MITIGARE (colchicine)

AbsorptionIn healthy adults, MITIGARE when given orally reached a mean C max of 3 ng/mL in 1.3 h (range 0.7 to 2.5 h) after 0.6 mg single dose administration. Absolute bioavailability is reported to be approximately 45%. Administration with food has no effect on the rate or extent of colchicine absorption. Colchicine is not effectively removed by hemodialysis.

DistributionColchicine has a mean apparent volume of distribution in healthy young volunteers of approximately 5 to 8 L/kg. Colchicine ...

The evidence for the efficacy of colchicine in patients with chronic gout is derived from the published literature. Two randomized clinical trials assessed the efficacy of colchicine 0.6 mg twice a day for the prophylaxis of gout flares in patients with gout initiating treatment with urate lowering therapy. In both trials, treatment with colchicine decreased the frequency of gout flares.

Gastrointestinal disorders are the most common adverse reactions with colchicine. They are often the first signs of toxicity and may indicate that the colchicine dosage needs to be reduced or therapy stopped. These 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, dissemi...

Patients with renal or hepatic impairment should not be given MITIGARE with drugs that inhibit both P-glycoprotein and CYP3A4 inhibitors [see Drug Interactions ( 7 )] . Combining these dual inhibitors with colchicine in patients with renal or hepatic impairment has resulted in life-threatening or fatal colchicine toxicity. Patients with both renal and hepatic impairment should not be given MITIGAR...

• Fatal overdoses have been reported with colchicine in adults and children. Keep MITIGARE 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 temporary interruption or discontinuation of colchicine ( 5.2 , 5.3 , 5.4 , 6 , 10 ).
• Drug interaction with dual P-gp and CYP3A4 inhibitors : Co-administration of colchicine with dua...

7 DRUG INTERACTIONS Colchicine is a substrate of the efflux transporter P-glycoprotein (P-gp), and the CYP3A4 metabolizing enzyme. Fatal drug interactions have been reported when colchicine is administered with clarithromycin, a dual inhibitor of CYP3A4 and P-glycoprotein. Toxicities have also been reported when colchicine is administered with inhibitors of CYP3A4 that may not be potent inhibitors...