Colchicine (Oral)
General Monograph,
Gout Therapy
Action And Clinical Pharmacology: Although its exact mode of action in the relief of gout is not completely understood, colchicine is known to decrease the inflammatory response to urate crystal deposition by inhibiting migration of leukocytes, to interfere with urate deposition by decreasing lactic acid production by leukocytes, to interfere with kinin formation and to diminish phagocytosis and the subsequent anti-inflammatory response. The anti-inflammatory effect of colchicine is relatively selective for acute gouty arthritis. However, other types of arthritis occasionally respond. It is neither an analgesic nor a uricosuric and will not prevent progression to chronic gouty arthritis. It does have a prophylactic, suppressive effect that helps to reduce the incidence of acute attacks and to relieve the residual pain and mild discomfort that patients with gout occasionally experience.
Pharmacokinetics: Colchicine is rapidly absorbed from the gastrointestinal tract. Peak concentrations occur in 0.5 to 2 hours. The drug and its metabolites are distributed in leukocytes, kidneys, liver, spleen and the intestinal tract. The plasma half-life is about 20 minutes while the half-life in leukocytes is approximately 60 hours. Colchicine is metabolized in the liver and excreted primarily in the feces with 10 to 20% eliminated unchanged in the urine.
Indications And Clinical Uses: The treatment of acute gout. Colchicine is effective in relieving the pain of acute attacks, especially if therapy is begun early in the attack and in adequate dosage. Because of the toxicity of colchicine in high doses, the use of NSAIDs is preferred for acute gout. However, colchicine is very effective in preventing recurrent attacks of gout and is not toxic in the lower doses used for prophylaxis.
Contra-Indications: Patients with serious gastrointestinal, renal and cardiac disease; known hypersensitivity to colchicine.
Manufacturers’ Warnings In Clinical States: Pregnancy: Cell division in animals and plants can be arrested by colchicine. In mice and hamsters it has produced teratogenic effects and has adversely affected spermatogenesis in animals and humans. The benefit of colchicine therapy in a pregnant woman must be weighed against the possible risk to the fetus.
Precautions: Use with care in geriatric or debilitated patients and those with cardiac, renal or gastrointestinal disease. Dosage reduction is indicated if weakness, anorexia, nausea, vomiting or diarrhea appears.
Drug Interactions: Colchicine has been shown to induce reversible malabsorption of Vitamin B12, apparently by altering the function of ileal mucosa.
Pregnancy: See Warnings.
Lactation: It is not known if colchicine is distributed into human milk.
Children: Safety and effectiveness in this age group have not been established.
Adverse Reactions: Reactions to colchicine appear to be dose-related. The most prominent symptoms are related to the gastrointestinal tract (e.g., nausea, vomiting, abdominal pain, diarrhea) and may be particularly troublesome in the presence of peptic ulcer or spastic colon. If these symptoms appear, colchicine should be discontinued as they are early signs of toxicity.
Hypersensitivity to colchicine is a very rare but possible occurrence.
When given for a prolonged period, colchicine may cause bone marrow depression and aplastic anemia. Periodic blood counts should be performed during long-term therapy. Peripheral neuritis or neuropathy, myopathy, hair loss, vesicular dermatitis, anuria, renal damage and hematuria have also been reported with prolonged administration.
Symptoms And Treatment Of Overdose: There is usually a latent period between overdosage and the onset of symptoms, regardless of the route of administration. Deaths have been reported with as little as 7 mg, although higher doses have been taken without fatal results.Symptoms: The first symptoms to appear are gastrointestinal – nausea, vomiting, abdominal pain and diarrhea. The diarrhea may be severe and bloody owing to hemorrhagic gastroenteritis. Burning sensations in the throat, stomach and skin may also occur. Extensive vascular damage may result in shock. Renal dysfunction may occur. Hematuria and oliguria are common manifestations. Muscular weakness is marked and an ascending CNS paralysis may develop. The patient usually remains conscious. However, delirium and convulsions may occur. Death usually is the result of respiratory depression.
Treatment: Induce emesis or perform gastric lavage followed by the administration of activated charcoal. Symptomatic and supportive treatment. Analgesics may relieve the abdominal pain, but monitor carefully for possible paralytic ileus. Respiratory assistance may be needed to insure proper oxygenation and ventilation.
Dosage And Administration: Acute Gouty Arthritis: Colchicine therapy must be initated at the first warning of an acute attack; a delay of a few hours impairs its effectiveness. The usual oral adult dose is 1 or 1.2 mg initially, followed by subsequent doses of 0.5 or 0.6 mg every 2 hours until pain is relieved or toxic symptoms appear. The total amount of colchicine required to alleviate an acute attack is usually 4 to 8 mg. However, as there may be a delay in the effect of colchicine of up to 12 to 48 hours, some clinicians recommend a schedule of 1.2 mg orally every 12 hours, for a maximum of 3 doses. This results in a total dose of up to 3.6 mg for an acute attack and minimizes adverse effects.
To prevent cumulative toxicity, a second course of therapy should not be initiated before 3 days have elapsed since treating the previous attack.
For prophylaxis of recurrent gouty arthritis, the dose of colchicine may range from 0.5 mg 1 to 4 times weekly to 1.8 mg daily, depending on the frequency of attacks. The usual dose is 1 mg daily.
Colchicine (Oral) General Monograph, Gout Therapy
Posted by RxMed