Colchicine

# Colchicine ## Overview - **Classification**: Anti-gout agent, anti-inflammatory. - **Mechanism**: Inhibits neutrophil migration and activity by disrupting microtubules. Reduces uric acid crystal-induced inflammation. ## Primary Indications 1. **Acute Gouty Arthritis** - Treatment of acute flares. 2. **Gout Prophylaxis** - Prevention of recurrent gout flares. 3. **Familial Mediterranean Fever (FMF)** - Management of inflammation and attacks. ## Adult Dosing ### Standard Dosing **Acute Gout Flare** - **Dose**: **1.2 mg** initially - **Frequency**: Followed by **0.6 mg** 1 hour later - **Route**: Oral - **Maximum dose**: **1.8 mg** for a single treatment course (over 1 hour). Do not repeat for at least **3 days (72 hours)**. **Gout Flare Prophylaxis** - **Dose**: **0.6 mg** - **Frequency**: Once daily or twice daily - **Route**: Oral - **Duration**: Typically 6 months or longer, based on clinical status. **Familial Mediterranean Fever (FMF)** - **Dose**: **0.6 mg** to **1.8 mg** - **Frequency**: Once daily or divided twice daily - **Route**: Oral - **Maximum dose**: **1.8 mg/day** ### Dose Adjustments - **Renal Impairment**: - **CrCl <30 mL/min**: Generally avoid for acute gout. - **CrCl <30 mL/min (prophylaxis/FMF)**: Reduce dose (e.g., **0.3 mg** daily or **0.6 mg** every other day) or increase interval. - **CrCl <10 mL/min**: Contraindicated due to high toxicity risk. - **Hepatic Impairment**: - **Mild-moderate**: Monitor closely, consider dose reduction. - **Severe**: Contraindicated due to high toxicity risk. - **Elderly Patients**: - Increased risk of adverse effects. Consider lower doses, especially if renal/hepatic function is impaired. - For prophylaxis/FMF, start with **0.3 mg** to **0.6 mg** daily. ## Pediatric Dosing ### Neonates (0-28 days) - **Special Notes**: Limited data. Generally not recommended for this age group. ### Infants (1-12 months) - **FMF**: - **Dose**: **0.03-0.07 mg/kg/day** - **Frequency**: Once daily or divided BID. - **Maximum**: **0.5 mg/day**. - **Special Notes**: Requires careful titration. Liquid formulation may be needed (extemporaneous compounding). ### Children (1-12 years) - **FMF (1-4 years)**: - **Dose**: **0.03-0.07 mg/kg/day** (typically **0.3 mg** to **0.6 mg** daily). - **Frequency**: Once daily or divided BID. - **Maximum**: **1.2 mg/day**. - **FMF (4-12 years)**: - **Dose**: **0.03-0.07 mg/kg/day** (typically **0.6 mg** to **1.2 mg** daily). - **Frequency**: Once daily or divided BID. - **Maximum**: **1.8 mg/day**. - **Safety**: Monitor for GI upset, muscle weakness, and blood dyscrasias. ### Adolescents (13-18 years) - **FMF**: - **Dose**: Follow adult dosing, **0.6 mg** to **1.8 mg** daily. - **Frequency**: Once daily or divided BID. - **Maximum**: **1.8 mg/day**. - **Acute Gout Flare**: Follow adult dosing, with caution regarding renal function. ## Safety Information ### Contraindications - **Absolute**: Concomitant use with strong **CYP3A4 inhibitors** or **P-glycoprotein (P-gp) inhibitors** in patients with **renal or hepatic impairment**. - **Absolute**: Serious **renal impairment** (CrCl <10 mL/min). - **Absolute**: Serious **hepatic impairment**. - **Relative**: Pre-existing blood dyscrasias. ### Common Adverse Effects - **Very Common (>10%)**: Diarrhea, nausea, abdominal pain/cramps. - **Common (1-10%)**: Vomiting. - **Serious but Rare**: Myelosuppression (agranulocytosis, aplastic anemia, thrombocytopenia), rhabdomyolysis, myopathy, peripheral neuropathy. ### Key Drug Interactions - **Strong CYP3A4 inhibitors** (e.g., clarithromycin, ketoconazole, ritonavir): Significantly increases colchicine levels; contraindicated in renal/hepatic impairment. - **P-glycoprotein (P-gp) inhibitors** (e.g., cyclosporine, verapamil): Increases colchicine levels; contraindicated in renal/hepatic impairment. - **Grapefruit juice**: Inhibits CYP3A4 and P-gp; avoid consumption. - **Statins, Fibrates**: Increased risk of myopathy/rhabdomyolysis; monitor for muscle pain/weakness. ## Monitoring & Follow-up - **Before Treatment**: Baseline CBC with differential, renal function (CrCl), hepatic function (LFTs). - **During Treatment**: - Monitor CBC with differential periodically (especially with long-term use). - Monitor renal and hepatic function, especially with dose changes or interacting drugs. - **Clinical Signs**: Watch for muscle pain/weakness, numbness/tingling, unusual bruising/bleeding, fever, persistent GI symptoms (signs of toxicity). ## Clinical Pearls - 💡 **Tip 1**: For acute gout, administer as soon as possible after symptom onset (within **36 hours** for best efficacy). - 💡 **Tip 2**: The current preferred acute gout regimen (**1.2 mg** then **0.6 mg** one hour later) significantly reduces toxicity compared to older, higher dose regimens. - 💡 **Tip 3**: Discontinue colchicine if severe gastrointestinal symptoms (diarrhea, nausea, vomiting) occur, as these may signal impending serious toxicity. - 💡 **Tip 4**: Counsel patients to immediately report any muscle pain, weakness, numbness, or tingling. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.