Dosing & Uses
Dosage Forms & Strengths
tablet
- 0.6mg (Colcrys)
capsule
- 0.6mg (Mitigare)
oral solution
- 0.6mg/5mL (Gloperba)
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, Gloperba
- Indicated for prophylaxis of gout flares
- 0.6 mg PO qDay 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; increase in 0.3-mg/day increments as necessary to control disease; decrease in 0.3-mg/day increments if intolerable adverse effects develop; not to exceed 2.4 mg/day
Dosage Modifications
Renal impairment (gout)
- Mild-to-severe (CrCl <80 mL/min): No dosage adjustment necessary; monitor for adverse effects
- Severe (CrCl <30 mL/min): Do not repeat more frequently than q2Weeks
- Hemodialysis: 0.6 mg once; do not repeat more frequently than q2Weeks
Renal impairment (familial Mediterranean fever [FMF])
- Mild-to-moderate (CrCl 30-80 mL/min): Monitor 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-severe: No dosage adjustment necessary; monitor for adverse effects
- Severe: Do not repeat more frequently than q2Weeks; consider alternative therapy if repeated courses are required
Hepatic impairment (FMF)
- Mild-to-moderate: Monitor for adverse effects
- Severe: Consider dosage reduction; do not repeat more frequently than q2Weeks
Strong CYP3A4 inhibitors
- Mitigare or Gloperba: Avoid use; if coadministration with strong CYP3A4 inhibitor is necessary, consider reducing the colchicine dose and closely monitor
- Colcrys
- Treatment of acute gout flares: 0.6 mg, then 0.3 mg 1 hr later; to be repeated no earlier than 3 days later
- Prophylaxis of acute gout flares: If original colchicine regimen was 0.6 mg BID, decrease dose to 0.3 mg qDay; if original colchicine regimen was 0.6 mg qDay, decrease dose to 0.3 mg once every other day
- FMF: Not to exceed 0.6 mg/day; 0.6 mg can be given as 0.3 mg q12hr
Moderate CYP3A4 inhibitors
- Colcrys
- 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
- Mitigare or Gloperba: Avoid use; if coadministration with P-gp inhibitor is necessary, consider reducing the colchicine dose and closely monitor
- Colcrys
- 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
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
Dosing Considerations
Limitations of use
- Safety and effectiveness for acute treatment of gout flares during prophylaxis has not been studied
- Not an analgesic medication and should not be used to treat pain from other causes
Dosage Forms & Strengths
tablet
- 0.6mg (Colcrys)
capsule
- 0.6mg (Mitigare)
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
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%)
Frequency Not Defined
Neuromuscular toxicity (eg, muscle pain, weakness)
Myelosuppression
Disseminated intravascular coagulation Injury to cells in the renal, hepatic, circulatory, and central nervous systems
Postmarketing Reports
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
Patients with both renal and hepatic impairment
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 reported in both adults and children
Blood dyscrasias (eg, leukopenia, myelosuppression, thrombocytopenia, pancytopenia, granulocytopenia, aplastic anemia) reported at therapeutic dosages
Rhabdomyolysis and neuromuscular toxicity reported with long-term treatment at therapeutic dosages; increased risk in renal dysfunction, elderly patients, and concomitant therapy with myotoxic drugs; symptoms generally resolve within 1 week to few months upon discontinuance
Drug interactions overview
- Colchicine is a CYP3A4 and P-gp substrate
- Inhibition of both CYP3A4 and P-gp by dual inhibitors (ie, clarithromycin) reported to produce life-threatening or fatal colchicine toxicity due to significant increases in systemic colchicine levels
- Coadministration with P-gp and strong CYP3A4 inhibitors may warrant dosage reduction or interruption of therapy
- HMG-CoA reductase inhibitors and fibrates may increase the risk of myopathy when combined with colchicine; check serum creatinine kinase levels if patient reports muscle pain or weakness
Pregnancy & Lactation
Pregnancy
Available human data from published literature on colchicine use in pregnancy over several decades have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes
Animal data
- Published animal reproduction and development studies indicate that colchicine causes embryofetal toxicity and altered postnatal development at exposures within or above the clinical therapeutic range
Lactation
Colchicine is present in human milk
No adverse events in breastfed infants in the published literature after administration of colchicine to lactating women
No data available on the effects of colchicine on milk production
Consider developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Infertility
- Case reports and epidemiology studies in males on colchicine therapy indicate that infertility from colchicine is rare and may be reversible
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
Mechanism of Action
Gout: Disruption of cytoskeletal functions through inhibition of β-tubulin polymerization into microtubules, which prevents activation, degranulation, and migration of neutrophils
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
Fasted
- Peak plasma concentration: 3 ng/mL (Mitigare); 2.16 ng/mL (Gloperba); 2.5-3.6 ng/mL (Colcrys)
- Peak plasma time: 1 hr (Gloperba); 1.3-1.5 hr (Colcrys)
- AUC: 19.9 hr·ng/mL (Gloperba)
Fed
- Peak plasma concentration: 1.68 ng/mL (Gloperba)
- Peak plasma time: 2 hr (Gloperba)
- AUC: 18.47 hr·ng/mL (Gloperba)
Distribution
Vd: ~1420L (Colcrys); ~5-8L/kg (Mitigare); 341-1150 L (Colcrys)
Protein bound: 39%
Colchicine crosses the placenta (plasma levels in the fetus reported to be ~15% of the maternal concentration)
Metabolism
Metabolized by P-gp and CYP3A4
May also be metabolized by glucuronidation
Metabolites: Demethylated to 2 primary metabolites and 1 minor metabolite
Elimination
Half-life: 31 hr (Mitigare and Gloperba); 26.6-31.2 hr (Colcrys)
Dialyzable: No (hemodialysis)
Excretion: Urine (40-65%)
Administration
Oral Administration
Administered orally, without regard to meals
Storage
All formulations: Store at 20-25°C (68-77°F)
Tablets or capsules: Protect from light
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Formulary
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