Generic Name

Diclofenac

Mechanism

• Diclofenac is a non‑steroidal anti‑inflammatory drug (NSAID) that inhibits cyclooxygenase (COX‑1 and COX‑2), thereby reducing the synthesis of prostaglandins involved in pain, fever, and inflammation.
• Inhibition of COX‑1 decreases protective gastric prostaglandins, while COX‑2 inhibition dampens inflammatory prostaglandin production.
• The net effect is a reduction in edema, hyperalgesia, and joint inflammation typical of rheumatologic disorders.

Pharmacokinetics

• Absorption: Oral tablets achieve ~70 % bioavailability; topical formulations penetrate the epidermis to reach a 1–2 % dermal concentration.
• Distribution: ~99 % protein‑bound (primarily to albumin and α‑1‑acid glycoprotein).
• Metabolism: Hepatic phase I (oxidative metabolism) to form 4‑hydroxy‑diclofenac and other metabolites; phase II conjugation.
• Excretion: Primarily renal (~70 %) via glomerular filtration and tubular secretion; a minor biliary route.
• Half‑life: 1–4 h (oral), 3–4 h (IV).

Indications

• Osteoarthritis (knee, hand, hip)
• Rheumatoid arthritis (early disease, flares)
• Acute musculoskeletal injuries (sprains, strains)
• Ankle, wrist, and low back pain
• Dysmenorrhea (short‑term oral or topical use)
• Temporomandibular joint disorders

Contraindications

• Contraindicated in:
• History of hypersensitivity to diclofenac or other NSAIDs
• Active gastrointestinal (GI) ulceration or GI bleeding
• Severe hepatic or renal impairment (eGFR < 30 mL/min/1.73 m²)
• Uncontrolled hypertension, congestive heart failure, or significant cardiac disease
• Pregnancy (3rd trimester) and lactation (avoid systemic forms)
• Warnings:
• GI irritation; consider proton‑pump inhibitors (PPIs) or H₂ blockers.
• Renal function: potential for acute kidney injury, especially with volume depletion.
• Cardiotoxicity: risk of hypertension, edema, myocardial infarction, or stroke.
• Hepatotoxicity: monitor LFTs in long‑term therapy.
• Dermatologic reactions: rare but serious (e.g., Stevens–Johnson syndrome).

Dosing

• Adjust dosing for renal impairment: reduce frequency or dose.
• For elderly patients, start at the lowest effective dose.
• Do not exceed 150 mg/day oral or 2 × patches/day transdermal.

Adverse Effects

• Common:
• GI dyspepsia, heartburn
• Headache, dizziness
• Rash, pruritus
• Edema, constipation
• Serious:
• GI ulcer/bleeding, perforation
• Acute kidney injury, renal failure
• Myocardial infarction, stroke
• Hepatotoxicity (transaminase elevation)
• Severe cutaneous adverse reactions (SJS/TEN)

Monitoring

• Baseline: CBC, electrolytes, renal panel, liver function tests (LFTs).
• During therapy:
• Renal function every 3 months for long‑term users or more frequent in CKD.
• LFTs every 3 months if therapy >3 months.
• Blood pressure at each visit (≥4 h after dose).
• Signs/symptoms of GI bleeding: red or black stools, vomiting blood.

Clinical Pearls

• Topical first for localized pain: Achieves high dermal concentrations with minimal systemic exposure, reducing GI/renal risks.
• Patch vs. gel: Patches provide steady release; gels offer faster onset and are better for acute flare management.
• Avoid poly‑NSAID use: Combining with other NSAIDs or aspirin markedly increases GI and cardiovascular risks.
• Use a PPI when long‑term systemic therapy is required to mitigate GI complications, especially in older adults or those on anticoagulants.
• Check for drug interactions: Diclofenac inhibits CYP2C9 and CYP3A4; caution with warfarin, methotrexate, or other drugs cleared by these enzymes.
• Pregnancy considerations: Safe in early trimesters; avoid in the third trimester due to renal impairment of the fetus and closure of ductus arteriosus.
• Monitoring for cardiotoxicity: In patients with pre‑existing cardiovascular disease, limit daily dose to ≤50 mg and monitor ECG and cardiac biomarkers if symptomatic.
• Rapid tapering: Abrupt discontinuation after long‑term use has minimal withdrawal risk but watch for rebound pain; taper if pain escalates.

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• *This drug card provides concise, evidence‑based information for medical students and clinicians seeking quick reference on Voltaren (diclofenac).*