Interactions between tao(troleandomycin) and Colchicine (colchicine)
colchicine and troleandomycin (Major Drug-Drug)
MONITOR CLOSELY: Coadministration with certain macrolide antibiotics may increase the serum concentrations of colchicine, which may result in toxicity. The proposed mechanism is macrolide inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of colchicine. Macrolides that may significantly inhibit CYP450 3A4 include clarithromycin, erythromycin, and troleandomycin. Azithromycin and dirithromycin are generally believed to have little, if any, effect on CYP450 3A4. In one case report, a patient with familial Mediterranean fever and amyloidosis involving the kidney, liver, and gastrointestinal tract was admitted to the hospital with life-threatening colchicine toxicity after a two-week course of oral erythromycin. During the year prior to admission, the patient had developed recurrent diarrhea and abdominal pain and demonstrated toxic levels of colchicine on two occasions. It is likely the patient had acute colchicine toxicity brought on by the addition of erythromycin and superimposed on chronic colchicine intoxication secondary to renal and hepatic impairment. The patient improved with supportive therapy and intensive hemodialysis and was discharged on day 70 of hospitalization. Another report describes two fatal cases of agranulocytosis due to presumed interaction between clarithromycin and colchicine. One patient had mild liver function test abnormalities, while the other patient had end-stage renal failure and was on continuous ambulatory peritoneal dialysis.
MANAGEMENT: Pharmacologic response and serum colchicine levels should be monitored more closely whenever clarithromycin, erythromycin, or troleandomycin is added to or withdrawn from therapy, and the colchicine dosage adjusted as necessary. This precaution may be particularly important in patients with underlying renal or hepatic impairment, since they are already at risk for colchicine toxicity. Patients should be advised to contact their physician if they experience early symptoms of toxicity such as abdominal pain, nausea, vomiting, or diarrhea. Azithromycin may be a safer alternative during therapy with colchicine, since it is not thought to significantly inhibit CYP450 3A4.
