colchicine

Available forms
Available by prescription only
Injection: 0.5 mg/ml
Tablets: 0.5 mg, 0.6 mg

Indications and dosages
 To prevent acute attacks of gout as prophylactic or maintenance therapy. Adults: 0.5 or 0.6 mg P.O. three to four times weekly or daily.
 To prevent attacks of gout in patients undergoing surgery. Adults: 0.5 to 0.6 mg P.O. t.i.d. 3 days before and 3 days after surgery.
 Acute gout, acute gouty arthritis. Adults: Initially, 1 to 1.2 mg P.O., followed by 0.5 to 1.2 mg P.O. q 1 to 2 hours; total daily dose is usually 4 to 8 mg P.O.; give until pain is relieved or until nausea, vomiting, or diarrhea ensues. Or, 2 mg I.V. followed by 0.5 mg I.V. q 6 hours if needed. Total I.V. dose over 24 hours (one course of treatment) not to exceed 4 mg.
 Familial Mediterranean fever ◇. Adults: 1 to 2 mg P.O. daily in divided doses.
 Amyloidosis suppressant ◇. Adults: 500 mcg P.O. once daily to b.i.d.
 Dermatitis herpetiformis suppressant ◇. Adults: 600 mcg P.O. b.i.d. or t.i.d.
 Hepatic cirrhosis ◇. Adults: 1 mg P.O. 5 days weekly.
 Primary biliary cirrhosis ◇. Adults: 0.6 mg b.i.d.

Pharmacodynamics
Antigout action: Colchicine’s exact mechanism of action is unknown, but it’s involved in leukocyte migration inhibition; reduction of lactic acid production by leukocytes, resulting in decreased deposits of uric acid; and interference with kinin formation. Colchicine also reduces the inflammatory response to deposited uric acid crystals and diminishes phagocytosis.

Pharmacokinetics
Absorption: When given P.O., rapidly absorbed from the GI tract. Unchanged drug may be reabsorbed from the intestine by biliary processes.
Distribution: Distributed rapidly into various tissues after reabsorption from the intestine. It’s concentrated in leukocytes and distributed into the kidneys, liver, spleen, and intestinal tract, but is absent in the heart, skeletal muscle, and brain.
Metabolism: Metabolized partially in the liver and also slowly metabolized in other tissues.
Excretion: Excreted primarily in the feces, with lesser amounts excreted in urine.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in those with blood dyscrasias or serious CV, renal, or GI disease. Use cautiously in geriatric or debilitated patients and in those with early signs of CV, renal, or GI disease.

Interactions
Drug-drug. Erythromycin: Increases serum colchicine levels. May need to reduce colchicine dosage.
Loop diuretics: May decrease efficacy of colchicine prophylaxis. Avoid use together.
Phenylbutazone: May increase risk of leukopenia or thrombocytopenia. Avoid use together.
Vitamin B: Impairs absorption. Avoid use together.
Drug-lifestyle. Alcohol use: May inhibit drug action. Discourage alcohol use.

Adverse reactions
CNS: peripheral neuritis.
GI: nausea, vomiting, abdominal pain, diarrhea.
GU: reversible azoospermia.
Hematologic: aplastic anemia, thrombocytopenia, and agranulocytosis (with long-term use); nonthrombocytopenic purpura.
Musculoskeletal: myopathy.
Skin: alopecia, urticaria, dermatitis.
Other: severe local irritation if extravasation occurs, hypersensitivity reactions.

Effects on lab test results
• May increase alkaline phosphatase, AST, and ALT levels. May decrease carotene and cholesterol levels.
• May decrease hemoglobin, hematocrit, and platelet and granulocyte counts.

Overdose and treatment
Signs and symptoms of overdose include nausea, vomiting, abdominal pain, and diarrhea. Diarrhea may be severe and bloody from hemorrhagic gastroenteritis. Burning sensations in the throat, stomach, and skin also may occur. Extensive vascular damage may result in shock, hematuria, and oliguria, indicating kidney damage. Patient develops severe dehydration, hypotension, and muscle weakness with an ascending paralysis of the CNS. Patient usually remains conscious, but delirium and convulsions may occur. Death may result from respiratory depression.
 There’s no known antidote. Treatment begins with gastric lavage and preventive measures for shock. Recent studies support the use of hemodialysis and peritoneal dialysis; atropine and morphine may relieve abdominal pain; paregoric usually is administered to control diarrhea and cramps. Respiratory assistance may be needed.

Special considerations
• To avoid cumulative toxicity, a course of oral colchicine shouldn’t be repeated for at least 3 days; a course of I.V. colchicine shouldn’t be repeated for several weeks.
• Don’t administer I.M. or S.C.; severe local irritation occurs.
• Give colchicine by slow I.V. push over 2 to 5 minutes by direct I.V. injection or into tubing of a free-flowing I.V. with compatible I.V. fluid. Avoid extravasation. Don’t dilute colchicine injection with bacteriostatic normal saline solution, D₅W, or any other fluid that might change pH of colchicine solution. If lower concentration of colchicine injection is needed, dilute with sterile water or normal saline solution. However, if diluted solution becomes turbid, don’t inject.
• Drug must be discontinued if weakness, anorexia, nausea, vomiting, or diarrhea occurs. First sign of acute overdose may be GI symptoms, followed by vascular damage, muscle weakness, and ascending paralysis. Delirium and seizures may occur without loss of consciousness.
• Store drug in a tightly closed, light-resistant container, away from moisture and heat.
• Colchicine may cause false-positive results of urine tests for RBCs or hemoglobin.
• Obtain baseline laboratory studies, including CBC, before starting therapy and periodically thereafter.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Safety hasn’t been established in breast-feeding women.
Pediatric patients
• Safety and efficacy in children haven’t been established.
Geriatric patients
• Administer with caution to elderly or debilitated patients, especially those with renal, GI, or heart disease or hematologic disorders. Reduce dosage if weakness, anorexia, nausea, vomiting, or diarrhea occurs.

Patient education
• Advise patient to report rash, sore throat, fever, unusual bleeding, bruising, tiredness, weakness, numbness, or tingling.
• Tell patient to discontinue drug as soon as gout pain is relieved or at the first sign of nausea, vomiting, stomach pain, or diarrhea, and to report persistent symptoms.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use