gloperba

0.6 mg (5 mL) once or twice daily. Maximum dose 1.2 mg/day. ( 2.1 ) GLOPERBA is administered orally, without regard to meals ( 2.1 ) 2.1 Gout Prophylaxis For prophylaxis of gout flares, the recommended dosage of GLOPERBA is 0.6 mg (5 mL) once or twice daily. The maximum dose is 1.2 mg/day. GLOPERBA is administered orally, without regard to meals.

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…

Patients with renal or hepatic impairment should not be given GLOPERBA in conjunction with drugs that inhibit both CYP3A4 and P-gp [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 GLOPERBA. Patients with renal or hepatic impairment should not be given GLOPERBA in conjunction with drugs that inhibit both CYP3A4 and P-gp ( 4 ). Patients with both renal and hepatic impairment should not be given GLOPERBA ( 4 ).

The dose of colchicine that would induce significant toxicity for an individual is unknown. Fatalities have occurred after ingestion of a dose as low as 7 mg over a four day period, while other patients have survived after ingesting more than 60 mg. A review of 150 patients who overdosed on colchicine found that those who ingested less than 0.5 mg/kg survived and tended to have milder adverse reactions such as gastrointestinal symptoms, whereas those who took 0.5 to 0.8 mg/kg had more severe adverse reactions, including myelosuppression. There was 100% mortality in those who ingested more than 0.8 mg/kg. The first stage of acute colchicine toxicity typically begins within 24 hours of ingestion and includes gastrointestinal symptoms such as abdominal pain, nausea, vomiting, diarrhea and significant fluid loss, leading to volume depletion. Peripheral leukocytosis may also be seen. Life threatening complications occur during the second stage, which occurs 24 to 72 hours after drug administration, attributed to multiorgan failure and its consequences. Death is usually a result of respiratory depression and cardiovascular collapse. If the patient survives, recovery of multiorgan injury may be accompanied by rebound leukocytosis and alopecia starting about one week after the initial ingestion. Treatment of colchicine poisoning should begin with gastric lavage and measures to prevent…

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

Colchicine is a substrate of the CYP3A4 metabolizing enzyme and the P-glycoprotein (P-gp) efflux transporter. 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 of P-gp (e.g., grapefruit juice, erythromycin, verapamil), or inhibitors of P-gp that may not be potent inhibitors of CYP3A4 (e.g., cyclosporine). Patients with renal or hepatic impairment should not be given GLOPERBA with drugs that inhibit both CYP3A4 and P-glycoprotein [see Contraindications (4) ] . Combining these dual inhibitors with GLOPERBA in patients with renal and hepatic impairment has resulted in life threatening or fatal colchicine toxicity. Physicians should ensure that patients are suitable candidates for treatment with GLOPERBA and remain alert for signs and symptoms of toxic reactions associated with increased colchicine exposure due to drug interactions. Signs and symptoms of colchicine toxicity should be evaluated promptly and, if toxicity is suspected, consider lowering the dose, interruption or discontinuation of GLOPERBA. Co-administration of CYP3A4 or P-gp inhibitors or inhibitors of both CYP3A4 and P-gp (e.g., clarithromycin or cyclosporine) have been reported to lead to colchicine toxicity. The potential for drug-drug interactions must be considered prior to and during therapy ( 7 ). Concomitant use of GLOPERBA and inhibitors of both CYP3A4 and P-gp should be avoided if possible. If co-administration with a CYP3A4 and P-gp inhibitor is required, the patients' dose of colchicine may need to be reduced or interrupted, and the patient should be monitored carefully for colchicine toxicity ( 7 ). 7.1 CYP3A4 The concomitant use of GLOPERBA and CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole, grapefruit juice, erythromycin, verapamil, etc.) should be avoided due to the potential for serious and life threatening toxicity [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3) ] . If co-administration of GLOPERBA and a CYP3A4 inhibitor is necessary, the dose of GLOPERBA should be adjusted by either reducing the daily dose or reducing the dose frequency, and the patient should be monitored carefully for colchicine toxicity [see Clinical Pharmacology (12.3) ]. 7.2 P-Glycoprotein The concomitant use of GLOPERBA and inhibitors of P-glycoprotein (e.g. clarithromycin, ketoconazole, cyclosporine, etc.) should be avoided due to the potential for serious and life threatening toxicity [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3) ] . If co-administration of GLOPERBA and a P-gp inhibitor is necessary, the dose of GLOPERBA should be adjusted by either reducing the daily dose or reducing the dose frequency, and the patient should be monitored carefully for colchicine toxicity [see Clinical Pharmacology (12.3) ] . 7.3 HMG-CoA Reductase Inhibitors and Fibrates Some drugs such as HMG-CoA reductase inhibitors and fibrates may increase the risk of myopathy when combined with GLOPERBA. Complaints of muscle pain or weakness could be an indication to check serum creatinine kinase levels for signs of myopathy. 7.4 Drug Interaction Studies Two pharmacokinetic studies evaluated the effects of co-administration of posaconazole (300 mg QD), ciprofloxacin (500 mg BID), amlodipine (5 to 10 mg QD), and carvedilol (20 to 40 mg QD) on the systemic levels of colchicine. GLOPERBA can be administered with amlodipine, carvedilol, and ciprofloxacin at the tested doses without a need for dose adjustment. However, the results should not be extrapolated to other co-administered drugs. Colchicine plasma levels were markedly elevated when GLOPERBA was co-administered with posaconazole. The recommended dose of GLOPERBA when co-administered with posaconazole is 0.24 mg (2 mL).