Colchiquim

Rating: 5 - 1 review(s)
What are the side effects you encounter while taking this medicine?
advertisement

Colchiquim uses


1 INDICATIONS AND USAGE

Colchiquim tablets are an alkaloid indicated for:


Colchiquim is not an analgesic medication and should not be used to treat pain from other causes.

1.1 Gout Flares

Colchiquim® (colchicine, USP) tablets are indicated for prophylaxis and the treatment of acute gout flares.

1.2 Familial Mediterranean fever

Colchiquim® (colchicine, USP) tablets are indicated in adults and children 4 years or older for treatment of familial Mediterranean fever (FMF).

2 DOSAGE AND ADMINISTRATION

The long term use of Colchiquim 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 Colchiquim are different for each indication and must be individualized.

The recommended dosage of Colchiquim 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 ].

Colchiquim tablets are administered orally, without regard to meals.

Colchiquim is not an analgesic medication and should not be used to treat pain from other causes.


Colchiquim tablets are administered orally, without regard to meals.

2.1 Gout Flares

Prophylaxis of Gout Flares:

The recommended dosage of Colchiquim 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 Colchiquim 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. Colchiquim 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 FMF

The recommended dosage of Colchiquim for FMF in adults is 1.2 mg to 2.4 mg daily.

Colchiquim 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 Colchiquim dose may be administered in one to two divided doses.

2.3 Recommended Pediatric Dosage

Prophylaxis and Treatment of Gout Flares:

Colchiquim is not recommended for pediatric use in prophylaxis or treatment of gout flares.

FMF:

The recommended dosage of Colchiquim 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:

2.4 Dose Modification for Co-administration of Interacting Drugs

Concomitant Therapy:

Co-administration of Colchiquim with drugs known to inhibit CYP3A4 and/or P-glycoprotein 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) ].

Strong CYP3A4 InhibitorsPatients with renal or hepatic impairment should not be given Colchiquim in conjunction with strong CYP3A4 or P-gp 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/

RitonavirWhen used in combination with Ritonavir, see dosing recommendations for strong CYP3A4 inhibitors [see CONTRAINDICATIONS (4) ].

Indinavir

Itraconazole Ketoconazole

Lopinavir/

Ritonavir

Nefazodone

Nelfinavir

Ritonavir

Saquinavir Telithromycin

Tipranavir/

Ritonavir

Significant increase in Colchiquim plasma levels; fatal Colchiquim toxicity has been reported with clarithromycin, a strong CYP3A4 inhibitor. Similarly, significant increase in Colchiquim 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 Colchiquim 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 Colchiquim plasma levels; fatal Colchiquim toxicity has been reported with cyclosporine, a

P-gp inhibitor. Similarly, significant increase in Colchiquim 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)

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 Colchiquim 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 Colchiquim 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 Colchiquim 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 Colchiquim 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 Colchiquim 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 Colchiquim 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 Colchiquim 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 Colchiquim 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 Colchiquim 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 Colchiquim 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 day


Treatment of gout flares with Colchiquim is not recommended in patients receiving prophylactic dose of Colchiquim and CYP3A4 inhibitors.

2.5 Dose Modification in Renal Impairment

Colchiquim 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 Colchiquim. 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 Colchiquim. 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 Colchiquim is not recommended in patients with renal impairment who are receiving Colchiquim 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 Colchiquim. 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 Colchiquim [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 Colchiquim [see Clinical Pharmacology (12.3) and Renal Impairment (8.6) ].

2.6 Dose Modification in Hepatic Impairment

Gout Flares

Prophylaxis of Gout Flares:

For prophylaxis of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of Colchiquim. 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 Colchiquim. 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 Colchiquim is not recommended in patients with hepatic impairment who are receiving Colchiquim for prophylaxis.

FMF:

Patients with mild to moderate hepatic impairment should be monitored closely for adverse effects of Colchiquim. Dose reduction should be considered in patients with severe hepatic impairment [see Hepatic Impairment (8.7) ].

advertisement

3 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.

4 CONTRAINDICATIONS

Patients with renal or hepatic impairment should not be given Colchiquim in conjunction with P-gp or strong CYP3A4 inhibitors (this includes all protease inhibitors, except fosamprenavir). In these patients, life-threatening and fatal Colchiquim toxicity has been reported with Colchiquim taken in therapeutic doses.

Patients with renal or hepatic impairment should not be given Colchiquim in conjunction with P-gp or strong CYP3A4 inhibitors (5.3). In these patients, life-threatening and fatal Colchiquim toxicity has been reported with Colchiquim taken in therapeutic doses (7).

5 WARNINGS AND PRECAUTIONS

5.1 Fatal Overdose

Fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested Colchiquim [see OVERDOSAGE (10) ]. Colchiquim should be kept out of the reach of children.

5.2 Blood Dyscrasias

Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia have been reported with Colchiquim used in therapeutic doses.

5.3 Drug Interactions

Colchiquim is a P-gp and CYP3A4 substrate. Life-threatening and fatal drug interactions have been reported in patients treated with Colchiquim 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 Colchiquim may need to be reduced or interrupted [see DRUG INTERACTIONS ]. Use of Colchiquim 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 (4) ].

5.4 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 Colchiquim may potentiate the development of myopathy [see DRUG INTERACTIONS (7) ]. Once Colchiquim is stopped, the symptoms generally resolve within 1 week to several months.

advertisement

6 ADVERSE REACTIONS

Prophylaxis of Gout Flares: The most commonly reported adverse reaction in clinical trials for the prophylaxis of gout was diarrhea.

Treatment of Gout Flares: The most common adverse reactions reported in the clinical trial for gout were diarrhea and pharyngolaryngeal pain (3%).

FMF: Most common adverse reactions (up to 20%) are abdominal pain, diarrhea, nausea, and vomiting. These effects are usually mild, transient, and reversible upon lowering the dose (6).

To report SUSPECTED ADVERSE REACTIONS, contact Mutual Pharmaceutical Company, Inc. at 1-888-351-3786 or drugsafetyColchiquimurlpharma.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Prophylaxis of Gout Flares:

The most commonly reported adverse reaction in clinical trials of Colchiquim for the prophylaxis of gout was diarrhea.

Treatment of Gout Flares:

The most common adverse reactions reported in the clinical trial with Colchiquim 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 Colchiquim, 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.

6.1 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 1 hour) of Colchiquim compared to 77% of patients taking a non-recommended high-dose (4.8 mg over 6 hours) of Colchiquim 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 Colchiquim 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 non-recommended high-dose Colchiquim regimen but did not occur in the recommended low-dose Colchiquim regimen.

MedDRA System Organ Class Colchiquim Dose Placebo
MedDRA Preferred Term High (N=52)

n (%)

Low (N=74)

n (%)

(N=59)

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

6.2 Postmarketing Experience

Serious toxic manifestations associated with Colchiquim 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 (10) ].

The following adverse reactions have been reported with Colchiquim. These have been generally reversible upon temporarily interrupting treatment or lowering the dose of Colchiquim.

advertisement

7 DRUG INTERACTIONS

Colchiquim (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 Colchiquim. If Colchiquim is administered with drugs that inhibit P-gp, most of which also inhibit CYP3A4, increased concentrations of Colchiquim are likely. Fatal drug interactions have been reported.

Physicians should ensure that patients are suitable candidates for treatment with Colchiquim and remain alert for signs and symptoms of toxicities related to increased Colchiquim exposure as a result of a drug interaction. Signs and symptoms of Colchiquim toxicity should be evaluated promptly and, if toxicity is suspected, Colchiquim 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.

Concomitant Drug Class or Food Noted or anticipated Outcome Clinical Comment
HMG-Co A Reductase Inhibitors:

atorvastatin, 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

Co-administration of P-gp and/or CYP3A4 inhibitors (e.g., clarithromycin or cyclosporine) have been demonstrated to alter the concentration of Colchiquim. The potential for drug-drug interactions must be considered prior to and during therapy. See full prescribing information for a complete list of reported and potential interactions (2.4, 5.3, 7).

advertisement

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies with Colchiquim in pregnant women. Colchiquim 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 Colchiquim to treat familial Mediterranean fever (FMF). Although animal reproductive and developmental studies were not conducted with Colchiquim, published animal reproduction and development studies indicate that Colchiquim causes embryofetal toxicity, teratogenicity, and altered postnatal development at exposures within or above the clinical therapeutic range. Colchiquim should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

8.2 Labor and Delivery

The effect of Colchiquim on labor and delivery is unknown.

8.3 Nursing Mothers

Colchiquim is excreted into human milk. Limited information suggests that exclusively breast-fed infants receive less than 10 percent of the maternal weight-adjusted dose. While there are no published reports of adverse effects in breast-feeding infants of mothers taking Colchiquim, Colchiquim can affect gastrointestinal cell renewal and permeability. Caution should be exercised and breast-feeding infants should be observed for adverse effects when Colchiquim is administered to a nursing woman.

8.4 Pediatric Use

The safety and efficacy of Colchiquim 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 Colchiquim. Gout is rare in pediatric patients, safety and effectiveness of Colchiquim in pediatric patients has not been established.

8.5 Geriatric Use

Clinical studies with Colchiquim 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 Co-administration of Interacting Drugs ].

8.6 Renal Impairment

Colchiquim is significantly excreted in urine in healthy subjects. Clearance of Colchiquim is decreased in patients with impaired renal function. Total body clearance of Colchiquim 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 – 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 Colchiquim. 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 (2.5) ].

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 Colchiquim. 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 Dose Modification in Renal Impairment (2.5) ].

FMF

Although, pharmacokinetics of Colchiquim in patients with mild (Clcr 50 – 80 mL/min) and moderate (Clcr 30 – 50 mL/min) renal impairment is not known, these patients should be monitored closely for adverse effects of Colchiquim. Dose reduction may be necessary. In patients with severe renal failure (Clcr less than 30 mL/minute) and end-stage renal disease requiring dialysis, Colchiquim 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 Colchiquim [see Pharmacokinetics (12.3) and Dose Modification in Renal Impairment (2.5) ].

8.7 Hepatic Impairment

The clearance of Colchiquim may be significantly reduced and plasma half-life prolonged in patients with chronic hepatic impairment, compared to healthy subjects [see Pharmacokinetics (12.3) ].

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 Colchiquim. Dose reduction should be considered for the prophylaxis of gout flares in patients with severe hepatic impairment [see Dose Modification in Hepatic Impairment (2.6) ].

Treatment of Gout Flares:

For treatment of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended Colchiquim dose is not required, but patients should be monitored closely for adverse effects of Colchiquim. 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 2 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 (2.6) ].

FMF

In patients with severe hepatic disease, dose reduction should be considered with careful monitoring [see Pharmacokinetics (12.3) and Dose Modification in Hepatic Impairment (2.6) ].

9 DRUG ABUSE AND DEPENDENCE

Tolerance, abuse, or dependence with Colchiquim has not been reported.

10 OVERDOSAGE

The exact dose of Colchiquim that produces significant toxicity is unknown. Fatalities have occurred after ingestion of a dose as low as 7 mg over a 4-day period, while other patients have survived after ingesting more than 60 mg. A review of 150 patients who overdosed on Colchiquim 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 Colchiquim 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 multi-organ failure and its consequences. Death is usually a result of respiratory depression and cardiovascular collapse. If the patient survives, recovery of multi-organ injury may be accompanied by rebound leukocytosis and alopecia starting about 1 week after the initial ingestion.

Treatment of Colchiquim poisoning should begin with gastric lavage and measures to prevent shock. Otherwise, treatment is symptomatic and supportive. No specific antidote is known. Colchiquim is not effectively removed by dialysis [see Pharmacokinetics (12.3) ].

11 DESCRIPTION

Colchiquim 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 Colchiquim is given below.

Colchiquim occurs as a pale yellow powder that is soluble in water.

Colchiquim® (colchicine, USP) tablets are supplied for oral administration as purple, film-coated, capsule-shaped tablets (0.1575" × 0.3030"), debossed with 'AR 374' on one side and scored on the other, containing 0.6 mg of the active ingredient Colchiquim 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.

Chemical Structure

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The mechanism by which Colchiquim exerts its beneficial effect in patients with FMF has not been fully elucidated; however, evidence suggests that Colchiquim may interfere with the intracellular assembly of the inflammasome complex present in neutrophils and monocytes that mediates activation of interleukin-1β. Additionally, Colchiquim disrupts cytoskeletal functions through inhibition of β-tubulin polymerization into microtubules, and consequently prevents the activation, degranulation, and migration of neutrophils thought to mediate some gout symptoms.

12.3 Pharmacokinetics

Absorption

In healthy adults, Colchiquim is absorbed when given orally, reaching a mean Cmax of 2.5 ng/mL (range 1.1 to 4.4 ng/mL) in 1 to 2 hours (range 0.5 to 3 hours) after a single dose administered under fasting conditions.

Following oral administration of Colchiquim given as 1.8 mg Colchiquim over 1 hour to healthy, young adults under fasting conditions, Colchiquim appears to be readily absorbed, reaching mean maximum plasma concentrations of 6.2 ng/mL at a median 1.81 hours (range: 1.0 to 2.5 hours). Following administration of the non-recommended high-dose regimen (4.8 mg over 6 hours), mean maximal plasma concentrations were 6.8 ng/mL, at a median 4.47 hours (range: 3.1 to 7.5 hours).

After 10 days on a regimen of 0.6 mg twice daily, peak concentrations are 3.1 to 3.6 ng/mL (range 1.6 to 6.0 ng/mL), occurring 1.3 to 1.4 hours post-dose (range 0.5 to 3.0 hours). Mean pharmacokinetic parameter values in healthy adults are shown in Table 5 below.

Cmax (colchicine ng/mL) Tmax Tmax mean (range) (h) Vd/F (L) CL/F (L/hr) t1/2 (h)
CL= Dose/AUC0-t (Calculated from mean values)

Vd = CL/Ke (Calculated from mean values)

Colchiquim 0.6 mg Single Dose (N=13)
2.5 (28.7) 1.5 (1.0 – 3.0) 341.5 (54.4) 54.1 (31.0) --
Colchiquim 0.6 mg b.i.d. × 10 days (N=13)
3.6 (23.7) 1.3 (0.5 – 3.0) 1150 (18.7) 30.3 (19.0) 26.6 (16.3)

In some subjects, secondary Colchiquim peaks are seen, occurring between 3 and 36 hours post-dose and ranging from 39% to 155% of the height of the initial peak. These observations are attributed to intestinal secretion and reabsorption and/or biliary recirculation.

Absolute bioavailability is reported to be approximately 45%.

Administration of Colchiquim with food has no effect on the rate of Colchiquim absorption, but did decrease the extent of Colchiquim by approximately 15%. This is without clinical significance.

Distribution

The mean apparent volume of distribution in healthy young volunteers was approximately 5 to 8 L/kg.

Colchiquim binding to serum protein is low, 39 ± 5%, primarily to albumin regardless of concentration.

Colchiquim crosses the placenta (plasma levels in the fetus are reported to be approximately 15% of the maternal concentration). Colchiquim also distributes into breast milk at concentrations similar to those found in the maternal serum [see Pregnancy (8.1) and Nursing Mothers (8.3) ].

Metabolism

Colchiquim is demethylated to two primary metabolites, 2-O-demethylcolchicine and 3-O-demethylcolchicine (2- and 3-DMC, respectively), and one minor metabolite, 10-O-demethylcolchicine (also known as colchiceine). In vitro studies using human liver microsomes have shown that CYP3A4 is involved in the metabolism of Colchiquim to 2- and 3-DMC. Plasma levels of these metabolites are minimal (less than 5% of parent drug).

Elimination/Excretion

In healthy volunteers (n=12) 40 – 65% of 1 mg orally administered Colchiquim was recovered unchanged in urine. Enterohepatic recirculation and biliary excretion are also postulated to play a role in Colchiquim elimination. Following multiple oral doses (0.6 mg twice daily), the mean elimination half-lives in young healthy volunteers (mean age 25 to 28 years of age) is 26.6 to 31.2 hours. Colchiquim is a substrate of P-gp.

Extracorporeal Elimination: Colchiquim is not removed by hemodialysis.

Special Populations

There is no difference between men and women in the pharmacokinetic disposition of Colchiquim.

Pediatric Patients: Pharmacokinetics of Colchiquim was not evaluated in pediatric patients.

Elderly: Pharmacokinetics of Colchiquim has not been determined in elderly patients. A published report described the pharmacokinetics of 1 mg oral Colchiquim tablet in four elderly women compared to six young healthy males. The mean age of the four elderly women was 83 years (range 75 – 93), mean weight was 47 kg (38 – 61 kg) and mean creatinine clearance was 46 mL/min (range 25 – 75 mL/min). Mean peak plasma levels and AUC of Colchiquim were two times higher in elderly subjects compared to young healthy males. However, it is possible that the higher exposure in the elderly subjects was due to decreased renal function.

Renal impairment: Pharmacokinetics of Colchiquim in patients with mild and moderate renal impairment is not known. A published report described the disposition of Colchiquim (1 mg) in young adult men and women with FMF who had normal renal function or end-stage renal disease requiring dialysis. Patients with end-stage renal disease had 75% lower Colchiquim clearance (0.17 vs 0.73 L/hr/kg) and prolonged plasma elimination half-life (18.8 hrs vs 4.4 hrs) as compared to subjects with FMF and normal renal function [see Dose Modification in Renal Impairment (2.5) and Renal Impairment (8.6) ].

Hepatic impairment: Published reports on the pharmacokinetics of IV Colchiquim in patients with severe chronic liver disease, as well as those with alcoholic or primary biliary cirrhosis, and normal renal function suggest wide inter-patient variability. In some subjects with mild to moderate cirrhosis, the clearance of Colchiquim is significantly reduced and plasma half-life prolonged compared to healthy subjects. In subjects with primary biliary cirrhosis, no consistent trends were noted [see Dose Modification in Hepatic Impairment (2.6) and Hepatic Impairment (8.7) ]. No pharmacokinetic data are available for patients with severe hepatic impairment (Child-Pugh C).

Drug interactions:

In vitro drug interactions:

In vitro studies in human liver microsomes have shown that Colchiquim is not an inhibitor or inducer of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4 activity.

In vivo drug interactions:

The effects of co-administration of other drugs with Colchiquim on Cmax, AUC, and Cmin are summarized in Table 6 (effect of other drugs on Colchiquim) and Table 7 (effect of Colchiquim on other drugs). For information regarding clinical recommendations, see Table 1 in Dose Modification for Co-administration of Interacting Drugs [see Dose Modification for Co-administration of Interacting Drugs (2.4) ].

Co-administered Drug Dose of Co-administered Drug (mg) Dose of Colchiquim (mg) N % Change in Colchiquim Concentrations from Baseline

(Range: Min - Max)

Cmax AUC0-t
Cyclosporine 100 mg

single-dose

0.6 mg

single-dose

23 270.0

(62.0 to 606.9)

259.0

(75.8 to 511.9)

Clarithromycin 250 mg BID,

7 days

0.6 mg

single-dose

23 227.2

(65.7 to 591.1)

281.5

(88.7 to 851.6)

Ketoconazole 200 mg BID,

5 days

0.6 mg

single-dose

24 101.7

(19.6 to 219.0)

212.2

(76.7 to 419.6)

Ritonavir 100 mg BID,

5 days

0.6 mg

single-dose

18 184.4

(79.2 to 447.4)

296.0

(53.8 to 924.4)

Verapamil 240 mg daily,

5 days

0.6 mg

single-dose

24 40.1

(-47.1 to 149.5)

103.3

(-9.8 to 217.2)

Diltiazem 240 mg daily,

7 days

0.6 mg

single-dose

20 44.2

(-46.0 to 318.3)

93.4

(-30.2 to 338.6)

Azithromycin 500 mg × 1 day, then

250 mg × 4 days

0.6 mg

single-dose

21 21.6

(-41.7 to 222.0)

57.1

(-24.3 to 241.1)

Grapefruit Juice 240 mL BID,

4 days

0.6 mg

single-dose

21 -2.55

(-53.4 to 55.0)

-2.36

(-46.4 to 62.2)


Estrogen-containing oral contraceptives: In healthy female volunteers given ethinyl estradiol and norethindrone (Ortho-Novum® 1/35) co-administered with Colchiquim (0.6 mg b.i.d. × 14 days), hormone concentrations are not affected.

In healthy volunteers given theophylline co-administered with Colchiquim (0.6 mg b.i.d. × 14 days), theophylline concentrations were not affected.

Co-administered Drug Dose of Co-administered Drug (mg) Dose of Colchiquim (mg) N % Change in Co-Administered Drug Concentrations from Baseline

(Range: Min - Max)

Cmax AUC0-t
Theophylline 300 mg (elixir) single-dose 0.6 mg BID × 14 days 27 1.6

(-30.4 to 23.1)

1.6

(-28.5 to 27.1)

Ethinyl Estradiol (Ortho-Novum® 1/35) 21-Day Cycle (Active Treatment) + 7-Day Placebo 0.6 mg BID × 14 days 27Conducted in healthy adult females -6.7

(-40.3 to 44.7)

-3.0AUCτ

(-25.3 to 24.9)

Norethindrone (Ortho-Novum® 1/35) 0.94

(-37.3 to 59.4)

-1.6

(-32.0 to 33.7)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Carcinogenicity studies of Colchiquim have not been conducted. Due to the potential for Colchiquim to produce aneuploid cells (cells with an unequal number of chromosomes), there is theoretically an increased risk of malignancy.

Mutagenesis

Colchiquim was negative for mutagenicity in the bacterial reverse mutation assay. In a chromosomal aberration assay in cultured human white blood cells, Colchiquim treatment resulted in the formation of micronuclei. Since published studies demonstrated that Colchiquim induces aneuploidy from the process of mitotic nondisjunction without structural DNA changes, Colchiquim is not considered clastogenic, although micronuclei are formed.

Impairment of Fertility

No studies of Colchiquim effects on fertility were conducted with Colchiquim. 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 Colchiquim. Colchiquim 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 Colchiquim therapy indicated that infertility from Colchiquim is rare. A case report indicated that azoospermia was reversed when therapy was stopped. Case reports and epidemiology studies in female subjects on Colchiquim therapy have not established a clear relationship between Colchiquim use and female infertility. However, since the progression of FMF without treatment may result in infertility, the use of Colchiquim needs to be weighed against the potential risks.

14 CLINICAL STUDIES

The evidence for the efficacy of Colchiquim in patients with chronic gout is derived from the published literature. Two randomized clinical trials assessed the efficacy of Colchiquim 0.6 mg twice a day for the prophylaxis of gout flares in patients with gout initiating treatment with urate lowering therapy. In both trials, treatment with Colchiquim decreased the frequency of gout flares.

The efficacy of a low dosage regimen of oral Colchiquim (COLCRYS total dose 1.8 mg over 1 hour) for treatment of gout flares was assessed in a multicenter, randomized, double-blind, placebo-controlled, parallel group, 1 week, dose comparison study. Patients meeting American College of Rheumatology criteria for gout were randomly assigned to three groups: high-dose Colchiquim (1.2 mg, then 0.6 mg hourly × 6 hours [4.8 mg total]); low-dose Colchiquim (1.2 mg, then 0.6 mg in 1 hour [1.8 mg total] followed by 5 placebo doses hourly); or placebo (2 capsules, then 1 capsule hourly × 6 hours). Patients took the first dose within 12 hours of the onset of the flare and recorded pain intensity (11-point Likert scale) and adverse events over 72 hours. The efficacy of Colchiquim was measured based on response to treatment in the target joint, using patient self assessment of pain at 24 hours following the time of first dose as recorded in the diary. A responder was one who achieved at least a 50% reduction in pain score at the 24-hour post-dose assessment relative to the pre-treatment score and did not use rescue medication prior to the actual time of 24-hour post-dose assessment.

Rates of response were similar for the recommended low-dose treatment group (38%) and the non-recommended high-dose group (33%) but were higher as compared to the placebo group (16%) as shown in Table 8.

Colchiquim Dose Responders n (%) Placebo

n (%)

(n=58)

% Differences in Proportion
Low-dose

(n=74)

High-dose

(n=52)

Low-dose vs Placebo

(95% CI)

High-dose vs Placebo

(95% CI)

28 (38%) 17 (33%) 9 (16%) 22 (8, 37) 17 (1, 33)

Figure 1 below shows the percentage of patients achieving varying degrees of improvement in pain from baseline at 24 hours.

Figure 1

Pain Relief on Low and High Doses of Colchiquim and Placebo (Cumulative)


The evidence for the efficacy of Colchiquim in patients with FMF is derived from the published literature. Three randomized, placebo-controlled studies were identified. The three placebo-controlled studies randomized a total of 48 adult patients diagnosed with FMF and reported similar efficacy endpoints as well as inclusion and exclusion criteria.

One of the studies randomized 15 patients with FMF to a 6-month crossover study during which 5 patients discontinued due to study non-compliance. The 10 patients completing the study experienced 5 attacks over the course of 90 days while treated with Colchiquim compared to 59 attacks over the course of 90 days while treated with placebo. Similarly, the second study randomized 22 patients with FMF to a 4-month crossover study during which 9 patients discontinued due to lack of efficacy while receiving placebo or study non-compliance. The 13 patients completing the study experienced 18 attacks over the course of 60 days while treated with Colchiquim compared to 68 attacks over the course of 60 days while treated with placebo. The third study was discontinued after an interim analysis of 6 of the 11 patients enrolled had completed the study; results could not be confirmed.

Open-label experience with Colchiquim in adults and children with FMF is consistent with the randomized, controlled trial experience, and was utilized to support information on the safety profile of Colchiquim and for dosing recommendations.

Figure 1

16 HOW SUPPLIED / STORAGE AND HANDLING

16.1 How Supplied

Colchiquim® 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 13310-119-07
Bottles of 60 NDC 13310-119-06
Bottles of 100 NDC 13310-119-01
Bottles of 250 NDC 13310-119-03
Bottles of 500 NDC 13310-119-05
Bottles of 1000 NDC 13310-119-10

16.2 Storage

Store at 20° to 25°C (68° to 77°F).

Protect from light.

DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.

17 PATIENT COUNSELING INFORMATION


17.1 Dosing Instructions

Patients should be advised to take Colchiquim 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 Colchiquim is missed:

17.2 Fatal Overdose

Instruct patient that fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested Colchiquim. Colchiquim should be kept out of the reach of children.

17.3 Blood Dyscrasias

Patients should be informed that bone marrow depression with agranulocytosis, aplastic anemia, and thrombocytopenia may occur with Colchiquim.

17.4 Drug and Food Interactions

Patients should be advised that many drugs or other substances may interact with Colchiquim 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 non-prescription medication or herbal products. Grapefruit and grapefruit juice may also interact and should not be consumed during Colchiquim treatment.

17.5 Neuromuscular Toxicity

Patients should be informed that muscle pain or weakness, tingling or numbness in fingers or toes may occur with Colchiquim alone or when it is used with certain other drugs. Patients developing any of these signs or symptoms must discontinue Colchiquim and seek medical evaluation immediately.

17.6 Medication Guide

Colchiquim® is a registered U.S. trademark of the URL Pharma, Inc. group of companies. © 2009 AR Holding Company, Inc., a URL Pharma, Inc. company

U.S. Patent Nos. 7,601,758; 7,619,004 and other patents pending

Manufactured for:

AR SCIENTIFIC, INC.

Philadelphia, PA 19124 USA

by:

MUTUAL PHARMACEUTICAL COMPANY, INC.

Philadelphia, PA 19124 USA

Rev 14, March 2012

MEDICATION GUIDE

Colchiquim

(KOL-kris)

(colchicine) tablets

Read the Medication Guide that comes with Colchiquim before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. You and your healthcare provider should talk about Colchiquim when you start taking it and at regular checkups.

What is the most important information I should know about Colchiquim?

Colchiquim can cause serious side effects or death if levels of Colchiquim are too high in your body.

  • atazanavir sulfate (Reyataz®)
  • cyclosporine (Neoral®, Gengraf®, Sandimmune®)
  • fosamprenavir (Lexiva®) with ritonavir
  • indinavir (Crixivan®)
  • ketoconazole (Nizoral®)
  • nefazodone (Serzone®)
  • ritonavir (Norvir®)
  • telithromycin (Ketek®)
  • clarithromycin (Biaxin®)
  • darunavir (Prezista®)
  • fosamprenavir (Lexiva®)
  • itraconazole (Sporanox®)
  • lopinavir/ritonavir (Kaletra®)
  • nelfinavir mesylate (Viracept®)
  • saquinavir mesylate (Invirase®)
  • tipranavir (Aptivus®)

Ask your healthcare provider or pharmacist if you are not sure if you take any of the medicines listed above. This is not a complete list of all the medicines that can interact with Colchiquim.


What is Colchiquim?

Colchiquim is a prescription medicine used to:


Colchiquim is not a pain medicine and it should not be taken to treat pain related to other conditions unless specifically prescribed for those conditions.

Who should not take Colchiquim?

Do not take Colchiquim if you have liver or kidney problems and you take certain other medicines. Serious side effects, including death, have been reported in these patients even when taken as directed. See "What is the most important information I should know about Colchiquim?"

What should I tell my healthcare provider before starting Colchiquim?

See "What is the most important information I should know about Colchiquim?"

Before you take Colchiquim tell your healthcare provider about all your medical conditions including if you:


Tell your healthcare provider about all the medicines you take, including ones that you may only be taking for a short time, such as antibiotics. See "What is the most important information I should know about Colchiquim?" Do not start a new medicine without talking to your healthcare provider.

Using Colchiquim with certain other medicines, such as cholesterol-lowering medications and digoxin, can affect each other causing serious side effects. Your healthcare provider may need to change your dose of Colchiquim. Talk to your healthcare provider about whether the medications you are taking might interact with Colchiquim, and what side effects to look for.

How should I take Colchiquim?


What should I avoid while taking Colchiquim?


What are the possible side effects of Colchiquim?

Colchiquim can cause serious side effects or even cause death. See "What is the most important information I should know about Colchiquim?"

Get medical help right away, if you have:


Gout Flares: The most common side effect of Colchiquim in people who have gout flares is diarrhea.

FMF: The most common side effects of Colchiquim in people who have FMF are abdominal pain, diarrhea, nausea and vomiting.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all of the possible side effects of Colchiquim. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Colchiquim?


Keep Colchiquim and all medicines out of the reach of children.

General Information about Colchiquim

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Colchiquim for a condition for which it was not prescribed. Do not give Colchiquim to other people, even if they have the same symptoms that you have. It may harm them. This Medication Guide summarizes the most important information about Colchiquim. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about Colchiquim that is written for healthcare professionals.

For more information, go to www. COLCRYS.com or call 1-888-351-3786.

What are the ingredients in Colchiquim?

Active Ingredient: Colchiquim

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.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Colchiquim® is a registered U.S. trademark of the URL Pharma, Inc. group of companies. © 2009 AR Holding Company, Inc., a URL Pharma, Inc. company

U.S. Patent Nos. 7,601,758; 7,619,004 and other patents pending

Manufactured for:

AR SCIENTIFIC, INC.

Philadelphia, PA 19124 USA

by:

MUTUAL PHARMACEUTICAL COMPANY, INC.

Rev 14, March 2012

PRINCIPAL DISPLAY PANEL - 0.6 mg Tablet Bottle Label

100 TABLETS

NDC 13310-119-01

Colchiquim®

(colchicine, USP) tablets

0.6 mg

PHARMACIST:

PLEASE DISPENSE WITH

MEDICATION GUIDE ATTACHED

AR

SCIENTIFIC

Rx only

Colchiquim pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Colchiquim available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Colchiquim destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Colchiquim Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Colchiquim pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


advertisement

References

  1. Dailymed."COLCRYS (COLCHICINE) TABLET, FILM COATED [AR SCIENTIFIC INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."COLCHICINE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. "colchicine". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Colchiquim?

Depending on the reaction of the Colchiquim after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Colchiquim not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Colchiquim addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

advertisement

Review

sdrugs.com conducted a study on Colchiquim, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Colchiquim consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

Visitor reports

One visitor reported useful

How is the drug Colchiquim useful in reducing or relieving the symptoms? How useful is it?
According to the survey conducted by the website sdrugs.com, there are variable results and below are the percentages of the users that say the medicine is useful to them and that say it is not helping them much. It is not ideal to continue taking the medication if you feel it is not helping you much. Contact your healthcare provider to check if there is a need to change the medicine or if there is a need to re-evaluate your condition. The usefulness of the medicine may vary from patient to patient, depending on the other diseases he is suffering from and slightly depends on the brand name.
Visitors%
Useful1
100.0%

Visitor reported side effects

No survey data has been collected yet

Visitor reported price estimates

No survey data has been collected yet

One visitor reported frequency of use

How often in a day do you take the medicine?
Are you taking the Colchiquim drug as prescribed by the doctor?

Few medications can be taken Once in a day more than prescribed when the doctor's advice mentions the medicine can be taken according to frequency or severity of symptoms. Most times, be very careful and clear about the number of times you are taking the medication. The report of sdrugs.com website users about the frequency of taking the drug Colchiquim is mentioned below.
Visitors%
Once in a day1
100.0%

One visitor reported doses

What is the dose of Colchiquim drug you are taking?
According to the survey conducted among sdrugs.com website users, the maximum number of people are using the following dose 1-5mg. Few medications come in only one or two doses. Few are specific for adult dose and child dose. The dose of the medicine given to the patient depends on the severity of the symptom/disease. There can be dose adjustments made by the doctor, based on the progression of the disease. Follow-up is important.
Visitors%
1-5mg1
100.0%

One visitor reported time for results

What is the time duration Colchiquim drug must be taken for it to be effective or for it to reduce the symptoms?
Most chronic conditions need at least some time so the dose and the drug action gets adjusted to the body to get the desired effect. The stastistics say sdrugs.com website users needed 1 day to notice the result from using Colchiquim drug. The time needed to show improvement in health condition after using the medicine Colchiquim need not be same for all the users. It varies based on other factors.
Visitors%
1 day1
100.0%

Visitor reported administration

No survey data has been collected yet

Visitor reported age

No survey data has been collected yet

Visitor reviews


There are no reviews yet. Be the first to write one!


Your name: 
Email: 
Spam protection:  < Type 13 here

The information was verified by Dr. Rachana Salvi, MD Pharmacology

© 2002 - 2022 "sdrugs.com". All Rights Reserved