Preparations with no effect on uric acid metabolism

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Approved 26 Sept 2014OralCapsule

Indications

Colchicine capsules are indicated for prophylaxis of gout flares in adults. Limitations of Use : The safety and effectiveness of colchicine capsules for acute treatment of gout flares during prophylaxis has not been studied. Colchicine capsules are not an analgesic medication and should not be used to treat pain from other causes. Colchicine capsules are an alkaloid indicated for prophylaxis of gout flares in adults ( 1 ).

Limitations of Use :

The safety and effectiveness of colchicine capsules for acute treatment of gout flares during prophylaxis has not been studied.
Colchicine capsules are not an analgesic medication and should not be used to treat pain from other causes.

Contraindications

Patients with renal or hepatic impairment should not be given colchicine capsules 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 colchicine capsules.

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

Warnings and precautions

Fatal overdoses have been reported with colchicine in adults and children. Keep colchicine capsules 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 dual P-gp and CYP3A4 inhibitors has resulted in life-threatening interactions and death ( 5.3 , 7 ).

Indications

Limitations of Use :

The safety and effectiveness of colchicine capsules for acute treatment of gout flares during prophylaxis has not been studied.
Colchicine capsules are not an analgesic medication and should not be used to treat pain from other causes.

Contraindications

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

Warnings and precautions

Fatal overdoses have been reported with colchicine in adults and children. Keep colchicine capsules 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 dual P-gp and CYP3A4 inhibitors has resulted in life-threatening interactions and death ( 5.3 , 7 ).

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 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 colchicine capsules with drugs that inhibit both P-glycoprotein and CYP3A4 [see Contraindications (4) ] . Combining these dual inhibitors with colchicine capsules 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 colchicine capsules 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, colchicine capsules should be discontinued immediately.

Co-administration of P-gp or CYP3A4 inhibitors or inhibitors of both P-gp and CYP3A4 (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.
Concomitant use of colchicine capsules and inhibitors of CYP3A4 or P-gp should be avoided if possible. If co-administration of colchicine capsules and an inhibitor of CYP3A4 or P-gp is necessary, the dose of colchicine capsules should be reduced and the patient should be monitored carefully for colchicine toxicity ( 7 , 12.3 ).

7.1CYP3A4

The concomitant use of colchicine capsules 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) ] . If co-administration of colchicine capsules and a CYP3A4 inhibitor is necessary, the dose of colchicine capsules 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) ] .

7.2P-glycoprotein

The concomitant use of colchicine capsules 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) ] . If co-administration of colchicine capsules and a P-gp inhibitor is necessary, the dose of colchicine capsules 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) ] .

7.3HMG-CoA Reductase Inhibitors and Fibrates

Some drugs such as HMG-CoA reductase inhibitors and fibrates may increase the risk of myopathy when combined with colchicine capsules. Complaints of muscle pain or weakness could be an indication to check serum creatinine kinase levels for signs of myopathy.

7.4Drug-Drug Interaction Studies

Four pharmacokinetic studies evaluated the effects of co-administration of voriconazole (200 mg BID), fluconazole (200 mg QD), cimetidine (800 mg BID), and propafenone (225 mg BID) on systemic levels of colchicine. Colchicine can be administered with these drugs at the tested doses without a need for dose adjustment. However, these results should not be extrapolated to other co-administered drugs [see Drug-Drug Interactions ( 7.1 , 7.2 ) and Pharmacokinetics (12.3) ] .

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Indications

Contraindications

Warnings and precautions

Two medicines in one question?

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Indications

Contraindications

Warnings and precautions

Two medicines in one question?

5.1Fatal Overdose

5.2Blood Dyscrasias

5.3Interactions with CYP3A4 and P-gp Inhibitors

5.4Neuromuscular Toxicity

Interactions

7.1CYP3A4

7.2P-glycoprotein

7.3HMG-CoA Reductase Inhibitors and Fibrates

7.4Drug-Drug Interaction Studies

Pregnancy and breastfeeding

8.1Pregnancy

Adverse reactions

Composition

Official product information

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