Colchicine

Colchicine is a prescription drug to treat conditions such as gout and familial Mediterranean fever.

Colchicine is available under the following different brand names: Colcrys, and Mitigare.

Adult and pediatric dosages:

Tablet

• 0.6 mg

Capsule

• 0.6 mg

Dosage Considerations – Should be Given as Follows:

Gout

Adults

• Prophylaxis (Colcrys, Mitigare): 0.6 mg orally once daily or every 12 hours, not to exceed 1.2 mg per day. After a gout flare, wait 12 hours to continue prophylaxis

Pediatrics

• Children under 16 years old: not recommended
• Children older than 16 years old: Treatment of acute gout flares (Colcrys): 1.2 mg orally at first sign of flare, then 0.6 mg 1 hour later, not to exceed 1.8 mg in 1 hour period

Familial Mediterranean Fever

Adults

• Colcrys: 1.2-2.4 mg per day orally in a single daily dose or divided every 12 hours, increase in 0.3 mg/day increments as necessary to control disease, decreased in 0.3 mg per day increments if intolerable side effects develop, not to exceed 2.4 mg per day

Pediatrics

• Children under 4 years old: Safety and efficacy not established
• 4-6 years: 0.3-1.8 mg per day orally in a single dose or divided every 12 hours
• 6-12 years: 0.9-1.8 mg per day orally in a single dose or divided every 12 hours
• Children older than 12 years old: 1.2-2.4 mg per day orally in a single dose or divided every 12 hours

Dosage Modifications

Renal Impairment

• Mild (creatinine clearance 50-80 ml/minute) and moderate (creatinine clearance 30-50 ml/minute): Dosage adjustment not necessary, monitor patients for adverse effects
• Severe (creatinine clearance under 30 ml/minute): Dosage adjustment not necessary, do not repeat more frequently than every 2 weeks
• Hemodialysis: 0.6 orally once, do not repeat more frequently than every 2 weeks

Renal impairment (familial Mediterranean fever)

• Mild (creatinine clearance 50-80 ml/minute) and moderate (creatinine clearance 30-50 ml/minute): Monitor patients for adverse effects, dosage adjustment may be required
• Severe (creatinine clearance under 30 ml/minute): 0.3 mg per day initially. Dosage increases should be done with adequate monitoring for adverse effects
• Hemodialysis: 0.3 orally 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: dosage adjustment not necessary, do not repeat more frequently than every 2 weeks, consider alternative therapy if repeated courses are required

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 twice daily, decrease dose to 0.3 mg each day. If the original colchicine regimen was 0.6 mg per day, decrease dose to 0.3 mg once every other day
• Familial Mediterranean Fever (FMF): Not to exceed 0.6 mg per day, 0.6 mg can be given as 0.3 mg every 12 hours

Moderate CYP3A4 inhibitors

• Gout: 1.2 mg orally once, to be repeated no earlier than 3 days later
• Familial Mediterranean Fever: Not to be exceed 1.2 mg per day, 0.6 mg can be given as 0.6 mg every 12 hours

P-gp inhibitors

• Gout: 0.6 mg orally once, to be repeated no earlier than 3 days later
• Familial Mediterranean fever: Not to exceed 0.6 mg per day, 0.6 mg can be given as 0.3 mg every 12 hours

Administration

• Dosing regimens must be individualized to indication. Administered orally, without regard to meals

Post-STEMI Pericarditis (off label)

• Treatment of pericarditis after ST-elevation myocardial infarction (STEMI)
• 0.6 mg orally every 12 hours

Pediatric dosing considerations:

• Increased or decreased in 0.3 mg per day increments as necessary, not to exceed maximum recommended daily dose

Side effects associated with use of Colchicine, include the following:

• gastrointestinal effects (diarrhea, lactose intolerance, nausea, cramping, abdominal pain, vomiting)
• fatigue
• gout
• pain in the throat and vocal cords
• headache

Post-marketing side effects of Colchicine reported include:

• disseminated intravascular coagulation
• cellular injury (to kidneys, vasculature, liver and central nervous system)
• myelosuppression
• neurologic: sensory motor malfunction of the nerves (neuropathy)
• dermatologic: hair loss, bruising (purpura), maculopapular rash, rash
• gastrointestinal: lactose intolerance, abdominal cramping, abdominal pain, vomiting, diarrhea, nausea
• hematologic: low red blood cell count (thrombocytopenia), low white blood cell count, reduced white blood cell count (granulocytopenia), shortage of red, white blood cells and platelets (pancytopenia), failure of the bone marrow to produce red and white blood cells (aplastic anemia)
• hepatobiliary: elevated liver transaminases
• musculoskeletal: muscle disease (myotonia), muscle weakness, myopathy, elevated creatinine phosphokinase (CPK), muscle pain, breakdown of skeletal muscle (rhabdomyolysis)
• reproductive: infertility (azoospermia), reduced sperm count (oligospermia)

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Colchicine has no known severe interactions with any drugs.
• Serious Interactions of Colchicine include:
  • clarithromycin
  • darunavir
  • itraconazole
  • ombitasvir/paritaprevir/ritonavir
  • ombitasvis/paritaprevir/ritonavir and dasabuvir
  • telithromycin
• Colchicine has serious interactions with at least 31 different drugs.
• Colchicine has moderate interactions with at least 125 different drugs.
• Mild Interactions of Colchicine include:
  • cyanocobalamin
  • efavirenz

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns or for more information about this medicine.

Warnings

• Must be kept out of reach of children; fatal overdoses have been reported
• This medication contains colchicine. Do not take Colcrys or Mitigare, if you are allergic to colchicine or any ingredients contained in this drug
• Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately

Contraindications

• Avoid coadministration with P-gp or strong CY3A4 inhibitors in patients with hepatic or renal impairment as life-threatening and fatal colchicine toxicity has been reported with therapeutic dosages
• Hypersensitivity to colchicine

Effects of Drug Abuse

• No information provided

Short-Term Effects

• See "What Are Side Effects Associated with Using Colchicine?"

Long-Term Effects

• Long-term use is established for Familial Mediterranean Fever, but safety and efficacy of repeat treatment in gout flares has not been evaluated
• Muscle injury and neuromuscular toxicity have been reported with long-term treatment at therapeutic dosages; increased risk with kidney (renal) dysfunction, elderly patients, concomitant therapy with myotoxic drugs; symptoms generally resolve within 1 week to few months upon discontinuance
• See "What Are Side Effects Associated with Using Colchicine?"

Cautions

• Long-term use is established for Familial Mediterranean Fever, but safety and efficacy of repeat treatment in gout flares has not been evaluated
• Not to be used to treat pain from other causes, as colchicine is not an analgesic
• Must be kept out of reach of children; fatal overdoses have been reported
• Blood dyscrasias (decrease of white blood cells, decrease of red blood cells (myelosuppression), low red blood cell (thrombocytopenia), reduction of red and white blood cells, as well as platelets (pancytopenia), reduced white blood cell count (granulocytopenia), failure of the bone marrow to produce red and white blood cells (aplastic anemia) have been reported at therapeutic dosages
• Coadministration with P-gp and strong CYP3A4 inhibitors may warrant dosage reduction or interruption of therapy
• Muscle injury 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 greater than 1.8 mg/day provide no additional efficacy
• Dose reduction recommended in patients who develop gastrointestinal symptoms including loss of appetite (anorexia), diarrhea, vomiting, or nausea due to the therapy
• Clearance is decreased in kidney (renal) and liver (hepatic) impairment; monitor for toxicity and adjust dose if necessary
• Use with caution in the elderly; consider adjusting dose

Pregnancy and Lactation

• Use colchicine during pregnancy with caution if benefits outweigh risks
• Animal studies show risk and human studies are not available, or neither animal nor human studies were done
• Colchicine enters breast milk, therefore use with caution. The American Academy of Pediatrics Committee states that colchicine is "compatible" with breastfeeding