Colchicine (Monograph)

Brand names: Colcrys, Gloperba, Mitigare
Drug class: Cardiovascular Drugs, Nonsteroidal Anti-inflammatory
- Antimitotic Agents

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Antigout and antimitotic agent.^a

Uses for Colchicine

Gout Flare

Treatment to relieve pain in attacks of acute gout flare (gouty arthritis).¹²³ ¹²⁴ ¹²⁵ ¹²⁶ ¹²⁷ ¹⁴² ¹⁴³ ¹⁵² Initiate at the first sign of gout flare.¹⁵² Used as a second-line agent in patients who have not responded to or who cannot tolerate other recommended therapy (i.e., NSAIAs, corticosteroids).¹⁴² ¹⁴³

Prophylactic treatment of recurrent gout flare.¹⁵² Has no effect on plasma concentrations or urinary excretion of uric acid;¹²³ ¹²⁴ ¹²⁹ ¹³⁰ ¹⁴³ ¹⁴⁶ use concomitantly with allopurinol or a uricosuric agent (e.g., febuxostat, probenecid, sulfinpyrazone) to decrease serum urate concentrations.¹²³ ¹²⁴ ¹²⁹ ¹³⁰ ¹⁴³ ¹⁴⁶ Colchicine/probenecid fixed-dosage preparation has limited usefulness for prophylactic therapy because colchicine present exceeds the amount required by most patients.^a

Familial Mediterranean Fever

Management of familial Mediterranean fever.¹⁰⁰ ¹⁰³ ¹⁰⁴ ¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁰⁹ ¹¹⁰ ¹¹¹ ¹⁴⁹ ¹⁵² Used for chronic prophylactic therapy to reduce frequency and severity of episodic attacks of painful serositis in patients with familial Mediterranean fever.¹⁰⁰ ¹⁰³ ¹⁰⁴ ¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹⁰⁹ ¹⁴⁹ ¹⁵⁰ ¹⁵²

Not curative; manifestations return to pretreatment levels following discontinuance.¹⁰⁰ ¹⁰⁴ ¹⁰⁷ ¹⁰⁸ ¹⁰⁹

Chronic prophylactic therapy appears to prevent amyloidosis (manifested by nephropathy) when there is no evidence of it at initiation of therapy;¹⁰⁰ 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.¹⁴⁹ ¹⁵⁰ May prevent deterioration during proteinuric phase of the disease (when amyloid involvement is minimal).¹⁰⁰

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.¹⁴⁴ ¹⁴⁵ (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.¹²⁴ ¹²⁵ ¹²⁷ ¹²⁹
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).¹²⁴ ¹²⁶ ¹⁴³

Administration

Administer orally.¹⁵² Has been administered IV; parenteral preparation no longer available in the US.¹⁴⁴ ¹⁴⁵ (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.¹⁵²

Administer without regard to meals.¹⁵²

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.¹⁵²

Pediatric Patients

Prophylactic Treatment of Recurrent Gout Flares

Oral

Manufacturer states that adolescents ≥16 years of age may receive adult dosages.¹⁵²

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).¹⁵² 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.¹⁵²

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.¹⁵²

Table 1. Recommended Dosage of Colchicine for Chronic Prophylactic Therapy of Familial Mediterranean Fever in Children Not Receiving Concomitant Therapy with Moderate or Potent CYP3A4 Inhibitors or with P-glycoprotein Inhibitors
Child’s Age (years)	Recommended Colchicine Dosage
4–6	0.3–1.8 mg daily (given as 1 dose or 2 divided doses)¹⁵²
6–12	0.9–1.8 mg daily (given as 1 dose or 2 divided doses)¹⁵²
>12	1.2–2.4 mg daily (given as 1 dose or 2 divided doses)¹⁵²

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).¹⁵²

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.¹⁵²

Do not repeat courses of colchicine therapy (see Table 2) until 3 days have elapsed.¹⁵² ¹⁵⁴

Table 2. Recommended Adult Dosage of Colchicine for Treatment of Gout Flare
Recent (within 14 days) or Concomitant Therapy	Recommended Colchicine Dosage
No recent or concomitant therapy with a moderate or potent CYP3A4 inhibitor or a P-glycoprotein inhibitor	1.2 mg at first sign of flare followed by 0.6 mg one hour later;¹⁵² wait 12 hours before resuming prophylactic doses of colchicine¹⁵²
Potent CYP3A4 inhibitor (e.g., atazanavir, boceprevir, clarithromycin, darunavir with low-dose ritonavir [ritonavir-boosted darunavir], ritonavir-boosted fosamprenavir, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, telithromycin, ritonavir-boosted tipranavir, the fixed combination of lopinavir and ritonavir [lopinavir/ritonavir], the fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir)	0.6 mg at first sign of flare followed by 0.3 mg one hour later¹⁵² ¹⁵⁴ ¹⁵⁵ ¹⁶³ ¹⁶⁴
Moderate CYP3A4 inhibitor (e.g., aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir [without ritonavir], grapefruit juice, verapamil)	1.2 mg at first sign of flare¹⁵² ¹⁵⁴
P-glycoprotein inhibitor (e.g., cyclosporine, ranolazine)	0.6 mg at first sign of flare¹⁵²

Prophylactic Treatment of Recurrent Gout Flares

Oral

Table 3. Recommended Adult Dosage of Colchicine for Prophylactic Treatment of Recurrent Gout Flares
Recent (within 14 days) or Concomitant Therapy	Recommended Colchicine Dosage
No recent or concomitant therapy with a moderate or potent CYP3A4 inhibitor or a P-glycoprotein inhibitor	0.6 mg once or twice daily (maximum 1.2 mg daily)¹⁵²
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)	0.3 mg daily or every other day¹⁵² ¹⁵⁴ ¹⁵⁵ ¹⁶³ ¹⁶⁴
Moderate CYP3A4 inhibitor (e.g., aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir [without ritonavir], grapefruit juice, verapamil)	0.3 mg twice daily, 0.6 mg once daily, or 0.3 mg once daily¹⁵² ¹⁵⁴
P-glycoprotein inhibitor (e.g., cyclosporine, ranolazine)	0.3 mg once daily or every other day¹⁵²

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.^a

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.¹⁴⁶ 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).¹⁴⁶

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.¹⁴⁶

Familial Mediterranean Fever

Oral

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.¹⁵²

Table 4. Recommended Adult Dosage of Colchicine for Chronic Prophylactic Therapy of Familial Mediterranean Fever
Recent (within 14 days) or Concomitant Therapy	Maximum Recommended Colchicine Dosage
No recent or concomitant therapy with a moderate or potent CYP3A4 inhibitor or a P-glycoprotein inhibitor	1.2–2.4 mg daily (given as 1 dose or 2 divided doses)¹⁵²
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)	0.6 mg daily (may be given as 0.3 mg twice daily)¹⁵² ¹⁵⁴ ¹⁵⁵ ¹⁶³ ¹⁶⁴
Moderate CYP3A4 inhibitor (e.g., aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir [without ritonavir], grapefruit juice, verapamil)	1.2 mg daily (may be given as 0.6 mg twice daily)¹⁵² ¹⁵⁴
P-glycoprotein inhibitor (e.g., cyclosporine, ranolazine)	0.6 mg daily (may be given as 0.3 mg twice daily)¹⁵²

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.¹⁵² (See Contraindications under Cautions.)

Treatment of Gout Flare

Oral

Mild to moderate hepatic impairment: Dosage adjustment is not needed, but monitor for adverse effects.¹⁵²

Severe hepatic impairment: Dosage adjustment is not needed, but do not repeat courses of colchicine therapy until 2 weeks have elapsed.¹⁵² Consider alternative therapy for patients requiring repeat courses of therapy.¹⁵²

Prophylactic Treatment of Recurrent Gout Flares

Oral

Mild to moderate hepatic impairment: Dosage adjustment is not needed, but monitor for adverse effects.¹⁵²

Severe hepatic impairment: Consider dosage reduction.¹⁵²

Familial Mediterranean Fever

Oral

Mild to moderate hepatic impairment: Dosage adjustment is not needed, but monitor for adverse effects.¹⁵²

Severe hepatic impairment: Consider dosage reduction.¹⁵²

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.¹⁵² (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.¹⁵²

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.¹⁵²

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.¹⁵² Consider alternative therapy for patients requiring repeat courses of therapy.¹⁵²

Dialysis: 0.6 mg at first sign of gout flare.¹⁵² Do not repeat courses of colchicine therapy until 2 weeks have elapsed.¹⁵²

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.¹⁵²

Severe renal impairment (Cl_cr <30 mL/minute): Initial dosage is 0.3 mg daily; monitor closely if dosage is increased.¹⁵²

Dialysis: Initial dosage is 0.3 mg twice weekly; monitor closely.¹⁵²

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.¹⁵²

Severe renal impairment (Cl_cr <30 mL/minute) or dialysis: Initial dosage is 0.3 mg daily; dosage can be increased with careful monitoring.¹⁵²

Geriatric Patients

Select dosage with caution because of age-related decreases in renal function and concomitant disease and drug therapy.¹⁵²

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).¹⁵² ¹⁵⁴ ¹⁵⁵ ¹⁶³ ¹⁶⁴

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.¹²² ¹⁴⁸ Oral ingestion of as little as 7 mg has resulted in death, although larger oral doses have been survived.¹⁴⁷ ^a

Serious Adverse Effects Related to Colchicine Injection

Serious adverse events, including some deaths, reported in patients receiving IV colchicine;¹⁴⁴ ¹⁴⁵ ¹⁴⁸ many events associated with colchicine toxicity.¹⁴⁴ ¹⁴⁵ As of June 2007, FDA was aware of 50 reports of adverse effects linked to IV colchicine; 23 of these events were fatal.¹⁴⁴ ¹⁴⁵ Neutropenia, acute renal failure, thrombocytopenia, CHF, and pancytopenia reported.¹⁴⁴ ¹⁴⁵ ¹⁴⁸

Compounded IV colchicine linked to 3 deaths.¹⁴⁴ ¹⁴⁵ ¹⁴⁸ Compounded colchicine injection from the same lot as these patients received contained 8 times the labeled amount of colchicine.¹⁴⁸

FDA announced enforcement action would be taken against all firms, including compounding pharmacies, attempting to manufacture, ship, or deliver colchicine injection.¹⁴⁵ Oral preparations containing colchicine remain on the market; risks believed to be lower with oral preparations.¹⁴⁴ ¹⁴⁵

Hematologic Effects

Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia reported.¹⁵²

Drug Interactions

Concomitant use with certain drugs is contraindicated or requires particular caution.¹⁵² (See Interactions and also see Dosage under Dosage and Administration.)

Neuromuscular Effects

Neuromuscular toxicity and rhabdomyolysis reported with long-term use.¹⁵² Individuals with renal impairment and geriatric individuals are at increased risk.¹⁵² Concomitant use of certain drugs may increase risk of myotoxicity.¹⁵² (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.¹⁴⁶

Specific Populations

Pregnancy

Category C.¹⁵²

Effect on labor and delivery not known.¹⁵²

Lactation

Distributed into milk.¹⁵² However, AAP states colchicine usually is compatible with breast-feeding;¹³⁹ ¹⁴⁰ use caution.¹⁵²

Pediatric Use

Safety and efficacy not established for gout.¹⁵²

Safety and efficacy for familial Mediterranean fever in children evaluated in uncontrolled studies.¹⁵² Long-term use of colchicine did not appear to affect growth in children with familial Mediterranean fever.¹⁵²

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.¹⁵²

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.¹⁵²

Hepatic Impairment

Use with caution; dosage adjustment may be needed.¹⁵² (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.¹⁵² (See Contraindications under Cautions.) Fatal or life-threatening colchicine toxicity reported.¹⁵²

Renal Impairment

Use with caution; dosage adjustment may be needed.¹⁵² (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.¹⁵² (See Contraindications under Cautions.) Fatal or life-threatening colchicine toxicity reported.¹⁵²

Common Adverse Effects

Treatment of gout flare: Diarrhea, pharyngolaryngeal pain.¹⁵²

Prophylactic treatment of recurrent gout flares: Diarrhea.¹⁵²

Familial Mediterranean fever: Abdominal pain, diarrhea, nausea, vomiting.¹⁵²

Drug Interactions

Metabolized by CYP3A4.¹⁵² Does not inhibit or induce CYP isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4.¹⁵²

A P-glycoprotein substrate.¹⁵²

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inhibitors: Potential pharmacokinetic interaction (increased plasma colchicine concentrations); increased risk of colchicine toxicity.¹⁵² Fatal reactions reported with concomitant use of potent CYP3A4 inhibitors.¹⁵² 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).¹⁵² Concomitant use of colchicine and potent CYP3A4 inhibitors is contraindicated in renal or hepatic impairment.¹⁵²

Drugs Affecting P-Glycoprotein Transport

P-glycoprotein inhibitors: Pharmacokinetic interaction (increased plasma concentrations of colchicine) likely; increased risk of colchicine toxicity.¹⁵² Fatal reactions reported.¹⁵² 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).¹⁵² Concomitant use of colchicine and P-glycoprotein inhibitors is contraindicated in renal or hepatic impairment.¹⁵²

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Antifungals, azoles (fluconazole, itraconazole, ketoconazole)	Increased plasma concentrations of colchicine expected¹⁵² Ketoconazole: Increased plasma concentrations of colchicine reported¹⁵²	Adjust colchicine dosage (see Dosage under Dosage and Administration)¹⁵² Itraconazole, ketoconazole: Concomitant use contraindicated in renal or hepatic impairment¹⁵²
Aprepitant	Increased plasma concentrations of colchicine expected¹⁵²	Adjust colchicine dosage (see Dosage under Dosage and Administration)¹⁵²
Boceprevir	Increased plasma concentrations of colchicine expected¹⁶³	Adjust colchicine dosage (see Dosage under Dosage and Administration)¹⁶³
Cyclosporine	Possible additive nephrotoxic effects; increased concentrations of cyclosporine in blood¹⁵⁹ ¹⁶¹ ¹⁶² Increased colchicine concentrations; fatal colchicine toxicity reported¹⁵² ¹⁶¹ ¹⁶²	Monitor cyclosporine concentration and renal function if colchicine is initiated, discontinued, or dosage altered; adjust cyclosporine dosage accordingly¹⁵⁹ ¹⁶¹ ¹⁶² Adjust colchicine dosage (see Dosage under Dosage and Administration)¹⁵² ¹⁶¹ ¹⁶² Concomitant use contraindicated in renal or hepatic impairment¹⁵²
Digoxin	Rhabdomyolysis reported¹⁵²	Weigh potential benefits and risks;¹²⁰ ¹⁵² monitor for muscle pain, tenderness, or weakness, especially during the initial phase of such concomitant therapy¹⁵²
Diltiazem	Increased plasma concentrations of colchicine; neuromuscular toxicity reported¹⁵²	Adjust colchicine dosage (see Dosage under Dosage and Administration)¹⁵²
Elvitegravir/cobicistat/emtricitabine/tenofovir fixed combination	Increased plasma concentrations of colchicine expected¹⁵⁴ ¹⁵⁵	Adjust colchicine dosage (see Dosage under Dosage and Administration)¹⁵⁴ ¹⁵⁵ Concomitant use contraindicated in renal or hepatic impairment¹⁵⁴ ¹⁵⁵
Estrogens or progestins	Oral contraceptives: No change in plasma concentrations of ethinyl estradiol or norethindrone¹⁵²
Fibric acid derivatives (gemfibrozil, fenofibrate)	Addition of a fibrate to long-term colchicine therapy or addition of colchicine to long-term fibrate therapy has resulted in myopathy and rhabdomyolysis¹⁵²	Weigh potential benefits and risks; monitor for muscle pain, tenderness, or weakness, especially during the initial phase of such concomitant therapy¹⁵²
Grapefruit juice	Minimal change in plasma colchicine concentration reported, though increased colchicine concentrations reported with other moderate CYP3A4 inhibitors;¹⁵² increased colchicine concentrations possible¹⁵²	Adjust colchicine dosage (see Dosage under Dosage and Administration)¹⁵² Advise patient to avoid grapefruit juice¹⁵²
HIV protease inhibitors (PIs)	Increased plasma concentrations of colchicine expected¹⁵² ¹⁵⁴ Ritonavir: Increased plasma concentrations of colchicine reported¹⁵² ¹⁵⁴	Adjust colchicine dosage (see Dosage under Dosage and Administration)¹⁵² ¹⁵⁴ HIV PIs that are potent CYP3A4 inhibitors: Concomitant use contraindicated in renal or hepatic impairment¹⁵² ¹⁵⁴
HMG-CoA reductase inhibitors (statins)	Addition of a statin to long-term colchicine therapy or addition of colchicine to long-term statin therapy has resulted in myopathy and rhabdomyolysis¹⁵² ¹⁵⁶ ¹⁵⁷	Weigh potential benefits and risks; monitor for muscle pain, tenderness, or weakness, especially during the initial phase of such concomitant therapy¹⁵²
Macrolides (azithromycin, clarithromycin, erythromycin, telithromycin)	Increased plasma concentrations of colchicine expected¹⁵² Azithromycin: Increased plasma concentrations of colchicine¹⁵² Clarithromycin: Decreased metabolism and increased plasma concentrations of colchicine; severe or fatal colchicine toxicity reported¹⁵² ¹⁵⁸ ¹⁶⁰	Clarithromycin, erythromycin, telithromycin: Adjust colchicine dosage (see Dosage under Dosage and Administration)¹⁵² Clarithromycin, telithromycin: Concomitant use contraindicated in renal or hepatic impairment¹⁵²
Nefazodone	Increased plasma concentrations of colchicine expected¹⁵²	Adjust colchicine dosage (see Dosage under Dosage and Administration)¹⁵² Concomitant use contraindicated in renal or hepatic impairment¹⁵²
Ranolazine	Increased plasma concentrations of colchicine expected¹⁵²	Adjust colchicine dosage (see Dosage under Dosage and Administration)¹⁵² Concomitant use contraindicated in renal or hepatic impairment¹⁵²
Telaprevir	Increased plasma concentrations of colchicine expected¹⁶⁴	Adjust colchicine dosage (see Dosage under Dosage and Administration)¹⁶⁴
Theophylline	No change in plasma concentrations of theophylline¹⁵²
Verapamil	Increased plasma concentrations of colchicine; neuromuscular toxicity reported¹⁵²	Adjust colchicine dosage (see Dosage under Dosage and Administration)¹⁵²

Colchicine Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from the GI tract following oral administration.¹⁴⁷ ^a ^f

Drug and metabolites reenter intestinal tract via biliary and intestinal secretions after partial metabolism in liver.¹⁴⁷ ¹⁵² ^a ^f

Unchanged drug may be reabsorbed from the intestine.^a

Following oral administration, peak plasma concentrations occur within 0.5–2 hours.^f ¹⁵² Enterohepatic circulation may occur; secondary peak present in some individuals 3–36 hours after dose.¹⁵²

Absolute bioavailability reported to be about 45%.¹⁵²

Food

Administration with food did not affect rate of absorption but decreased extent of absorption by 15%.¹⁵²

Distribution

Extent

Crosses the placenta and is distributed into milk.¹³⁹ ¹⁵²

Plasma Protein Binding

39% (mainly albumin).¹⁵²

Elimination

Metabolism

Demethylated in the liver by CYP3A4.¹⁵²

Elimination Route

40–65% recovered unchanged in urine.¹⁵² Enterohepatic circulation and biliary excretion may occur.¹⁵² Not removed by hemodialysis.¹⁵²

Half-life

26.6–31.2 hours.¹⁵²

Special Populations

Hepatic impairment: Substantial interpatient variability in pharmacokinetics.¹⁵² 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.¹⁵²

End-stage renal disease requiring dialysis: Colchicine clearance decreased by 75%, elimination half-life increased.¹⁵²

Stability

Storage

Oral

Tablets

20–25°C.¹⁵² Protect from light.¹⁵²

Actions

Has weak anti-inflammatory activity, but no analgesic activity.^a
Has no effect on urinary excretion of uric acid or on serum urate concentration, solubility, or binding to serum proteins.^a ^f
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.¹⁵²
Mechanism of beneficial effects in familial Mediterranean fever not fully elucidated.¹⁵² Colchicine may interfere with the intracellular assembly of inflammasome complex in neutrophils and monocytes that mediates activation of interleukin-1β.¹⁵²

Advice to Patients

Importance of patients not altering colchicine dosage without consulting a clinician.¹⁵²
Importance of instructing patients on how to resume colchicine therapy if they miss taking a dose.¹⁵² If used to treat an acute gout flare and not for prophylaxis of recurrent flares, take the missed dose as soon as possible.¹⁵² 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.¹⁵² 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.¹⁵²
Possibility of serious adverse effects (e.g., blood dyscrasias, myotoxicity and rhabdomyolysis).¹⁵²
Potential for fatal overdosage in adults or children following colchicine ingestion.¹⁵² Importance of keeping colchicine out of children's reach.¹⁵²
Potential for fatal drug interactions.¹⁵² 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.¹⁵² Importance of avoiding grapefruit and grapefruit juice while taking the drug.¹⁵²
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.¹⁵²
Importance of informing patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.

Colchicine
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	0.6 mg	Mitigare	Hikma
	Solution	0.6 mg/5 mL	Gloperba	Romeg
	Tablets	0.6 mg	Colcrys (scored)	Takeda

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

Probenecid and Colchicine
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	500 mg Probenecid and Colchicine 0.5 mg*	Probenecid and Colchicine Tablets

References

Only references cited for selected revisions after 1984 are available electronically.

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