Colchicine


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Acute gout Treatment: Initial: 1 mg followed by 0.5 mg after 1 hour, given within 12 hours of flare onset. May resume after 12 hours if necessary, with a max dose of 0.5 mg 8 hourly. Treatment course ends when symptoms are relieved or when a total of 6 mg has been given. Another course may be repeated after at least 3 days. Prophylaxis: 0.5 mg bid. Familial Mediterranean fever 1.2-2.4 mg/day given as a single dose or in 2 divided doses, may be increased or decreased as necessary in increments of 0.3 mg/day.
Dosage Details
Oral
Familial Mediterranean fever
Adult: 1.2-2.4 mg daily given as a single dose or in 2 divided doses, may be increased or decreased as necessary in increments of 0.3 mg daily.
Child: 4-6 years 0.3 mg-1.8 mg daily; 6-12 years 0.9-1.8 mg daily; ≥12 years Same as adult dose. All doses may be given as a single dose or in 2 divided doses.

Oral
Acute gout
Adult: Treatment: Initially, 1 mg followed by 0.5 mg after 1 hour, given within 12 hours of flare onset. Treatment may resume after 12 hours, if necessary, with a max dose of 0.5 mg 8 hourly. Treatment course ends when symptoms are relieved or when a total of 6 mg has been given. Another course may be repeated after at least 3 days. Prophylaxis: 0.5 mg bid.
Special Patient Group
Patients taking P-gp inhibitors and moderate or strong CYP3A4 inhibitors (with normal renal and hepatic function): Dose reduction or interruption is recommended.
Renal Impairment
Acute gout
Moderate: Reduce dose or increase dosing interval. Severe or patients on haemodialysis: Contraindicated.

Familial Mediterranean fever
Patients on haemodialysis: Initially, 0.3 mg daily, increase if necessary, according to individual safety and tolerability.
CrCl (mL/min) Dosage
30-80
Dose reduction may be necessary with close monitoring.
<30
Initially, 0.3 mg daily, increase if necessary, according to individual safety and tolerability.
Hepatic Impairment
Acute gout
Severe: Contraindicated.

Familial Mediterranean fever
Severe: Dose reduction may be necessary.
Administration
May be taken with or without food.
Contraindications
Blood dyscrasias. Severe renal (including haemodialysis patients), and hepatic impairment (except in familial Mediterranean fever). Concomitant use with P-glycoprotein (P-gp) inhibitors or strong CYP3A4 inhibitors in patients with renal or hepatic impairment.
Special Precautions
Patient with CV disease, gastrointestinal disorders, corneal wounds or ulcers; abnormalities in blood counts. Mild to moderate renal and hepatic impairment. Elderly, children. Pregnancy and lactation. Debilitated patients. Not indicated as an analgesic to treat pain from other causes.
Adverse Reactions
Significant: Myelosuppression (e.g. thrombocytopenia, leucopenia, granulocytopenia, agranulocytosis, aplastic anaemia, thrombocytopenia), neuromuscular toxicity including rhabdomyolysis, gastrointestinal symptoms (e.g. anorexia, nausea, vomiting, diarrhoea).
Eye disorders: Delayed corneal wound healing.
Gastrointestinal disorders: Abdominal pain, gastrointestinal haemorrhage.
General disorders and administration site conditions: Fatigue.
Investigations: Increased ALT/AST, elevated creatine phosphokinase.
Musculoskeletal and connective tissue disorders: Myotonia, muscle weakness, myopathy.
Nervous system disorders: Headache, neuropathy, peripheral neuritis.
Reproductive system and breast disorders: Amenorrhoea, oligospermia, azoospermia.
Respiratory, thoracic and mediastinal disorders: Pharyngolaryngeal pain.
Skin and subcutaneous tissue disorders: Rash, alopecia.
Patient Counseling Information
This drug may cause dizziness and drowsiness, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor CBC, serum uric acid, renal function, LFT. Monitor for signs and symptoms of blood dyscrasias.
Overdosage
Symptoms: 1st stage: Nausea, vomiting, abdominal pain, haemorrhagic gastroenteritis, electrolyte imbalance, volume depletion, leucocytosis, hypotension in severe cases. 2nd stage: Multisystem organ dysfunction, acute renal failure, confusion, coma, ascending peripheral motor and sensory neuropathy, myocardial depression, pancytopenia, dysrhythmias, respiratory failure, and consumption coagulopathy. Management: Symptomatic and supportive treatment. Perform gastric lavage within 1 hour of ingestion. Consider activated charcoal administration within 1 hour of presentation in adults who ingested doses >0.1 mg/kg and any amount in children.
Drug Interactions
Increased risk of myopathy and rhabdomyolysis with statins, fibrates, digoxin, ciclosporin. Increased plasma concentration with cimetidine and tolbutamide. May cause reversible malabsorption of vitamin B12. Concomitant use with phenylbutazone may increase risk of leucopenia, thrombocytopenia or bone marrow depression. NSAIDs may increase risk of gastrointestinal ulceration or haemorrhage. Reduced efficacy of prophylactic gout therapy with cytolytic antineoplastic agents.
Potentially Fatal: Increased risk of toxicity with CYP3A4 or P-gp inhibitors such as macrolides (e.g. clarithromycin, erythromycin), HIV protease inhibitors (e.g. ritonavir, atazanavir), Ca channel blockers (e.g. verapamil, diltiazem), ketoconazole, itraconazole, voriconazole, ciclosporin, disulfiram.
Food Interaction
Increased plasma concentrations with grapefruit juice. Increased blood uric acid levels and risk of gastrointestinal toxicity with alcohol.
Lab Interference
May cause false-positive results in urine tests for erythrocytes or Hb levels. May interfere with urinary determination of 17-hydroxycorticosteroids using the Reddy, Jenkins and Thorn procedures.
Action
Description: Colchicine reduces neutrophil-mediated inflammatory response by disrupting cytoskeletal functions thereby blocking the β-tubulin polymerisation into microtubules, and preventing the activation, degranulation, and migration of neutrophils into the inflamed area.  In familial Mediterranean fever, it may interfere with intracellular assembly of the inflammasome complex present in neutrophils and monocytes which mediates interleukin-1β activation.
Onset: Pain relief: Approx 18-24 hours.
Pharmacokinetics:
Absorption: Rapidly and almost completely absorbed from the gastrointestinal tract. Bioavailability: Approx 45%. Time to peak plasma concentration: 0.5-3 hours.
Distribution: Concentrated in leucocytes, kidney, spleen and liver (except the heart, skeletal muscle and brain). Crosses placenta, enters breast milk. Volume of distribution: 5-8 L/kg. Plasma protein binding: Approx 39%.
Metabolism: Metabolised in the liver via demethylation by CYP3A4 isoenzyme to form 2 primary metabolites (2-O-demethylcholchicine and 3-O-demethylcolchicine), and 1 minor metabolite (10-O-demethylcholchicine or known as colchiceine); undergoes enterohepatic recycling.
Excretion: Mainly via faeces (80%, as unchanged drug and metabolites); urine (10-20%). Elimination half-life: 27-31 hours.
Chemical Structure

Chemical Structure Image
Colchicine

Source: National Center for Biotechnology Information. PubChem Database. Colchicine, CID=6167, https://pubchem.ncbi.nlm.nih.gov/compound/Colchicine (accessed on Jan. 22, 2020)

Storage
Store between 20-25°C. Protect from light and moisture. Follow applicable procedures for receiving, handling, administration, and disposal.
ATC Classification
L01CC - Colchicine derivatives ; Used in the treatment of cancer.
References
Anon. Colchicine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 03/12/2019.

Buckingham R (ed). Colchicine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/12/2019.

Colcrys Film Coated Tablets (Takeda Pharmaceuticals America, Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 03/12/2019.

Gloperba Solution (Avion Pharmaceuticals , LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 03/12/2019.

Joint Formulary Committee. Colchicine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/12/2019.

Mitigare Capsule (Hikma Specialty USA Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 03/12/2019.

Disclaimer: This information is independently developed by MIMS based on Colchicine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in