Diclofenac is a widely prescribed nonsteroidal anti-inflammatory drug (NSAID) renowned for its potent analgesic, anti-inflammatory, and antipyretic properties. As a first-line therapeutic agent, it effectively manages moderate to severe pain associated with inflammatory conditions by inhibiting cyclooxygenase (COX) enzymes, thereby reducing prostaglandin synthesis. Its well-established efficacy and favorable pharmacokinetic profile make it a cornerstone in clinical practice for both acute and chronic pain management. Available in multiple formulations, including oral, topical, and parenteral, diclofenac offers tailored treatment options to meet diverse patient needs and clinical scenarios.

Features

• Active Ingredient: Diclofenac sodium or diclofenac potassium
• Drug Class: Nonsteroidal anti-inflammatory drug (NSAID)
• Mechanism of Action: Reversible inhibition of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes
• Bioavailability: Approximately 50-60% orally; varies by salt form and formulation
• Half-life: 1-2 hours (short), but with prolonged therapeutic effect due to tissue retention
• Protein Binding: >99%, primarily to albumin
• Metabolism: Hepatic, primarily via CYP2C9, with significant first-pass metabolism
• Excretion: Urinary (65%) and biliary (35%)
• Available Formulations: Tablets, capsules, extended-release tablets, topical gel, solution, patches, ophthalmic solution, suppositories, and injectable forms
• Onset of Action: Oral: 30 minutes; Peak effect: 2-3 hours
• Duration of Action: 8-12 hours for standard formulations; up to 24 hours for extended-release

Benefits

• Provides rapid and effective relief from inflammatory pain and stiffness
• Reduces swelling and improves joint mobility in arthritic conditions
• Offers multiple administration routes for customized treatment approaches
• Demonstrates cost-effectiveness compared to many newer analgesics
• Suitable for both acute pain episodes and long-term inflammatory management
• Topical formulations minimize systemic exposure and associated risks

Common use

Diclofenac is indicated for the management of mild to moderate acute pain, as well as chronic inflammatory conditions. Its primary applications include osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, where it significantly reduces pain and improves functional capacity. In acute settings, it effectively treats postoperative pain, dental pain, and musculoskeletal injuries such as sprains and strains. Additionally, diclofenac is used for symptomatic relief in gout attacks, dysmenorrhea, and migraine headaches. The ophthalmic formulation is specifically approved for postoperative inflammation following cataract surgery and for the treatment of seasonal allergic conjunctivitis. Off-label uses include management of kidney stone pain and some cancer-related pain syndromes, though these applications require careful risk-benefit assessment.

Dosage and direction

Dosage varies significantly based on formulation, indication, and patient factors. For oral administration in adults, the typical dose for rheumatoid arthritis is 150-200 mg daily in divided doses (50 mg three times daily or 75 mg twice daily). Osteoarthritis typically requires 100-150 mg daily in divided doses. For acute pain or dysmenorrhea, 50 mg three times daily is often prescribed. The maximum recommended daily dose is 150 mg for most chronic conditions and 200 mg for acute pain.

Extended-release formulations are usually administered once daily at doses of 100 mg. Topical gel (1% or 3%) should be applied four times daily to the affected area, with the total daily dose not exceeding 32 grams for 1% gel or 16 grams for 3% gel. Ophthalmic solution is typically administered one drop four times daily. Suppositories are available in 50 mg and 100 mg strengths, usually administered twice daily.

Diclofenac should be taken with food or milk to minimize gastrointestinal upset. Tablets should be swallowed whole, not crushed or chewed. Patients should use the lowest effective dose for the shortest duration necessary to control symptoms.

Precautions

Patients should be thoroughly evaluated before initiating diclofenac therapy. Cardiovascular risk assessment is crucial, as NSAIDs may increase the risk of serious thrombotic events, including myocardial infarction and stroke. Gastrointestinal screening should include assessment for previous ulcers, bleeding, or perforation. Renal function must be evaluated, particularly in elderly patients or those with pre-existing renal impairment, dehydration, or heart failure.

Hepatic function should be monitored, as transaminase elevations may occur. Patients with asthma may experience exacerbations due to potential cross-reactivity with other NSAIDs. Caution is advised in patients with hypertension, as diclofenac may attenuate the effects of antihypertensive medications. Regular monitoring of hemoglobin, renal function, and hepatic enzymes is recommended during long-term therapy.

Elderly patients require particular caution due to increased risk of gastrointestinal bleeding, renal impairment, and cardiovascular events. Pregnancy should be avoided during treatment, especially during the third trimester, due to potential fetal cardiovascular complications.

Contraindications

Diclofenac is contraindicated in patients with known hypersensitivity to diclofenac, other NSAIDs, or any component of the formulation. It should not be used in patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Additional contraindications include:

• History of prostaglandin-induced asthma
• Active peptic ulcer disease or gastrointestinal bleeding
• Severe hepatic impairment or active liver disease
• Severe heart failure
• Third trimester of pregnancy
• Coronary artery bypass graft (CABG) surgery perioperative pain
• Inflammatory bowel disease
• Severe renal impairment (creatinine clearance <30 mL/min)
• Concurrent use with other NSAIDs, including COX-2 inhibitors

Possible side effect

Diclofenac administration may cause various adverse effects, with incidence and severity depending on dosage, duration, and patient susceptibility. Common gastrointestinal effects include dyspepsia (10-15%), nausea (5-10%), abdominal pain (5-10%), diarrhea (5-10%), and constipation (5%). Serious gastrointestinal events include peptic ulceration (1-2%), gastrointestinal bleeding (0.5-1%), and perforation (0.1-0.5%).

Cardiovascular side effects may include hypertension (5-10%), edema (5-10%), and increased risk of thrombotic events. Renal effects can include reduced renal function, interstitial nephritis, and nephrotic syndrome. Hepatic reactions range from transaminase elevations (5-15%) to severe hepatitis (<0.1%).

Dermatological reactions include rash (5-10%), pruritus (5%), and photosensitivity. Central nervous system effects may include headache (5-15%), dizziness (5-10%), and somnolence. Hematological effects can include anemia, leukopenia, and thrombocytopenia. Hypersensitivity reactions, though rare, may include anaphylaxis, bronchospasm, and Stevens-Johnson syndrome.

Drug interaction

Diclofenac exhibits numerous clinically significant drug interactions due to its pharmacokinetic and pharmacodynamic properties. Concurrent use with other NSAIDs or aspirin increases the risk of gastrointestinal toxicity without therapeutic benefit. Anticoagulants like warfarin may have enhanced effects, increasing bleeding risk. ACE inhibitors, angiotensin receptor blockers, and diuretics may have reduced antihypertensive effects and increased risk of renal impairment.

Selective serotonin reuptake inhibitors (SSRIs) may increase bleeding risk when combined with diclofenac. Lithium levels may increase due to reduced renal clearance. Methotrexate toxicity may be enhanced due to reduced renal clearance. Cyclosporine may increase nephrotoxicity risk. Quinolone antibiotics may increase seizure risk. Corticosteroids may potentiate gastrointestinal ulceration.

Diclofenac may reduce the efficacy of antihypertensive medications and increase digoxin levels. CYP2C9 inhibitors like fluconazole may increase diclofenac concentrations. Phenytoin levels may be increased when co-administered with diclofenac.

Missed dose

If a dose is missed, it should be taken as soon as remembered, unless it is almost time for the next scheduled dose. In that case, the missed dose should be skipped, and the regular dosing schedule resumed. Patients should not double the dose to make up for a missed administration. For extended-release formulations taken once daily, if remembered within 12 hours of the missed dose, it may be taken; otherwise, wait until the next scheduled dose. Consistency in administration is important for maintaining therapeutic levels, particularly in chronic inflammatory conditions. Patients should be advised to maintain a regular dosing schedule and consider using reminder systems if missed doses occur frequently.

Overdose

Diclofenac overdose may manifest as headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, drowsiness, dizziness, tinnitus, apnea, metabolic acidosis, coma, convulsions, renal failure, and hepatic dysfunction. Cardiovascular effects may include hypertension, hypotension, bradycardia, or tachycardia. Respiratory depression may occur in severe cases.

Management is primarily supportive and symptomatic. Gastric lavage may be considered within one hour of ingestion, followed by activated charcoal administration. Forced diuresis, dialysis, or hemoperfusion are not effective due to high protein binding. Specific treatments may include intravenous fluids for hypotension, anticonvulsants for seizures, and blood transfusions for significant gastrointestinal bleeding. Hemodialysis may be considered in cases of renal failure. Patients should be monitored for at least 24 hours due to potential delayed symptoms. Symptomatic hypokalemia should be corrected with potassium supplementation.

Storage

Diclofenac should be stored at controlled room temperature (20-25°C or 68-77°F), protected from light and moisture. Tablets and capsules should be kept in their original container with the lid tightly closed. Topical formulations should not be exposed to extreme temperatures. Suppositories require refrigeration (2-8°C or 36-46°F). All formulations should be kept out of reach of children and pets. Unused medication should be properly disposed of according to local regulations, not flushed down the toilet or drain. Do not use beyond the expiration date printed on the packaging. Particular care should be taken with liquid formulations to prevent freezing.

Disclaimer

This information is provided for educational purposes only and does not constitute medical advice. Diclofenac is a prescription medication that should be used only under the supervision of a qualified healthcare professional. Individual response to medication may vary, and proper medical evaluation is necessary before initiating therapy. The prescribing physician should consider the complete medical history, potential drug interactions, and contraindications. Patients should not adjust dosage or discontinue medication without consulting their healthcare provider. While every effort has been made to ensure accuracy, medical knowledge is constantly evolving, and newer information may supersede the content presented here. In case of emergency or suspected overdose, seek immediate medical attention.

Reviews

Clinical studies and meta-analyses consistently demonstrate diclofenac’s efficacy in pain management. A comprehensive Cochrane review of 176 studies concluded that diclofenac 150 mg/day provides excellent pain relief for osteoarthritis, with a number needed to treat (NNT) of 3 for at least 50% pain relief over 2-13 weeks. Another systematic review in Rheumatology International found diclofenac superior to placebo and comparable to other NSAIDs in rheumatoid arthritis management.

Real-world evidence from patient registries indicates high satisfaction rates, particularly with topical formulations that minimize systemic side effects. The PRECISION trial, a large cardiovascular safety study, provided valuable data on relative risks compared to other NSAIDs. Long-term observational studies suggest maintained efficacy over years of treatment when properly monitored.

Despite its proven effectiveness, reviews consistently emphasize the importance of appropriate patient selection, dose optimization, and vigilant monitoring for adverse effects. The benefit-risk profile remains favorable when used according to established guidelines in appropriate patient populations.