Diclofenac
Diclofenac
Generic Name
Diclofenac
Mechanism
- Competitive inhibitor of cyclooxygenase‑1 (COX‑1) and cyclooxygenase‑2 (COX‑2) enzymes.
- Inhibits prostaglandin synthesis (PGE₂, PGI₂, PGF₂α) → ↓ inflammation, pain, and fever.
- Short‑term selective COX‑2 blockade accounts for its potent anti‑inflammatory effect; however, systemic COX‑1 inhibition contributes to GI, renal, and platelet side‑effects.
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Pharmacokinetics
| Parameter | Typical value | Notes |
| Absorption | Rapid oral absorption; peak plasma 0.5–2 h. | Bioavailability ≈ 30–40 % due to first‑pass metabolism. |
| Metabolism | Mostly hepatic (CYP2C9, CYP3A4). Primary metabolites are glucuronides. | CYP2C9 polymorphisms ↓ clearance → ↑ plasma levels. |
| Excretion | Renal (≈ 60 %); ~10 % biliary. | Clearance reduced in renal impairment; dose adjustment required. |
| Half‑life | 1.8–2.5 h after oral dosing; 4–6 h after IV infusion (due to volume distribution). | Short half‑life → dosing every 8–12 h for oral formulations. |
| Protein Binding | ~99 % (albumin, α‑1‑acid glycoprotein). | High binding → drug‑drug interactions possible (e.g., warfarin). |
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Indications
- Acute musculoskeletal pain (sprains, strains, myalgia).
- Chronic rheumatic disorders (osteoarthritis, rheumatoid arthritis).
- Intra‑articular inflammatory conditions (injected form).
- Migraine and tension headaches (topical or oral).
- Post‑operative pain when systemic NSAIDs are indicated.
- Arthroscopic joint lavage (local application during surgery).
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Contraindications
- Absolute:
– Known hypersensitivity to diclofenac or any NSAID.
– Active GI bleeding or ulcer disease.
– Severe hepatic or renal failure.
– Unstable angina, recent MI or stroke within 30 days.
• Relative:
– History of cardiovascular disease, uncontrolled hypertension, asthma/ulcer history (risk of bronchospasm).
– Pregnancy (3rd trimester) & lactation (avoid due to potential for neonatal thrombocytopenia).
• Warnings:
– Cardiovascular: ↑ risk of myocardial infarction, stroke, or heart failure, especially at high doses or long‑term use.
– Renal: ↓ glomerular filtration; watch for oliguria, electrolyte imbalance.
– Gastro‑intestinal: ulceration, perforation, bleeding.
– Hepatic: cholestasis, transaminitis; monitor liver function.
– Hematologic: thrombocytopenia, platelet dysfunction → bleeding.
– Photosensitivity: avoid excessive sun exposure.
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Dosing
| Form | Typical dose | Frequency | Notes | |
| Oral (tablet) | 50–75 mg BID | 12 h | Initiate at 50 mg; titrate up to 150 mg/day if needed. | |
| Oral (gel, 1 %) | 75 mg (12.5 g gel) QD | 24 h | Use on dorsum of foot/ankle for osteoarthritis. | |
| Injection (IV 50 mg) | 50 mg every 4–6 h | 4–6 h | For acute pain in hospital setting. Avoid >5 mg/kg/day. | |
| Intra‑articular (50 mg) | Single local injection | — | For joint synovitis or arthroscopy. | |
| Topical (suspension 75 mg/5 mL) | 1 % (1 mL) QD | 24 h | For mild to moderate knee osteoarthritis. |
• Special populations:
– Renal impairment: Reduce dose to 50 mg BID or alternative NSAID.
– Hepatic impairment: Dose 75 mg once daily; monitor LFTs.
– Elderly: Start low, monitor for renal/GI complications.
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Adverse Effects
- Common
- GI upset (nausea, dyspepsia).
- Headache, dizziness.
- Rash, pruritus.
- Acneiform eruption (especially topical).
- Serious
- GI bleeding, perforation.
- Cardiovascular events (MI, stroke, edema).
- Severe renal impairment, anuria.
- Hepatotoxicity (elevated transaminases, cholestasis).
- Severe hypersensitivity reactions (anaphylaxis).
- Drug‑induced thrombocytopenia.
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Monitoring
| Parameter | Frequency | Rationale |
| CBC & platelet count | Baseline; every 6 weeks if long‑term therapy | Detect thrombocytopenia or leukopenia. |
| Serum creatinine & BUN | Baseline; every 3 months | Renal function decline. |
| Liver function tests (AST/ALT, ALP, bilirubin) | Baseline; repeat if ↑ ALT/AST >3× ULN | Hepatotoxicity risk. |
| Blood pressure | Baseline; at each visit | Hypertension & fluid retention. |
| Gastro‑intestinal assessment | Baseline; symptom‑driven | Detect ulcers/bleeding. |
| Pregnancy test in women of childbearing potential | Baseline | Contraindicated in 3rd trimester. |
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Clinical Pearls
- Use the lowest effective dose for the shortest duration to mitigate CV and GI risks.
- Co‑prescribe a proton‑pump inhibitor (e.g., omeprazole) if chronic use (>15 days) is required to protect the GI mucosa.
- For patients with a high CV risk, favor diclofenac topical formulations or local injections which limit systemic exposure and reduce adverse events.
- CYP2C9 polymorphisms (e.g., *CYP2C9* *2/*3) markedly slow diclofenac metabolism; clinicians should dose‑reduce or choose an alternative NSAID.
- Topical 1 % diclofenac gel can be used once daily for knee osteoarthritis, providing comparable pain relief to oral NSAIDs while virtually eliminating GI toxicity.
- Avoid combining diclofenac with other COX‑1 inhibitors (e.g., aspirin) to reduce platelet inhibition and increase bleeding risk unless clinically justified.
- In surgical patients, a single IV dose may provide adequate analgesia and reduce the need for opioids, but monitor renal function closely in the elderly.
- Pregnancy and lactation: Diclofenac is classified as category D for pregnancy and should be avoided unless benefits outweigh risks. In lactation, infant monitoring for thrombocytopenia and hepatotoxicity is warranted.
- Drug‑drug interactions: Diclofenac displaces drugs from albumin (e.g., warfarin, phenytoin) increasing their concentrations; adjust doses accordingly.
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