Colchiceine

Dose Modification in Renal Impairment Colchicine dosing must be individualized according to the patient's renal function [see Use in Specific Populations]. Cl cr in mL/minute may be estimated from serum creatinine (mg/dL) determination using the following formula: Gout Flares Prophylaxis of Gout Flares For prophylaxis of gout flares in patients with mild (estimated creatinine clearance [Cl cr ] 50 mL/min to 80 mL/min) to moderate (Cl cr 30 mL/min to 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine.

However, in patients with severe impairment, the starting dose should be 0.3 mg/day and any increase in dose should be done with close monitoring. For the prophylaxis of gout flares in patients undergoing dialysis, the starting doses should be 0.3 mg given twice a week with close monitoring [see Clinical Pharmacology, Use in Specific Populations] .

Treatment of Gout Flares For treatment of gout flares in patients with mild (Cl cr 50 mL/min to 80 mL/min) to moderate (Cl cr 30 mL/min to 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. However, in patients with severe impairment, while the dose does not need to be adjusted for the treatment of gout flares, a treatment course should be repeated no more than once every two weeks.

For patients with gout flares requiring repeated courses, consideration should be given to alternate therapy. For patients undergoing dialysis, the total recommended dose for the treatment of gout flares should be reduced to a single dose of 0.6 mg (one tablet). For these patients, the treatment course should not be repeated more than once every two weeks [see Clinical Pharmacology, Use in Specific Populations] .

Treatment of gout flares with colchicine tablets are not recommended in patients with renal impairment who are receiving colchicine tablets for prophylaxis. FMF Caution should be taken in dosing patients with moderate and severe renal impairment and in patients undergoing dialysis. For these patients, the dosage should be reduced [see Use in Specific Populations] .

Patients with mild (Cl cr 50 mL/min to 80 mL/min) and moderate (Cl cr 30 mL/min to 50 mL/min) renal impairment should be monitored closely for adverse effects of colchicine. Dose reduction may be necessary. For patients with severe renal failure (Cl cr less than 30 mL/min), start with 0.3 mg/day; any increase in dose should be done with adequate monitoring of the patient for adverse effects of colchicine [see Use in Specific Populations] .

For patients undergoing dialysis, the total recommended starting dose should be 0.3 mg (half tablet) per day. Dosing can be increased with close monitoring. Any increase in dose should be done with adequate monitoring of the patient for adverse effects of colchicine [see Clinical Pharmacology, Use in Specific Populations].

Dose Modification in Hepatic Impairment Gout Flares Prophylaxis of Gout Flares For prophylaxis of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. Dose reduction should be considered for the prophylaxis of gout flares in patients with severe hepatic impairment [see Use in Specific Populations] .

Treatment of Gout Flares For treatment of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. However, for the treatment of gout flares in patients with severe impairment, while the dose does not need to be adjusted, a treatment course should be repeated no more than once every two weeks.

For these patients, requiring repeated courses for the treatment of gout flares, consideration should be given to alternate therapy [see Use in Specific Populations] . Treatment of gout flares with colchicine tablets are not recommended in patients with hepatic impairment who are receiving colchicine tablets for prophylaxis.

FMF Patients with mild to moderate hepatic impairment should be monitored closely for adverse effects of colchicine. Dose reduction should be considered in patients with severe hepatic impairment [see Use in Specific Populations] . Image

Dose Modification for Coadministration of Interacting Drugs Concomitant Therapy Coadministration of colchicine tablets 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 in the table below [see Drug Interactions] . [See table below.] Moderate CYP3A4 Inhibitors Gout Flares FMF Prophylaxis of Gout Flares Treatment of Gout Flares Drug Noted or Anticipated Outcome Original Intended Dosage Adjusted Dose Original Intended Dosage Adjusted Dose Original Intended Dosage Adjusted Dose Amprenavir ‡ Aprepitant Diltiazem Erythromycin Fluconazole Fosamprenavir ‡ (prodrug of Amprenavir) Grapefruit juice Verapamil Significant increase in colchicine plasma concentration is anticipated.

Neuromuscular toxicity has been reported with diltiazem and verapamil interactions. 0.6 mg twice a day 0.6 mg once a day 0.3 mg twice a day or 0.6 mg once a day 0.3 mg once a day 1.2 mg (two tablets) followed by 0.6 mg (one tablet) 1 hour later. Dose to be repeated no earlier than 3 days. 1.2 mg (two tablets) x 1 dose. Dose to be repeated no earlier than 3 days.

Maximum daily dose of 1.2 mg to 2.4 mg Maximum daily dose of 1.2 mg (may be given as 0.6 mg twice a day) P-gp Inhibitors † Gout Flares FMF Prophylaxis of Gout Flares Treatment of Gout Flares Drug Noted or Anticipated Outcome Original Intended Dosage Adjusted Dose Original Intended Dosage Adjusted Dose Original Intended Dosage Adjusted Dose Cyclosporine Ranolazine Significant increase in colchicine plasma levels * ; fatal colchicine toxicity has been reported with cyclosporine, a P-gp inhibitor.

Similarly, significant increase in colchicine plasma levels is anticipated with other P-gp inhibitors. 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day 1.2 mg (two tablets) followed by 0.6 mg (one tablet) 1 hour later. Dose to be repeated no earlier than 3 days. 0.6 mg (one tablet) x 1 dose.

Dose to be repeated no earlier than 3 days. Maximum daily dose of 1.2 mg to 2.4 mg Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) [See table below.] Darunavir (Prezista) Patients with renal or hepatic impairment should not be given colchicine with Prezista/ ritonavir. Original dose Adjusted dose 0.6 mg (one tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later.

Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.3 mg once a day 0.6 mg once a day 0.3 mg once every other day Fosamprenavir (Lexiva) with Ritonavir Patients with renal or hepatic impairment should not be given colchicine with Lexiva/ritonavir.

Original dose Adjusted dose 0.6 mg (one tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.3 mg once a day 0.6 mg once a day 0.3 mg once every other day Fosamprenavir (Lexiva) Patients with renal or hepatic impairment should not be given colchicine with Lexiva/ritonavir.

Original dose Adjusted dose 1.2 mg (two tablets) x 1 dose. Dose to be repeated no earlier than 3 days. Maximum daily dose of 1.2 mg (may be given as 0.6 mg twice a day) 0.6 mg twice a day 0.3 mg twice a day or 0.6 mg once a day 0.6 mg once a day 0.3 mg once a day Indinavir (Crixivan) Patients with renal or hepatic impairment should not be given colchicine with Crixivan.

Original dose Adjusted dose 0.6 mg (one tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.3 mg once a day 0.6 mg once a day 0.3 mg once every other day Lopinavir/ Ritonavir (Kaletra) Patients with renal or hepatic impairment should not be given colchicine with Kaletra Original dose Adjusted dose 0.6 mg (one tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later.

Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.3 mg once a day 0.6 mg once a day 0.3 mg once every other day Nelfinavir mesylate (Viracept) Patients with renal or hepatic impairment should not be given colchicine with Viracept. Original dose Adjusted dose 0.6 mg (one tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later.

Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.3 mg once a day 0.6 mg once a day 0.3 mg once every other day Ritonavir (Norvir) Patients with renal or hepatic impairment should not be given colchicine with Norvir. Original dose Adjusted dose 0.6 mg (one tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later.

Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.3 mg once a day 0.6 mg once a day 0.3 mg once every other day Saquinavir mesylate (Invirase) Patients with renal or hepatic impairment should not be given colchicine with Invirase/ ritonavir.

Original dose Adjusted dose 0.6 mg (one tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.3 mg once a day 0.6 mg once a day 0.3 mg once every other day Tipranavir (Aptivus) Patients with renal or hepatic impairment should not be given colchicine with Aptivus/ ritonavir.

Original dose Adjusted dose 0.6 mg (one tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.3 mg once a day 0.6 mg once a day 0.3 mg once every other day Treatment of gout flares with colchicine tablets are not recommended in patients receiving prophylactic dose of colchicine tablets and CYP3A4 inhibitors.