Alkaloid

Colchicine

Approved 29 Nov 2018OralCapsule

The FDA lists this product in 18 strengths and forms.

Indications

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

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

Contraindications

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

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

Warnings and precautions

5. WARNINGS AND PRECAUTIONS

Fatal overdoses have been reported with colchicine in adults and children. Keep colchicine 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).
D rug interaction with dual P-gp and CYP3A4 inhibitors : Coadministration of colchicine with dual P-gp and CYP3A4 inhibitors has resulted in life-threatening interactions and death (5.3, 7).
N e u romuscular toxicity : Myotoxicity including rhabdomyolysis may occur, especially in combination with other drugs known to cause this effect. Consider temporary interruption or discontinuation of colchicine (5.4, 7).

5.1Fatal Overdose

At a glance

Brand name: Colchicine
Pharmacologic class: Alkaloid
Route: Oral
Dosage form: Capsule
Applicant: PH Health
Status: Prescription
FDA approval: 29 Nov 2018
Application: ANDA208678-001

Indications

Contraindications

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

Warnings and precautions

5. WARNINGS AND PRECAUTIONS

Fatal overdoses have been reported with colchicine in adults and children. Keep colchicine 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).
D rug interaction with dual P-gp and CYP3A4 inhibitors : Coadministration of colchicine with dual P-gp and CYP3A4 inhibitors has resulted in life-threatening interactions and death (5.3, 7).
N e u romuscular toxicity : Myotoxicity including rhabdomyolysis may occur, especially in combination with other drugs known to cause this effect. Consider temporary interruption or discontinuation of colchicine (5.4, 7).

5.1Fatal Overdose

Interactions

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

Coadministration 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 and inhibitors of CYP3A4 or P-gp should be avoided if possible. If coadministration of colchicine and an inhibitor of CYP3A4 or P-gp is necessary, the dose of colchicine should be reduced and the patient should be monitored carefully for colchicine toxicity ( 7 , 12.3 ).

7.1CYP3A4

The concomitant use of colchicine 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 coadministration of colchicine and a CYP3A4 inhibitor is necessary, the dose of colchicine 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 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 coadministration of colchicine and a P-gp inhibitor is necessary, the dose of colchicine 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. 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 coadministration 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 coadministered drugs [See Drug-Drug Interactions ( 7.1 , 7.2 ) and Pharmacokinetics ( 12.3 )].

Colchicine

Indications

Contraindications

Warnings and precautions

5.1Fatal Overdose

At a glance

Two medicines in one question?

Colchicine

Indications

Contraindications

Warnings and precautions

5.1Fatal Overdose

At a glance

Two medicines in one question?

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 Risk Summary

Adverse reactions

Composition

Strengths and forms

Official product information