PMS-COLCHICINE

6mg (1 tablet) one hour later. 8 mg over one-hour period. Wait 12 hours to resume prophylactic dose. Wait at least three days to repeat. The treatment of gout flares with pms-COLCHICINE is not recommended in patients receiving prophylactic dose of colchicine and CYP3A4 inhibitors.

6 mg once or twice daily. 2 mg per day. Use with caution in geriatric patients; reduce prophylactic daily dose by 50% in individuals >70 years. 4 mg daily. 4 mg. 3 mg/day. The total daily dose of pms-COLCHICINE may be administered in one to two divided doses.

Dose Modification for Co-administration of Interacting Drugs Concomitant Therapy:

Co-administration of colchicine with drugs known to inhibit CYP3A4 and/or P-glycoprotein (P-gp) increases the risk of colchicine-induced toxic effects (Table 1). If patients are taking or have recently completed treatment with drugs listed in Table 1 within the prior 14 days, the dose adjustments are as shown on the table below (see Warnings and Drug Interactions).

pms-COLCHICINE Prescribing Information Page 8 of 10 Table 1: Colchicine Dose Adjustment for Co-administration with Interacting Drugs if no Alternative Available1 Drug Noted or Anticipated Outcome Gout Flares FMF Prophylaxis of Gout Flares Treatment of Gout Flares Original Intended Dosage Adjusted Dose Original Intended Dosage Adjusted Dose Original Intended Dosage Adjusted Dose Strong CYP3A4 Inhibitors2 Atazanavir Clarithromycin Darunavir/ Ritonavir3 Indinavir Itraconazole Ketoconazole Lopinavir/ Ritonavir3 Nefazodone Nelfinavir Ritonavir Saquinavir Telithromycin Tipranavir/ Ritonavir3 Significant increase in colchicine plasma levels1; fatal colchicine toxicity has been reported with clarithromycin, a strong CYP3A4 inhibitor.

Similarly, significant increase in colchicines plasma levels is anticipated with other strong CYP3A4 inhibitors. 6 mg (1 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. 3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.

3 mg twice a day) Moderate CYP3A4 Inhibitors Amprenavir3 Aprepitant Diltiazem Erythromycin Fluconazole Fosamprenavir3 (pro-drug of Amprenavir) Grapefruit Juice Verapamil Significant increase in colchicine plasma concentration is anticipated.

Neuromuscular toxicity has been reported with diltiazem and verapamil interactions. 6 mg (1 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. 2 mg (2 tablets) x 1 dose. Dose to be repeated no earlier than 3 days. 4 mg. 6 mg twice a day) P-gp Inhibitors2 Cyclosporine Ranolazine Significant increase in colchicine plasma levels1; fatal colchicine toxicity has been reported with cyclosporine, a P-gp inhibitor.