Schedule H

Oral

• Tablets: 0.5 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Acute Gout Flare

Step Dose Clinical Notes

Starting dose 1 mg orally at first sign of flare Most effective when given within 12–24 hours of symptom onset

Followed by 0.5 mg one hour later Total Day 1 dose: 1.5 mg maximum

Subsequent days 0.5 mg twice daily Continue until flare resolves (usually 3–5 days)

Maximum dose 1.5 mg on Day 1; thereafter 1 mg/day Do not repeat full loading within 3 days

Key points:

• Efficacy diminishes significantly if started >36 hours after flare onset

• Diarrhoea often signals approaching toxicity — reduce dose if occurs

• Not an analgesic — does not provide immediate pain relief

1. Gout Prophylaxis (During Urate-Lowering Therapy Initiation)

Step Dose Clinical Notes

Starting dose 0.5 mg once daily Begin when starting allopurinol or febuxostat

Usual maintenance dose 0.5 mg once or twice daily Adjust based on tolerability

Maximum dose 1 mg/day Higher doses do not improve prophylaxis

Duration 3–6 months after target serum uric acid achieved May extend if recurrent flares occur

1. Familial Mediterranean Fever (FMF) — Specialist Only

Step Dose Clinical Notes

Starting dose 0.5–1 mg once daily Single or divided doses

Titration Increase by 0.5 mg increments based on response Titrate every 2–4 weeks

Usual maintenance dose 1–1.5 mg/day Most patients controlled at this range

Maximum dose 2 mg/day in divided doses Higher doses rarely needed

Key points:

• FMF is rare in Indian population — confirm diagnosis before long-term therapy

• Lifelong treatment usually required

• Monitor CBC, renal and hepatic function every 3–6 months

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Acute/Recurrent Pericarditis 0.5 mg twice daily (or 0.5 mg once daily if <70 kg) Acute: 3 months; Recurrent: 6 months or longer OFF-LABEL; Specialist only; Evidence: COPE, ICAP, CORP trials; used in Indian cardiology centres

Behçet's Disease (mucocutaneous/articular manifestations) 0.5–1.5 mg/day in 1–2 divided doses Long-term; individualised OFF-LABEL; Specialist only; Evidence: Small cohort studies; Indian rheumatology practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

1. Familial Mediterranean Fever (FMF)

1–4 years 0.25–0.5 mg once daily 1 mg/day

5–10 years 0.5 mg once or twice daily 1.5 mg/day

10 years 0.5–1 mg once or twice daily 2 mg/day

Safety notes:

• Adjust dose based on clinical response and GI tolerability

• Monitor CBC, renal function, and hepatic function every 3–6 months

• Observe for myopathy (muscle weakness, elevated CPK)

Secondary Indications — Paediatrics (Off-label)

Indication Dose Duration Notes

Recurrent Pericarditis 0.5 mg once or twice daily (based on weight) 6 months or longer OFF-LABEL; Paediatric cardiology specialist only; Evidence: Extrapolated from adult CORP/CORP-2 trials; limited Indian paediatric data

Minimum age: Avoid below 1 year of age except under specialist supervision with confirmed diagnosis

50 No adjustment required

30–50 Use with caution; maximum 0.5 mg once daily

10–29 Maximum 0.5 mg every other day; close monitoring essential

<10 or dialysis Avoid if possible; if essential, 0.5 mg every 2–3 days under specialist supervision; not removed by dialysis

Note: Risk of accumulation and toxicity markedly increased in renal impairment — monitor closely for neuromuscular and haematological toxicity

Note: Hepatic metabolism is significant — accumulation risk in hepatic dysfunction

• Known hypersensitivity to colchicine

• Combined severe renal AND hepatic impairment

• Concurrent use of strong CYP3A4 inhibitors (clarithromycin, ketoconazole, itraconazole) or P-glycoprotein inhibitors in patients with renal or hepatic impairment — risk of fatal toxicity

• Blood dyscrasias or pre-existing bone marrow suppression

• Active serious gastrointestinal disease (e.g., active peptic ulcer disease, inflammatory bowel disease with bleeding)

• Renal impairment — risk of accumulation and dose-dependent toxicity; adjust dose

• Hepatic impairment — reduced clearance; monitor closely

• Elderly patients — increased sensitivity to adverse effects

• Concurrent statin or fibrate therapy — additive myopathy risk

• Gastrointestinal disorders — may exacerbate diarrhoea, nausea

• Cardiac disease — may unmask or worsen arrhythmias in toxicity

• Avoid repeating acute gout loading dose within 3 days

Parameter Recommendation

Safety category Limited data; animal studies suggest teratogenic potential at high doses

Preferred alternatives NSAIDs (second trimester only with caution); low-dose corticosteroids for acute gout flare

When it may be used FMF — may continue if essential for disease control; benefit usually outweighs risk; obstetric and rheumatology input required

Monitoring Fetal growth surveillance; maternal GI tolerance; consider first-trimester detailed anomaly scan

Parameter Recommendation

Compatibility Generally compatible; low levels excreted in breast milk

Drug levels in milk Low (infant receives <10% of maternal weight-adjusted dose)

Preferred alternatives Short-term NSAID use if needed for acute flare

Infant monitoring Observe for GI symptoms (loose stools, vomiting), feeding difficulties

• Recommended starting dose: 0.5 mg once daily

• Titration: Slower titration; increase only if tolerated and necessary

• Additional risks:

• Increased susceptibility to neuromuscular toxicity (myopathy, neuropathy)

• Age-related decline in renal function — adjust dose accordingly

• Higher risk of bone marrow suppression

• GI intolerance more common

• Monitoring: Regular renal function, CBC, and clinical assessment for muscle weakness

Drug Interaction Management

Clarithromycin / Erythromycin Strong CYP3A4 and P-gp inhibition → marked ↑ colchicine levels → fatal toxicity reported AVOID combination; if essential, reduce colchicine dose by 50–75% and limit duration

Ketoconazole / Itraconazole Strong CYP3A4 inhibition → ↑ colchicine toxicity AVOID in renal/hepatic impairment; significant dose reduction required if used

Cyclosporine P-gp inhibition + additive nephrotoxicity and myotoxicity Reduce colchicine dose; monitor renal function and CPK

Ritonavir-boosted antiretrovirals Potent CYP3A4 inhibition → severe colchicine toxicity AVOID combination if possible

Verapamil / Diltiazem CYP3A4 and P-gp inhibition → ↑ colchicine levels Reduce colchicine dose; monitor for toxicity

Drug Interaction Management

Statins (atorvastatin, simvastatin) Additive risk of myopathy/rhabdomyolysis Monitor for muscle symptoms; check CPK if symptomatic

Fibrates (fenofibrate, gemfibrozil) Additive myopathy risk Use with caution; clinical monitoring

Digoxin P-gp substrate; possible increased digoxin levels Monitor digoxin levels and signs of toxicity

Fluconazole Moderate CYP3A4 inhibition May need minor colchicine dose adjustment

Warfarin Minor interaction; possible INR fluctuation Monitor INR when initiating or changing colchicine dose

NSAIDs Additive GI toxicity with chronic co-administration Short-term use acceptable; avoid prolonged combination

• Diarrhoea (most common — often dose-limiting)

• Nausea and vomiting

• Abdominal pain/cramping

• Loss of appetite

• Fatigue

• Headache

Reaction Action Required

Bone marrow suppression (agranulocytosis, aplastic anaemia, pancytopenia) Discontinue immediately; haematology referral; supportive care

Myopathy / Rhabdomyolysis Discontinue; check CPK; hydration; nephrology input if renal impairment

Peripheral neuropathy (axonal) Discontinue; usually reversible over weeks to months

Severe hepatotoxicity Discontinue; monitor LFTs; hepatology referral

Multi-organ failure (in overdose) Emergency hospitalisation; supportive care; no specific antidote

Note: Toxicity has narrow therapeutic window — even modest overdose can be fatal

During acute treatment Clinical monitoring for GI symptoms (diarrhoea indicates approaching toxicity)

Chronic use (every 2–3 months initially) CBC, renal function, LFTs

Long-term (every 6–12 months) CBC, renal function, LFTs; periodic CPK if on concurrent statin/fibrate

Clinical note: Onset of diarrhoea often precedes serious toxicity — counsel to reduce dose or hold if significant GI upset develops

• Zycolchin (Zydus Cadila)

• Colgout (Glenmark)

• Colchicine (generic — multiple manufacturers)

• Goutnil (Alkem)

• Colchimax (Intas)

NLEM status: Colchicine 0.5 mg tablet is included in NLEM 2022 — ceiling price applicable under NPPA

• Timing is critical in acute gout: Colchicine works best within 12–24 hours of flare onset; efficacy drops significantly after 36 hours

• Diarrhoea is a warning sign: GI symptoms often herald toxicity — instruct patients to reduce dose or stop if significant diarrhoea develops

• Low-dose regimen is as effective as high-dose: Modern evidence (AGREE trial) shows 1.5 mg total on Day 1 is as effective as older high-dose regimens with far fewer side effects

• Never repeat loading within 3 days: Risk of cumulative toxicity is high

• Beware of drug interactions: CYP3A4/P-gp inhibitors (macrolides, azole antifungals, CCBs) can cause fatal toxicity — always check before prescribing

• Statin combination requires vigilance: Monitor for myopathy symptoms; consider CPK if muscle complaints arise

colchicine; gout; acute gout flare; gout prophylaxis; FMF; pericarditis; CYP3A4 interaction; P-glycoprotein; myopathy risk; renal-adjusted; NLEM India

RxIndia v1.1 — 14 Jun 2025

• CDSCO Approved Product Information

• Indian Pharmacopoeia 2022

• NLEM 2022 (National List of Essential Medicines)

• API Textbook of Medicine (11th Edition)

• AIIMS Rheumatology Clinical Protocols

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (13th Edition)

• Harrison's Principles of Internal Medicine (21st Edition)

• AGREE Trial (Arthritis Rheum 2010) — low-dose colchicine efficacy

• COPE, ICAP, CORP Trials — pericarditis evidence (off-label indication)