Alkaloid

Gloperba

Approved 30 Jan 2019OralSolution

Indications

GLOPERBA ® (colchicine) Oral Solution is indicated for prophylaxis of gout flares in adults. GLOPERBA is indicated for prophylaxis of gout flares in adults ( 1 ). Limitations of use: The safety and effectiveness of GLOPERBA for acute treatment of gout flares during prophylaxis has not been studied. GLOPERBA is not an analgesic medication and should not be used to treat pain from other causes ( 1 ). Limitations of use: The safety and effectiveness of GLOPERBA for acute treatment of gout flares during prophylaxis has not been studied.

GLOPERBA is 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 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 ).

Warnings and precautions

Fatal overdoses have been reported with colchicine in adults and children. Keep GLOPERBA 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 lowering the dose, temporary interruption or discontinuation of colchicine ( 5.2 , 5.3 , 5.4 , 6 , 10 ). Drug interaction with CYP3A4 and P-gp inhibitors: Co-administration of colchicine with dual CYP3A4 and P-gp inhibitors has resulted in life threatening interactions and death ( 5.3 , 7 ).

Neuromuscular toxicity: Myotoxicity including rhabdomyolysis may occur, especially in combination with other drugs known to cause this effect. Consider lowering the dose, temporary interruption or discontinuation of GLOPERBA ( 5.4 , 6 ).

5.1Fatal Overdose

Fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine [see Overdosage (10) ]. GLOPERBA should be kept out of the reach of children.

At a glance

Brand name: Gloperba
Active substance: colchicine
Pharmacologic class: Alkaloid
Route: Oral
Dosage form: Solution
Applicant: Scilex Pharms
Status: Prescription
FDA approval: 30 Jan 2019
Application: NDA210942-001

Indications

GLOPERBA is not an analgesic medication and should not be used to treat pain from other causes.

Contraindications

Patients with both renal and hepatic impairment should not be given GLOPERBA ( 4 ).

Warnings and precautions

5.1Fatal Overdose

Fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine [see Overdosage (10) ]. GLOPERBA should be kept out of the reach of children.

Interactions

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 ).

7.1CYP3A4

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) ].

7.2P-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) ] .

7.3HMG-CoA Reductase Inhibitors and Fibrates

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

7.4Drug 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).

Gloperba

Indications

Contraindications

Warnings and precautions

5.1Fatal Overdose

At a glance

Two medicines in one question?

Gloperba

Indications

Contraindications

Warnings and precautions

5.1Fatal Overdose

At a glance

Two medicines in one question?

5.2Blood Dyscrasias

5.3Drug Interactions

5.4Neuromuscular Toxicity

Interactions

7.1CYP3A4

7.2P-Glycoprotein

7.3HMG-CoA Reductase Inhibitors and Fibrates

7.4Drug Interaction Studies

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

Composition

Official product information