Indomethacin
INDOMETHACIN
Generic Name
INDOMETHACIN
Mechanism
The INDOMETHACIN is a non‑steroidal anti‑inflammatory drug (NSAID) that exerts its therapeutic effects through inhibition of cyclooxygenase (COX) enzymes.
• COX‑1 & COX‑2 inhibition: preferentially blocks COX‑2 produced during inflammation, thereby reducing prostaglandin E₂ (PGE₂) synthesis and diminishing pain, swelling, and fever.
• Anti‑inflammatory: ↓ PGE₂ → ↓ leukotriene production → ↓ vascular permeability.
• Analgesic & antipyretic: ↓ prostaglandin-mediated nociceptor sensitization and hypothalamic set‑point modulation.
The dual COX inhibition also accounts for the drug’s gastrointestinal (GI) and renal adverse effect profile.
---
Pharmacokinetics
- Absorption: Rapid oral absorption (~85 % bioavailability); peak plasma levels in 1–3 h.
- Distribution: Highly protein‑bound (~95 %) mainly to albumin and α‑1‑acid glycoprotein.
- Metabolism: Extensive hepatic metabolism (CYP2C9, CYP3A4) → glucuronide and sulfate conjugates.
- Excretion: Primarily renal (≈90 % excreted in urine) with a terminal half‑life of 3–4 h.
- Special populations: Accumulates in hepatic impairment; renal dysfunction prolongs clearance.
---
Indications
- Musculoskeletal: mild‑to‑moderate osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, gouty arthritis.
- Inflammatory: acute inflammatory bowel disease flare (colitis), localized inflammation (e.g., bursitis, tendinitis).
- Post‑operative pain: short‑term adjunct for moderate pain control.
- Other: prophylaxis of postoperative adhesions (topical).
---
Contraindications
- Absolute: active peptic ulcer, GI bleeding, hypersensitivity to NSAIDs.
- Relative:
- History of asthma or allergic rhinitis (potential bronchospasm).
- Severe cardiovascular disease (heart failure, ischemic heart disease).
- Severe hepatic or renal impairment.
- Pregnancy (especially 3rd trimester) and lactation.
- Warnings:
- GI ulceration, perforation, bleeding.
- Hypertension, congestive heart failure.
- Renal dysfunction (pre‑renal, intrinsic).
- Rebound hyperthermia if abruptly discontinued in treated fever.
---
Dosing
| Formulation | Typical Adult Dose | Route | Frequency | Notes |
| Oral capsule | 4–8 mg × 2 daily | PO | BID | Start low; titrate to effect. |
| Oral solution | 4–6 mg × 2 daily | PO | BID | Chewable tablets for dysphagia. |
| Topical ointment | 1 g (2 % w/w) | Applied to affected area | 2–3 × day | Reduced systemic exposure. |
| Injection (rare) | 5–15 mg IV | IV | PRN | Mainly research settings. |
• With food to minimize GI upset if tolerated.
• Co‑prescribe proton‑pump inhibitor (e.g., omeprazole) in at‑risk patients.
• Avoid aspirin concurrently to prevent additive GI toxicity.
--
•
Adverse Effects
- GI: nausea, dyspepsia, epigastric pain, ulcer, GI bleeding.
- Renal: decreased GFR, fluid retention, acute kidney injury.
- Cardiovascular: hypertension, edema, heart failure exacerbation.
- Central nervous system: headache, dizziness, tinnitus.
- Hepatic: transient ↑ ALT/AST; rarely fulminant hepatic failure.
- Allergic: rash, urticaria, anaphylaxis.
- Rebound: sudden withdrawal may precipitate hyperthermia.
---
Monitoring
| Parameter | Frequency | Rationale |
| Serum creatinine & eGFR | Baseline & monthly | Detect renal impairment. |
| Blood pressure | Baseline & each visit | Monitor for hypertension. |
| Liver function tests (ALT/AST, bilirubin) | Baseline & every 3 months | Detect hepatotoxicity. |
| Complete blood count | Baseline & every 3 months | Monitor for leukopenia, anemia. |
| Occult blood in stool | Baseline & if GI symptoms | Detect occult GI bleeding. |
| Symptom diary (itch, GI upset) | Ongoing | Capture early AE signals. |
--
•
Clinical Pearls
- Use the lowest effective dose for the shortest duration to limit GI and renal toxicity.
- Pre‑treat high‑risk patients with a proton‑pump inhibitor or misoprostol for gastroprotection.
- Topical formulation is preferable for localized joint pain when systemic exposure is undesirable.
- Avoid concomitant NSAIDs or high‑dose aspirin to reduce additive GI risk.
- In patients with chronic kidney disease, titrate to the minimal dose; consider alternative analgesics (e.g., acetaminophen).
- Pregnancy caution: Indomethacin is contraindicated after 20 weeks due to risk of premature ductus arteriosus closure and oligohydramnios.
- Watch for cardiovascular flare: Monitor blood pressure and fluid status in patients with heart failure.
- Rebound hyperthermia: If used for fever, taper rather than abruptly stop.
---