Usage
Colchicine is prescribed for the treatment and prevention of gout flares, as well as for the treatment of Familial Mediterranean Fever (FMF). It is classified as an anti-inflammatory agent and an antigout medication. Its mechanism of action involves inhibiting microtubule polymerization, thereby reducing neutrophil migration and activity, thus mitigating inflammation associated with gout and FMF.
Alternate Names
Colchicine is sometimes referred to as colchicina. Brand names for colchicine include Colcrys, Mitigare, and Gloperba.
How It Works
Pharmacodynamics: Colchicine’s primary effect is to reduce inflammation. It achieves this by inhibiting microtubule polymerization within neutrophils, preventing their activation and migration to sites of inflammation, such as those in gout flares. It also interferes with various cellular functions including chemotaxis, adhesion, and phagocytosis, all of which contribute to the inflammatory response. Although the exact mechanism is unclear, there may be an effect on the inflammasome, especially the NLRP3, and also may have a role in interleukin-1 beta production.
Pharmacokinetics: Colchicine is readily absorbed after oral administration and undergoes significant enterohepatic recirculation. It’s metabolized by CYP3A4 and is a substrate of P-glycoprotein (P-gp), both of which are relevant in drug interactions. It’s eliminated primarily through biliary excretion, with a smaller portion excreted renally. Renal impairment requires careful dose adjustments due to the possibility of accumulation. Its mean elimination half-life is approximately 27 hours (range: 10–47 hours), making it susceptible to drug interactions. It has been found to appear in breastmilk.
Dosage
Standard Dosage
Adults:
- Acute Gout Flare: 1.2 mg at the first sign of a flare, followed by 0.6 mg one hour later. The maximum dose over one hour is 1.8 mg. No further doses should be taken for 12 hours. After that, if needed, 0.6 mg every 8 hours until symptoms subside, not exceeding a total of 6 mg per course of treatment. Another course should not be started for at least 72 hours.
- Prophylaxis of Gout Flares (e.g., during initiation of urate-lowering therapy): 0.6 mg once or twice daily, not exceeding 1.2 mg per day.
- FMF: 1.2 mg to 2.4 mg daily, given as a single dose or in two divided doses. The dose can be adjusted in increments of 0.3 mg/day as needed.
Children:
- Acute Gout Flare: Colchicine is generally not recommended for treating acute gout flares in children.
- FMF: Dosing is based on age and ranges from 0.3 mg to 2.4 mg daily, adjusted as needed and tolerated. Specific recommendations vary based on age group.
- Children younger than 4: Use and dose must be determined by a physician.
Special Cases:
- Elderly Patients: Use with caution due to increased risk of toxicity. Lower doses or increased dosing intervals may be needed, especially in patients with renal or hepatic impairment.
- Patients with Renal Impairment: Reduced dose or increased interval between doses, depending on the severity of impairment. Close monitoring advised.
- Patients with Hepatic Dysfunction: Use with caution. Dose adjustment may be needed, especially in severe impairment.
- Patients with Comorbid Conditions: Careful monitoring is necessary due to potential interactions. Specific considerations should be made for patients with underlying cardiovascular, gastrointestinal, hematological, or neuromuscular disorders.
Clinical Use Cases
Colchicine’s primary clinical uses are for the treatment and prophylaxis of gout flares, and the treatment of FMF. It’s not typically indicated for procedures like intubation, surgery, or mechanical ventilation.
Dosage Adjustments
Dose adjustments are necessary in the elderly, and those with renal or hepatic impairment. Dose modifications should be based on clinical assessment, including creatinine clearance and liver function tests.
Side Effects
Common Side Effects
Diarrhea, nausea, vomiting, abdominal pain, and loss of appetite.
Rare but Serious Side Effects
Myelosuppression, leukopenia, thrombocytopenia, aplastic anemia, rhabdomyolysis (especially with concomitant statin use), neuropathy, and allergic reactions.
Long-Term Effects
Chronic use can lead to myopathy, bone marrow suppression, and potentially secondary malignancies with very high dosages.
Adverse Drug Reactions (ADR)
Severe allergic reactions (anaphylaxis), rhabdomyolysis with acute renal failure, and severe myelosuppression are serious ADRs that require immediate intervention.
Contraindications
Absolute contraindications include severe renal or hepatic impairment, combined hepatic and renal impairment, blood dyscrasias, and pregnancy. Patients with mild or moderate renal or hepatic impairment should not receive colchicine concomitantly with P-gp or strong CYP3A4 inhibitors.
Drug Interactions
Clinically significant interactions can occur with P-gp inhibitors (e.g., cyclosporine), strong CYP3A4 inhibitors (e.g., clarithromycin, azole antifungals, some HIV protease inhibitors), statins (increased risk of myopathy), and digoxin.
Pregnancy and Breastfeeding
Colchicine is contraindicated in pregnancy due to potential teratogenic effects. While colchicine is present in breast milk, it’s generally considered compatible with breastfeeding, particularly when used for FMF. However, careful monitoring of the infant is recommended.
Drug Profile Summary
- Mechanism of Action: Inhibits microtubule polymerization in neutrophils, reducing inflammation.
- Side Effects: Diarrhea, nausea, vomiting, abdominal pain, myelosuppression, rhabdomyolysis.
- Contraindications: Severe renal/hepatic impairment, blood dyscrasias, pregnancy.
- Drug Interactions: P-gp inhibitors, CYP3A4 inhibitors, statins, digoxin.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy; generally compatible with breastfeeding with monitoring.
- Dosage: Varies by condition and age; see detailed dosage section above.
- Monitoring Parameters: Complete blood count (CBC), renal function tests, liver function tests, creatine kinase (especially if on concomitant statins).
Popular Combinations
Colchicine is sometimes used in combination with allopurinol or probenecid during the initiation of urate-lowering therapy for gout prophylaxis.
Precautions
- Patients should be screened for renal and hepatic function, and blood disorders before starting colchicine.
- Close monitoring of blood counts and organ function during treatment, especially long-term use, is important.
- Counsel patients about the risk of gastrointestinal side effects and to report any unusual symptoms, particularly muscle weakness or pain.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Colchicine?
A: Dosage depends on indication and patient characteristics (age, renal/hepatic function). See the detailed Dosage section above.
Q2: What are the most common side effects of colchicine?
A: The most common side effects are gastrointestinal, including diarrhea, nausea, vomiting, and abdominal pain.
Q3: What are the serious side effects of Colchicine?
A: Serious side effects include myelosuppression, rhabdomyolysis, neuropathy, and allergic reactions.
Q4: What are the contraindications to using Colchicine?
A: Severe renal or hepatic impairment, pregnancy, and blood dyscrasias are contraindications.
Q5: What are the drug interactions I should be aware of with Colchicine?
A: Concomitant use with P-gp inhibitors, strong CYP3A4 inhibitors (like clarithromycin, azole antifungals), statins, and digoxin may lead to increased colchicine levels and increased risk of adverse events.
Q6: Can Colchicine be used during pregnancy or breastfeeding?
A: Colchicine is contraindicated in pregnancy. It is generally considered compatible with breastfeeding, especially for FMF, but infant monitoring is important.
Q7: How does Colchicine work in gout?
A: Colchicine works by inhibiting microtubule polymerization in neutrophils, thus reducing their migration to sites of inflammation and preventing the release of inflammatory mediators that cause gout pain.
Q8: What monitoring should I do for patients on long-term Colchicine?
A: Regular monitoring of complete blood counts (CBCs), renal function tests, and liver function tests are recommended for patients on long-term colchicine therapy. Creatine kinase monitoring is especially important for patients also taking statins.
Q9: How should I counsel patients taking Colchicine?
A: Patients should be advised about common side effects, such as gastrointestinal issues, and instructed to report any signs of muscle weakness or pain, as these could indicate rhabdomyolysis. They should also be informed about potential drug interactions and the need to avoid grapefruit juice. Patients with FMF should understand the importance of adherence even in the absence of symptoms.
A: It is predominantly metabolized in the liver by the cytochrome P450 isoenzyme 3A4 (CYP3A4), and is effluxed by P-glycoprotein (P-gp), two important sites of drug interactions.
