Diclofenac

Non-steroidal anti-inflammatory drugs (NSAIDs)

ATC code: M01AB05 (Diclofenac)

Mechanism of action

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.

Indications

Mild to moderate pain in adults

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.

Osteoarthritis

First line

For osteoarthritis, NICE 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.

Renal colic

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.

Rheumatoid arthritis

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.

Practical notes

Food and drinks

Take with or immediately after food, with a full glass of water. Do not crush enteric-coated tablets. For courses longer than 5 days, add a PPI for gastroprotection. Apply gel to clean, dry skin without occlusive dressing.

Special situations

Diclofenac carries the highest cardiovascular risk among NSAIDs – the CNT (Coxib and traditional NSAID Trialists) meta-analysis showed a one-third increase in vascular events. Contraindicated in established coronary artery disease, prior stroke or MI, heart failure, and uncontrolled hypertension. In patients with cardiovascular risk factors, naproxen or low-dose ibuprofen is preferred.

Safety

Contraindications

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)
Third trimester of pregnancy
Aspirin triad (aspirin-exacerbated respiratory disease)

Serious adverse effects

Cardiovascular thrombotic events (MI, stroke) – risk higher than other NSAIDs
GI bleeding, ulcer perforation
Acute kidney injury
Hepatotoxicity (rare, but higher than other NSAIDs)

Common adverse effects

Dyspepsia, epigastric pain, nausea
Headache, dizziness
Elevated liver transaminases
Fluid retention, edema

PregnancyFDA 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.

Breastfeeding

Excreted in breast milk in small amounts. Short-term use is acceptable. If prolonged treatment is needed, ibuprofen is preferred.