Dosing and uses of Colcrys, Mitigare (colchicine)
Adult dosage forms and strengths
tablet
- 0.6mg
capsule
- 0.6mg
Gout
Treatment of acute gout flares (Colcrys): 1.2 mg PO at first sign of flare, then 0.6 mg 1 hr later; not to exceed 1.8 mg in 1-hr period
Prophylaxis (Colcrys, Mitigare): 0.6 mg PO once daily or q12hr; not to exceed 1.2 mg/day; after gout flare, wait 12 hr to continue prophylaxis
Familial Mediterranean Fever
Colcrys: 1.2-2.4 mg/day PO in single daily dose or divided q12hr; increased in 0.3 mg/day increments as necessary to control disease; decreased in 0.3 mg/day increments if intolerable side effects develop; not to exceed 2.4 mg/day
Dosage modifications
Renal impairment (gout)
- Mild (CrCl 50-80 mL/min) and moderate (CrCl 30-50 mL/min): Dosage adjustment not necessary; monitor patients for adverse effects
- Severe (CrCl <30 mL/min): Dosage adjustment not necessary; do not repeat more frequently than every 2 weeks
- Hemodialysis: 0.6 mg once; do not repeat more frequently than every 2 weeks
Renal impairment (familial Mediterranean fever)
- Mild (CrCl 50-80 mL/min) and moderate (CrCl 30-50 mL/min): Monitor patients for adverse effects; dosage adjustment may be required
- Severe (CrCl <30 mL/min): 0.3 mg/day initially; dosage increases should be done with adequate monitoring for adverse effects
- Hemodialysis: 0.3 mg PO once; dosage increases should be done with adequate monitoring for adverse effects
Hepatic impairment (gout)
- Mild to moderate: Dosage adjustment not necessary; monitor patients for adverse effects
- Severe: Dosage adjustment not necessary; do not repeat more frequently than every 2 weeks; consider alternative therapy if repeated courses are required
Hepatic impairment (familial Mediterranean fever)
- Mild to moderate: Monitor patients for adverse effects
- Severe: Consider dosage reduction; do not repeat more frequently than every 2 weeks
Strong CYP3A4 inhibitors
- Treatment of acute gout flares: 0.6 mg, then 0.3 mg 1 hour later; to be repeated no earlier than 3 days later
- Prophylaxis of acute gout flares: If the original colchicine regimen was 0.6 mg BID, decrease dose to 0.3 mg qDay; if the original colchicine regimen was 0.6 mg qDay, decrease dose to 0.3 mg once every other day
- Familial Mediterranean fever (FMF): Not to exceed 0.6 mg/day; 0.6 mg can be given as 0.3 mg q12hr
Moderate CYP3A4 inhibitors
- Gout: 1.2 mg PO once; to be repeated no earlier than 3 days later
- FMF: Not to exceed 1.2 mg/day; 0.6 mg can be given as 0.6 mg q12hr
P-gp inhibitors
- Gout: 0.6 mg PO once; to be repeated no earlier than 3 days later
- FMF: Not to exceed 0.6 mg/day; 0.6 mg can be given as 0.3 mg q12hr
Administration
Dosing regimens must be individualized to indication
Administered PO, without regard to meals
Post-STEMI Pericarditis (Off-label)
Treatment of pericarditis after ST-elevation myocardial infarction (STEMI)
0.6 mg PO q12hr
Behcet Syndrome (Orphan)
Orphan sponsor
- AR Scientific, Inc, 1100 Orthodox Street, Philadelphia, PA 19124
Pediatric dosage forms and strengths
tablet
- 0.6mg
capsule
- 0.6mg
Gout
<16 years
- Not recommended
>16 years
- Treatment of acute gout flares (Colcrys): 1.2 mg PO at first sign of flare, then 0.6 mg 1 hr later; not to exceed 1.8 mg in 1-hr period
- Prophylaxis (Colcrys, Mitigare): 0.6 mg PO once daily or q12hr; not to exceed 1.2 mg/day; after gout flare, wait 12 hr to continue prophylaxis
Familial Mediterranean Fever
<4 years: Safety and efficacy not established
4-6 years: 0.3-1.8 mg/day PO in single daily dose or divided q12hr
6-12 years: 0.9-1.8 mg/day PO in single daily dose or divided q12hr
>12 years: 1.2-2.4 mg/day PO in single daily dose or divided q12hr
Dosing considerations
- Increased or decreased in 0.3 mg/day increments as necessary; not to exceed maximum recommended daily dose
Colcrys, Mitigare (colchicine) adverse (side) effects
>10%
Gastrointestinal (GI) effects (eg, diarrhea, nausea, cramping, abdominal pain, vomiting) (26-77%)
1-10%
Fatigue (1-4%)
Gout (0-4%)
Pharyngolaryngeal pain (2-3%)
Headache (1-2%)
Postmarketing Reports
Disseminated intravascular coagulation
Cellular injury (eg, to kidney, vasculature, liver, central nervous system)
Myelosuppression
Neurologic: Sensory motor neuropathy
Dermatologic: Alopecia, purpura, maculopapular rash, rash
GI: Lactose intolerance, abdominal cramping, abdominal pain, vomiting, diarrhea, nausea
Hematologic: Thrombocytopenia, leukopenia, granulocytopenia, pancytopenia, aplastic anemia
Hepatobiliary: Elevated liver transaminases
Musculoskeletal: Myotonia, muscle weakness, myopathy, elevated creatine phosphokinase, muscle pain, rhabdomyolysis
Reproductive: Azoospermia, oligospermia
Warnings
Contraindications
Coadministration with P-gp or strong CY3A4 inhibitors in patients with hepatic or renal impairment; life-threatening and fatal colchicine toxicity has been reported with therapeutic dosages
Hypersensitivity
Cautions
Long term use is established for FMF, but safety and efficacy of repeat treatment in gout flares has not been evaluated
Not to be used to treat pain from other causes; drug is not analgesic
Must be kept out of reach of children; fatal overdoses have been reported
Blood dyscrasias (eg, leukopenia, myelosuppression, thrombocytopenia, pancytopenia, granulocytopenia, aplastic anemia) have been reported at therapeutic dosages
Coadministration with P-gp and strong CYP3A4 inhibitors may warrant dosage reduction or interruption of therapy
Rhabdomyolysis and neuromuscular toxicity have been reported with long-term treatment at therapeutic dosages; increased risk with renal dysfunction, elderly patients, concomitant therapy with myotoxic drugs; symptoms generally resolve within 1 week to few months upon discontinuance
Acute gout: Dosages >1.8 mg/day provide no additional efficacy
Dose reduction recommended in patients who develop gastrointestinal symptoms including anorexia, diarrhea, vomiting, or nausea due to the therapy
Clearance is decreased in renal and hepatic impairment; monitor for toxicity and adjust dose if necessary
Use with caution in the elderly; consider adjusting dose
Pregnancy and lactation
Pregnancy category: C
Lactation: Drug enters breast milk; use with caution (American Academy of Pediatrics Committee states that drug is "compatible" with nursing)
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Colcrys, Mitigare (colchicine)
Mechanism of action
Gout: Disruption of cytoskeletal functions through inhibition of β-tubulin polymerization into microtubules; this prevents activation, degranulation, and migration of neutrophils thought to mediate some gout symptoms
FMF: Mechanism not established; may interfere with intracellular assembly of inflammasome complex present in neutrophils and monocytes, which mediates activation of interleukin-1β
Absorption
Bioavailability: 45%
Onset: 18-24 hr
Time to peak effect: 48-72 hr
Peak plasma concentration: 6.2-6.8 ng/mL
Distribution
Protein bound: 34-44%
Vd: 5-8 L/kg
Metabolism
Metabolized by P-gp and CYP3A4
Metabolites: Demethylated to 2 primary metabolites and 1 minor metabolite
Elimination
Half-life: 26.6-31.2 hr
Dialyzable: No (hemodialysis)
Excretion: Feces, urine (65%)
Administration
IV formulation currently not commercially available in United States
IV Incompatibilities
Dextrose or IV solutions with preservatives
IV Administration
Over 2-5 minutes, administer into tubing of NS-flowing IV line into large vein
Avoid extravasation
