FDA label 3a77b97f-df41-4712-9b4d-93a9fa64e3c2

5 WARNINGS AND PRECAUTIONS Fatal overdoses have been reported with colchicine in adults and children. Keep GLOPERBA out of the reach of children ( 5.1 , 10 ). Blood dyscrasias: myelosuppression, leukopenia, granulocytopenia, thrombocytopenia and aplastic anemia have been reported ( 5.2 ). Monitor for toxicity and, if present, consider lowering the dose, temporary interruption or discontinuation of colchicine ( 5.2 , 5.3 , 5.4 , 6 , 10 ). Drug interaction with CYP3A4 and P - gp inhibitors: Co-administration of colchicine with dual CYP3A4 and P-gp inhibitors has resulted in life-threatening interactions and death ( 5.3 , 7 ). Neuromuscular toxicity: Myotoxicity including rhabdomyolysis may occur, especially in combination with other drugs known to cause this effect. Consider lowering the dose, temporary interruption or discontinuation of GLOPERBA ( 5.4 , 6 ). 5.1 Fatal Overdose Fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine [ see Overdosage ( 10 ) ]. GLOPERBA should be kept out of the reach of children. 5.2 Blood Dyscrasias Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia and aplastic anemia have been reported with colchicine used in therapeutic doses. 5.3 Drug Interactions Because colchicine is a substrate for both the CYP3A4 metabolizing enzyme and the P-gp efflux transporter, inhibition of either of these pathways may lead to colchicine-related toxicity. Inhibition of both CYP3A4 and P-gp by dual inhibitors (i.e., clarithromycin) has been reported to produce life-threatening or fatal colchicine toxicity due to significant increases in systemic colchicine levels. Therefore, concomitant use of GLOPERBA with inhibitors of both CYP3A4 and P-gp should be avoided. If treatment with colchicine is necessary, a reduced daily dose should be considered and the patient should be closely monitored for colchicine toxicity [ see Drug Interactions ( 7 ) ]. Use of GLOPERBA in conjunction with drugs that inhibit both CYP3A4 and P-gp is contraindicated in patients with renal or hepatic impairment [ see Contraindications ( 4 ) ]. 5.4 Neuromuscular Toxicity Colchicine-induced neuromuscular toxicity and rhabdomyolysis have been reported with chronic treatment in therapeutic doses, especially in combination with other drugs known to cause this effect. Patients with impaired renal function and elderly patients, even those with normal renal and hepatic function, are at increased risk. Once colchicine treatment is stopped, the symptoms generally resolve within one week to several months.

6 ADVERSE REACTIONS Gastrointestinal disorders are the most common adverse reactions with colchicine. These disorders are often the first signs of toxicity and may indicate that the colchicine dose needs to be reduced or therapy stopped. These disorders include diarrhea, nausea, vomiting, and abdominal pain. Colchicine has been reported to cause neuromuscular toxicity, which may present as muscle pain or weakness [ see Warnings and Precautions ( 5.4 ) ]. Toxic manifestations associated with colchicine include myelosuppression, disseminated intravascular coagulation and injury to cells in the renal, hepatic, circulatory and central nervous systems. These toxicities most often occur with excessive accumulation or overdosage [ see Overdosage ( 10 ) ]. The following adverse reactions have been reported with colchicine. These adverse reactions have been generally reversible upon interrupting treatment or lowering the dose of colchicine. Neurological : sensory motor neuropathy Dermatological : alopecia, maculopapular rash, purpura, rash Digestive : abdominal cramping, abdominal pain, diarrhea, lactose intolerance, nausea, vomiting Hematological : leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, aplastic anemia Hepatobiliary : elevated AST, elevated ALT Musculoskeletal : myopathy, elevated CPK, myotonia, muscle weakness, muscle pain, rhabdomyolysis Reproductive : azoospermia, oligospermia The most commonly reported adverse reactions with colchicine are gastrointestinal symptoms, including diarrhea, nausea, vomiting, and abdominal pain ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Romeg Therapeutics, LLC at (1 800 758 9702) or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).