(KOL chi seen)
Familial Mediterranean fever (Colcrys only): Treatment of familial Mediterranean fever in adults and children 4 years and older.
Gout flares: Prophylaxis and the treatment of acute gout flares when taken at the first sign of a flare. Note: Mitigare is only approved for prophylaxis of gout flares.
Concomitant use of a P-glycoprotein (P-gp) or strong CYP3A4 inhibitor in presence of renal or hepatic impairment
Mitigare: 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
Familial Mediterranean fever (FMF): Oral: Colcrys: 1.2 to 2.4 mg daily in 1 to 2 divided doses. Titration: Increase or decrease dose in 0.3 mg daily increments based on efficacy or adverse effects
Gout: Oral:
US labeling:
Flare treatment (Colcrys): Initial: 1.2 mg at the first sign of flare, followed in 1 hour with a single dose of 0.6 mg (maximum: 1.8 mg within 1 hour). Patients receiving prophylaxis therapy may receive treatment dosing; wait 12 hours before resuming prophylaxis dose. Note: Current FDA-approved dose for gout flare is substantially lower than what has been historically used clinically. Doses larger than the currently recommended dosage for gout flare have not been proven to be more effective.
Prophylaxis (Colcrys and Mitigare): 0.6 mg once or twice daily; maximum: 1.2 mg daily. The duration of prophylaxis is 6 months or 3 months (patients without tophi) to 6 months ( ≥1 tophi) after achieving target serum uric acid levels (ACR guidelines [Khanna 2012]).
Canadian labeling:
Flare treatment: Initial: 1.2 mg at the first sign of flare, followed in 1 hour with a single dose of 0.6 mg (maximum: 1.8 mg within 1 hour). Do not repeat treatment for at least 3 days. Wait at least 12 hours to resume prophylactic dose.
Prophylaxis: 0.6 mg once or twice daily; maximum: 1.2 mg per 24 hours
Pericarditis, acute (off-label use): Note: The 0.5 mg tablets are not available in the US or Canada. However, the 0.6 mg tablets are used empirically in place of 0.5 mg tablets in countries where they are not available:
Patients >70 kg: 0.5 mg twice daily for 3 months (Imazio 2013)
Patients ≤70 kg or unable to tolerate higher dosing regimen: 0.5 mg once daily for 3 months (Imazio 2013)
Note: Loading doses of colchicine used in earlier studies may not be necessary in the treatment of acute pericarditis according to newer data; lower doses are proposed to improve patient compliance and reduce adverse effects (Adler 2015; Imazio 2010b; Imazio 2013).
Concomitant therapy: Use in combination with high-dose aspirin or ibuprofen for 7 to 14 days, followed by a gradual tapering of the dose over 3 to 4 weeks (ESC [Adler 2015]). In patients with contraindications to NSAIDS/aspirin, glucocorticoid therapy has been used (eg, prednisone for 2 weeks with gradual tapering) (Imazio 2013). Concurrent gastroduodenal prophylaxis with a proton pump inhibitor has been used and is recommended (ESC [Adler 2015]; Imazio 2005a; Imazio 2013)
Pericarditis, recurrent (off-label use): Note: The 0.5 mg or 1 mg tablets are not available in the US or Canada. However, the 0.6 mg tablets are used empirically in place of 0.5 mg tablets in countries where they are not available:
Regimens with loading dose:
Patients ≥70 kg: 0.5 to 1 mg every 12 hours on day 1, followed by 0.25 to 0.5 mg every 12 hours for 6 months (Imazio 2005b; Imazio 2011).
Patients <70 kg or unable to tolerate higher dosing regimen: 0.5 mg every 12 hours on day 1, followed by 0.5 mg once daily for 6 months (Imazio 2005b; Imazio 2011).
Regimens without loading dose:
Patients >70 kg: 0.5 mg twice daily for 6 months (Imazio 2014a).
Patients ≤70 kg or unable to tolerate higher dosing regimen: 0.5 mg once daily for 6 months (Imazio 2014a).
Note: Weight-based dosing without loading doses may improve compliance and reduce GI adverse effects according to expert opinion (ESC [Adler 2015]; Imazio 2010b; Imazio 2013). Recent data demonstrated comparable beneficial outcomes to studies that used loading doses (Imazio 2005b; Imazio 2011, Imazio 2014a).
Concomitant therapy: Use in combination with high-dose aspirin, ibuprofen, or indomethacin based on initial regimen used for the acute episode and type of pericarditis (eg, idiopathic, viral, autoimmune, or post-myocardial infarction). Coadministration with corticosteroids (prednisone) is reserved for refractory cases or patients with contraindications to NSAID therapy (ESC [Adler 2015]). Proton pump inhibitors have been administered during aspirin or NSAID therapy as gastroduodenal prophylaxis (Imazio 2005b; Imazio 2011; Imazio 2014a).
Postpericardiotomy syndrome (prevention) (off-label use): Note: Regimens without a loading dose may improve patient compliance and reduce side effects (Imazio 2014b). The 0.5 mg or 1 mg tablets are not available in the US or Canada. However, the 0.6 mg tablets are used empirically in place of 0.5 mg tablets in countries where they are not available:
Regimens with loading dose:
Patients ≥70 kg: 1 mg twice daily given on post-operative day 3, followed by 0.5 mg twice daily for 1 month (Imazio 2010a).
Patients <70 kg or unable to tolerate higher dosing regimen: 0.5 mg twice daily given on post-operative day 3, followed by 0.5 mg once daily for 1 month (Imazio 2010a).
Regimens without loading dose:
Patients ≥70 kg: 0.5 mg twice daily initiated 48 to 72 hours prior to surgery and continued for 1 month (Imazio 2014b).
Patients <70 kg: 0.5 mg once daily initiated 48 to 72 hours prior to surgery and continued for 1 month (Imazio 2014b).
Dosage adjustment for concomitant therapy with CYP3A4 or P-glycoprotein (P-gp) inhibitors: Note: Colcrys labeling recommends dosage adjustments in patients receiving CYP3A4 or P-gp inhibitors up to 14 days prior to initiation of colchicine. 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, lopinavir/ritonavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, tipranavir/ritonavir):
FMF: Maximum dose: 0.6 mg daily (0.3 mg twice daily)
Gout prophylaxis:
US labeling:
Colcrys:
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
Mitigare: Avoid concomitant use; if coadministration is necessary, reduce daily dosage or dose frequency and monitor closely.
Canadian labeling:
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:
US labeling: Initial: 0.6 mg, followed in 1 hour by a single dose of 0.3 mg; do not repeat for at least 3 days
Canadian labeling: Initial: 0.6 mg, followed in 1 hour by a single dose of 0.3 mg; do not repeat for at least 3 days
Coadministration of moderate CYP3A4 inhibitor (eg, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, verapamil):
FMF: Maximum dose: 1.2 mg daily (0.6 mg twice daily)
Gout prophylaxis:
US labeling:
Colcrys:
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
Mitigare: Avoid concomitant use; if coadministration is necessary, reduce daily dosage or dose frequency and monitor closely.
Canadian labeling:
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: 1.2 mg as a single dose; do not repeat for at least 3 days
Coadministration of P-gp inhibitor (eg, cyclosporine, ranolazine):
FMF: Maximum dose: 0.6 mg daily (0.3 mg twice daily)
Gout prophylaxis:
US labeling:
Colcrys:
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
Mitigare: Avoid concomitant use; if coadministration is necessary, reduce daily dosage or dose frequency and monitor closely.
Canadian labeling:
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: Initial: 0.6 mg as a single dose; do not repeat for at least 3 days
Use caution; reduce prophylactic daily dose by 50% in individuals >70 years (Terkeltaub 2009)
Familial Mediterranean fever (FMF): Oral:
US labeling: Colcrys only:
Children 4 to 6 years: 0.3 to 1.8 mg daily in 1 to 2 divided doses
Children 6 to 12 years: 0.9 to 1.8 mg daily in 1 to 2 divided doses
Adolescents >12 years: Refer to adult dosing.
Canadian labeling: Children >12 years and Adolescents: Refer to adult dosing.
Gout prophylaxis/treatment: Oral: Adolescents >16 years: Refer to adult dosing.
Concurrent use of colchicine and P-gp or strong CYP3A4 inhibitors is contraindicated in renal impairment. Fatal toxicity has been reported. Use of colchicine to treat gout flares is not recommended in patients with renal impairment receiving prophylactic colchicine.
FMF:
CrCl 30 to 80 mL/minute: Monitor closely for adverse effects; dose reduction may be necessary.
CrCl <30 mL/minute: Initial dose: 0.3 mg daily; use caution if dose titrated; monitor for adverse effects.
Dialysis: 0.3 mg as a single dose; use caution if dose titrated; dosing can be increased with close monitoring; monitor for adverse effects. Not removed by dialysis.
Gout prophylaxis:
CrCl 30 to 80 mL/minute:
Colcrys: Dosage adjustment not required; monitor closely for adverse effects.
Mitigare: There are no dosage adjustments provided in the manufacturers labeling (has not been studied).
CrCl <30 mL/minute:
Colcrys: Initial dose: 0.3 mg daily; use caution if dose titrated; monitor for adverse effects.
Mitigare: There is no specific dosage adjustment provided in the manufacturer 's labeling; dosage reduction or alternative therapy should be considered
Dialysis:
Colcrys: 0.3 mg twice weekly; monitor closely for adverse effects.
Mitigare: There are no dosage adjustments provided in the manufacturer 's labeling; monitor closely.
Gout flare treatment: Colcrys: Note: Treatment of gout flares is not recommended in patients with renal impairment who are receiving colchicine for prophylaxis.
CrCl 30 to 80 mL/minute: Dosage adjustment not required; monitor closely for adverse effects.
CrCl <30 mL/minute: Dosage reduction not required but may be considered; treatment course should not be repeated more frequently than every 14 days.
Dialysis: 0.6 mg as a single dose; treatment course should not be repeated more frequently than every 14 days. Not removed by dialysis.
Hemodialysis: Not dialyzable (0% to 5%); avoid chronic use of colchicine.
Concurrent use of colchicine and P-glycoprotein or strong CYP3A4 inhibitors is contraindicated in hepatic impairment. Fatal toxicity has been reported. Treatment of gout flare with colchicine is not recommended in patients with hepatic impairment receiving prophylactic colchicine.
FMF:
Mild to moderate impairment: Use caution; monitor closely for adverse effects.
Severe impairment: There is no specific dosage adjustment provided in the manufacturers labeling; dosage adjustment should be considered.
Gout prophylaxis:
Mild to moderate impairment:
Colcrys: Dosage adjustment not required; monitor closely for adverse effects.
Mitigare: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Severe impairment: Colcrys and Mitigare: There is no specific dosage adjustment provided in the manufacturer 's labeling; dosage adjustment should be considered.
Gout flare treatment:Note: Treatment of gout flares is not recommended in patients with hepatic impairment who are receiving colchicine for prophylaxis.
Mild to moderate impairment: Dosage adjustment not required; monitor closely for adverse effects.
Severe impairment: Dosage reduction not required but may be considered; treatment course should not be repeated more frequently than every 14 days.
Administer orally with water and maintain adequate fluid intake. May be administered without regard to meals.
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).
May be taken without regard to meals. May need to supplement with vitamin B12. Avoid grapefruit juice.
Store at 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F). Protect from light and moisture.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Mitigare: 0.6 mg [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow)]
Generic: 0.6 mg
Tablet, Oral:
Colcrys: 0.6 mg [DSC] [contains fd&c blue #2 (indigotine), fd&c red #40]
Colcrys: 0.6 mg [scored; contains fd&c blue #2 (indigotine), fd&c red #40]
Generic: 0.6 mg
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
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. 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. 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. Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Digoxin: May increase the serum concentration of Colchicine. 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. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
HMG-CoA Reductase Inhibitors: Colchicine may enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Lumacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. 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
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. 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. Consider therapy modification
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. 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
Telaprevir: May increase the serum concentration of Colchicine. Management: Colchicine should not be used with telaprevir 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 telaprevir. Consider therapy modification
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
CBC, renal and hepatic function tests
May cause false-positive results in urine tests for erythrocytes or hemoglobin
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% (Limited to important or life-threatening): Alopecia, bone marrow depression, dermatitis, disseminated intravascular coagulation, hepatotoxicity, hypersensitivity reaction, increased creatine phosphokinase, lactose intolerance, myalgia, myasthenia, oligospermia, purpura, rhabdomyolysis, toxic neuromuscular disease
Patients with ESRD had 75% lower clearance and prolonged elimination half-life.
Clearance is significantly reduced and plasma half-life prolonged in patients with mild to moderate cirrhosis.
Mean peak plasma levels and AUC were 2 times higher in elderly patients; however, this may be caused by decreased renal function.
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, 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 the elderly; literature suggests dosage adjustments should be considered.
Special handling:
- Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).
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).
C
Adverse events were observed in animal reproduction studies. Colchicine crosses the human placenta. Use during pregnancy in the treatment of familial Mediterranean fever has not shown an increase in miscarriage, stillbirth, or teratogenic effects (limited data).
Disrupts cytoskeletal functions by inhibiting Ž ²-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-1 Ž ².
Concentrates in leukocytes, kidney, spleen, and liver; does not distribute in heart, skeletal muscle, and brain
Vd: 5 to 8 L/kg
Hepatic via CYP3A4; 3 metabolites (2 primary, 1 minor)
Urine (40% to 65% as unchanged drug); enterohepatic recirculation and biliary excretion also possible
Oral: Pain relief: ~18 to 24 hours
Serum: Oral: 0.5 to 3 hours
27 to 31 hours (multiple oral doses; young, healthy volunteers)
~39%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Have patient report immediately to prescriber signs of infection, burning or numbness feeling, severe nausea, severe vomiting, severe diarrhea, severe abdominal pain, severe loss of strength and energy, bruising, bleeding, pale skin, muscle pain, muscle weakness, urinary retention, or change in amount of urine passed (HCAHPS).
- Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.