such as paracetamol.
Renal & hepatic adjustment
  • eGFR 0–29: Avoid in severe renal impairment (eGFR <30 mL/min). (avoid)
  • eGFR 30+: No dose adjustment required in mild to moderate renal impairment, but monitor renal function and use the lowest effective dose.
  • Hepatic impairment (mild): No adjustment required, but caution as hepatotoxicity has been reported.
  • Hepatic impairment (moderate): Use with caution; consider a reduced dose and monitor liver function tests.
  • Hepatic impairment (severe): Avoid in severe hepatic impairment. (avoid)
Monitoring, pregnancy & toxicity
  • Blood pressure · Baseline and periodically during treatment
  • Serum creatinine/eGFR · Baseline and periodically, especially in long-term use
  • Liver function tests · Baseline and periodically; monitor for signs of hepatotoxicity
  • Signs of GI bleeding (e.g., melena, hematemesis) · During treatment, especially in the first month
  • Cardiovascular events (e.g., chest pain, shortness of breath) · Periodically
  • Pregnancy: Diclofenac is contraindicated in the third trimester due to the risk of premature ductus arteriosus closure and oligohydramnios. In earlier pregnancy, avoid unless clearly necessary; use the lowest effective dose for the shortest duration.
  • Toxicity: Gastrointestinal irritation, bleeding, and ulceration. · Supportive care; consider activated charcoal within 1 hour if substantial overdose; monitor for GI bleeding; administer a proton-pump inhibitor if appropriate.
  • Toxicity: Acute kidney injury (e.g., oliguria, rising creatinine). · Stop the drug, provide supportive care, monitor renal function; consider fluid resuscitation; may require renal replacement therapy in severe cases.
  • Toxicity: CNS effects (headache, drowsiness, confusion, seizures). · Supportive; treat seizures with benzodiazepines; monitor and maintain the airway.
  • Toxicity: Cardiovascular effects (e.g., hypotension, tachycardia). · Supportive; monitor vital signs, ECG, and cardiac output; treat arrhythmias as needed.
Clinical notes
Diclofenac is used for acute and chronic pain, inflammation, and fever, particularly in musculoskeletal and joint disorders such as rheumatoid arthritis and osteoarthritis. It is available as oral, topical, ophthalmic, and parenteral formulations. Because of gastrointestinal and cardiovascular risks, it should be used at the lowest effective dose for the shortest duration. Gastroprotection with a proton pump inhibitor should be considered in high-risk patients. Topical formulations have lower systemic exposure and are preferred for localised pain. Caution is needed in patients with renal impairment, heart failure, or a history of gastrointestinal bleeding. It is contraindicated in pregnancy, especially in the third trimester.

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BNF; local formulary