Diclofenac
Diclofenac is a non-steroidal anti-inflammatory drug used in adults for inflammatory and musculoskeletal pain conditions. It is supplied as oral tablets, topical gels, suppositories and parenteral solution, with potent analgesic and anti-inflammatory effects.
- Chemical formula
- C14H11Cl2NO2
- CAS number
- 15307-86-5
- ATC code
- M01AB05
- Molecular weight
- 296.15 g/mol
- Drug class
- NSAID (phenylacetic acid)
- Also known as
- GP 45840, Diclofenaco
What is it?
Diclofenac is a phenylacetic acid derivative NSAID introduced in the 1970s. It is supplied as immediate-release and delayed-release tablets, capsules, oral solution, topical gel and patches, suppositories and parenteral solution. Diclofenac is dispensed both with and without prescription depending on the formulation and the country. Topical formulations are widely used in localised musculoskeletal pain because of their favourable systemic exposure profile.
Mechanism of action
Diclofenac reversibly inhibits cyclooxygenase enzymes COX-1 and COX-2, with somewhat greater selectivity for COX-2 than ibuprofen and naproxen. By reducing prostaglandin synthesis, it produces analgesic, anti-inflammatory and antipyretic effects. Additional postulated effects on lipoxygenase, lipoxin and arachidonic acid uptake may contribute. The COX-2 preference at therapeutic doses partially explains its cardiovascular risk profile.
Pharmacokinetics
Diclofenac is well absorbed orally, but undergoes extensive first-pass metabolism, resulting in a bioavailability of approximately 50%. Plasma protein binding exceeds 99%. Metabolism is mainly via CYP2C9 with minor CYP3A4 contribution to inactive and weakly active metabolites. The terminal half-life is approximately one to two hours. Topical formulations achieve high local tissue concentrations with very low systemic exposure.
Indications
Diclofenac is approved in adults for the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute musculoskeletal pain, post-surgical pain, primary dysmenorrhoea, acute migraine and ureteric colic. Topical diclofenac is approved for localised painful conditions such as actinic keratosis (in some markets) and musculoskeletal pain. According to clinical guidelines, the lowest effective dose for the shortest necessary duration should be used, particularly because of cardiovascular risk concerns.
Safety profile
Common adverse effects include gastrointestinal symptoms, headache, dizziness and elevated liver enzymes. Diclofenac carries class warnings on cardiovascular thrombotic events including myocardial infarction and stroke, with an increased risk compared with naproxen and ibuprofen at high doses. Serious gastrointestinal events, hepatotoxicity, renal impairment, hyperkalaemia and hypersensitivity reactions are documented. According to the prescribing information, contraindications include severe heart failure, recent CABG surgery and active peptic ulcer.
Products containing this ingredient
Frequently asked questions
Is diclofenac more effective than ibuprofen? ▾
At standard doses, diclofenac and ibuprofen produce comparable analgesic effects in many randomised trials, although diclofenac may be slightly more effective in some inflammatory conditions because of its longer COX-2 inhibition. The choice between NSAIDs depends on the indication, individual response, comorbidity and cardiovascular and gastrointestinal risk profile. According to clinical guidelines, the prescriber should weigh efficacy against the safety profile in each patient.
Why is diclofenac considered higher cardiovascular risk than naproxen? ▾
Pooled analyses of large randomised trials suggest that diclofenac at high doses is associated with a higher rate of cardiovascular thrombotic events than naproxen at standard doses. Several regulatory agencies have therefore added warnings or restrictions for diclofenac, particularly in patients with established cardiovascular disease. According to the prescribing information, the lowest effective dose for the shortest period should be used and risk reviewed by the prescriber.
Is topical diclofenac safer than oral? ▾
Topical diclofenac achieves high concentrations in superficial tissues with very low systemic exposure (approximately 5% to 10% of an equivalent oral dose). This usually translates into a lower risk of gastrointestinal, cardiovascular and renal adverse events. According to clinical guidelines, topical NSAIDs are recommended as first-line for many localised musculoskeletal pain conditions, particularly in older adults.
Can diclofenac be used long-term? ▾
Diclofenac can be used for chronic inflammatory conditions when needed, but according to clinical guidelines and the prescribing information, the lowest effective dose for the shortest necessary duration should be used. Long-term use should be supervised by the prescriber, with periodic reassessment of cardiovascular, gastrointestinal, renal and hepatic risk factors. Gastric protection is often added in patients with risk factors.
What are the main contraindications for diclofenac? ▾
Diclofenac is contraindicated in known hypersensitivity to diclofenac or other NSAIDs, in active peptic ulcer or gastrointestinal bleeding, in severe heart failure, in established ischaemic heart disease, peripheral arterial disease or cerebrovascular disease, in the perioperative period of coronary artery bypass graft surgery, in severe hepatic impairment and during the third trimester of pregnancy. According to the prescribing information, the medical history must be reviewed by a clinician before any prescription.
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