Pharmacokinetic studies evaluating changes in systemic levels of colchicine when co-administered with CYP3A4 inhibitors in healthy volunteers have been conducted with colchicine capsules. While voriconazole 200 mg BID for 5 days (considered a strong CYP3A4 inhibitor) and cimetidine 800 mg BID for 5 days (considered a weak CYP3A4 inhibitor) did not cause any changes in colchicine systemic levels, fluconazole 200 mg QD for 4 days with a 400 mg loading dose (considered a moderate CYP3A4 inhibitor) increased colchicine AUC by 40%. As voriconazole, cimetidine, and fluconazole are known as CYP3A4 inhibitors that do not inhibit P-gp, these studies show that CYP3A4 inhibition by itself may not lead to clinically significant increases in colchicine systemic levels in humans, and P-gp inhibition in addition to CYP3A4 inhibition may be necessary for clinically meaningful interactions of colchicine. However, based on published case reports that indicate the presence of colchicine toxicity when colchicine is co-administered with strong to moderate CYP3A4 inhibitors such as clarithromycin, erythromycin , grapefruit juice, etc., as well as the 40% increase in systemic levels of colchicine observed with concomitantly administered fluconazole (a moderate CYP3A4 inhibitor that is not known to inhibit P-gp) in a drug-drug interaction study, the drug-drug interaction potential of colchicine with strong or moderate CYP3A4 inhibitors that do not inhibit P-gp cannot be ruled out completely.
Administration advice :
-Take orally, with or without food
-If a dose is missed, do not double the next dose
Storage requirements :
-Protect from light
-This drug is not an analgesic medication and should not be used to treat pain from other causes.
-For the treatment of gout, the initial response occurs in about 12 to 24 hours; peak response is expected within 48 to 72 hours.
-This drug has a narrow therapeutic window; patients should be monitored for closely for toxicity.
-Monitor for drug toxicity, especially among geriatric and debilitated patients, patients with renal or hepatic impairment, and those with cardiac, renal, hepatic, or gastrointestinal disease.
-Monitor for hematologic toxicities; for patients developing signs or symptoms of blood cell dyscrasias, a full hematologic investigation should be conducted.
-Monitor renal function in patients at-risk for renal impairment
Patient advice :
-Instruct patients on proper use and inform patients that fatal overdose, both accidental and intentional, have occurred; this drug should be kept out of the reach of children.
-Inform patients that there are a number of potentially serious drug interactions; grapefruit, grapefruit juice, and some herbal products should be avoided; patients should check with their healthcare provider before starting any new medications including short-term medications such as antibiotics.
-Inform patients that bone marrow depression and neuromuscular toxicity may occur; patients should seek medical attention promptly for unusual bleeding or bruising, increased infections, weakness or fatigue, muscle pain or weakness, or numbness or tingling in fingers or toes.
-Inform patients that gastrointestinal adverse events occur, but if these events are severe or persistent, they should be reported promptly to their healthcare provider.