Drug: Colcrys

Colchicine is an alkaloid chemically described as (S)N-(5,6,7,9-tetrahydro-1,2,3, 10-tetramethoxy-9-oxobenzo [alpha] heptalen-7-yl) acetamide with a molecular formula of C22H25NO6 and a molecular weight of 399.4. The structural formula of colchicine is given below. Colchicine occurs as a pale yellow powder that is soluble in water. COLCRYS (colchicine, USP) tablets are supplied for oral administration as purple, film-coated, capsule-shaped tablets (0.1575” x 0.3030”), debossed with “AR 374” on one side and scored on the other, containing 0.6 mg of the active ingredient colchicine USP. Inactive ingredients: carnauba wax, FD&C blue #2, FD&C red #40, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, pregelatinized starch, sodium starch glycolate, titanium dioxide and triacetin.

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Prophylaxis of Gout Flares The most commonly reported adverse reaction in clinical trials of colchicine for the prophylaxis of gout was diarrhea. Treatment of Gout Flares The most common adverse reactions reported in the clinical trial with COLCRYS for treatment of gout flares were diarrhea (23%) and pharyngolaryngeal pain (3%). FMF Gastrointestinal tract adverse effects are the most frequent side effects in patients initiating COLCRYS, usually presenting within 24 hours, and occurring in up to 20% of patients given therapeutic doses. Typical symptoms include cramping, nausea, diarrhea, abdominal pain and vomiting. These events should be viewed as dose-limiting if severe, as they can herald the onset of more significant toxicity. Clinical Trials Experience In Gout Because clinical studies are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not predict the rates observed in a broader patient population in clinical practice. In a randomized, double-blind, placebo-controlled trial in patients with a gout flare, gastrointestinal adverse reactions occurred in 26% of patients using the recommended dose (1.8 mg over one hour) of COLCRYS compared to 77% of patients taking a nonrecommended high dose (4.8 mg over six hours) of colchicine and 20% of patients taking placebo. Diarrhea was the most commonly reported drug-related gastrointestinal adverse event. As shown in Table 3, diarrhea is associated with COLCRYS treatment. Diarrhea was more likely to occur in patients taking the high-dose regimen than the low-dose regimen. Severe diarrhea occurred in 19% and vomiting occurred in 17% of patients taking the nonrecommended high-dose colchicine regimen but did not occur in the recommended low-dose COLCRYS regimen. Table 3: Number (%) of Patients with at Least One Drug-Related Treatment-Emergent Adverse Event with an Incidence of ≥ 2% of Patients in Any Treatment Group
MedDRA System Organ Class MedDRA Preferred Term COLCRYS Dose Placebo
(N=59)
n (%) High
(N=52)
n (%) Low
(N=74)
n (%) Number of Patients with at Least One Drug-Related TEAE 40 (77) 27 (37) 16 (27) Gastrointestinal Disorders 40 (77) 19 (26) 12 (20)   Diarrhea 40 (77) 17 (23) 8 (14)   Nausea 9 (17) 3 (4) 3 (5)   Vomiting 9 (17) 0 0   Abdominal Discomfort 0 0 2 (3) General Disorders and Administration Site Conditions 4 (8) 1 (1) 1 (2)   Fatigue 2 (4) 1 (1) 1 (2) Metabolic and Nutrition Disorders 0 3 (4) 2 (3)   Gout 0 3 (4) 1 (2) Nervous System Disorders 1 (2) 1 (1.4) 2 (3)   Headache 1 (2) 1 (1) 2 (3) Respiratory Thoracic Mediastinal Disorders 1 (2) 2 (3) 0   Pharyngolaryngeal Pain 1 (2) 2 (3) 0 Postmarketing Experience Serious toxic manifestations associated with colchicine include myelosuppression, disseminated intravascular coagulation and injury to cells in the renal, hepatic, circulatory and central nervous systems. These most often occur with excessive accumulation or overdosage [see OVERDOSAGE]. The following adverse reactions have been reported with colchicine. These have been generally reversible upon temporarily interrupting treatment or lowering the dose of colchicine. Neurological: sensory motor neuropathy Dermatological: alopecia, maculopapular rash, purpura, rash Digestive: abdominal cramping, abdominal pain, diarrhea, lactose intolerance, nausea, vomiting Hematological: leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, aplastic anemia Hepatobiliary: elevated AST, elevated ALT Musculoskeletal: myopathy, elevated CPK, myotonia, muscle weakness, muscle pain, rhabdomyolysis Reproductive: azoospermia, oligospermia Read the Colcrys (colchicine tablets) Side Effects Center for a complete guide to possible side effectsLearn More »

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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 coadministered drugs [see Dose Modification for Coadministration of Interacting Drugs]. 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 one-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]. 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 0.6 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) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 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) x 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) x 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) *For magnitude of effect on colchicine plasma concentrations [see Pharmacokinetics]
†Patients with renal or hepatic impairment should not be given COLCRYS in conjunction with strong CYP3A4 or P-gp inhibitors [see CONTRAINDICATIONS]
‡When us ed in combination with Ritonavir, see dosing recommendations for strong CYP3A4 inhibitors [see CONTRAINDICATIONS] 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) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day
0.6 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) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day
0.6 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) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day
0.6 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) x 1 dose. Dose to be repeated no earlier than 3 days. Maximum daily dose of 1.2 mg (may be given as 0.6 mg twice a day) 0.6 mg twice a day
0.6 mg once a day 0.3 mg twice a day or 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) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day
0.6 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) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day
0.6 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) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day
0.6 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) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day
0.6 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) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day
0.6 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) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day
0.6 mg once a day 0.3 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 Renal Impairment]. Clcr in mL/minute may be estimated from serum creatinine (mg/dL) determination using the following formula: Males: (weight in kg) x (140 – age) (72) x serum creatinine (mg/100 mL) Females (0.85) x (above value) 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 and Renal Impairment]. 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 and Renal Impairment]. 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]. 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 Renal Impairment]. 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 and Renal Impairment]. 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 Hepatic Impairment]. 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 Hepatic Impairment]. 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].

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COLCRYS (colchicine) is a substrate of the efflux transporter P-glycoprotein (P-gp). Of the cytochrome P450 enzymes tested, CYP3A4 was mainly involved in the metabolism of colchicine. If COLCRYS is administered with drugs that inhibit P-gp, most of which also inhibit CYP3A4, increased concentrations of colchicine are likely. Fatal drug interactions have been reported. Physicians should ensure that patients are suitable candidates for treatment with COLCRYS and remain alert for signs and symptoms of toxicities related to increased colchicine exposure as a result of a drug interaction. Signs and symptoms of COLCRYS toxicity should be evaluated promptly and, if toxicity is suspected, COLCRYS should be discontinued immediately. Table 4 provides recommendations as a result of other potentially significant drug interactions. Table 1 provides recommendations for strong and moderate CYP3A4 inhibitors and P-gp inhibitors. Table 4: Other Potentially Significant Drug Interactions
Concomitant Drug Class or Food Noted or Anticipated Outcome Clinical Comment HMG-Co A Reductase Inhibitors: atorv astatin, fluvastatin, lovastatin, pravastatin, simvastatin Pharmacokinetic and/or pharmacodynamic interaction: the addition of one drug to a stable long-term regimen of the other has resulted in myopathy and rhabdomyolysis (including a fatality) Weigh the potential benefits and risks and carefully monitor patients for any signs or symptoms of muscle pain, tenderness, or weakness, particularly during initial therapy; monitoring CPK (creatine phosphokinase) will not necessarily prevent the occurrence of severe myopathy. Other Lipid-Lowering Drugs: fibrates, gemfibrozil Digitalis Glycosides: digoxin P-gp substrate; rhabdomyolysis has been reported Drug Abuse And Dependence Tolerance, abuse or dependence with colchicine has not been reported. Read the Colcrys Drug Interactions Center for a complete guide to possible interactions Learn More »

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Gout Flares COLCRYS (colchicine, USP) tablets are indicated for prophylaxis and the treatment of acute gout flares.
  • Prophylaxis of Gout Flares
    COLCRYS is indicated for prophylaxis of gout flares.
  • Treatment of Gout Flares
    COLCRYS tablets are indicated for treatment of acute gout flares when taken at the first sign of a flare.
Familial Mediterranean Fever (FMF) COLCRYS (colchicine, USP) tablets are indicated in adults and children 4 years or older for treatment of familial Mediterranean fever (FMF).

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Patients with renal or hepatic impairment should not be given COLCRYS in conjunction with P-gp or strong CYP3A4 inhibitors (this includes all protease inhibitors except fosamprenavir). In these patients, life-threatening and fatal colchicine toxicity has been reported with colchicine taken in therapeutic doses. Last reviewed on RxList: 8/27/2014
This monograph has been modified to include the generic and brand name in many instances.

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The exact dose of colchicine that produces significant toxicity is unknown. Fatalities have occurred after ingestion of a dose as low as 7 mg over a four-day period, while other patients have survived after ingesting more than 60 mg. A review of 150 patients who overdosed on colchicine found that those who ingested less than 0.5 mg/kg survived and tended to have milder toxicities such as gastrointestinal symptoms, whereas those who took 0.5 to 0.8 mg/kg had more severe reactions such as myelosuppression. There was 100% mortality in those who ingested more than 0.8 mg/kg. The first stage of acute colchicine toxicity typically begins within 24 hours of ingestion and includes gastrointestinal symptoms such as abdominal pain, nausea, vomiting, diarrhea and significant fluid loss, leading to volume depletion. Peripheral leukocytosis may also be seen. Life-threatening complications occur during the second stage, which occurs 24 to 72 hours after drug administration, attributed to multiorgan failure and its consequences. Death is usually a result of respiratory depression and cardiovascular collapse. If the patient survives, recovery of multiorgan injury may be accompanied by rebound leukocytosis and alopecia starting about one week after the initial ingestion. Treatment of colchicine poisoning should begin with gastric lavage and measures to prevent shock. Otherwise, treatment is symptomatic and supportive. No specific antidote is known. Colchicine is not effectively removed by dialysis [see Pharmacokinetics].

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Dosage Forms And Strengths 0.6 mg tablets — purple capsule-shaped, film-coated with “AR 374” debossed on one side and scored on the other side. Storage And Handling COLCRYS (colchicine, USP) tablets 0.6 mg are purple, film-coated, capsule-shaped tablets debossed with “AR 374” on one side and scored on the other side. Bottles of 30 NDC 64764-119-07
Bottles of 60 NDC 64764-119-06
Bottles of 100 NDC 64764-119-01
Bottles of 250 NDC 64764-119-03
Bottles of 500 NDC 64764-119-05
Bottles of 1000 NDC 64764-119-10 Storage Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from light. DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER. Distributed by: Takeda Pharmaceuticals America, Inc. Deerfield, IL 60015. Revised: November 2012 Last reviewed on RxList: 8/27/2014
This monograph has been modified to include the generic and brand name in many instances.

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Fatal Overdose Fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine [see OVERDOSAGE]. COLCRYS should be kept out of the reach of children. Blood Dyscrasias Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia and aplastic anemia have been reported with colchicine used in therapeutic doses. Drug Interactions Colchicine is a P-gp and CYP3A4 substrate. Life-threatening and fatal drug interactions have been reported in patients treated with colchicine given with P-gp and strong CYP3A4 inhibitors. If treatment with a P-gp or strong CYP3A4 inhibitor is required in patients with normal renal and hepatic function, the patient's dose of colchicine may need to be reduced or interrupted [see DRUG INTERACTIONS]. Use of COLCRYS in conjunction with P-gp or strong CYP3A4 inhibitors (this includes all protease inhibitors except fosamprenavir) is contraindicated in patients with renal or hepatic impairment [see CONTRAINDICATIONS]. Neuromuscular Toxicity Colchicine-induced neuromuscular toxicity and rhabdomyolysis have been reported with chronic treatment in therapeutic doses. Patients with renal dysfunction and elderly patients, even those with normal renal and hepatic function, are at increased risk. Concomitant use of atorvastatin, simvastatin, pravastatin, fluvastatin, lovastatin, gemfibrozil, fenofibrate, fenofibric acid or benzafibrate (themselves associated with myotoxicity) or cyclosporine with COLCRYS may potentiate the development of myopathy [see DRUG INTERACTIONS]. Once colchicine is stopped, the symptoms generally resolve within one week to several months. Patient Counseling Information See FDA-approved Medication Guide. Dosing Instructions Patients should be advised to take COLCRYS as prescribed, even if they are feeling better. Patients should not alter the dose or discontinue treatment without consulting with their doctor. If a dose of COLCRYS is missed:
  • For treatment of a gout flare when the patient is not being dosed for prophylaxis, take the missed dose as soon as possible.
  • For treatment of a gout flare during prophylaxis, take the missed dose immediately, wait 12 hours, then resume the previous dosing schedule.
  • For prophylaxis without treatment for a gout flare, or FMF, take the dose as soon as possible and then return to the normal dosing schedule. However, if a dose is skipped the patient should not double the next dose.
Fatal Overdose Instruct patient that fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine. COLCRYS should be kept out of the reach of children. Blood Dyscrasias Patients should be informed that bone marrow depression with agranulocytosis, aplastic anemia and thrombocytopenia may occur with COLCRYS. Drug And Food Interactions Patients should be advised that many drugs or other substances may interact with COLCRYS and some interactions could be fatal. Therefore, patients should report to their healthcare provider all of the current medications they are taking and check with their healthcare provider before starting any new medications, particularly antibiotics. Patients should also be advised to report the use of nonprescription medication or herbal products. Grapefruit and grapefruit juice may also interact and should not be consumed during COLCRYS treatment. Neuromuscular Toxicity Patients should be informed that muscle pain or weakness, tingling or numbness in fingers or toes may occur with COLCRYS alone or when it is used with certain other drugs. Patients developing any of these signs or symptoms must discontinue COLCRYS and seek medical evaluation immediately. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Carcinogenesis Carcinogenicity studies of colchicine have not been conducted. Due to the potential for colchicine to produce aneuploid cells (cells with an unequal number of chromosomes), there is theoretically an increased risk of malignancy. Mutagenesis Colchicine was negative for mutagenicity in the bacterial reverse mutation assay. In a chromosomal aberration assay in cultured human white blood cells, colchicine treatment resulted in the formation of micronuclei. Since published studies demonstrated that colchicine induces aneuploidy from the process of mitotic nondisjunction without structural DNA changes, colchicine is not considered clastogenic, although micronuclei are formed. Impairment of Fertility No studies of colchicine effects on fertility were conducted with COLCRYS. However, published nonclinical studies demonstrated that colchicine-induced disruption of microtubule formation affects meiosis and mitosis. Reproductive studies also reported abnormal sperm morphology and reduced sperm counts in males, and interference with sperm penetration, second meiotic division and normal cleavage in females when exposed to colchicine. Colchicine administered to pregnant animals resulted in fetal death and teratogenicity. These effects were dose-dependent, with the timing of exposure critical for the effects on embryofetal development. The nonclinical doses evaluated were generally higher than an equivalent human therapeutic dose, but safety margins for reproductive and developmental toxicity could not be determined. Case reports and epidemiology studies in human male subjects on colchicine therapy indicated that infertility from colchicine is rare. A case report indicated that azoospermia was reversed when therapy was stopped. Case reports and epidemiology studies in female subjects on colchicine therapy have not established a clear relationship between colchicine use and female infertility. However, since the progression of FMF without treatment may result in infertility, the use of colchicine needs to be weighed against the potential risks. Use In Specific Populations Pregnancy Pregnancy Category C. There are no adequate and well-controlled studies with colchicine in pregnant women. Colchicine crosses the human placenta. While not studied in the treatment of gout flares, data from a limited number of published studies found no evidence of an increased risk of miscarriage, stillbirth or teratogenic effects among pregnant women using colchicine to treat familial Mediterranean fever (FMF). Although animal reproductive and developmental studies were not conducted with COLCRYS, published animal reproduction and development studies indicate that colchicine causes embryofetal toxicity, teratogenicity and altered postnatal development at exposures within or above the clinical therapeutic range. COLCRYS should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Labor And Delivery The effect of colchicine on labor and delivery is unknown. Nursing Mothers Colchicine is excreted into human milk. Limited information suggests that exclusively breastfed infants receive less than 10 percent of the maternal weight-adjusted dose. While there are no published reports of adverse effects in breastfeeding infants of mothers taking colchicine, colchicine can affect gastrointestinal cell renewal and permeability. Caution should be exercised, and breastfeeding infants should be observed for adverse effects when COLCRYS is administered to a nursing woman. Pediatric Use The safety and efficacy of colchicine in children of all ages with FMF has been evaluated in uncontrolled studies. There does not appear to be an adverse effect on growth in children with FMF treated long-term with colchicine. Gout is rare in pediatric patients; safety and effectiveness of colchicine in pediatric patients has not been established. Geriatric Use Clinical studies with colchicine for prophylaxis and treatment of gout flares and for treatment of FMF did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient with gout should be cautious, reflecting the greater frequency of decreased renal function, concomitant disease or other drug therapy [see Dose Modification for Coadministration of Interacting Drugs and Pharmacokinetics]. Renal Impairment Colchicine is significantly excreted in urine in healthy subjects. Clearance of colchicine is decreased in patients with impaired renal function. Total body clearance of colchicine was reduced by 75% in patients with end-stage renal disease undergoing dialysis. 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 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 Dose Modification in Renal Impairment]. 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 COLCRYS. 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 Dose Modification in Renal Impairment]. FMF Although, pharmacokinetics of colchicine in patients with mild (Clcr 50 to 80 mL/min) and moderate (Clcr 30 to 50 mL/min) renal impairment is not known, these patients should be monitored closely for adverse effects of colchicine. Dose reduction may be necessary. In patients with severe renal failure (Clcr less than 30 mL/min) and end-stage renal disease requiring dialysis, COLCRYS may be started at the dose of 0.3 mg/day. Any increase in dose should be done with adequate monitoring of the patient for adverse effects of COLCRYS [see Pharmacokinetics and Dose Modification in Renal Impairment]. Hepatic Impairment The clearance of colchicine may be significantly reduced and plasma half-life prolonged in patients with chronic hepatic impairment compared to healthy subjects [see Pharmacokinetics]. 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 Dose Modification in Hepatic Impairment]. Treatment of Gout Flares For treatment of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended COLCRYS dose is not required, but patients should be monitored closely for adverse effects of COLCRYS. However, for the treatment of gout flares in patients with severe impairment, while the dose does not need to be adjusted, the 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 Dose Modification in Hepatic Impairment]. FMF In patients with severe hepatic disease, dose reduction should be considered with careful monitoring [see Pharmacokinetics and Dose Modification in Hepatic Impairment]. Last reviewed on RxList: 8/27/2014
This monograph has been modified to include the generic and brand name in many instances.

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