Drug Detail:Colcrys (Colchicine [ kol-chi-seen ])
Generic Name: Colchicine 0.6mg
Dosage Form: tablet, film coated
Drug Class: Antigout agents
The long-term use of colchicine is established for FMF and the prophylaxis of gout flares, but the safety and efficacy of repeat treatment for gout flares has not been evaluated. The dosing regimens for COLCRYS are different for each indication and must be individualized.
The recommended dosage of COLCRYS depends on the patient's age, renal function, hepatic function and use of coadministered drugs [see Dosage and Administration (2.4, 2.5, 2.6)].
COLCRYS tablets are administered orally without regard to meals.
COLCRYS is not an analgesic medication and should not be used to treat pain from other causes.
Gout Flares
Prophylaxis of Gout Flares
The recommended dosage of COLCRYS for prophylaxis of gout flares for adults and adolescents older than 16 years of age is 0.6 mg once or twice daily. The maximum recommended dose for prophylaxis of gout flares is 1.2 mg/day.
An increase in gout flares may occur after initiation of uric acid-lowering therapy, including pegloticase, febuxostat and allopurinol, due to changing serum uric acid levels resulting in mobilization of urate from tissue deposits. COLCRYS is recommended upon initiation of gout flare prophylaxis with uric acid-lowering therapy. Prophylactic therapy may be beneficial for at least the first six months of uric acid-lowering therapy.
Treatment of Gout Flares
The recommended dose of COLCRYS for treatment of a gout flare is 1.2 mg (two tablets) at the first sign of the flare followed by 0.6 mg (one tablet) one hour later. Higher doses have not been found to be more effective. The maximum recommended dose for treatment of gout flares is 1.8 mg over a 1-hour period. COLCRYS may be administered for treatment of a gout flare during prophylaxis at doses not to exceed 1.2 mg (two tablets) at the first sign of the flare followed by 0.6 mg (one tablet) one hour later. Wait 12 hours and then resume the prophylactic dose.
FMF
The recommended dosage of COLCRYS for FMF in adults is 1.2 mg to 2.4 mg daily.
COLCRYS should be increased as needed to control disease and as tolerated in increments of 0.3 mg/day to a maximum recommended daily dose. If intolerable side effects develop, the dose should be decreased in increments of 0.3 mg/day. The total daily COLCRYS dose may be administered in one to two divided doses.
Recommended Pediatric Dosage
Prophylaxis and Treatment of Gout Flares
COLCRYS is not recommended for pediatric use in prophylaxis or treatment of gout flares.
FMF
The recommended dosage of COLCRYS for FMF in pediatric patients 4 years of age and older is based on age. The following daily doses may be given as a single or divided dose twice daily:
- Children 4 to 6 years: 0.3 mg to 1.8 mg daily
- Children 6 to 12 years: 0.9 mg to 1.8 mg daily
- Adolescents older than 12 years: 1.2 mg to 2.4 mg daily
Dose Modification for Coadministration of Interacting Drugs
Concomitant Therapy
Coadministration of COLCRYS 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 (7)].
| Table 1. COLCRYS Dose Adjustment for Coadministration with Interacting Drugs if No Alternative Available* | |||||||
|---|---|---|---|---|---|---|---|
|
|||||||
| Strong CYP3A4 Inhibitors† | |||||||
| 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 | ||
| Atazanavir Clarithromycin Darunavir/Ritonavir‡ Indinavir Itraconazole Ketoconazole Lopinavir/Ritonavir‡ Nefazodone Nelfinavir Ritonavir Saquinavir Telithromycin Tipranavir/Ritonavir‡ |
Significant increase in colchicine plasma levels*; fatal colchicine toxicity has been reported with clarithromycin, a strong CYP3A4 inhibitor. Similarly, significant increase in colchicine plasma levels is anticipated with other strong CYP3A4 inhibitors. | 0.6 mg twice a day | 0.3 mg once a day | 1.2 mg (2 tablets) followed by 0.6 mg (1 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. | 0.6 mg (1 tablet) × 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 1.2 – 2.4 mg | Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) |
| 0.6 mg once a day | 0.3 mg once every other day | ||||||
| Moderate CYP3A4 Inhibitors | |||||||
| 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 | ||
| 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 | 0.3 mg twice a day or 0.6 mg once a day | 1.2 mg (2 tablets) followed by 0.6 mg (1 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. | 1.2 mg (2 tablets) × 1 dose. Dose to be repeated no earlier than 3 days. | Maximum daily dose of 1.2 – 2.4 mg | Maximum daily dose of 1.2 mg (may be given as 0.6 mg twice a day) |
| 0.6 mg once a day | 0.3 mg once a day | ||||||
| P-gp Inhibitors† | |||||||
| 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 | ||
| 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 | 0.3 mg once a day | 1.2 mg (2 tablets) followed by 0.6 mg (1 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. | 0.6 mg (1 tablet) × 1 dose. Dose to be repeated no earlier than 3 days. | Maximum daily dose of 1.2 – 2.4 mg | Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) |
| 0.6 mg once a day | 0.3 mg once every other day | ||||||
| Table 2. COLCRYS Dose Adjustment for Coadministration with Protease Inhibitors | |||||
|---|---|---|---|---|---|
| Protease Inhibitor | Clinical Comment | w/Colchicine - Prophylaxis of Gout Flares | w/Colchicine - Treatment of Gout Flares | w/Colchicine - Treatment of FMF | |
| Atazanavir sulfate (Reyataz) |
Patients with renal or hepatic impairment should not be given colchicine with Reyataz. | Original dose | Adjusted dose | 0.6 mg (1 tablet) × 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 | ||||
| Darunavir (Prezista) |
Patients with renal or hepatic impairment should not be given colchicine with Prezista/ritonavir. | Original dose | Adjusted dose | 0.6 mg (1 tablet) × 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 (1 tablet) × 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 (2 tablets) × 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 (1 tablet) × 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 (1 tablet) × 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 (1 tablet) × 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 (1 tablet) × 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 (1 tablet) × 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 (1 tablet) × 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 COLCRYS is not recommended in patients receiving prophylactic dose of COLCRYS and CYP3A4 inhibitors.
Dose Modification in Renal Impairment
Colchicine dosing must be individualized according to the patient's renal function [see Use in Specific Populations (8.6)].
Clcr in mL/minute may be estimated from serum creatinine (mg/dL) determination using the following formula:
| [140-age (years) × weight (kg)] | |
| Clcr = | 72 × serum creatinine (mg/dL) × 0.85 for female patients |
Gout Flares
Prophylaxis of Gout Flares
For prophylaxis of gout flares in patients with mild (estimated creatinine clearance [Clcr] 50 to 80 mL/min) to moderate (Clcr 30 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 (12.3), Use in Specific Populations (8.6)].
Treatment of Gout Flares
For treatment of gout flares in patients with mild (Clcr 50 to 80 mL/min) to moderate (Clcr 30 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 (12.3), Use in Specific Populations (8.6)].
Treatment of gout flares with COLCRYS is not recommended in patients with renal impairment who are receiving COLCRYS 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 Clinical Pharmacology (12.3)]. Patients with mild (Clcr 50 to 80 mL/min) and moderate (Clcr 30 to 50 mL/min) renal impairment should be monitored closely for adverse effects of COLCRYS. Dose reduction may be necessary. For patients with severe renal failure (Clcr 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 (8.6)]. 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 (12.3), Use in Specific Populations (8.6)].
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 (8.7)].
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 (8.7)].
Treatment of gout flares with COLCRYS is not recommended in patients with hepatic impairment who are receiving COLCRYS for prophylaxis.
