Colchicine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Mitigare: 0.6 mg [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow)]

Generic: 0.6 mg

Solution, Oral:

Gloperba: 0.6 mg/5 mL (150 mL) [contains benzyl alcohol, fd&c red #40, propylene glycol; cherry flavor]

Tablet, Oral:

Colcrys: 0.6 mg [scored; contains fd&c blue #2 (indigotine), fd&c red #40]

Generic: 0.6 mg

Pharmacology

Mechanism of Action

Disrupts cytoskeletal functions by inhibiting β-tubulin polymerization into microtubules, preventing activation, degranulation, and migration of neutrophils associated with mediating some gout symptoms. In familial Mediterranean fever, may interfere with intracellular assembly of the inflammasome complex present in neutrophils and monocytes that mediate activation of interleukin-1β.

Pharmacokinetics/Pharmacodynamics

Distribution

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

V_d: 5 to 8 L/kg

Metabolism

Hepatic via CYP3A4 and glucuronidation; 3 metabolites (2 primary, 1 minor)

Excretion

Urine (40% to 65% as unchanged drug); enterohepatic recirculation, biliary excretion, and p-glycoprotein efflux also possible

Onset of Action

Oral: Pain relief: ~18 to 24 hours

Time to Peak

Serum: Oral: 0.5 to 3 hours

Half-Life Elimination

27 to 31 hours (multiple oral doses; young, healthy volunteers)

Protein Binding

~39%

Use in Specific Populations

Special Populations: Renal Function Impairment

Patients with ESRD had 75% lower clearance and prolonged elimination half-life.

Special Populations: Hepatic Function Impairment

Clearance is significantly reduced and plasma half-life prolonged in patients with mild to moderate cirrhosis.

Special Populations: Elderly

Mean peak plasma levels and AUC were 2 times higher in elderly patients; however, this may be caused by decreased renal function.

Use: Labeled Indications

Familial Mediterranean fever (tablet [eg, Colcrys] only): Treatment of familial Mediterranean fever in adults and children 4 years and older.

Gout flares: Prophylaxis and treatment of acute gout flares when taken at the first sign of a flare.

Limitations of use: Gloperba and Mitigare are only approved for prophylaxis of gout flares; use for acute treatment during gout flares has not been studied.

Use: Off Label

Behçet syndromeayes

Data from controlled trials indicate that colchicine as monotherapy has benefits over placebo for treatment of arthritis in patients with Behçet syndrome. Other benefits such as reduction in genital ulceration and erythema nodosum were limited to women. Oral ulcerations and folliculitis were not improved. Cyclosporine was superior to colchicine for treatment of ocular manifestations, dermal lesions, and aphthous ulcers. Based on the reviewed information, colchicine alone may be useful for patients with milder disease without ocular involvement; however, more aggressive treatment with alternative or combination therapy may be necessary for more severe disease.

Based on the European League Against Rheumatism (EULAR) guidelines for the management of Behçet syndrome, colchicine is recommended as the first-line agent for the treatment of patients with Behçet syndrome with acute arthritis and for the prevention of recurrent mucocutaneous lesions, especially when the lesion is erythema nodosum or genital ulcer

Calcium pyrophosphate (CPP) crystal arthritis ("pseudogout")cyes

Data from a randomized, double-blind, placebo-controlled trial demonstrated efficacy in the treatment of chronic CPP crystal arthritis Das 2002; use of colchicine in the prophylaxis and treatment of acute CPP crystal arthritis is limited to noncontrolled trials Alvarellos 1986 and extrapolation of data in patients with gout.

Based on EULAR guidelines for the treatment of CPP deposition, colchicine is recommended for the prophylaxis and treatment of acute and chronic CPP crystal arthritis EULAR [Zhang 2011].

Pericarditis, acuteayes

Data from a meta-analysis and from a double-blind, placebo-controlled, multicenter trial and an earlier open-label study by the same investigative group (conducted in Italy) indicate that the addition of colchicine to aspirin or ibuprofen significantly reduces the incidence of symptoms at 72 hours and the risk of recurrence.

Based on American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines for the management of ST-segment elevation myocardial infarction (STEMI), Brazilian Society of Cardiology guidelines for the management of myocarditis and pericarditis, and European Society of Cardiology (ESC) guidelines for the management of pericardial diseases, colchicine is an effective and recommended treatment option in the management of patients with pericarditis after STEMI and idiopathic or viral acute pericarditis.

Pericarditis, recurrentayes

Evidence from controlled trials and meta-analyses supports the use of colchicine as an adjunct to aspirin or NSAIDs to prevent and treat recurrence of pericarditis. Colchicine reduces the risk of recurrent pericarditis, with a number needed to treat (NNT) ranging from 3 to 5 to prevent 1 recurrence. Adding colchicine also resolved pericarditis symptoms more quickly.

Based on Brazilian Society of Cardiology guidelines for the management of myocarditis and pericarditis and ESC guidelines for the management of pericardial diseases, the use of colchicine in combination with aspirin/NSAIDs is effective and recommended to prevent and treat recurrent pericarditis.

Postpericardiotomy syndrome, preventiona

Data from 2 major randomized controlled trials demonstrated significant reductions in the incidence of postpericardiotomy syndrome (PPS) with colchicine prophylaxis compared to placebo

Sweet syndrome (acute febrile neutrophilic dermatosis)c

Data from a limited number of patients in a small number of case reports and case series suggest that colchicine may be beneficial for the treatment of Sweet syndrome (acute febrile neutrophilic dermatosis) Maillard 1999, Nestor 2017, Suehisa 1981, Suehisa 1983. Additional data may be necessary to further define the role of colchicine in this condition.

Vasculitis, cutaneous small-vessel (idiopathic)c

Data from a limited number of patients in a small number of case reports and case series suggest that colchicine may be beneficial for the treatment of idiopathic cutaneous small-vessel vasculitis Callen 1985, Callen 1987.

Contraindications

Tablet (eg, Colcrys): Concomitant use of a P-glycoprotein (P-gp) inhibitor or strong CYP3A4 inhibitor in presence of renal or hepatic impairment

Gloperba, Mitigare: Concomitant use of drugs that inhibit both P-gp and CYP3A4 in presence of renal or hepatic impairment; patients with both renal and hepatic impairment

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to colchicine; serious gastrointestinal, hepatic, renal, and cardiac disease

Dosage and Administration

Dosing: Adult

Note: Colchicine has a narrow therapeutic index; drug accumulation is associated with severe, including fatal, consequences. During use, close monitoring for signs/symptoms of colchicine toxicity and factors contributing to colchicine accumulation, such as hepatic/renal function or concomitant interacting medications, are essential, particularly when titrating the dose upwards and with prolonged or repeated courses.

In the United States, the 0.6 mg tablets (eg, Colcrys), the 0.6 mg per 5 mL oral solution (eg, Gloperba), and the 0.6 mg capsules (eg, Mitigare) are available. In Canada, only the 0.6 mg tablets are available. For some uses, the dosage range studied is based on the internationally available dosage forms (0.5 mg or 1 mg tablets). In countries where the 0.5 mg tablets are not available, the 0.6 mg tablets are used empirically.

Behçet syndrome (off-label use): Treatment and/or prevention of recurrence in patients with arthritis, cutaneous lesions, and/or mucocutaneous ulcers: Oral: 1 to 2 mg/day (or 1.2 to 1.8 mg/day) in 2 to 3 divided doses (Aktulga 1980; Dalvi 2012; Davatchi 2009; EULAR [Hatemi 2018]; Smith 2018).

Calcium pyrophosphate (CPP) crystal arthritis ("pseudogout") (off-label use): Due to limited data, experts often approach treatment and prophylaxis of these patients the same as patients with gout (Becker 2018a; EULAR [Zhang 2011]):

Prophylaxis: Patients with ≥3 CPP crystal arthritis attacks annually: Limited data available: Oral: 0.6 mg twice daily (maximum: 1.2 mg/day) (Alvarellos 1986; Becker 2018a). In patients with GI intolerance, some experts give 0.6 mg once daily or 0.6 mg every other day; however, evidence for a decrease in incidence of acute CPP crystal arthritis flare with doses lower than 0.6 mg twice daily is lacking (Becker 2018a).

Treatment: Note: Treatment should be initiated within 24 hours of onset (Becker 2018a). Limited data available; dosing based on expert opinion:

Day 1: Oral: 1.2 mg at the first sign of flare, followed in 1 hour with a single dose of 0.6 mg or 0.6 mg 3 times daily on the first day of flare; maximum total dose: 1.8 mg on day 1 of flare (Becker 2018a)

Day 2 and thereafter: Oral: 0.6 mg twice daily until flare resolves (Becker 2018a)

Familial Mediterranean fever (FMF): Prevention of attacks, and prevention of development and progression of amyloidosis:

Initial: Oral: 1 to 1.5 mg/day (or 1.2 to 1.8 mg/day) in a single daily dose; if single daily doses are not tolerated, give in divided doses. May consider a lower initial dose of 0.5 mg (or 0.6 mg) with subsequent dose escalation to improve tolerance (EULAR [Ozen 2016]). Note: Consider a higher initial dose (eg, up to 2 mg/day) in patients with greater disease activity and renal amyloidosis (but preserved renal function); in patients with secondary (AA) amyloidosis, daily doses >1.5 mg have been associated with prevention of disease progression and a reduction in protein excretion (Livneh 1992; Zemer 1992).

Titration: Oral: Increase the dose in 0.5 mg (or 0.6 mg) increments as clinically indicated (EULAR [Ozen 2016]); upwards titration is recommended in patients with attacks more frequent than every 3 months and/or with persistently elevated inflammatory markers. In general, a 3-month period of steady colchicine dosing is advised before judging response, although a more rapid titration schedule may be considered based on frequency of attacks (Hentgen 2013).

Maximum: Oral: 3 mg/day (EULAR [Ozen 2016]; Hentgen 2013)

Gout, prophylaxis during initiation of urate-lowering therapy: Oral: 0.6 mg once or twice daily (maximum: 1.2 mg/day). In patients with GI intolerance, some experts give 0.6 mg every other day (Becker 2019).

Duration of prophylaxis:

Patients without tophi: 3 to 6 months after achieving target serum uric acid levels with urate-lowering therapy (Becker 2019) or for the first 6 months of urate-lowering therapy (ACR [Khanna 2012]; EULAR [Richette 2017])

Patients with ≥1 tophi: Optimal duration is unclear; some experts continue colchicine therapy for 6 to 12 months after achieving target serum uric acid levels with urate-lowering therapy and resolution of tophi, unless it is clear that tophi will not resolve despite persistent normal urate levels (ACR [Khanna 2012]; Becker 2019).

Gout, treatment (acute flares):

Note: Treatment should be initiated as soon as possible at the first sign of flare, but within 24 hours (preferably) to 36 hours of flare onset (ACR [Khanna 2012]; Becker 2018b). Combination therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) or glucocorticoids may be considered in patients with severe and/or polyarticular gout flare (ACR [Khanna 2012]; EULAR [Richette 2017]).

Day 1: Oral: 1.2 mg at the first sign of flare, followed in 1 hour with a single dose of 0.6 mg (ACP [Qaseem 2017]; EULAR [Richette 2017]; Terkeltaub 2010) or 0.6 mg 3 times daily on the first day of flare; maximum total dose: 1.8 mg on day 1 (Becker 2018b). Note: In patients who were already receiving prophylactic colchicine at the time of their flare, some experts give the higher 1.8 mg/day dosing regimen on day 1 of the flare, in place of the usual prophylactic dose (Becker 2018b).

Day 2 and thereafter: Oral: 0.6 mg once or twice daily until flare resolves (ACP [Qaseem 2017]; ACR [Khanna 2012]; EULAR [Richette 2017]). Some experts continue for 2 to 3 days after flare resolves (Becker 2018b). Note: In patients who were already receiving prophylaxis at the time of their flare, some experts give 0.6 mg twice daily (total dose: 1.2 mg/day) from day 2 until ~48 hours after flare resolution, and then resume the previous prophylactic dose (Becker 2018b).

Note: Historically, higher dose regimens have been given for gout flares; however, high-dose regimens have not been proven more effective than low-dose regimens and low-dose regimens have a better safety profile (EULAR [Richette 2017]; Terkeltaub 2010; Wechalekar 2014).

Pericarditis, acute or recurrent (treatment) (off-label use): Patients with acute idiopathic or viral pericarditis:

Loading dose: Loading doses are not necessary; avoiding loading doses may improve patient compliance and reduce adverse effects (Adler 2018; ESC [Adler 2015]; Imazio 2020). If a decision to use a loading dose is made, the following is recommended:

Patients ≥70 kg: Oral: 1 mg (or 1.2 mg) every 12 hours on day 1, followed by maintenance dosing (Imazio 2005; Imazio 2011).

Patients <70 kg or unable to tolerate higher dosing regimen: Oral: 0.5 mg (or 0.6 mg) every 12 hours on day 1, followed by maintenance dosing (Imazio 2005; Imazio 2011).

Maintenance dosing:

Patients ≥70 kg: Oral: 0.5 mg (or 0.6 mg) twice daily (Imazio 2005; Imazio 2011; Imazio 2013; Imazio 2014a)

Patients <70 kg or unable to tolerate higher dosing regimen: Oral: 0.5 mg (or 0.6 mg) once daily (Imazio 2005; Imazio 2011; Imazio 2013; Imazio 2014a)

Duration of therapy:

Initial treatment (first occurrence): 3 months (Imazio 2013)

Recurrence treatment (first recurrence or multiple recurrences): 6 months (Imazio 2014a)

Concomitant therapy: Colchicine is adjunctive therapy to be used in combination with aspirin or an NSAID; aspirin or NSAID therapy should be continued until resolution of symptoms and then tapered gradually over several weeks. In patients at risk of NSAID-related GI toxicity, concurrent gastroduodenal prophylaxis (generally with a proton pump inhibitor) is also recommended. Coadministration of colchicine with corticosteroids (prednisone) is reserved for refractory cases (ESC [Adler 2015]).

Postpericardiotomy syndrome, prevention (off-label use): Note: Initiate preventive therapy preoperatively (48 to 72 hours prior to surgery [Imazio 2014b]) or postoperatively (24 to 72 hours after surgery [Hoit 2018; Imazio 2010]).

Patients ≥70 kg: Oral: 0.5 mg (or 0.6 mg) twice daily for 1 month

Patients <70 kg: Oral: 0.5 mg (or 0.6 mg) once daily for 1 month

Sweet syndrome (acute febrile neutrophilic dermatosis) (alternative agent) (off-label use): Oral: Dosage range studied: 1 to 1.5 mg/day (1.2 to 1.8 mg/day) in 1 to 3 divided doses; the mean duration of therapy in one case series was reported as 15 days (range: 10 to 21 days) (Maillard 1999; Suehisa 1981; Suehisa 1983).

Vasculitis, cutaneous small-vessel (idiopathic) (alternative agent) (off-label use): Oral: Usual dose studied: 0.6 mg twice daily (Callen 1985; Callen 1987); if no response after 1 to 2 weeks, may consider increasing to 0.6 mg 3 times daily (Goeser 2014; Kinney 2012).

Dosage adjustment for concomitant therapy with CYP3A4 inhibitors or P-gp inhibitors:

Note: In general, colchicine should not be used in patients who are on or have recently completed treatment (ie, within the past 14 days) with a drug that is a strong or moderate inhibitor of CYP3A4 or a P-gp inhibitor. Severe and fatal drug interactions have been reported, particularly in patients with renal or hepatic impairment. If no other therapeutic options are available and the patient has normal renal and hepatic function, colchicine use may be considered if administered at a reduced dosage under close monitoring for toxicity (see below for these recommendations) (manufacturer's labeling [Colcrys]). Patients receiving colchicine for gout prophylaxis who are being treated with or recently completed treatment with a drug that is a strong or moderate CYP3A4 inhibitor or a P-gp inhibitor should not be treated with colchicine for gout flares (Becker 2018b). Dose adjustments recommended below are based on the 0.6 mg dosage forms available in the United States. To deliver a 0.3 mg dose for the following dose adjustments, the 0.6 mg tablet (scored) may be divided and 2.5 mL of the 0.6 mg per 5 mL oral solution can be given.

Strong CYP3A4 inhibitor (eg, protease inhibitors, HIV antiretroviral-boosting agents [cobicistat, ritonavir], clarithromycin, itraconazole, ketoconazole, posaconazole, voriconazole, nefazodone)

FMF: Oral: Maximum dose: 0.6 mg daily (or 0.3 mg twice daily)

Gout, prophylaxis: Oral:

If original dose is 0.6 mg twice daily, adjust dose to 0.3 mg once daily. Note: When using the oral solution (eg, Gloperba) specifically with posaconazole, the manufacturer’s label recommends reducing the dose to 0.24 mg (2 mL) once daily.

If original dose is 0.6 mg once daily, adjust dose to 0.3 mg every other day. Note: When using the oral solution (eg, Gloperba) specifically with posaconazole, the manufacturer’s label recommends reducing the dose to 0.24 mg (2 mL) every other day.

Gout, treatment (acute flare): Oral: Initial: 0.6 mg, followed in 1 hour by a single dose of 0.3 mg, with next dose no sooner than 3 days later

Moderate CYP3A4 inhibitor (eg, aprepitant, diltiazem, erythromycin, fluconazole, verapamil):

FMF: Oral: Maximum dose: 1.2 mg daily (or 0.6 mg twice daily)

Gout, prophylaxis: Oral:

If original dose is 0.6 mg twice daily, adjust dose to 0.3 mg twice daily or 0.6 mg once daily.

If original dose is 0.6 mg once daily, adjust dose to 0.3 mg once daily.

Gout, treatment (acute flare): Oral: 1.2 mg as a single dose, with next dose no sooner than 3 days later

P-gp inhibitor (eg, amiodarone, itraconazole, ketoconazole, cyclosporine, erythromycin, azithromycin, clarithromycin, ranolazine, verapamil):

FMF: Oral: Maximum dose: 0.6 mg daily (or 0.3 mg twice daily)

Gout, prophylaxis: Oral:

If original dose is 0.6 mg twice daily, adjust dose to 0.3 mg once daily.

If original dose is 0.6 mg once daily, adjust dose to 0.3 mg every other day.

Gout, treatment (acute flare): Oral: Initial: 0.6 mg as a single dose, with next dose no sooner than 3 days later

Grapefruit juice: Patients should avoid consuming grapefruit juice while taking colchicine.

Dosing: Geriatric

Use caution.

Gout: Reduce prophylactic daily dose by 50% in individuals ≥70 years (Terkeltaub 2003).

Dosing: Pediatric

Familial Mediterranean Fever (FMF): Colcrys:

Children 4 to 6 years: Oral: 0.3 to 1.8 mg/day in 1 to 2 divided doses; titrate by increasing or decreasing dose in 0.3 mg/day increments based on efficacy or adverse effects; maximum dose: 2.4 mg/day; some guidelines recommend a lower maximum daily dose (2 mg/day) (EULAR [Ozen 2016])

Children >6 to 12 years: Oral: 0.9 to 1.8 mg/day in 1 to 2 divided doses; titrate by increasing or decreasing dose in 0.3 mg/day increments based on efficacy or adverse effects; maximum dose: 2.4 mg/day; some guidelines recommend a lower maximum daily dose (2 mg/day) (EULAR [Ozen 2016])

Children >12 years and Adolescents: Oral: 1.2 to 2.4 mg/day in 1 to 2 divided doses; titrate by increasing or decreasing dose in 0.3 mg/day increments based on efficacy or adverse effects; maximum dose: 2.4 mg/day; some guidelines recommend a lower maximum daily dose (2 mg/day) (EULAR [Ozen 2016])

Gout: Colcrys: Adolescents >16 years:

Flare treatment: Initial: Oral: 1.2 mg at the first sign of flare, followed in 1 hour with a single dose of 0.6 mg (maximum dose: 1.8 mg over 1 hour). Patients receiving prophylaxis treatment may receive treatment dosing; wait 12 hours before resuming prophylactic dose; wait at least 3 days before repeating treatment dose.

Prophylaxis: Oral: 0.6 mg once or twice daily; maximum daily dose: 1.2 mg/day

Dosage adjustment for concomitant therapy with CYP3A4 or P-gp inhibitors: Dosage adjustment is required in patients receiving CYP3A4 or P-gp inhibitors up to 14 days prior to initiation of colchicine. Note: Treatment of gout flare with colchicine is not recommended in patients receiving prophylactic colchicine and CYP3A4 inhibitors.

Coadministration of strong CYP3A4 inhibitor (eg, atazanavir, clarithromycin, darunavir/ritonavir, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, tipranavir/ritonavir):

FMF: Children ≥4 years and Adolescents: Oral: Reduce maximum dose to 0.6 mg once daily or 0.3 mg twice daily

Gout prophylaxis: Adolescents >16 years: Oral:

If original dose is 0.6 mg twice daily, adjust dose to 0.3 mg once daily

If original dose is 0.6 mg once daily, adjust dose to 0.3 mg every other day

Gout flare treatment: Adolescents >16 years: Oral: Initial: 0.6 mg, followed in 1 hour by a single dose of 0.3 mg; wait at least 3 days to repeat

Coadministration of moderate CYP3A4 inhibitor (eg, amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, verapamil):

FMF: Children ≥4 years and Adolescents: Oral: Reduce maximum dose to 1.2 mg once daily or 0.6 mg twice daily

Gout prophylaxis: Adolescents >16 years: Oral:

If original dose is 0.6 mg twice daily, adjust dose to 0.3 mg twice daily or 0.6 mg once daily

If original dose is 0.6 mg once daily, adjust dose to 0.3 mg once daily

Gout flare treatment: Adolescents >16 years: Oral: 1.2 mg as a single dose; wait at least 3 days to repeat days

Coadministration of P-gp inhibitor (eg, cyclosporine, ranolazine):

FMF: Children ≥4 years and Adolescents: Oral: Reduce maximum dose to 0.6 mg once daily or 0.3 mg twice daily

Gout prophylaxis: Adolescents >16 years: Oral:

If original dose is 0.6 mg twice daily, adjust dose to 0.3 mg once daily

If original dose is 0.6 mg once daily, adjust dose to 0.3 mg every other day

Gout flare treatment: Adolescents >16 years: Oral: Initial: 0.6 mg as a single dose; wait at least 3 days to repeat

Administration

Oral: Administer with water and maintain adequate fluid intake. May be administered without regard to meals.

Dietary Considerations

May need to supplement with vitamin B₁₂. Avoid grapefruit juice.

Storage

Store at 20°C to 25°C (68°F to 77°F). Protect from light and moisture.

Drug Interactions

Antihepaciviral Combination Products: May increase the serum concentration of Colchicine. Avoid combination

Choline C 11: Colchicine may diminish the therapeutic effect of Choline C 11. Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Cyanocobalamin: Colchicine may decrease the serum concentration of Cyanocobalamin. Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. See full monograph for details. Use extra caution in patients with impaired renal and/or hepatic function. Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Colchicine. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a strong CYP3A4 inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See full monograph for details. Consider therapy modification

Digoxin: May increase the serum concentration of Colchicine. Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Fibric Acid Derivatives: May enhance the myopathic (rhabdomyolysis) effect of Colchicine. Monitor therapy

Fosamprenavir: May increase the serum concentration of Colchicine. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are receiving ritonavir-boosted fosamprenavir. In those with normal renal and hepatic function, reduce colchicine dose as directed. Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Grapefruit Juice: May increase the serum concentration of Colchicine. Avoid combination

HMG-CoA Reductase Inhibitors (Statins): Colchicine may enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Consider therapy modification

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Avoid combination

Lumacaftor and Ivacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor and Ivacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Multivitamins/Fluoride (with ADE): Colchicine may decrease the serum concentration of Multivitamins/Fluoride (with ADE). Specifically, colchicine may decrease absorption of cyanocobalamin (vitamin B12). Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): Colchicine may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, colchicine may decrease the serum concentration of Cyanocobalamin. Monitor therapy

Multivitamins/Minerals (with AE, No Iron): Colchicine may decrease the serum concentration of Multivitamins/Minerals (with AE, No Iron). Specifically, colchicine may decrease absorption of cyanocobalamin (vitamin B12). Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See full monograph for details. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tacrolimus (Systemic): May increase the serum concentration of Colchicine. Monitor therapy

Tipranavir: May increase the serum concentration of Colchicine. Management: Colchicine should not be used with tipranavir in patients with impaired renal or hepatic function. In those with normal renal and hepatic function, reduced colchicine doses (as directed) are required if used with tipranavir. Consider therapy modification

Test Interactions

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

Adverse Reactions

Frequency not always defined.

>10%: Gastrointestinal: Gastrointestinal disease (26% to 77%), diarrhea (23% to 77%), vomiting (17%), nausea (4% to 17%)

1% to 10%:

Central nervous system: Fatigue (1% to 4%), headache (1% to 2%)

Endocrine & metabolic: Gout (4%)

Gastrointestinal: Abdominal cramps, abdominal pain

Respiratory: Pharyngolaryngeal pain (2% to 3%)

<1%, postmarketing, and/or case reports: Alopecia, aplastic anemia, azoospermia, bone marrow depression, dermatitis, disseminated intravascular coagulation, dysgeusia (Syed 2016), granulocytopenia, hepatotoxicity, hypersensitivity reaction, increased creatine phosphokinase in blood specimen, increased serum alanine aminotransferase, increased serum aspartate aminotransferase, lactose intolerance, leukopenia, maculopapular rash, myalgia, myasthenia, myopathy, myotonia, neuropathy, oligospermia, pancytopenia, peripheral neuritis, nonthrombocytopenic purpura, rhabdomyolysis, skin rash, thrombocytopenia, toxic neuromuscular disease

Warnings/Precautions

Concerns related to adverse effects:

• Blood dyscrasias: Myelosuppression (eg, thrombocytopenia, leukopenia, granulocytopenia, pancytopenia) and aplastic anemia have been reported in patients receiving therapeutic doses.
• Gastrointestinal symptoms: Dosage reduction is recommended in patients who develop gastrointestinal symptoms (anorexia, diarrhea, nausea, vomiting) related to drug therapy.
• Neuromuscular toxicity: Myotoxicity (including rhabdomyolysis) has been reported in patients receiving therapeutic doses; patients with renal dysfunction and elderly patients are at increased risk. Concomitant use of cyclosporine, or drugs known to cause this effect (such as diltiazem, verapamil, fibrates, and statins) may increase the risk of myopathy. Symptoms typically resolve within 1 week to several months of colchicine discontinuation.

Disease-related concerns:

• Hepatic impairment: Clearance is decreased in hepatic impairment; monitor closely for adverse effects/toxicity. Dosage adjustments may be considered depending on degree of impairment or indication, and may be affected by the use of concurrent medication (CYP3A4 or P-gp inhibitors). Concurrent use of P-gp or strong CYP3A4 inhibitors is contraindicated in hepatic impairment. Fatal toxicity has been reported.
• Renal impairment: Clearance is decreased in renal impairment; monitor closely for adverse effects/toxicity. Dosage adjustments may be required depending on degree of impairment or indication, and may be affected by the use of concurrent medication (CYP3A4 or P-gp inhibitors). Concurrent use of P-gp or strong CYP3A4 inhibitors is contraindicated in renal impairment. Fatal toxicity has been reported.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution in elderly patients; consider dosage adjustments.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP 1997; CDC 1982); some data suggest that benzoate displaces bilirubin from protein-binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer’s labeling.

Other warnings/precautions:

• Appropriate use: Colchicine is not an analgesic and should not be used to treat pain from other causes.
• Fatal overdose: Accidental and intentional fatal overdoses have been reported. Dosage associated with fatal toxicity is variable (eg, wide dosage range).

Monitoring Parameters

CBC, renal and hepatic function tests

Pregnancy

Pregnancy Considerations

Colchicine crosses the placenta in concentrations ~15% of those in the maternal plasma.

Use during pregnancy in the treatment of rheumatic diseases, such as familial Mediterranean fever, have not shown an increase in miscarriage, stillbirth, or teratogenic effects.

Colchicine may be continued during pregnancy when needed to maintain remission of rheumatic disease or treat disease flair, including patients with familial Mediterranean fever (EULAR [Götestam Skorpen 2016]; EULAR [Ozen 2016]).

Use in males may rarely be associated with reversible infertility. A temporary dose reduction or discontinuation may be needed if azoospermia or oligospermia is related to use; however, men generally do not need to discontinue colchicine prior to conception (EULAR [Ozen 2016]).

Patient Education

What is this drug used for?

• It is used to treat gout attacks.
• It is used to prevent gout attacks.
• It is used to treat familial Mediterranean fever.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Diarrhea
• Nausea
• Vomiting
• Abdominal pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection
• Burning or numbness feeling
• Severe loss of strength and energy
• Bruising
• Bleeding
• Pale skin
• Muscle pain
• Muscle weakness
• Unable to pass urine
• Change in amount of urine passed
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.