Colchicine

Pronunciation

(KOL chi seen)

Generic Available

Yes

Canadian Brand Names

ratio-Colchicine

Use

Treatment of acute gouty arthritis attacks and prevention of recurrences of such attacks

Use - Unlabeled/Investigational

Primary biliary cirrhosis; management of familial Mediterranean fever; pericarditis

Pregnancy Risk Factor

C (oral); D (parenteral)

Lactation

Enters breast milk/use caution (AAP rates "compatible")

Contraindications

Hypersensitivity to colchicine or any component of the formulation; severe renal, gastrointestinal, hepatic, or cardiac disorders; blood dyscrasias; pregnancy (parenteral)

Warnings/Precautions

Use with caution in debilitated patients or elderly patients; use caution in patients with mild-to-moderate cardiac, GI, renal, or liver disease. Severe local irritation can occur following SubQ or I.M. administration. Dosage reduction is recommended in patients who develop weakness or gastrointestinal symptoms (anorexia, diarrhea, nausea, vomiting) related to drug therapy.

Intravenous: Use only with extreme caution; potential for serious, life-threatening complications. Should not be administered to patients with renal insufficiency, hepatobiliary obstruction, patients >70 years of age, or recent oral colchicine use. Should be reserved for hospitalized patients who are under the care of a physician experienced in the use of intravenous colchicine.

Adverse Reactions

>10%: Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain

1% to 10%:

Dermatologic: Alopecia

Gastrointestinal: Anorexia

<1%: Rash, azoospermia, agranulocytosis, aplastic anemia, bone marrow suppression, hepatotoxicity, myopathy, peripheral neuritis

Overdosage/Toxicology

Symptoms of overdose include acute nausea, vomiting, abdominal pain, shock, kidney damage, muscle weakness, burning in throat, watery to bloody diarrhea, hypotension, anuria, cardiovascular collapse, delirium, convulsions, and respiratory paralysis. Treatment includes gastric lavage and measures to prevent shock, hemodialysis or peritoneal dialysis. Atropine and morphine may relieve abdominal pain.

Drug Interactions

Substrate of CYP3A4 (major); Induces CYP2C8/9 (weak), 2E1 (weak), 3A4 (weak)

Cyclosporine: Concurrent use with colchicine may increase toxicity of colchicine.

CYP3A4 inhibitors: May increase the levels/effects of colchicine. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.

Ethanol/Nutrition/Herb Interactions

Ethanol: Avoid ethanol.

Food: Cyanocobalamin (vitamin B12): Malabsorption of the substrate. May result in macrocytic anemia or neurologic dysfunction.

Herb/Nutraceutical: Vitamin B12 absorption may be decreased by colchicine.

Stability

Protect tablets from light.

Compatibility

I.V. colchicine is incompatible with dextrose or I.V. solutions with preservatives.

Mechanism of Action

Decreases leukocyte motility, decreases phagocytosis in joints and lactic acid production, thereby reducing the deposition of urate crystals that perpetuates the inflammatory response

Pharmacodynamics/Kinetics

Onset of action: Oral: Pain relief: ~12 hours if adequately dosed

Distribution: Concentrates in leukocytes, kidney, spleen, and liver; does not distribute in heart, skeletal muscle, and brain

Protein binding: 10% to 31%

Metabolism: Partially hepatic via deacetylation

Half-life elimination: 12-30 minutes; End-stage renal disease: 45 minutes

Time to peak, serum: Oral: 0.5-2 hours, declining for the next 2 hours before increasing again due to enterohepatic recycling

Excretion: Primarily feces; urine (10% to 20%)

Dosage

Familial Mediterranean fever (unlabeled use): Prophylaxis: Oral:

Children:

5 years: 0.5 mg/day

>5 years: 1-1.5 mg/day in 2-3 divided doses

Adults: 1-2 mg daily in divided doses (occasionally reduced to 0.6 mg/day in patients with GI intolerance)

Gouty arthritis: Adults:

Prophylaxis of acute attacks: Oral: 0.6 mg twice daily; initial and/or subsequent dosage may be decreased (ie, 0.6 mg once daily) in patients at risk of toxicity or in those who are intolerant (including weakness, loose stools, or diarrhea); range: 0.6 mg every other day to 0.6 mg 3 times/day

Acute attacks:

Oral: Initial: 0.6-1.2 mg, followed by 0.6 every 1-2 hours; some clinicians recommend a maximum of 3 doses; more aggressive approaches have recommended a maximum dose of up to 6 mg. Wait at least 3 days before initiating another course of therapy

I.V.: Initial: 1-2 mg, then 0.5 mg every 6 hours until response, not to exceed total dose of 4 mg. If pain recurs, it may be necessary to administer additional daily doses. The amount of colchicine administered intravenously in an acute treatment period (generally ~1 week) should not exceed a total dose of 4 mg. Do not administer more colchicine by any route for at least 7 days after a full course of I.V. therapy.

Note: Many experts would avoid use because of potential for serious, life-threatening complications. Should not be administered to patients with renal insufficiency, hepatobiliary obstruction, patients >70 years of age, or recent oral colchicine use. Should be reserved for hospitalized patients who are under the care of a physician experienced in the use of intravenous colchicine.

Surgery: Gouty arthritis, prophylaxis of recurrent attacks: Adults: Oral: 0.6 mg/day or every other day; patients who are to undergo surgical procedures may receive 0.6 mg 3 times/day for 3 days before and 3 days after surgery

Primary biliary cirrhosis (unlabeled use): Adults: Oral: 0.6 mg twice daily

Pericarditis (unlabeled use): Adults: Oral: 0.6 mg twice daily

Elderly: Reduce maintenance/prophylactic dose by 50% in individuals >70 years

Dosing adjustment in renal impairment: Gouty arthritis, acute attacks: Oral: Specific dosing recommendations not available from the manufacturer:

Prophylaxis:

Clcr 35-49 mL/minute: 0.6 mg once daily

Clcr 10-34 mL/minute: 0.6 mg every 2-3 days

Clcr<10 mL/minute: Avoid chronic use of colchicine. Use in serious renal impairment is contraindicated by the manufacturer.

Treatment: Clcr<10 mL/minute: Use in serious renal impairment is contraindicated by the manufacturer. If a decision is made to use colchicine, decrease dose by 75%.

Peritoneal dialysis: Supplemental dose is not necessary

Dosage adjustment in hepatic impairment: Avoid in hepatobiliary dysfunction and in patients with hepatic disease.

Administration

I.V.: Injection should be made over 2-5 minutes into tubing of free-flowing I.V. with compatible fluid. Do not administer I.M. or SubQ; severe local irritation can occur following SubQ or I.M. administration. Extravasation can cause tissue irritation.

Tablet: Administer orally with water and maintain adequate fluid intake.

Monitoring Parameters

CBC and renal function test

Test Interactions

May cause false-positive results in urine tests for erythrocytes or hemoglobin

Dietary Considerations

May need to supplement with vitamin B12.

Patient Education

Take as directed; do not exceed recommended dosage. Consult prescriber about a low-purine diet. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. Do not use alcohol or aspirin-containing medication without consulting prescriber. You may experience nausea, vomiting, or anorexia (small, frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); hair loss (reversible). Stop medication and report to prescriber if severe vomiting, watery or bloody diarrhea, or abdominal pain occurs. Report muscle tremors or weakness; fatigue; easy bruising or bleeding; yellowing of eyes or skin; or pale stool or dark urine. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

May cause drowsiness

Mental Health: Effects on Psychiatric Treatment

Rare reports of agranulocytosis; use caution with clozapine and carbamazepine; CNS depressant effects may be enhanced

Dosage Forms

Injection, solution: 0.5 mg/mL (2 mL)

Tablet: 0.6 mg

References

Antman EM, Anbe SC, Alpert JS, et al, "ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction - Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction)," Circulation, 2004, 110:588-636. Available at: http://www.circulationaha.org/cgi/content/full/110/5/588. Last accessed October 26, 2004.

Baud FJ, Sabouraud A, Vicaut E, et al, "Treatment of Severe Colchicine Overdose With Colchicine-Specific Fab Fragments," N Engl J Med , 1995, 332(10):642-5.

Becker MA, "Treatment of Gout," UpToDate (12.1), 2003.

Burnakis TG, "Colchicine Treatment of Progressive Systemic Sclerosis," Hosp Pharm , 1995, 30:536-7.

Emmerson BT, "The Management of Gout," N Engl J Med , 1996, 334(7):445-51.

Folpini A and Furfori P, "Colchicine Toxicity - Clinical Features and Treatment: Massive Overdose Case Report," J Toxicol Clin Toxicol , 1995, 33(1):71-7.

Heaney D, Derghazarian CB, Pineo GF, et al, "Massive Colchicine Overdose. A Report on the Toxicity," Am J Med Sci , 1976, 271(2):233-8.

Kaplan MM, Schmid C, Provenzale D, et al, "A Prospective Trial of Colchicine and Methotrexate in the Treatment of Primary Biliary Cirrhosis," Gastroenterology , 1999, 117(5):1173-80.

Levy M, Spino M, and Read SE, "Colchicine: A State-of-the-Art Review," Pharmacotherapy , 1991, 11(3):196-211.

Majeed HA, Carroll JE, Khuffash FA, et al, "Long-Term Colchicine Prophylaxis in Children With Familial Mediterranean Fever (Recurrent Hereditary Polyserositis)," J Pediatr , 1990, 116(6):997-9.

Murray SS, Kramlinger KG, McMichan JC, et al, "Acute Toxicity After Excessive Ingestion of Colchicine," Mayo Clin Proc , 1983, 58(8):523-32.

Nagy LL, De Roos F, Hoffman RS, et al, "Colchicine-Induced Neutropenia, Treated With Granulocyte Colony Stimulating Factor," Vet Hum Toxicol , 1994, 36:366.

Pitts FN Jr, "Colchicine Therapy for Palmer Fibromatosis," N Engl J Med , 1995, 333(6):393.

Scherrmann JM, "Antibody Treatment of Toxin Poisoning - Recent Advances," J Toxicol Clin Toxicol , 1994, 32(4):363-75.

Stapczynski JS, Rothstein RJ, Gaye WA, et al, "Colchicine Overdose: Report of Two Cases and Review of the Literature," Ann Emerg Med , 1981, 10(7):364-9.

Terkeltaub RA, "Gout," N Engl J Med , 2003, 349(17):1647-55.

Valenzuela P, Paris E, Oberpauer B, et al, "Overdose of Colchicine in a Three-Year-Old Child," Vet Hum Toxicol , 1995, 37(4):366-7.

Wallace SL and Singer JZ, "Review: Systemic Toxicity Associated With the Intravenous Administration of Colchicine - Guidelines for Use," J Rheumatol , 1988, 15(3):495-9.

Wallace SL, Singer JZ, Duncan GJ, et al, "Renal Function Predicts Colchicine Toxicity: Guidelines for the Prophylactic Use of Colchicine in Gout," J Rheumatol , 1991, 18(2):264-9.

International Brand Names

Apsen Colchicina® (BR); Artrichine® (EC); Cholchicin "Agepha"® (AT); Cochic® (TH); Colchicina® (BR, CO, RO); Colchicin Agepha® (AT); Colchicina L.CH.® (CL); Colchicina Lirca® (IT); Colchicina Phoenix® (AR); Colchicine® (BE, GB, IL, NZ); Colchicine Evans® (SG); Colchicine Houdé® (AR, BE, ES, LU, PT, ZA); Colchicine Opocalcium® (FR); Colchicum-Dispert® (BG, CZ, HU, PL, TR); Colchily® (TH); Colchimedio® (CO, DO, GT, HN, PA, SV); Colchiquim® (MX); Colcine® (TH); Colgout® (AU); Goutichine® (TH); Goutnil® (IN); Gout Tab® (TH); Kolchicin® (NO); Kolchivan® (GT); Kolsin® (TR); Lennon - Colchicine® (ZA); ratio-Colchicine (CA); Tolchicine® (TH)

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