Colchicine intravenous

This high incidence of gastrointestinal side effects may be circumvented by administering colchicine intravenously. Except in patients with renal insufficiency, the initial intravenous dose of colchicine is 2 mg. If relief is not obtained, an additional 1-mg dose may be given at 6 and 12 hours to a total dose of 4 mg for a specific attack. The colchicine should be diluted with 20 ruL normal saline before administration to minimize sclerosis of the vein. The intravenous administration of colchicine eliminates most of the gas-... 

An 18-year-old male was given 2 mg of colchicine intravenously by a Triend under the false impression that it would induce euphoria. In addition to the recognized complications of colchicine poisoning the patient developed mediastinal emphysema (201 ). 

Bone marrow depression and agranulocytosis have been observed after therapeutic doses of colchicine (202, 203 ). Fatal bone marrow depression occurred in a 70-year-old man with gout shortly after operation for perforation of a gastric ulcer associated with administration of phenylbutazone. He had been given 12 mg of colchicine intravenously over a period of 5 days (202 ). Acute myelomonocytic leukaemia and multiple myeloma occurred in 3 of 25 patients with gout given sulphinpyrazone and colchicine. Colchicine was taken intermittently and for shorter periods than the sulphinpyrazone (204 ). 

Use of intravenous colchicine to circumvent adverse gastrointestinal effects is discouraged due to the increased risk of serious and potentially fatal systemic effects with this route. The intravenous form should not be used in patients with moderate or more severe renal impairment (creatinine clearance less than or equal to 50 mL/minute), and total doses should not exceed 4 mg in a 7-day period. The potential extravasation of intravenous colchicine is also a concern. 

Bonnel RA, Villalba ML, Karwoski CB, Beitz J. Deaths associated with inappropriate intravenous colchicine administration. J Emerg Med 2002 22 385-387. 

Colchicine (a drug used in treatment of gout) and vinblastine (a cancer chemotherapy agent) may decrease liver uptake of americium. In rats that received an intraperitoneal injection of either colchicine and vinblastine prior to an intravenous or intramuscular injection of americium citrate, liver uptake of americium was lower, relative to controls, and kidney and skeletal americium uptake were higher (Seidel 1984, 1985). The effect is thought to involve disruption of hepatic microtubule formation, which is critical to the formation and intracellular processing of lysosomes, the initial site of accumulation of americium in the liver. 

Colchicine is rapidly absorbed after oral administration and tends to concentrate in the spleen, kidney, liver, and gastrointestinal tract. Leukocytes also avidly accumulate and store colchicine even after a single intravenous injection. Since colchicine can accumulate in cells against a concentration gradient, it is postulated that an active transport process may be involved in its cellular uptake. The drug is metabolized, primarily in the liver, by deacetylation. Fecal excretion plays a major role in colchicine elimination, since it and its metabolites are readily secreted into the bile. Only about 15 to 30% of the drug is eliminated in the urine except in patients with liver disease urinary excretion is more important in these individuals. 

Although colchicine is more specific in gout than the NSAIDs, NSAIDs (eg, indomethacin and other NSAIDs [except aspirin]) have replaced it in the treatment of acute gout because of the troublesome diarrhea sometimes associated with colchicine therapy. Colchicine is now used for the prophylaxis of recurrent episodes of gouty arthritis, is effective in preventing attacks of acute Mediterranean fever, and may have a mild beneficial effect in sarcoid arthritis and in hepatic cirrhosis. Although it can be given intravenously, this route should be used cautiously because of increased bone marrow toxicity. 

Colchicine often causes diarrhea and may occasionally cause nausea, vomiting, and abdominal pain. Hepatic necrosis, acute renal failure, disseminated intravascular coagulation, and seizures have also been observed. Colchicine may rarely cause hair loss and bone marrow depression as well as peripheral neuritis, myopathy, and in some cases death. The more severe adverse events have been associated with the intravenous administration of colchicine. 

Wallace SL, Singer JZ Systemic toxicity associated with intravenous administration of colchicine-guidelines for use. J Rheumatol 1988 15 495. [PMID 3288754]... 

The prophylactic dose of colchicine is 0.6 mg one to three times daily. For terminating an attack of gout, the traditional initial dose of colchicine is usually 0.6 or 1.2 mg, followed by 0.6 mg every 2 hours until pain is relieved or nausea and diarrhea appear. The total dose can be given intravenously if necessary, but it should be remembered that as little as 8 mg in 24 hours may be fatal. 

Bone marrow depression is common after colchicine overdose and intoxication and less common in therapeutic doses. Fatal cases of agranulocytosis are more often associated with bone marrow aplasia (SEDA-4, 70) (5). Bone marrow depression usually occurs between the third and sixth days of acute intoxication. Cytoplasmic inclusions in neutrophils and megaloblastic anemia have been described. Administration of therapeutic doses intravenously and orally to two patients with reduced renal function caused profound prolonged neutropenia complicated by septicemia, which ended in death (SEDA-13, 84). 

Intravenous administration is potentially much more toxic than oral administration because of its unfavorable benefit to harm, balance and the availability of less dangerous treatments, colchicine should not be given intravenously (SEDA-5,109) (SEDA-13, 84) (SEDA-16,115). 

As a result of the inflammatory nature of asthma and the risk of toxicities from corticosteroids, a number of the drugs with antiinflammatory or immunomodulatory activity such as hydroxychloroquine, dapsone, gold, intravenous gamma-globulin, cyclosporine, and colchicine have been studied in severe steroid-dependent asthma with mixed results. ... 

Intravenous colchicine is rapidly effective but cannot be administered to individuals with renal impairment or ex-trahepatic biliary obstruction. A single intravenous dose should not exceed 2 to 3 mg, with a cumulative total dose not exceeding 4 to 5 mg per episode. 

Because of the risk of bone marrow toxicity, colchicine should be discontinued for 7 days following initial therapy with either oral or intravenous administration. Colchicine should not be used intravenously in individuals who are neutropenic, have severe renal impairment (a creatinine clearance of <10 mL/min), or have combined renal and hepatic insufficiency. The dose should be decreased by 50% in individuals with renal insufficiency (a creatinine clearance of 10 to 50 mL/min) and limited to a total dose of 2 mg in patients receiving oral maintenance colchicine. ... 

Evans TI, Wheeler MT, Small RE, et al. A comprehensive investigation of inpatient intravenous colchicine use shows more education is needed. J Rheumatol 1996 23 143-148. 

The absorption of colchicine is rapid but variable. Peak plasma concentrations occur 0.5 to 2 hours after dosing. In plasma, 50% of colchicine is protein-bound. There is significant enterohepatic circulation. The exact metabolism of colchicine is unknown but seems to involve deacetylation by the liver. Only 10 to 20% is excreted in the urine, although this increases in patients with liver disease. The kidney, liver, and spleen also contain high concentrations of colchicine, but it apparently is largely exclnded from heart skeletal muscle and brain. The plasma half-life of colchicine is approximately 9 hours, but it can be detected in leukocytes and in the urine for at least 9 days after a single intravenous dose. 

Freeman DL Frequent doses of intravenous colchicine can be lethal. N Engl J Med 309 310, 1983... 

---