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Questions & Answers
Side Effects & Adverse Reactions
In the presence of high environmental temperature, heat prostration can occur with drug use (fever and heat stroke due to decreased sweating). Diarrhea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. In this instance, treatment with this drug would be inappropriate and possibly harmful. Like other anticholinergic agents, hyoscyamine sulfate may produce drowsiness, dizziness or blurred vision. In this event, the patient should be warned not to engage in activities requiring mental alertness such as operating a motor vehicle or other machinery or to perform hazardous work while taking this drug.
Psychosis has been reported in sensitive individuals given anticholinergic drugs including hyoscyamine sulfate. CNS signs and symptoms include confusion, disorientation, short-term memory loss, hallucinations, dysarthria, ataxia, coma, euphoria, anxiety, decreased anxiety, fatigue, insomnia, agitation and mannerisms and inappropriate affect. These CNS signs and symptoms usually resolve within 12 to 48 hours after discontinuation of the drug.
Legal Issues
There is currently no legal information available for this drug.
FDA Safety Alerts
There are currently no FDA safety alerts available for this drug.
Manufacturer Warnings
There is currently no manufacturer warning information available for this drug.
FDA Labeling Changes
There are currently no FDA labeling changes available for this drug.
Uses
Hyoscyamine Sulfate Tablets, USP are effective as adjunctive therapy in the treatment of peptic ulcer. They can also be used to control gastric secretions, visceral spasm and hypermotility in spastic colitis, spastic bladder, cystitis, pylorospasm and associated abdominal cramps. May be used in functional intestinal disorders to reduce symptoms such as those seen in mild dysenteries, diverticulitis and acute enterocolitis. For use as adjunctive therapy in the treatment of irritable bowel syndrome (irritable colon, spastic colon, mucous colitis) and functional gastrointestinal disorders. Also used as adjunctive therapy in the treatment of neurogenic bladder and neurogenic bowel disturbances (including the splenic flexure syndrome and neurogenic colon). Hyoscyamine Sulfate Tablets, USP are indicated along with morphine or other narcotics in symptomatic relief of biliary and renal colic; as a “drying agent” in the relief of symptoms of acute rhinitis; in the therapy of parkinsonism to reduce rigidity and tremors and to control associated sialorrhea and hyperhidrosis. May be used in the therapy of poisoning by anticholinesterase agents.
History
There is currently no drug history available for this drug.
Other Information
Hyoscyamine Sulfate Tablets, USP contain 0.125 mg hyoscyamine sulfate formulated for oral administration.
Hyoscyamine sulfate is one of the principal anticholinergic/antispasmodic components of belladonna alkaloids. The empirical formula is (C17H23NO3)2•H2SO4•2H2O and the molecular weight is 712.85. Chemically, it is benzeneacetic acid, α-(hydroxymethyl)-, 8-methyl-8-azabicyclo [3.2.1] oct-3-yl ester, [3(S)-endo]-, sulfate (2:1), dihydrate with the following structure:
Each tablet also contains as inactive ingredients: Colloidal silicon dioxide, crospovidone, magnesium stearate and microcrystalline cellulose.
Sources
Colcrys Manufacturers
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Proficient Rx Lp
![Colcrys (Colchicine) Tablet, Film Coated [Proficient Rx Lp]](/wp-content/themes/bootstrap/assets/img/loading2.gif)
Colcrys | Proficient Rx Lp
Dosage may be adjusted according to the conditions and severity of symptoms.
Adults and pediatric patients 12 years of age and older: 1 to 2 tablets every four hours or as needed. Do not exceed 12 tablets in 24 hours.
Pediatric patients 2 to under 12 years of age: 1/2 to 1 tablet every four hours or as needed. Do not exceed 6 tablets in 24 hours.
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Physicians Total Care, Inc.
Colcrys | Physicians Total Care, Inc.
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 co-administered drugs [see Dose Modification for Co-administration of Interacting Drugs (2.4)].
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.
2.1 Gout FlaresProphylaxis 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.
Treatment of Gout Flares:
The recommended dose of COLCRYS for treatment of a gout flare is 1.2 mg (2 tablets) at the first sign of the flare followed by 0.6 mg (1 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 (2 tablets) at the first sign of the flare followed by 0.6 mg (1 tablet) one hour later. Wait 12 hours and then resume the prophylactic dose.
2.2 FMFThe 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.
2.3 Recommended Pediatric DosageProphylaxis 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 – 6 years: 0.3 mg to 1.8 mg daily Children 6 – 12 years: 0.9 mg to 1.8 mg daily Adolescents older than 12 years: 1.2 mg to 2.4 mg daily 2.4 Dose Modification for Co-administration of Interacting DrugsConcomitant Therapy:
Co-administration 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 on the table below [see DRUG INTERACTIONS (7)].
Table 1 COLCRYS Dose Adjustment for Co-administration with Interacting Drugs if no Alternative Available* Strong CYP3A4 Inhibitors† * For magnitude of effect on colchicine plasma concentrations [ see Pharmacokinetics (12.3)] † Patients with renal or hepatic impairment should not be given COLCRYS in conjunction with strong CYP3A4 or P-gp inhibitors [ see CONTRAINDICATIONS (4)]. ‡ When used in combination with Ritonavir, see dosing recommendations for strong CYP3A4 inhibitors [ see CONTRAINDICATIONS (4)]. 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
0.6 mg once a day
0.3 mg once a day
0.3 mg once every other 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) 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‡
(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. 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
(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) 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
0.6 mg once a day
0.3 mg once a day
0.3 mg once every other 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) Table 2 COLCRYS Dose Adjustment for Co-administration 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 mg once a day
0.3 mg once every other dayTreatment of gout flares with COLCRYS is not recommended in patients receiving prophylactic dose of COLCRYS and CYP3A4 inhibitors.
2.5 Dose Modification in Renal ImpairmentColchicine dosing must be individualized according to the patient's renal function [see Renal Impairment (8.6)].
Clcr in mL/minute may be estimated from serum creatinine (mg/dL) determination using the following formula:
Clcr = [140-age (years) × weight (kg)] × 0.85 for female patients 72 × serum creatinine (mg/dL)Gout Flares:
Prophylaxis of Gout Flares:
For prophylaxis of gout flares in patients with mild (estimated creatinine clearance Clcr 50 – 80 mL/min) to moderate (Clcr 30 – 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 per 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) and Renal Impairment (8.6)].
Treatment of Gout Flares:
For treatment of gout flares in patients with mild (Clcr 50 – 80 mL/min) to moderate (Clcr 30 – 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 2 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 (1 tablet). For these patients, the treatment course should not be repeated more than once every 2 weeks [see Clinical Pharmacology (12.3) and Renal Impairment (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 – 80 mL/min) and moderate (Clcr 30 – 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/minute), 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 Renal Impairment (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) and Renal Impairment (8.6)].
2.6 Dose Modification in Hepatic ImpairmentGout 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 Hepatic Impairment (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, but a treatment course should be repeated no more than once every 2 weeks. For these patients, requiring repeated courses for the treatment of gout flares, consideration should be given to alternate therapy [see Hepatic Impairment (8.7)].
Treatment of gout flares with COLCRYS is not recommended in patients with hepatic impairment who are receiving COLCRYS 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 Hepatic Impairment (8.7)].
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Ar Scientific Inc.
Colcrys | Ar Scientific Inc.
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 co-administered drugs [see Dose Modification for Co-administration of Interacting Drugs (2.4)].
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.
2.1 Gout FlaresProphylaxis 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.
Treatment of Gout Flares:
The recommended dose of COLCRYS for treatment of a gout flare is 1.2 mg (2 tablets) at the first sign of the flare followed by 0.6 mg (1 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 (2 tablets) at the first sign of the flare followed by 0.6 mg (1 tablet) one hour later. Wait 12 hours and then resume the prophylactic dose.
2.2 FMFThe 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.
2.3 Recommended Pediatric DosageProphylaxis 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 – 6 years: 0.3 mg to 1.8 mg daily Children 6 – 12 years: 0.9 mg to 1.8 mg daily Adolescents older than 12 years: 1.2 mg to 2.4 mg daily 2.4 Dose Modification for Co-administration of Interacting DrugsConcomitant Therapy:
Co-administration 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 on the table below [see DRUG INTERACTIONS (7)].
Table 1 COLCRYS Dose Adjustment for Co-administration with Interacting Drugs if no Alternative Available* Strong CYP3A4 Inhibitors† * For magnitude of effect on colchicine plasma concentrations [ see Pharmacokinetics (12.3)] † Patients with renal or hepatic impairment should not be given COLCRYS in conjunction with strong CYP3A4 or P-gp inhibitors [ see CONTRAINDICATIONS (4)]. ‡ When used in combination with Ritonavir, see dosing recommendations for strong CYP3A4 inhibitors [ see CONTRAINDICATIONS (4)]. 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
0.6 mg once a day
0.3 mg once a day
0.3 mg once every other 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) 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‡
(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. 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
(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) 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
0.6 mg once a day
0.3 mg once a day
0.3 mg once every other 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) Table 2 COLCRYS Dose Adjustment for Co-administration 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 mg once a day
0.3 mg once every other dayTreatment of gout flares with COLCRYS is not recommended in patients receiving prophylactic dose of COLCRYS and CYP3A4 inhibitors.
2.5 Dose Modification in Renal ImpairmentColchicine dosing must be individualized according to the patient's renal function [see Renal Impairment (8.6)].
Clcr in mL/minute may be estimated from serum creatinine (mg/dL) determination using the following formula:
Clcr = [140-age (years) × weight (kg)] × 0.85 for female patients 72 × serum creatinine (mg/dL)Gout Flares:
Prophylaxis of Gout Flares:
For prophylaxis of gout flares in patients with mild (estimated creatinine clearance Clcr 50 – 80 mL/min) to moderate (Clcr 30 – 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 per 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) and Renal Impairment (8.6)].
Treatment of Gout Flares:
For treatment of gout flares in patients with mild (Clcr 50 – 80 mL/min) to moderate (Clcr 30 – 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 2 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 (1 tablet). For these patients, the treatment course should not be repeated more than once every 2 weeks [see Clinical Pharmacology (12.3) and Renal Impairment (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 – 80 mL/min) and moderate (Clcr 30 – 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/minute), 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 Renal Impairment (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) and Renal Impairment (8.6)].
2.6 Dose Modification in Hepatic ImpairmentGout 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 Hepatic Impairment (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, but a treatment course should be repeated no more than once every 2 weeks. For these patients, requiring repeated courses for the treatment of gout flares, consideration should be given to alternate therapy [see Hepatic Impairment (8.7)].
Treatment of gout flares with COLCRYS is not recommended in patients with hepatic impairment who are receiving COLCRYS 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 Hepatic Impairment (8.7)].
-
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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 co-administered drugs [see Dose Modification for Co-administration of Interacting Drugs (2.4)].
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.
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.
Treatment of Gout Flares:
The recommended dose of COLCRYS for treatment of a gout flare is 1.2 mg (2 tablets) at the first sign of the flare followed by 0.6 mg (1 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 (2 tablets) at the first sign of the flare followed by 0.6 mg (1 tablet) one hour later. Wait 12 hours and then resume the prophylactic dose.
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.
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 – 6 years: 0.3 mg to 1.8 mg daily Children 6 – 12 years: 0.9 mg to 1.8 mg daily Adolescents older than 12 years: 1.2 mg to 2.4 mg dailyConcomitant Therapy:
Co-administration 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 on the table below [see DRUG INTERACTIONS (7)].
Table 1 COLCRYS Dose Adjustment for Co-administration 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/
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 colchicine plasma levels is anticipated with other strong CYP3A4 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
(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) 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 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. 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
(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) P-gp Inhibitors2 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 levels1; 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
(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) Table 2 COLCRYS Dose Adjustment for Co-administration 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 mg once a day
0.3 mg once every other dayTreatment of gout flares with COLCRYS is not recommended in patients receiving prophylactic dose of COLCRYS and CYP3A4 inhibitors.
Colchicine dosing must be individualized according to the patient's renal function [see Renal Impairment (8.6)].
Clcr in mL/minute may be estimated from serum creatinine (mg/dL) determination using the following formula:
Clcr = [140-age (years) × weight (kg)] × 0.85 for female patients 72 × serum creatinine (mg/dL)Gout Flares:
Prophylaxis of Gout Flares:
For prophylaxis of gout flares in patients with mild (estimated creatinine clearance Clcr 50 – 80 mL/min) to moderate (Clcr 30 – 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 per 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) and Renal Impairment (8.6)].
Treatment of Gout Flares:
For treatment of gout flares in patients with mild (Clcr 50 – 80 mL/min) to moderate (Clcr 30 – 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 2 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 (1 tablet). For these patients, the treatment course should not be repeated more than once every 2 weeks [see Clinical Pharmacology (12.3) and Renal Impairment (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 – 80 mL/min) and moderate (Clcr 30 – 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/minute), 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 Renal Impairment (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) and Renal Impairment (8.6)].
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 Hepatic Impairment (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, but a treatment course should be repeated no more than once every 2 weeks. For these patients, requiring repeated courses for the treatment of gout flares, consideration should be given to alternate therapy [see Hepatic Impairment (8.7)].
Treatment of gout flares with COLCRYS is not recommended in patients with hepatic impairment who are receiving COLCRYS 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 Hepatic Impairment (8.7)].
1 For magnitude of effect on colchicine plasma concentrations [ 2 Patients with renal or hepatic impairment should not be given COLCRYS in conjunction with strong CYP3A4 or P-gp inhibitors [ 3 When used in combination with Ritonavir, see dosing recommendations for strong CYP3A4 inhibitors [ -
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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 co-administered drugs [see Dose Modification for Co-administration of Interacting Drugs (2.4)].
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.
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.
Treatment of Gout Flares:
The recommended dose of COLCRYS for treatment of a gout flare is 1.2 mg (2 tablets) at the first sign of the flare followed by 0.6 mg (1 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 (2 tablets) at the first sign of the flare followed by 0.6 mg (1 tablet) one hour later. Wait 12 hours and then resume the prophylactic dose.
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.
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 – 6 years: 0.3 mg to 1.8 mg daily Children 6 – 12 years: 0.9 mg to 1.8 mg daily Adolescents older than 12 years: 1.2 mg to 2.4 mg dailyConcomitant Therapy:
Co-administration 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 on the table below [see DRUG INTERACTIONS (7)].
Table 1 COLCRYS Dose Adjustment for Co-administration 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/
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 colchicine plasma levels is anticipated with other strong CYP3A4 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
(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) 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 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. 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
(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) P-gp Inhibitors2 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 levels1; 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
(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)1
2
3
Table 2 COLCRYS Dose Adjustment for Co-administration 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 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
0.6 mg once a day 0.3 mg once a day
0.3 mg once every other dayTreatment of gout flares with COLCRYS is not recommended in patients receiving prophylactic dose of COLCRYS and CYP3A4 inhibitors.
Colchicine dosing must be individualized according to the patient's renal function [see Renal Impairment (8.6)].
Clcr in mL/minute may be estimated from serum creatinine (mg/dL) determination using the following formula:
Clcr = [140-age (years) × weight (kg)] × 0.85 for female patients 72 × serum creatinine (mg/dL)Gout Flares:
Prophylaxis of Gout Flares:
For prophylaxis of gout flares in patients with mild (estimated creatinine clearance Clcr 50 – 80 mL/min) to moderate (Clcr 30 – 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 per 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) and Renal Impairment (8.6)].
Treatment of Gout Flares:
For treatment of gout flares in patients with mild (Clcr 50 – 80 mL/min) to moderate (Clcr 30 – 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 2 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 (1 tablet). For these patients, the treatment course should not be repeated more than once every 2 weeks [see Clinical Pharmacology (12.3) and Renal Impairment (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 – 80 mL/min) and moderate (Clcr 30 – 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/minute), 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 Renal Impairment (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) and Renal Impairment (8.6)].
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 Hepatic Impairment (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, but a treatment course should be repeated no more than once every 2 weeks. For these patients, requiring repeated courses for the treatment of gout flares, consideration should be given to alternate therapy [see Hepatic Impairment (8.7)].
Treatment of gout flares with COLCRYS is not recommended in patients with hepatic impairment who are receiving COLCRYS 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 Hepatic Impairment (8.7)].
1 For magnitude of effect on colchicine plasma concentrations [ 2 Patients with renal or hepatic impairment should not be given COLCRYS in conjunction with strong CYP3A4 or P-gp inhibitors [ 3 When used in combination with Ritonavir, see dosing recommendations for strong CYP3A4 inhibitors [ -
Takeda Pharmaceuticals America, Inc.
Colcrys | Brigham And Women`s Hospital, Inc., The
Fludeoxyglucose F18 Injection emits radiation. Use procedures to minimize radiation exposure. Calculate the final dose from the end of synthesis (EOS) time using proper radioactive decay factors. Assay the final dose in a properly calibrated dose calibrator before administration to the patient [see Description(11.2)].
2.1 Recommended Dose for AdultsWithin the oncology, cardiology and neurology settings, the recommended dose for adults is 5 – 10 mCi (185 – 370 MBq) as an intravenous injection.
2.2 Recommended Dose for Pediatric PatientsWithin the neurology setting, the recommended dose for pediatric patients is 2.6 mCi, as an intravenous injection. The optimal dose adjustment on the basis of body size or weight has not been determined [see Use in Special Populations(8.4)].
2.3 Patient Preparation To minimize the radiation absorbed dose to the bladder, encourage adequate hydration. Encourage the patient to drink water or other fluids (as tolerated) in the 4 hours before their PET study. Encourage the patient to void as soon as the imaging study is completed and as often as possible thereafter for at least one hour. Screen patients for clinically significant blood glucose abnormalities by obtaining a history and/or laboratory tests [see Warnings and Precautions(5.2)]. Prior to Fludeoxyglucose F 18 PET imaging in the oncology and neurology settings, instruct patient to fast for 4 – 6 hours prior to the drug’s injection. In the cardiology setting, administration of glucose-containing food or liquids (e.g., 50 – 75 grams) prior to Fludeoxyglucose F 18 Injection facilitates localization of cardiac ischemia. 2.4 Radiation DosimetryThe estimated human absorbed radiation doses (rem/mCi) to a newborn (3.4 kg), 1-year old (9.8 kg), 5-year old (19 kg), 10-year old (32 kg), 15-year old (57 kg), and adult (70 kg) from intravenous administration of Fludeoxyglucose F 18 Injection are shown in Table 1. These estimates were calculated based on human2 data and using the data published by the International Commission on Radiological Protection4 for Fludeoxyglucose 18F. The dosimetry data show that there are slight variations in absorbed radiation dose for various organs in each of the age groups. These dissimilarities in absorbed radiation dose are due to developmental age variations (e.g., organ size, location, and overall metabolic rate for each age group). The identified critical organs (in descending order) across all age groups evaluated are the urinary bladder, heart, pancreas, spleen, and lungs.
Table 1. Estimated Absorbed Radiation Doses (rem/mCi) After Intravenous Administration of Fludeoxyglucose F 18 Injection * Organ Newborn
(3.4 kg) 1-year old
(9.8 kg) 5-year old
(19 kg) 10-year old
(32 kg) 15-year old
(57 kg) Adult
(70 kg) * MIRDOSE 2 software was used to calculate the radiation absorbed dose. Assumptions on the biodistribution based on data from Gallagher et al.1 and Jones et al.2 † The dynamic bladder model with a uniform voiding frequency of 1.5 hours was used. ‡ LLI = lower large intestine; § ULI = upper large intestine Bladder wall† 4.3 1.7 0.93 0.60 0.40 0.32 Heart wall 2.4 1.2 0.70 0.44 0.29 0.22 Pancreas 2.2 0.68 0.33 0.25 0.13 0.096 Spleen 2.2 0.84 0.46 0.29 0.19 0.14 Lungs 0.96 0.38 0.20 0.13 0.092 0.064 Kidneys 0.81 0.34 0.19 0.13 0.089 0.074 Ovaries 0.80 0.8 0.19 0.11 0.058 0.053 Uterus 0.79 0.35 0.19 0.12 0.076 0.062 LLI wall‡ 0.69 0.28 0.15 0.097 0.060 0.051 Liver 0.69 0.31 0.17 0.11 0.076 0.058 Gallbladder wall 0.69 0.26 0.14 0.093 0.059 0.049 Small intestine 0.68 0.29 0.15 0.096 0.060 0.047 ULI wall§ 0.67 0.27 0.15 0.090 0.057 0.046 Stomach wall 0.65 0.27 0.14 0.089 0.057 0.047 Adrenals 0.65 0.28 0.15 0.095 0.061 0.048 Testes 0.64 0.27 0.14 0.085 0.052 0.041 Red marrow 0.62 0.26 0.14 0.089 0.057 0.047 Thymus 0.61 0.26 0.14 0.086 0.056 0.044 Thyroid 0.61 0.26 0.13 0.080 0.049 0.039 Muscle 0.58 0.25 0.13 0.078 0.049 0.039 Bone surface 0.57 0.24 0.12 0.079 0.052 0.041 Breast 0.54 0.22 0.11 0.068 0.043 0.034 Skin 0.49 0.20 0.10 0.060 0.037 0.030 Brain 0.29 0.13 0.09 0.078 0.072 0.070 Other tissues 0.59 0.25 0.13 0.083 0.052 0.042 2.5 Radiation Safety – Drug Handling Use waterproof gloves, effective radiation shielding, and appropriate safety measures when handling Fludeoxyglucose F18 Injection to avoid unnecessary radiation exposure to the patient, occupational workers, clinical personnel and other persons. Radiopharmaceuticals should be used by or under the control of physicians who are qualified by specific training and experience in the safe use and handling of radionuclides, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radionuclides. Calculate the final dose from the end of synthesis (EOS) time using proper radioactive decay factors. Assay the final dose in a properly calibrated dose calibrator before administration to the patient [see Description (11.2)]. The dose of Fludeoxyglucose F18 used in a given patient should be minimized consistent with the objectives of the procedure, and the nature of the radiation detection devices employed. 2.6 Drug Preparation and Administration Calculate the necessary volume to administer based on calibration time and dose. Aseptically withdraw Fludeoxyglucose F18 Injection from its container. Inspect Fludeoxyglucose F18 Injection visually for particulate matter and discoloration before administration, whenever solution and container permit. Do not administer the drug if it contains particulate matter or discoloration; dispose of these unacceptable or unused preparations in a safe manner, in compliance with applicable regulations. Use Fludeoxyglucose F 18 Injection within 12 hours from the EOS. 2.7 Imaging Guidelines Initiate imaging within 40 minutes following Fludeoxyglucose F 18 Injection administration. Acquire static emission images 30 – 100 minutes from the time of injection. -
Aphena Pharma Solutions – Tennessee, Llc
Colcrys | Aphena Pharma Solutions - Tennessee, Llc
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 co-administered drugs [see Dose Modification for Co-administration of Interacting Drugs (2.4)].
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.
2.1 Gout FlaresProphylaxis 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.
Treatment of Gout Flares:
The recommended dose of COLCRYS for treatment of a gout flare is 1.2 mg (2 tablets) at the first sign of the flare followed by 0.6 mg (1 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 (2 tablets) at the first sign of the flare followed by 0.6 mg (1 tablet) one hour later. Wait 12 hours and then resume the prophylactic dose.
2.2 FMFThe 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.
2.3 Recommended Pediatric DosageProphylaxis 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 – 6 years: 0.3 mg to 1.8 mg daily • Children 6 – 12 years: 0.9 mg to 1.8 mg daily • Adolescents older than 12 years: 1.2 mg to 2.4 mg daily 2.4 Dose Modification for Co-administration of Interacting DrugsConcomitant Therapy:
Co-administration 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 on the table below [see DRUG INTERACTIONS (7)].
Table 1 COLCRYS Dose Adjustment for Co-administration with Interacting Drugs if no Alternative Available* * For magnitude of effect on colchicine plasma concentrations [ see Pharmacokinetics (12.3)] † Patients with renal or hepatic impairment should not be given COLCRYS in conjunction with strong CYP3A4 or P-gp inhibitors [ see CONTRAINDICATIONS (4)]. ‡ When used in combination with Ritonavir, see dosing recommendations for strong CYP3A4 inhibitors [ see CONTRAINDICATIONS (4)].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
0.6 mg once a day0.3 mg once a day
0.3 mg once every other day1.2 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)
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‡
(pro-drug of
Amprenavir)
Grapefruit Juice
VerapamilSignificant 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 day0.3 mg twice a day or 0.6 mg once a day
0.3 mg once a day1.2 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)
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
0.6 mg once a day0.3 mg once a day
0.3 mg once every other day1.2 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)
Table 2 COLCRYS Dose Adjustment for Co-administration with Protease InhibitorsProtease Inhibitor
Clinical Comment
w/Colchicine – Prophylaxis of Gout Flares
w/Colchicine –
Treatment of Gout Flaresw/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
0.6 mg once a day0.3 mg once a day
0.3 mg once every other dayDarunavir (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
0.6 mg once a day0.3 mg once a day
0.3 mg once every other dayFosamprenavir (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
0.6 mg once a day0.3 mg once a day
0.3 mg once every other dayFosamprenavir (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
0.6 mg once a day0.3 mg twice a day or 0.6 mg once a day
0.3 mg once a dayIndinavir (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
0.6 mg once a day0.3 mg once a day
0.3 mg once every other dayLopinavir/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
0.6 mg once a day0.3 mg once a day
0.3 mg once every other dayNelfinavir 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
0.6 mg once a day0.3 mg once a day
0.3 mg once every other dayRitonavir (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
0.6 mg once a day0.3 mg once a day
0.3 mg once every other daySaquinavir 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
0.6 mg once a day0.3 mg once a day
0.3 mg once every other dayTipranavir (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
0.6 mg once a day0.3 mg once a day
0.3 mg once every other dayTreatment of gout flares with COLCRYS is not recommended in patients receiving prophylactic dose of COLCRYS and CYP3A4 inhibitors.
2.5 Dose Modification in Renal ImpairmentColchicine dosing must be individualized according to the patient's renal function [see Renal Impairment (8.6)].
Clcr in mL/minute may be estimated from serum creatinine (mg/dL) determination using the following formula:
Clcr =
[140-age (years) × weight (kg)]
× 0.85 for female patients
72 × serum creatinine (mg/dL)
Gout Flares:
Prophylaxis of Gout Flares:
For prophylaxis of gout flares in patients with mild (estimated creatinine clearance Clcr 50 – 80 mL/min) to moderate (Clcr 30 – 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 per 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) and Renal Impairment (8.6)].
Treatment of Gout Flares:
For treatment of gout flares in patients with mild (Clcr 50 – 80 mL/min) to moderate (Clcr 30 – 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 2 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 (1 tablet). For these patients, the treatment course should not be repeated more than once every 2 weeks [see Clinical Pharmacology (12.3) and Renal Impairment (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 – 80 mL/min) and moderate (Clcr 30 – 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/minute), 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 Renal Impairment (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) and Renal Impairment (8.6)].
2.6 Dose Modification in Hepatic ImpairmentGout 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 Hepatic Impairment (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, but a treatment course should be repeated no more than once every 2 weeks. For these patients, requiring repeated courses for the treatment of gout flares, consideration should be given to alternate therapy [see Hepatic Impairment (8.7)].
Treatment of gout flares with COLCRYS is not recommended in patients with hepatic impairment who are receiving COLCRYS 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 Hepatic Impairment (8.7)].
-
Cardinal Health
Colcrys | Apotex Corp.
2.1 Important Administration Instructions Cefuroxime axetil tablets and Cefuroxime axetil for suspension are not bioequivalent and are therefore not substitutable on a milligram-per-milligram basis [see Clinical Pharmacology (12.3)]. Administer cefuroxime axetil tablets as described in the appropriate dosage guidelines [see Dosage and Administration (2.2, 2.3, 2.4)]. Administer cefuroxime axetil tablets with or without food. Pediatric patients (aged 13 years and older) who cannot swallow the cefuroxime axetil tablets whole should receive cefuroxime axetil for oral suspension because the tablet has a strong, persistent bitter taste when crushed [see Dosage and Administration (2.2)]. 2.2 Dosage for Cefuroxime Axetil TabletsAdminister cefuroxime axetil tablets as described in the dosage guidelines table below with or without food.
Table 1. Adult Patients and Pediatric Patients Dosage Guidelines for Cefuroxime Axetil Tablets
Infection Dosage Duration (Days) Adults and Adolescents (13 years and older) Pharyngitis/tonsillitis (mild to moderate) 250 mg every 12 hours 10 Acute bacterial maxillary sinusitis (mild to moderate) 250 mg every 12 hours 10 Acute bacterial exacerbations of chronic bronchitis (mild 250 or 500 mg every 12 hours 10a to moderate) Secondary bacterial infections of acute bronchitis 250 or 500 mg every 12 hours 5 to 10 Uncomplicated skin and skin-structure infections 250 or 500 mg every 12 hours 10 Uncomplicated urinary tract infections 250 mg every 12 hours 7 to 10 Uncomplicated gonorrhea 1,000 mg single dose Early Lyme disease 500 mg every 12 hours 20 Pediatric Patients younger than 13 years (who can swallow tablets whole)b Acute bacterial otitis media 250 mg every 12 hours 10 Acute bacterial maxillary sinusitis 250 mg every 12 hours 10a The safety and effectiveness of cefuroxime axetil administered for less than 10 days in patients with acute exacerbations of chronic bronchitis have not been established.
b When crushed, the tablet has a strong, persistent bitter taste. Therefore, patients who cannot swallow the tablet whole should receive the oral suspension.
2.5 Dosage in Patients with Impaired Renal FunctionA dosage interval adjustment is required for patients whose creatinine clearance is <30 mL/min, as listed in Table 4 below, because cefuroxime is eliminated primarily by the kidney [see Clinical Pharmacology (12.3)].
Table 4. Dosing in Adults with Renal Impairment
Creatinine Clearance (mL/min) Recommended Dosage ≥30 No dosage adjustment 10 to <30 Standard individual dose given every 24 hours <10 Standard individual dose given every 24 hours Hemodialysis A single additional standard dose should be given at the end of each dialysis
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