Included as part of the "PRECAUTIONS" Section
Fatal overdoses, both accidental and intentional, have been reported in adults and children who have
ingested colchicine [See OVERDOSE]. Colchicine capsules should be kept out of the reach of
Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia
have been reported with colchicine used in therapeutic doses.
Interactions With CYP3A4 And P-Gp Inhibitors
Because colchicine is a substrate for both the CYP3A4 metabolizing enzyme and the P-glycoprotein
efflux transporter, inhibition of either of these pathways may lead to colchicine-related toxicity.
Inhibition of both CYP3A4 and P-gp by dual inhibitors such as clarithromycin has been reported to
produce life-threatening or fatal colchicine toxicity due to significant increases in systemic colchicine
levels. Therefore, concomitant use of colchicine capsules and inhibitors of CYP3A4 or P-glycoprotein
should be avoided [See DRUG INTERACTIONS]. If avoidance is not possible, reduced daily dose should
be considered and the patient should be monitored closely for colchicine toxicity. Use of colchicine
capsules in conjunction with drugs that inhibit both P-gp and CYP3A4 is contraindicated in patients with
renal or hepatic impairment [See CONTRAINDICATIONS].
Neuromuscular toxicity and rhabdomyolysis have been reported from chronic treatment with colchicine
in therapeutic doses, especially in combination with other drugs known to cause this effect. Patients
with impaired renal function and elderly patients (even those with normal renal and hepatic function) are
at increased risk. Once colchicine treatment is ceased, the symptoms generally resolve within 1 week to
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
If a dose of colchicine capsules is missed, advise the patient to take the dose as soon as possible and
then return to the normal dosing schedule. However, if a dose is skipped, the patient should not double
the next dose.
Advise the patient that fatal overdoses, both accidental and intentional, have been reported in adults and
children who have ingested colchicine. Colchicine capsules should be kept out of the reach of
Advise patients that bone marrow depression with agranulocytosis, aplastic anemia, and
thrombocytopenia may occur with colchicine capsules.
Drug And Food Interactions
Advise patients that many drugs or other substances may interact with colchicine capsules and some
interactions could be fatal. Therefore, patients should report to their healthcare provider all of the
current medications they are taking, and check with their healthcare provider before starting any new
medications, including short-term medications such as antibiotics. Patients should also be advised to
report the use of non-prescription medication or herbal products. Grapefruit and grapefruit juice may
also interact and should not be consumed during treatment with colchicine capsules.
Advise patients that muscle pain or weakness, tingling or numbness in fingers or toes may occur with
colchicine capsules alone or when it is used with certain other drugs. Patients developing any of these
signs or symptoms must discontinue colchicine capsules and seek medical evaluation immediately.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Carcinogenicity studies of colchicine have not been conducted. Due to the potential for colchicine to
produce aneuploid cells (cells with an unequal number of chromosomes), colchicine presents a
theoretical increased risk of malignancy.
Published studies demonstrated that colchicine was negative for mutagenicity in the bacterial reverse
mutation assay. However, in vitro chromosomal aberration assays demonstrated the formation of
micronuclei following colchicine treatment. Because published studies demonstrated that colchicine
induces aneuploidy through the process of mitotic nondisjunction without structural DNA changes,
colchicine is not considered clastogenic, although micronuclei are formed.
Impairment Of Fertility
There were no studies of the effects of colchicine capsules on fertility. However, published
nonclinical studies have demonstrated that colchicine-induced disruption of microtubule formation
affects meiosis and mitosis. Published reproductive studies with colchicine reported abnormal sperm
morphology and reduced sperm counts in males, and interference with sperm penetration, second
meiotic division, and normal cleavage in females.
Case reports and epidemiology studies in human male subjects on colchicine therapy indicate that
infertility from colchicine is rare. A case report indicated that azoospermia was reversed when therapy
was stopped. Case reports and epidemiology studies in female subjects on colchicine therapy have not
established a clear relationship between colchicine use and female infertility.
Use In Specific Populations
Use In Pregnancy
Pregnancy Category C
There are no adequate and well-controlled studies with colchicine capsules in
pregnant women. Colchicine crosses the human placenta. Developmental studies in animals were not
conducted with colchicine capsules, however published animal reproduction and development studies
with colchicine demonstrated embryofetal toxicity, teratogenicity, and altered postnatal development at
exposures within or above the clinical therapeutic range. Colchicine should be used during pregnancy
only if the potential benefit justifies the potential risk to the fetus.
Labor And Delivery
The effect of colchicine on labor and delivery is unknown.
Use In Nursing Mothers
Colchicine is excreted into human milk. Limited information suggests that infants exclusively breastfed
receive less than 10 percent of the maternal weight-adjusted dose. While there are no published reports
of adverse effects in breast-feeding infants of mothers taking colchicine, colchicine can affect
gastrointestinal cell renewal and permeability. Caution should be exercised and breastfeeding infants
should be observed for adverse effects when colchicine capsules is administered to a nursing woman.
Gout is rare in pediatric patients; the safety and effectiveness of colchicine capsules in pediatric
patients has not been evaluated in controlled studies.
Because of the increased incidence of decreased renal function in the elderly population, and the higher
incidence of other co-morbid conditions in the elderly population requiring the use of other
medications, reducing the dosage of colchicine when elderly patients are treated with colchicine
should be carefully considered.
No dedicated pharmacokinetic study has been conducted using colchicine capsules in patients with
varying degrees of renal impairment. Colchicine is known to be excreted in urine in humans and the
presence of severe renal impairment has been associated with colchicine toxicity. Urinary clearance of
colchicine and its metabolites may be decreased in patients with impaired renal function. Dose reduction
or alternatives should be considered for the prophylaxis of gout flares in patients with severe renal
impairment. Colchicine is not effectively removed by hemodialysis. Patients who are undergoing
hemodialysis should be monitored carefully for colchicine toxicity.
No dedicated pharmacokinetic study using colchicine capsules has been conducted in patients with
varying degrees of hepatic impairment. Colchicine is known to be metabolized in humans and the
presence of severe hepatic impairment has been associated with colchicine toxicity. Hepatic clearance
of colchicine may be significantly reduced and plasma half-life prolonged in patients with chronic
Dose reduction or alternatives should be considered for the prophylaxis of gout flares in patients with
severe hepatic impairment.