Colchicine is used to relieve acute gout flares (acute attacks of gouty arthritis). Nonsteroidal anti-inflammatory agents (NSAIAs) (e.g., indomethacin, ibuprofen, naproxen, sulindac, piroxicam, ketoprofen) are as effective as, and better tolerated than, usual dosages of colchicine for short-term use in relieving acute attacks of gouty arthritis. Corticosteroids also are used to relieve acute attacks of gouty arthritis. Colchicine is considered a second-line agent; colchicine may be used for the treatment of acute gouty arthritis in patients who have not responded to or who cannot tolerate recommended therapies (i.e., NSAIAs, corticosteroids).
Colchicine should be initiated at the first sign of an acute gout flare. When colchicine is administered orally within 12 hours of the onset of an acute gout flare, 38% of patients receiving the drug in the currently recommended dosage have a favorable response.
Colchicine also is used in the prophylactic treatment of recurrent gout flares. Colchicine has no effect on plasma concentrations or urinary excretion of uric acid; therefore, concomitant administration of allopurinol or a uricosuric agent (e.g., febuxostat, probenecid, sulfinpyrazone) is necessary to decrease serum urate concentrations. Prophylactic doses of colchicine should be administered before the initiation of allopurinol or uricosuric therapy because sudden changes in serum urate concentrations may precipitate acute gout attacks. After the serum urate concentration has been reduced to the desired level and acute gout attacks have not occurred for 3-6 months (some clinicians suggest 1-12 months), colchicine may be discontinued and the patient may be treated with urate-lowering agents alone. Colchicine is frequently used in combination with probenecid to facilitate prophylactic therapy in patients with chronic gouty arthritis. The usefulness of the commercially available fixed-dosage preparation is limited, however, because the colchicine present exceeds the amount required by most patients.
Familial Mediterranean Fever
Colchicine is used in the management of familial Mediterranean fever. The drug has been used effectively for chronic prophylactic therapy to reduce the frequency and severity of the episodic attacks of painful serositis in patients with familial Mediterranean fever. Chronic prophylactic therapy reportedly is associated with marked amelioration of attacks (both frequency and severity) or remission in about 90% of patients with this condition, but therapy with the drug is not curative and manifestations of this condition return to pretreatment levels following discontinuance of colchicine. Chronic prophylactic therapy also appears to prevent amyloidosis, manifested by nephropathy, in patients with familial Mediterranean fever who lack evidence of amyloidosis when therapy is initiated. Colchicine appears to be effective in preventing amyloidosis regardless of whether patients continue to experience episodic attacks of serositis during chronic prophylactic therapy with the drug. Colchicine may prevent deterioration in patients in the proteinuric phase of the disease when amyloid involvement is minimal. The drug generally appears to be of limited value in altering the effects of amyloid deposits when clinical amyloidosis is evident, particularly when proteinuria has progressed to nephrosis, although a beneficial effect (e.g., restoration of serum albumin concentrations toward normal, slight improvement in renal function) may be evident in some patients.
Regulatory Actions Affecting Colchicine
Colchicine injection became available in the US in the 1950s and has been used for the treatment of acute attacks of gout. Colchicine injection preparations that have been commercially available have not been approved by the US Food and Drug Administration (FDA). Serious adverse events, some fatal, have been reported in patients receiving colchicine injection.
(See Cautions: Adverse Effects.)Because of the potentially serious health risks associated with unapproved colchicine injection, FDA announced on February 8, 2008, that it would take enforcement action (e.g., seizure, injunction, other judicial proceeding) against all firms, including compounding pharmacies, attempting to manufacture, ship, or deliver colchicine injection.
Although commercially available, single-entity, oral preparations of colchicine also lacked FDA approval, FDA did not take action against colchicine tablets in February 2008; risks associated with use of the tablets are believed to be lower than those associated with use of the injection. In July 2009, FDA approved a single-ingredient oral colchicine preparation. During the review process, FDA identified 2 safety concerns associated with use of colchicine. Reports suggested that drug interactions play an important role in the development of colchicine toxicity. There also was evidence that the dosage of colchicine previously used for treatment of acute gout flares could be reduced without reducing the drug's efficacy. The labeling now includes extensive information on drug interactions and a new (lower) dosage for acute gout flare. Colchicine in fixed combination with probenecid is approved by the FDA for the management of recurrent gouty arthritis.