Brand names: Colcrys, Gloperba, Mitigare
Drug class: Antigout Agents
- Antimitotic Agents
VA class: MS400
CAS number: 64-86-8

Medically reviewed by Drugs.com on Jun 20, 2023. Written by ASHP.

Introduction

Antigout and antimitotic agent.

Uses for Colchicine

Gout Flare

Treatment to relieve pain in attacks of acute gout flare (gouty arthritis). Initiate at the first sign of gout flare. Used as a second-line agent in patients who have not responded to or who cannot tolerate other recommended therapy (i.e., NSAIAs, corticosteroids).

Prophylactic treatment of recurrent gout flare. Has no effect on plasma concentrations or urinary excretion of uric acid; use concomitantly with allopurinol or a uricosuric agent (e.g., febuxostat, probenecid, sulfinpyrazone) to decrease serum urate concentrations. Colchicine/probenecid fixed-dosage preparation has limited usefulness for prophylactic therapy because colchicine present exceeds the amount required by most patients.

Familial Mediterranean Fever

Management of familial Mediterranean fever. Used for chronic prophylactic therapy to reduce frequency and severity of episodic attacks of painful serositis in patients with familial Mediterranean fever.

Not curative; manifestations return to pretreatment levels following discontinuance.

Chronic prophylactic therapy appears to prevent amyloidosis (manifested by nephropathy) when there is no evidence of it at initiation of therapy; appears to be effective for preventing amyloidosis regardless of whether patients continue to experience episodic attacks of serositis during chronic prophylactic therapy with the drug. May prevent deterioration during proteinuric phase of the disease (when amyloid involvement is minimal).

Regulations Governing Colchicine Injection

On February 8, 2008, FDA announced that it would take enforcement action (e.g., seizure, injunction, other judicial proceeding) against all firms, including compounding pharmacies, attempting to manufacture, ship, or deliver colchicine injection because of potentially serious health risks associated with use of the injection. (See Serious Adverse Effects Related to Colchicine Injection under Cautions.)

Colchicine Dosage and Administration

General

Gout

• Administer prophylactic doses of colchicine before initiation of allopurinol or uricosurics because sudden changes in serum urate concentrations may precipitate acute gout flare.

• May discontinue colchicine and use urate-lowering agents alone after serum urate concentration is reduced to the desired level, and acute gout flares have not occurred for 3–6 months (some clinicians suggest 1–12 months).

Administration

Administer orally. Has been administered IV; parenteral preparation no longer available in the US. (See Serious Adverse Effects Related to Colchicine Injection under Cautions.)

Oral Administration

Initiate therapy for acute gout flare at the first sign of an attack.

Administer without regard to meals.

Dosage

Dosage depends on the patient’s age, renal and hepatic function, and recent (within 14 days) or concomitant use of moderate or potent CYP3A4 inhibitors or inhibitors of the P-glycoprotein transport system.

Pediatric Patients

Prophylactic Treatment of Recurrent Gout Flares

Oral

Manufacturer states that adolescents ≥16 years of age may receive adult dosages.

Familial Mediterranean Fever

Oral

Recommended dosage in children not receiving concomitant therapy with a moderate or potent CYP3A4 inhibitor or a P-glycoprotein inhibitor depends on child’s age (see Table 1). Manufacturer makes no specific recommendations for children who are receiving or have recently received therapy with a moderate or potent CYP3A4 inhibitor or an inhibitor of the P-glycoprotein transport system.

Dosage can be increased in increments of 0.3 mg daily to the maximum recommended dosage or decreased in decrements of 0.3 mg daily in individuals who develop intolerable adverse effects.

Adults

Treatment of Gout Flare

Oral

Recommended dosage of colchicine depends on whether patient is receiving or has recently (within 14 days) received a moderate or potent CYP3A4 inhibitor or an inhibitor of the P-glycoprotein transport system (see Table 2).

Use of colchicine for treatment of gout flare is not recommended in patients receiving the drug for prevention of gout flare and also receiving a CYP3A4 inhibitor.

Do not repeat courses of colchicine therapy (see Table 2) until 3 days have elapsed.

Prophylactic Treatment of Recurrent Gout Flares

Oral

Recommended dosage of colchicine depends on whether patient is receiving or has recently (within 14 days) received a moderate or potent CYP3A4 inhibitor or an inhibitor of the P-glycoprotein transport system (see Table 3).

Colchicine/Probenecid Fixed-Combination Therapy

Oral

Fixed-dosage preparation has limited usefulness for prophylactic therapy because colchicine present exceeds the amount required by most patients.

Manufacturer recommends initial dosage of colchicine 0.5 mg in fixed combination with probenecid 500 mg (1 tablet) daily for 1 week, then 1 tablet twice daily. If gouty arthritis is not controlled or if 24-hour uric acid excretion is ≤700 mg, increase daily dosage by 1 tablet every 4 weeks as tolerated (generally not exceeding 4 tablets [colchicine 2 mg and probenecid 2 g] daily).

If acute attacks have been absent ≥6 months and serum urate concentrations are controlled, manufacturer recommends reducing dosage by 1 tablet every 6 months as long as serum urate concentrations remain controlled.

Familial Mediterranean Fever

Oral

Recommended dosage of colchicine depends on whether patient is receiving or has recently (within 14 days) received a moderate or potent CYP3A4 inhibitor or an inhibitor of the P-glycoprotein transport system (see Table 4).

Dosage can be increased in increments of 0.3 mg daily to the maximum recommended dosage or decreased in decrements of 0.3 mg daily in individuals who develop intolerable adverse effects.

Special Populations

Hepatic Impairment

Contraindicated in patients with hepatic impairment who are receiving or have recently received therapy with a potent CYP3A4 inhibitor or an inhibitor of the P-glycoprotein transport system. (See Contraindications under Cautions.)

Treatment of Gout Flare

Oral

Mild to moderate hepatic impairment: Dosage adjustment is not needed, but monitor for adverse effects.

Severe hepatic impairment: Dosage adjustment is not needed, but do not repeat courses of colchicine therapy until 2 weeks have elapsed. Consider alternative therapy for patients requiring repeat courses of therapy.

Prophylactic Treatment of Recurrent Gout Flares

Oral

Mild to moderate hepatic impairment: Dosage adjustment is not needed, but monitor for adverse effects.

Severe hepatic impairment: Consider dosage reduction.

Familial Mediterranean Fever

Oral

Mild to moderate hepatic impairment: Dosage adjustment is not needed, but monitor for adverse effects.

Severe hepatic impairment: Consider dosage reduction.

Renal Impairment

Contraindicated in patients with renal impairment who are receiving or have recently received therapy with a potent CYP3A4 inhibitor or an inhibitor of the P-glycoprotein transport system. (See Contraindications under Cautions.)

Treatment of Gout Flare

Oral

Use of colchicine for treatment of gout flare is not recommended in patients with renal impairment who are receiving the drug for prevention of gout flares.

Mild to moderate renal impairment (Cl_cr 50–80 or 30–50 mL/minute, respectively): Dosage adjustment is not needed, but monitor for adverse effects.

Severe renal impairment (Cl_cr <30 mL/minute): Dosage adjustment is not needed, but do not repeat courses of colchicine therapy until 2 weeks have elapsed. Consider alternative therapy for patients requiring repeat courses of therapy.

Dialysis: 0.6 mg at first sign of gout flare. Do not repeat courses of colchicine therapy until 2 weeks have elapsed.

Prophylactic Treatment of Recurrent Gout Flares

Oral

Mild to moderate renal impairment (Cl_cr 50–80 or 30–50 mL/minute, respectively): Dosage adjustment is not needed, but monitor for adverse effects.

Severe renal impairment (Cl_cr <30 mL/minute): Initial dosage is 0.3 mg daily; monitor closely if dosage is increased.

Dialysis: Initial dosage is 0.3 mg twice weekly; monitor closely.

Familial Mediterranean Fever

Oral

Mild to moderate renal impairment (Cl_cr 50–80 or 30–50 mL/minute, respectively): Monitor for adverse effects; dosage adjustment may be needed.

Severe renal impairment (Cl_cr <30 mL/minute) or dialysis: Initial dosage is 0.3 mg daily; dosage can be increased with careful monitoring.

Geriatric Patients

Select dosage with caution because of age-related decreases in renal function and concomitant disease and drug therapy.

Cautions for Colchicine

Contraindications

• Individuals with renal or hepatic impairment receiving a drug that inhibits the P-glycoprotein transport system (e.g., cyclosporine, ranolazine) or is a potent CYP3A4 inhibitor (e.g., atazanavir, boceprevir, clarithromycin, ritonavir-boosted darunavir, ritonavir-boosted fosamprenavir, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, telithromycin, ritonavir-boosted tipranavir, lopinavir/ritonavir, the fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir).

Warnings/Precautions

Overdosage-related Mortality

Cumulative IV doses >4 mg (e.g., 7 mg administered acutely) have resulted in irreversible multiple organ failure and death. Oral ingestion of as little as 7 mg has resulted in death, although larger oral doses have been survived.

Serious Adverse Effects Related to Colchicine Injection

Serious adverse events, including some deaths, reported in patients receiving IV colchicine; many events associated with colchicine toxicity. As of June 2007, FDA was aware of 50 reports of adverse effects linked to IV colchicine; 23 of these events were fatal. Neutropenia, acute renal failure, thrombocytopenia, CHF, and pancytopenia reported.

Compounded IV colchicine linked to 3 deaths. Compounded colchicine injection from the same lot as these patients received contained 8 times the labeled amount of colchicine.

FDA announced enforcement action would be taken against all firms, including compounding pharmacies, attempting to manufacture, ship, or deliver colchicine injection. Oral preparations containing colchicine remain on the market; risks believed to be lower with oral preparations.

Hematologic Effects

Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia reported.

Drug Interactions

Concomitant use with certain drugs is contraindicated or requires particular caution. (See Interactions and also see Dosage under Dosage and Administration.)

Neuromuscular Effects

Neuromuscular toxicity and rhabdomyolysis reported with long-term use. Individuals with renal impairment and geriatric individuals are at increased risk. Concomitant use of certain drugs may increase risk of myotoxicity. (See Specific Drugs and Laboratory Tests under Interactions.)

Use of Fixed Combination

When colchicine is used in fixed combination with probenecid, consider the cautions, precautions, and contraindications associated with probenecid.

Specific Populations

Pregnancy

Category C.

Effect on labor and delivery not known.

Lactation

Distributed into milk. However, AAP states colchicine usually is compatible with breast-feeding; use caution.

Pediatric Use

Safety and efficacy not established for gout.

Safety and efficacy for familial Mediterranean fever in children evaluated in uncontrolled studies. Long-term use of colchicine did not appear to affect growth in children with familial Mediterranean fever.

Geriatric Use

Clinical studies of colchicine for treatment of gout flares, prophylactic treatment of recurrent gout flares, or management of familial Mediterranean fever did not include sufficient numbers of patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.

Select dosage carefully in geriatric patients with gout; consider the greater frequency of decreased renal function and of concomitant disease and drug therapy observed in geriatric patients.

Hepatic Impairment

Use with caution; dosage adjustment may be needed. (See Hepatic Impairment under Dosage and Administration.)

Contraindicated in patients with hepatic impairment receiving therapy with a potent CYP3A4 inhibitor or an inhibitor of the P-glycoprotein transport system. (See Contraindications under Cautions.) Fatal or life-threatening colchicine toxicity reported.

Renal Impairment

Use with caution; dosage adjustment may be needed. (See Renal Impairment under Dosage and Administration.)

Contraindicated in patients with renal impairment receiving therapy with a potent CYP3A4 inhibitor or an inhibitor of the P-glycoprotein transport system. (See Contraindications under Cautions.) Fatal or life-threatening colchicine toxicity reported.

Common Adverse Effects

Treatment of gout flare: Diarrhea, pharyngolaryngeal pain.

Prophylactic treatment of recurrent gout flares: Diarrhea.

Familial Mediterranean fever: Abdominal pain, diarrhea, nausea, vomiting.

Interactions for Colchicine

Metabolized by CYP3A4. Does not inhibit or induce CYP isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4.

A P-glycoprotein substrate.

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inhibitors: Potential pharmacokinetic interaction (increased plasma colchicine concentrations); increased risk of colchicine toxicity. Fatal reactions reported with concomitant use of potent CYP3A4 inhibitors. Adjust colchicine dosage if patient is receiving or has recently (within 14 days) received therapy with a moderate or potent CYP3A4 inhibitor (see Dosage under Dosage and Administration). Concomitant use of colchicine and potent CYP3A4 inhibitors is contraindicated in renal or hepatic impairment.

Drugs Affecting P-Glycoprotein Transport

P-glycoprotein inhibitors: Pharmacokinetic interaction (increased plasma concentrations of colchicine) likely; increased risk of colchicine toxicity. Fatal reactions reported. Adjust colchicine dosage if patient is receiving or has recently (within 14 days) received therapy with a P-glycoprotein inhibitor (see Dosage under Dosage and Administration). Concomitant use of colchicine and P-glycoprotein inhibitors is contraindicated in renal or hepatic impairment.

Specific Drugs and Laboratory Tests

Colchicine Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from the GI tract following oral administration.

Drug and metabolites reenter intestinal tract via biliary and intestinal secretions after partial metabolism in liver.

Unchanged drug may be reabsorbed from the intestine.

Following oral administration, peak plasma concentrations occur within 0.5–2 hours. Enterohepatic circulation may occur; secondary peak present in some individuals 3–36 hours after dose.

Absolute bioavailability reported to be about 45%.

Food

Administration with food did not affect rate of absorption but decreased extent of absorption by 15%.

Distribution

Extent

Crosses the placenta and is distributed into milk.

Plasma Protein Binding

39% (mainly albumin).

Elimination

Metabolism

Demethylated in the liver by CYP3A4.

Elimination Route

40–65% recovered unchanged in urine. Enterohepatic circulation and biliary excretion may occur. Not removed by hemodialysis.

Half-life

26.6–31.2 hours.

Special Populations

Hepatic impairment: Substantial interpatient variability in pharmacokinetics. Decreased clearance and prolonged half-life observed in some patients with mild to moderate cirrhosis; however, no consistent trends observed in those with primary biliary cirrhosis.

End-stage renal disease requiring dialysis: Colchicine clearance decreased by 75%, elimination half-life increased.

Stability

Storage

Oral

Tablets

20–25°C. Protect from light.

Actions

• Has weak anti-inflammatory activity, but no analgesic activity.

• Has no effect on urinary excretion of uric acid or on serum urate concentration, solubility, or binding to serum proteins.

• Mechanism of principal (antigout) effect is not completely known; drug appears to disrupt cytoskeletal functions through inhibition of β-tubulin polymerization into microtubules thus preventing activation, degranulation, and migration of neutrophils believed to mediate some gout symptoms.

• Mechanism of beneficial effects in familial Mediterranean fever not fully elucidated. Colchicine may interfere with the intracellular assembly of inflammasome complex in neutrophils and monocytes that mediates activation of interleukin-1β.

Advice to Patients

• Importance of patients not altering colchicine dosage without consulting a clinician.

• Importance of instructing patients on how to resume colchicine therapy if they miss taking a dose. If used to treat an acute gout flare and not for prophylaxis of recurrent flares, take the missed dose as soon as possible. If used to treat an acute gout flare during colchicine prophylaxis, take the missed dose immediately, then wait 12 hours before resuming previous dosing schedule. If used for treatment of familial Mediterranean fever or for prophylaxis of recurrent gout flares (without treatment for an acute gout flare), take the missed dose as soon as possible and then resume usual dosing schedule, but do not take a double dose to make up for a missed dose.

• Possibility of serious adverse effects (e.g., blood dyscrasias, myotoxicity and rhabdomyolysis).

• Potential for fatal overdosage in adults or children following colchicine ingestion. Importance of keeping colchicine out of children's reach.

• Potential for fatal drug interactions. Importance of informing clinicians of existing, recent, or contemplated therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses. Importance of avoiding grapefruit and grapefruit juice while taking the drug.

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Reload page with references included

Frequently asked questions

• Can Colchicine be used to treat COVID-19 (coronavirus)?

Medical Disclaimer