1. Clinical Overview
Diclofenac is a prototypical non-steroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class, widely used in the Indian market for its potent analgesic, anti-inflammatory, and antipyretic properties. It is a non-selective inhibitor of cyclooxygenase (COX) enzymes, with a preferential inhibition of COX-2. It is extensively used for acute and chronic pain management, particularly in musculoskeletal and arthritic conditions. The 'NA' designation typically refers to the Sodium salt, which is the most common and rapidly absorbed form.
| Onset | Duration | Bioavailability |
|---|---|---|
| Oral: 30 minutes; Topical: 1-2 hours; Intramuscular: 10-30 minutes. | Approximately 8-12 hours for oral formulations. | Oral: ~50-60% (due to first-pass metabolism); Topical: Systemic bioavailability is low (<6% for gel/cream). |
2. Mechanism of Action
Diclofenac exerts its therapeutic effects primarily by inhibiting the enzyme prostaglandin-endoperoxide synthase, commonly known as cyclooxygenase (COX). COX exists in two isoforms: COX-1 (constitutive, involved in gastric cytoprotection and platelet function) and COX-2 (inducible, involved in inflammation, pain, and fever). Diclofenac is a non-selective NSAID but shows a relative preference for inhibiting COX-2 over COX-1. By inhibiting COX, it blocks the conversion of arachidonic acid to prostaglandin G2 and subsequently to prostaglandin H2, the precursor for various prostanoids (PGE2, PGI2, thromboxane A2). The reduction in prostaglandin E2 (PGE2) at the site of injury leads to decreased vasodilation, edema, and sensitization of pain receptors.
3. Indications & Uses
- Osteoarthritis
- Rheumatoid Arthritis
- Ankylosing Spondylitis
- Acute Musculoskeletal Pain (e.g., sprains, strains)
- Post-operative Pain
- Dysmenorrhea (painful periods)
4. Dosage & Administration
Adult Dosage: Oral (Sodium/Potassium salt): 75-150 mg per day in 2-3 divided doses. Sustained/Extended Release: 100 mg once daily. Topical Gel (1%): Apply 2-4 g to affected area 3-4 times daily. IM Injection: 75 mg once or twice daily (short-term use).
Administration: Take oral tablets with or after food to reduce GI upset. Swallow SR/ER tablets whole, do not crush or chew. For topical gel, apply to clean, intact skin; wash hands after application; do not apply to wounds, infected skin, or under occlusive dressings unless directed. IM injection should be given deep into gluteal muscle.
5. Side Effects
Common side effects may include:
- Dyspepsia (indigestion), heartburn, epigastric pain
- Nausea, vomiting
- Diarrhea or constipation
- Headache, dizziness
- Skin rash, pruritus
- Elevated liver enzymes (transaminases)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Aspirin, other NSAIDs | Increased risk of GI ulceration and bleeding; pharmacodynamic antagonism. | Major |
| Anticoagulants (Warfarin, Acenocoumarol) | Increased risk of bleeding due to antiplatelet effect and displacement from protein binding. | Major |
| Anti-platelets (Clopidogrel, Aspirin) | Additive risk of bleeding. | Major |
| ACE Inhibitors (Ramipril, Enalapril), ARBs (Losartan) | Reduced antihypertensive effect; increased risk of renal impairment. | Moderate |
| Diuretics (Furosemide, Hydrochlorothiazide) | Reduced diuretic and antihypertensive efficacy; increased nephrotoxicity risk. | Moderate |
| Lithium | Increased serum lithium levels and toxicity risk due to reduced renal clearance. | Major |
| Methotrexate | Increased methotrexate levels and toxicity risk (especially with high-dose MTX). | Major |
| Cyclosporine, Tacrolimus | Increased risk of nephrotoxicity. | Major |
| Corticosteroids (Prednisolone) | Markedly increased risk of GI ulceration and bleeding. | Major |
| SSRIs (Fluoxetine, Sertraline) | Increased risk of upper GI bleeding. | Moderate |
| Antidiabetics (Glibenclamide, Metformin) | May potentiate hypoglycemic effect; monitor blood glucose. | Moderate |
| Quinolone Antibiotics (Ciprofloxacin) | Increased risk of CNS stimulation and seizures. | Moderate |
7. Patient Counselling
- DO take the tablet with food or milk to reduce stomach upset.
- DO use the lowest effective dose for the shortest possible time.
- DO inform your doctor about all other medicines you are taking, including over-the-counter drugs and supplements.
- DO apply topical gel to clean, dry, intact skin only. Wash hands before and after application.
- DO NOT take if you are pregnant (especially last 3 months) or planning pregnancy without consulting your doctor.
- DO NOT exceed the prescribed dose or duration.
- DO NOT take with other painkillers like aspirin, ibuprofen, or naproxen unless advised.
- DO NOT use the gel on broken skin, wounds, or infected areas.
- DO NOT cover the applied gel area with tight bandages unless directed.
8. Toxicology & Storage
Overdose: Nausea, vomiting, epigastric pain, GI bleeding, headache, dizziness, drowsiness, tinnitus, hyperventilation, convulsions, acute renal failure, liver damage, respiratory depression, coma. In severe cases, hypertension, metabolic acidosis, and cardiac arrest may occur.
Storage: Store at room temperature (15-30°C), protected from light and moisture. Keep out of reach of children. Do not freeze. For topical formulations, keep the tube/container tightly closed.