Can colchicine cause leukopenia?/nA 77-year-old woman with gout and diabetes has been treated with

Fråga: Can colchicine cause leukopenia? A 77-year-old woman with gout and diabetes has been treated with colchicine 1.5 mg daily for approximately six weeks. Her total leukocyte count has now decreased from normal (>4.0) to 2.7. Her other medicines (none of which has been recently introduces or changed) include insulin, enalapril, lansoprazole, furosemide, allopurinol and zolpidem.

Sammanfattning: Leukopenia is known side-effect of colchicine, mainly in connection with overdosing, but has also been reported occasionally with therapeutic doses.

Svar: Colchicine is an antiinflammatory agent with two specific indications: gout and familial Mediterranean fever. The mechanism of action is unclear, but has been suggested to involve inhibition of mitosis and migration of granulocytes. Colchicine has a short initial plasma half-life of 10-60 minutes, followed by extensive enterohepatic recirculation. A minor part (10-20%) is excreted unchanged in the urine. Elimination is said to be delayed in renal failure. Colchicine accumulates in leukocytes with a half-life of 60 hours (1).

Side-effects of cholchicine mainly involve gastrointestinal symtoms. Bone marrow depression and leukopenia is common after colchicine overdose, but has also been reported with therapeutic doses, especially in patients with reduced renal function (2). An 86-year-old woman with chronic renal failure and gout developed agranulocytosis after seven days of 0.5 mg colchicine treatment. Serum colchicine concentration was 6 ug/L four days after drug withdrawal, with a reported "normal range" of 1-3 ug/L (3). A 19-year-old girl with familial Mediterranean fever who displayed distinct decreases in her leukocyte count at two subsequent challenges with colchicine. This reaction was possibly aggravated by a concomitant viral infection (4). A 68-year-old diabetic man developed leukopenia (2000/cubic mm) one week after his colchicine dose was increased to 2-3 mg daily due to an acute gout attack. He recovered after discontinuation of colchicine and two doses of filgrastim (5).

The Swedish adverse drug reaction register contains only 22 reports related to colchicine. One of these reports concern leukopenia, but the causal relation to colchicine has been determined as unclassified (6).

Colchicine may well be the cause of leukopenia in the present case. We recommend that the case be reported to the regional adverse drug reaction monitoring centre.