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Colchicine

Pronunciation

Class: Antigout Agents
VA Class: MS400
CAS Number: 64-86-8

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

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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

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).152

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

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).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 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 (Clcr 50–80 or 30–50 mL/minute, respectively): Dosage adjustment is not needed, but monitor for adverse effects.152

Severe renal impairment (Clcr <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 (Clcr 50–80 or 30–50 mL/minute, respectively): Dosage adjustment is not needed, but monitor for adverse effects.152

Severe renal impairment (Clcr <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 (Clcr 50–80 or 30–50 mL/minute, respectively): Monitor for adverse effects; dosage adjustment may be needed.152

Severe renal impairment (Clcr <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

Interactions for Colchicine

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.)

Preparations

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

Colchicine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

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

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 07/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Colchicine-Probenecid 0.5-500MG Tablets (WATSON LABS): 30/$35.99 or 90/$95.97

Colcrys 0.6MG Tablets (AR SCIENTIFIC): 30/$169.99 or 90/$499.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 30, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

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

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101. Kaplan MM, Alling DW, Zimmerman HJ et al. A prospective trial of colchicine for primary biliary cirrhosis. N Engl J Med. 1986; 315:1448-54. [IDIS 223206] [PubMed 3537784]

102. Kaplan MM. Another treatment for primary biliary cirrhosis. Gastroenterology. 1987; 92:255-7. [IDIS 223601] [PubMed 3781194]

103. Anon. Colchicine for familial Mediterranean fever. FDA Drug Bull. 1983; 13:4.

104. Goldfinger SE. Colchicine for familial Mediterranean fever. N Engl J Med. 1972; 287:1302. [PubMed 4636899]

105. Ravid M, Robson M, Kedar I. Prolonged colchicine treatment in four patients with amyloidosis. Ann Intern Med. 1977; 87:568-70. [PubMed 921085]

106. Zemer D, Pras M, Sohar E et al. Colchicine in familial Mediterranean fever. N Engl J Med. 1976; 294:170-1. [IDIS 61568] [PubMed 1244524]

107. Dinarello CA, Wolff SM, Goldfinger SE et al. Colchicine therapy for familial Mediterranean fever: a double-blind trial. N Engl J Med. 1974; 291:934-7. [IDIS 47250] [PubMed 4606353]

108. Goldstein RC, Schwabe AD. Prophylactic colchicine therapy in familial Mediterranean fever: a controlled, double-blind study. Ann Intern Med. 1974; 31:792-4.

109. Zemer D, Revach M, Pras M et al. A controlled trial of colchicine in preventing attacks of familial Mediterranean fever. N Engl J Med. 1974; 291:932-4. [IDIS 47249] [PubMed 4606109]

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111. Milano AM. Familial Mediterranean fever associated with menstruation: efficacy of intermittent colchicine therapy. Am J Gastroenterol. 1981; 76:363-4. [IDIS 165286] [PubMed 7198867]

112. Rojkind M, Uribe M, Kershenobich D. Colchicine and the treatment of liver cirrhosis. Lancet. 1973; 1:38-9.

113. Kershenobich D, Uribe M, Suarez GI et al. Colchicine, serum albumin, and alkaline phosphatase. Ann Intern Med. 1978; 89:144. [PubMed 352218]

114. Kershenobich D, Uribe M, Suarez GI et al. Treatment of cirrhosis with colchicine: a double-blind randomized trial. Gastroenterology. 1979; 77:532-6. [IDIS 109539] [PubMed 378754]

115. Tapalaga D, Dumitrascu D, Cotul S et al. Colchicine treatment effects on liver cirrhosis assessed by liver blood flow measurements. Rev Roum Med, Med Interne. 1986; 24:69-73.

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