Colchicine
Colchicine
Generic Name
Colchicine
Mechanism
Colchicine exerts its therapeutic effect primarily by binding tubulin and inhibiting microtubule polymerization.
• ↓ Neutrophil chemotaxis, adhesion, and degranulation.
• ↓ Cytokine release (IL‑1β, TNF‑α) by blocking the NLRP3 inflammasome.
• ↓ DNA synthesis and cellular proliferation of inflammatory cells.
• Result: rapid attenuation of acute inflammation in gout and familial Mediterranean fever (FMF).
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Pharmacokinetics
- Absorption: Oral bioavailability ≈ 40 %; peak plasma concentration in 4–5 h.
- Distribution: Large volume (~410 L) → extensive tissue penetration (GI tract, synovial fluid, skin).
- Metabolism: Hepatic via CYP3A4 and CYP1A2; is a strong P‑glycoprotein substrate.
- Elimination: 25 % renally cleared; 75 % excreted fecally.
- Half‑life: 27 h in healthy adults; prolonged in renal impairment.
- Drug interactions: Strong CYP‑3A4 and P‑gp inhibitors (e.g., clarithromycin, ritonavir) increase serum levels.
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Indications
- Acute gout‑induced arthritis – single or repeated doses to lower inflammation.
- Familial Mediterranean fever (FMF) prophylaxis – daily suppression of attacks.
- Behçet’s disease – reduces mucosal ulcer pain when used adjunctively.
- Pericarditis – adjunctive therapy for inflammatory flare control.
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Contraindications
| Category | Detail |
| Contraindicated | Severe hepatic or renal impairment (CrCl < 30 mL/min), myasthenia gravis, pregnancy (Category C), active gastrointestinal bleeding. |
| Warnings |
• Co‑administration with CYP‑3A4 and P‑gp inhibitors increases toxicity risk. • Dose escalation in patients with low body weight (< 50 kg) may precipitate myopathy. • High doses (> 1.8 mg/day) → severe GI distress and bone‑marrow suppression. |
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Dosing
| Indication | Adult Dose | Pediatric Dose |
| Acute gout | 0.6 mg at onset + 0.6 mg 12–24 h later; maintenance 0.6 mg q 12–24 h (max 1.8 mg/day). | 0.1–0.15 mg/kg/day; split into 2–3 doses (max 1.2 mg/day). |
| FMF prophylaxis | 1 mg/day (1 mg noctis). | 0.2–0.5 mg/kg/day (max 1 mg). |
| Pericarditis | 0.6 mg BID until inflammation resolves (usually 2–3 day course). | 0.05–0.1 mg/kg/dose, divided. |
*Take with food to reduce GI upset. Use the lowest effective dose to mitigate adverse effects.*
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Adverse Effects
- Gastrointestinal: nausea, vomiting, abdominal pain, diarrhea (most frequent).
- Hematologic: thrombocytopenia, leukopenia – ≥ 3 % risk at > 1.8 mg/day.
- Musculoskeletal: myopathy, rhabdomyolysis (especially with statins).
- Toxicopneumonitis – rare, dose‑related.
- Insuff.e – hepatic dysfunction (↑ALT/AST).
- Peripheral neuropathy – reversible with dose reduction.
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Monitoring
| Parameter | Frequency | Rationale |
| CBC & differential | Baseline, then 1–2 weeks after initiating high‑dose regimens | Detect bone‑marrow suppression early. |
| Serum creatinine & CrCl | Baseline; then every 4–6 weeks in renal impairment | Adjust dose to avoid accumulation. |
| Liver function tests | Baseline; then every 4–6 weeks | Identify hepatotoxicity. |
| Electrolytes (Mg²⁺, K⁺) | Baseline; every 4–6 weeks | Hypomagnesemia can enhance toxicity. |
| NEC (if on statins) | Baseline, then monthly | Prevent rhabdomyolysis. |
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Clinical Pearls
- Dose‑Capping Strategy: 1.8 mg/day is the upper therapeutic limit; higher totals rapidly increase toxicity.
- Interaction Hot‑Spot: Patients on clarithromycin, ritonavir, or ketoconazole require a dose reduction to 0.6 mg/day.
- Renal‑Impaired Kinetics: In CrCl < 30 mL/min, use oral 0.6 mg BID for ≤ 48 h, then switch to IV colchicine (0.6 mg) when renal function improves.
- Pericarditis Trick: Colchicine 0.6 mg BID can shorten the resolution time from 12–15 days (standard therapy) to 3–5 days.
- Avoid Over‑esting: Do not use concomitantly with copidamol or diuretic‑laden regimens unless hepatic/renal function is closely monitored.
- Prescribing in Pregnancy: Category C – use only if benefits outweigh risks; prior safety data are limited.
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• Key take‑away: Colchicine’s anti‑inflammatory power stems from microtubule disruption, but its narrow therapeutic window demands meticulous dose management, vigilant monitoring, and awareness of drug interactions.