ColchicineRx

Drug Class: Antigout agent

Trade Name: Colcrys

Preparations
Tablets 0.6 mg

Dose
Acute gout: Oral: 1.2 mg at first sign of  flare and the 0.6 mg  1 hour later. Maximum dose 1.8 mg – do not repeat for at least 3  days
Prophylaxis of gout: 0.6 mg once or twice daily

Marked dose reduction required for patients who have taken interacting drugs such as CYP3A and P-glycoprotein inhibitors in the  past 14 days (see label for  dose guidance). Strong CYP3A inhibitors and P-glycoprotein inhibitors (see Drug Interactions for examples) require a decrease in colchicine dose of 75% (e.g., 0.6 mg daily dose  for prophylaxis becomes o.3 mg every second day). For moderate CYP3A inhibitors decrease colchicine dose by 50% (e.g., if original dose is 0.6 mg daily use 0.3 mg daily). Avoid colchicine for treatment of acute gout flares in patients already receiving prophylactic colchicine with a CYP3A or P-glycoprotein inhibitor. Avoid colchicine in patients with mild-moderate hepatic or renal impairment who are receiving a CYP3A or P-glycoprotein inhibitor.

Indications: Treatment of acute gout and prophylaxis of acute gout; also used in the treatment of familial Mediterranean fever and pericarditis

Mechanism of Action: Decreases leukocyte migration and phagocytosis

Contraindications: Hypersensitivity to colchicine; significant renal or hepatic impairment; use of CYP3A or P-glycoprotein inhibiting drugs in the presence of hepatic or renal impairment

Precautions: Use caution in mild-moderate renal or hepatic impairment and the elderly – dose reduction is required. Frequent drug interactions.

Pregnancy Risk: C

Adverse Effects
Common: Nausea, vomiting, GI cramps, diarrhea
Less common: Neuropathy, myopathy, rash, bone marrow suppression, leucopenia, hepatic damage, alopecia

Drug Interactions
CYP3A inhibitors (strong inhibitors include clarithromycin,telithromycin, ketoconazole, itraconazole, nefazodone  and many HIV drugs; moderate inhibitors include aprepitant, diltiazem, verapamil, erythromycin, fluconazole, posaconazole, voriconazole, grapefruit juice) and P-glycoprotein inhibitors (e.g., cyclosporine, ranolazine, quinidine, tacrolimus): Increased colchicine concentrations and increased risk of toxicity and myopathy
Cimetidine, tolbutamide: Increased colchicine concentrations
Statins, fibrates and digoxin: Increased risk of myopathy and rhabdomyolysis

Patient Instructions: Discontinue if nausea or vomiting occurs. Avoid grapefruit juice.

Comments: The dose (maximum 1.8 mg) used to treat acute gout is as effective as previous older high-dose regimens.  Generic colchicine was cheap but is not available in the US until the patent disputes related to Colcrys are resolved. In treatment of acute gout colchicine is more effective if used early in the attack. Intravenous colchicine is no longer available because of  toxicity and fatalities. Depot corticosteroids (intramuscular or intraarticular), ACTH, or anakinra are alternatives for acute gout in patients in whom colchicine and NSAIDs are contraindicated. Colchicine is effective in the treatment of acute pericarditis and in reducing recurrences.

Clinical Pharmacology: Time to onset of action in gout is slow (6–12 hours); peak effect is 24–48 hours after first oral dose. Hepatic biotransformation (CYP3A substrate) and renal and hepatic elimination by the P-glycoprotein efflux transporter; high degree of tissue uptake, half-life 26-31 hours.

Cost: $$

BIBLIOGRAPHY

Khanna D,Khanna PP, Fitzgerald JD et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2  Arthritis Care Res 2012;64:1447-61. PMID:23024029

Terkeltaub RA, Furst DE, Digiacinto JL et al. Novel evidence-based colchicine dose-reduction algorithm to predict and prevent colchicine toxicity in the presence of cytochrome P450 3A4/P-glycoprotein inhibitors. Arthritis Rheum. 2011;63:2226-37. Erratum in: Arthritis Rheum. 2011;63:3521. Dosage error in article text. PMID: 21480191

Terkeltaub RA, Furst DE, Bennett K et al. High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum. 2010;62:1060-8.PMID:20131255