apefruit juice, erythromycin, verapamil, etc.) should be avoided due to the potential for serious andlife-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 shouldbe adjusted by either reducing the daily dose or reducing the dose frequency, and the patient shouldbe 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 [seeWarnings 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 beadjusted by either reducing the daily dose or reducing the dose frequency, and the patient should bemonitored 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 whencombined with GLOPERBA. Complaints of muscle pain or weakness could be an indication to checkserum creatinine kinase levels for signs of myopathy.
7.4 Drug Interaction Studies
Two pharmacokinetic studies eva luated 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 systemiclevels of colchicine.
GLOPERBA can be administered with amlodipine, carvedilol, and ciprofloxacin at the tested doses withouta 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 withposaconazole. The recommended dose of GLOPERBA when co-administered with posaconazole is0.24 mg (2 mL).
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Available human data from published literature on colchicine use in pregnancy over several decades havenot identified any drug associated risks for major birth defects, miscarriage, or adverse maternal or fetaloutcomes (see Data). Although animal reproduction and development studies were not conducted withGLOPERBA, published animal reproduction and development studies indicate that colchicine causesembryofetal toxicity and altered postnatal development at exposures within or above the clinical therapeuticrange.
The estimated background risk of major birth defects and miscarriage for the indicated population isunknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In theU.S. general population, the estimated background risk of major birth defects and miscarriage in clinicallyrecognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data
Available data from published observational studies, case series, and case reports over several decades donot suggest an increased risk for major birth defects or miscarriage in pregnant women with rheumaticdiseases (such as rheumatoid arthritis, Behçet’s disease, or familial Mediterranean fever (FMF)) treated with
colchicine at therapeutic doses during pregnancy. Limitations of these data include the lack ofrandomization and inability to control for confounders such as u |
