COLCHICINE tablet, film coated

United States - English - NLM (National Library of Medicine)

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Active ingredient:
Colchicine (UNII: SML2Y3J35T) (Colchicine - UNII:SML2Y3J35T)
Available from:
Proficient Rx LP
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Colchicine Tablets, USP are indicated for prophylaxis and the treatment of acute gout flares. Colchicine Tablets, USP are indicated in adults and children four years or older for treatment of familial Mediterranean fever (FMF). Patients with renal or hepatic impairment should not be given Colchicine Tablets, USP 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. 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 stud
Product summary:
Colchicine Tablets, USP 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 71205-310-30 Bottles of 60 71205-310-60 Bottles of 90 71205-310-90 Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from light. DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.
Authorization status:
New Drug Application Authorized Generic
Authorization number:
71205-310-30, 71205-310-60, 71205-310-90

Proficient Rx LP

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MEDICATION GUIDE

Colchicine Tablets, USP

Read the Medication Guide that comes with Colchicine Tablets, USP 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 Colchicine Tablets, USP when you start taking it and at regular checkups.

What is the most important information that I should know about Colchicine Tablets, USP?

Colchicine Tablets, USP can cause serious side effects or death if levels of colchicine are too high in your

body.

Taking certain medicines with Colchicine Tablets, USP can cause your level of colchicine to be too

high, especially if you have kidney or liver problems.

Tell your healthcare provider about all your medical conditions, including if you have kidney or liver

problems. Your dose of Colchicine Tablets, USP may need to be changed.

Tell your healthcare provider about all the medicines you take, including prescription and

nonprescription medicines, vitamins and herbal supplements.

Even medicines that you take for a short period of time, such as antibiotics, can interact with

Colchicine Tablets, USP and cause serious side effects or death.

Talk to your healthcare provider or pharmacist before taking any new medicine.

Especially tell your healthcare provider if you take:

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 Colchicine Tablets, USP.

Know the medicines you take. Keep a list of them and show it to your healthcare provider and

pharmacist when you get a new medicine.

Keep Colchicine Tablets, USP out of the reach of children.

What are Colchicine Tablets, USP?

Colchicine Tablets, USP are a prescription medicine used to:

prevent and treat gout flares in adults

treat familial Mediterranean fever (FMF) in adults and children age 4 or older

Colchicine Tablets, USP are not a pain medicine, and should not be taken to treat pain related to other

conditions unless specifically prescribed for those conditions.

Who should not take Colchicine Tablets, USP?

Do not take Colchicine Tablets, USP 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 that I should know about Colchicine Tablets, USP? "

What should I tell my healthcare provider before starting Colchicine Tablets, USP?

See " What is the most important information that I should know about Colchicine Tablets, USP? "

Before you take Colchicine Tablets, USP tell your healthcare provider about all your medical conditions,

including if you:

have liver or kidney problems.

are pregnant or plan to become pregnant. It is not known if Colchicine Tablets, USP will harm your

unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant.

are breastfeeding or plan to breastfeed. Colchicine passes into your breast milk. You and your

healthcare provider should decide if you will take Colchicine Tablets, USP or breastfeed. If you take

Colchicine Tablets, USP and breastfeed, you should talk to your child's healthcare provider about how

to watch for side effects in your child.

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 that I should know about

Colchicine Tablets, USP? " Do not start a new medicine without talking to your healthcare provider.

Using Colchicine Tablets, USP 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 Colchicine Tablets, USP. Talk to your healthcare provider about whether the medications you

are taking might interact with Colchicine Tablets, USP and what side effects to look for.

How should I take Colchicine Tablets, USP?

Take Colchicine Tablets, USP exactly as your healthcare provider tells you to take them. If you are not

sure about your dosing , call your healthcare provider.

Colchicine Tablets, USP can be taken with or without food.

If you take too many Colchicine Tablets, USP go to the nearest hospital emergency room right away.

Do not stop taking Colchicine Tablets, USP even if you start to feel better, unless your healthcare

provider tells you.

Your healthcare provider may do blood tests while you take Colchicine Tablets, USP.

If you take Colchicine Tablets, USP daily and you miss a dose, then take it as soon as you remember. If

it is almost time for your next dose, just skip the missed dose. Take the next dose at your regular time.

Do not take 2 doses at the same time.

If you have a gout flare while taking Colchicine Tablets, USP daily, report this to your healthcare

provider.

What should I avoid while taking Colchicine Tablets, USP?

Avoid eating grapefruit or drinking grapefruit juice while taking Colchicine Tablets, USP. It can

increase your chances of getting serious side effects.

What are the possible side effects of Colchicine Tablets, USP?

Colchicine Tablets, USP can cause serious side effects or even cause death. See " What is the most important

information that I should know about Colchicine Tablets, USP? "

Get medical help right away if you have:

Muscle weakness or pain

Numbness or tingling in your fingers or toes

Unusual bleeding or bruising

Increased infections

Feel weak or tired

Pale or gray color to your lips, tongue or palms of your hands

Severe diarrhea or vomiting

Gout Flares: The most common side effect of Colchicine Tablets, USP in people who have gout flares is

diarrhea.

FMF: The most common side effects of Colchicine Tablets, USP 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 Colchicine Tablets, USP. 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 Colchicine Tablets, USP?

Store Colchicine Tablets, USP at room temperature between 68°F and 77°F (20°C and 25°C).

Keep Colchicine Tablets, USP in a tightly closed container.

Keep Colchicine Tablets, USP out of the light.

Keep Colchicine Tablets, USP and all medicines out of the reach of children.

General Information about Colchicine Tablets, USP

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use

Colchicine Tablets, USP for a condition for which it was not prescribed. Do not give Colchicine Tablets,

USP 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 Colchicine Tablets, USP. If you would

like more information, talk with your healthcare provider. You can ask your healthcare provider or

pharmacist for information about Colchicine Tablets, USP that is written for healthcare professionals.

For more information, call 1-877-825-3327.

What are the ingredients in Colchicine Tablets, USP?

Active Ingredient: colchicine

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.

All trademarks are the property of their respective owners.

Distributed by:

Par Pharmaceutical

Chestnut Ridge, NY 10977

Relabeled by:

Proficient Rx LP

Thousand Oaks, CA 91320

OS2008-01-75-01

COL345 R1

February 2018

Revised: 10/2019

Document Id: b8b1efe2-3a84-4611-b4f7-722579c9c01e

34391-3

Set id: 8138028f-9b6a-4a77-9ae4-bf11c950e4d7

Version: 2

Effective Time: 20191001

Proficient Rx LP

COLCHICINE- colchicine tablet, film coated

Proficient Rx LP

----------

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use colchicine safely and effectively. See full

prescribing information for Colchicine Tablets, USP.

Colchicine Tablets, USP, for oral use

Initial U.S. Approval: 1961

INDICATIONS AND USAGE

Colchicine Tablets, USP are an alkaloid indicated for:

Colchicine Tablets, USP are not an analgesic medication and should not be used to treat pain from other causes.

DOSAGE AND ADMINISTRATION

Colchicine Tablets, USP are administered orally without regard to meals.

See full prescribing information for dose adjustment regarding patients with impaired renal function (2.5), impaired hepatic

function (2.6), the patient's age (2.3, 8.5) or use of coadministered drugs (2.4).

DOSAGE FORMS AND STRENGTHS

0.6 mg tablets (3).

CONTRAINDICATIONS

Patients with renal or hepatic impairment should not be given Colchicine Tablets, USP in conjunction with P-gp or strong

CYP3A4 inhibitors (5.3). In these patients, life-threatening and fatal colchicine toxicity has been reported with colchicine

taken in therapeutic doses (7).

WARNINGS AND PRECAUTIONS

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

(23%) and pharyngolaryngeal pain (3%).

FMF: Most common adverse reactions (up to 20%) are abdominal pain, diarrhea, nausea and vomiting. These effects are

Prophylaxis and treatment of gout flares in adults (1.1).

Familial Mediterranean fever (FMF) in adults and children 4 years or older (1.2).

Gout Flares:

Prophylaxis of Gout Flares: 0.6 mg once or twice daily in adults and adolescents older than 16 years of age (2.1).

Maximum dose 1.2 mg/day.

Treatment of Gout Flares: 1.2 mg (two tablets) at the first sign of a gout flare followed by 0.6 mg (one tablet) one

hour later (2.1).

FMF: Adults and children older than 12 years 1.2 – 2.4 mg; children 6 to 12 years 0.9 – 1.8 mg; children 4 to 6 years

0.3 – 1.8 mg (2.2, 2.3).

Give total daily dose in one or two divided doses (2.2).

Increase or decrease the dose as indicated and as tolerated in increments of 0.3 mg/day, not to exceed the

maximum recommended daily dose (2.2).

Fatal overdoses have been reported with colchicine in adults and children. Keep Colchicine Tablets, USP out of the

reach of children (5.1, 10).

Blood dyscrasias: myelosuppression, leukopenia, granulocytopenia, thrombocytopenia and aplastic anemia have been

reported (5.2).

Monitor for toxicity and if present consider temporary interruption or discontinuation of colchicine (5.2, 5.3, 5.4, 6,

10).

Drug interaction P-gp and/or CYP3A4 inhibitors: Coadministration of colchicine with P-gp and/or strong CYP3A4

inhibitors has resulted in life-threatening interactions and death (5.3, 7).

Neuromuscular toxicity: Myotoxicity including rhabdomyolysis may occur, especially in combination with other drugs

known to cause this effect. Consider temporary interruption or discontinuation of Colchicine Tablets, USP (5.4, 7).

usually mild, transient and reversible upon lowering the dose (6).

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-877-825-3327 or FDA at

1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Coadministration of P-gp and/or CYP3A4 inhibitors (e.g., clarithromycin or cyclosporine) have been demonstrated to alter

the concentration of colchicine. 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).

USE IN SPECIFIC POPULATIONS

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 10/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

1.1 Gout Flares

1.2 Familial Mediterranean Fever (FMF)

2 DOSAGE AND ADMINISTRATION

2.1 Gout Flares

2.2 FMF

2.3 Recommended Pediatric Dosage

2.4 Dose Modification for Coadministration of Interacting Drugs

2.5 Dose Modification in Renal Impairment

2.6 Dose Modification in Hepatic Impairment

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Fatal Overdose

5.2 Blood Dyscrasias

5.3 Drug Interactions

5.4 Neuromuscular Toxicity

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience in Gout

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

In the presence of mild to moderate renal or hepatic impairment, adjustment of dosing is not required for treatment

of gout flare, prophylaxis of gout flare and FMF, but patients should be monitored closely (2.5, 8.6).

In patients with severe renal impairment for prophylaxis of gout flares, the starting dose should be 0.3 mg/day for

gout flares, no dose adjustment is required, but a treatment course should be repeated no more than once every two

weeks. In FMF patients, start with 0.3 mg/day, and any increase in dose should be done with close monitoring (2.5,

8.6).

In patients with severe hepatic impairment, a dose reduction may be needed in prophylaxis of gout flares and FMF

patients; while a dose reduction may not be needed in gout flares, a treatment course should be repeated no more

than once every two weeks (2.5, 2.6, 8.6, 8.7).

For patients undergoing dialysis, the total recommended dose for prophylaxis of gout flares should be 0.3 mg given

twice a week with close monitoring. For treatment of gout flares, the total recommended dose should be reduced to

0.6 mg (one tablet) × 1 dose and the treatment course should not be repeated more than once every two weeks. For

FMF patients, the starting dose should be 0.3 mg/day and dosing can be increased with close monitoring (2.5, 8.6).

Pregnancy: Use only if the potential benefit justifies the potential risk to the fetus (8.1).

Nursing Mothers: Caution should be exercised when administered to a nursing woman (8.3).

Geriatric Use: The recommended dose of colchicine should be based on renal function (2.5, 8.5).

8.2 Labor and Delivery

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Renal Impairment

8.7 Hepatic Impairment

9 DRUG ABUSE AND DEPENDENCE

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

16.2 Storage

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

1.1 Gout Flares

Colchicine Tablets, USP are indicated for prophylaxis and the treatment of acute gout flares.

1.2 Familial Mediterranean Fever (FMF)

Colchicine Tablets, USP are indicated in adults and children four years or older for treatment of

familial Mediterranean fever (FMF).

2 DOSAGE AND ADMINISTRATION

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

Colchicine Tablets, USP are different for each indication and must be individualized.

The recommended dosage of Colchicine Tablets, USP depends on the patient's age, renal function,

hepatic function and use of coadministered drugs [see Dosage and Administration (2.4)].

Colchicine Tablets, USP are administered orally without regard to meals.

Colchicine Tablets, USP are not an analgesic medication and should not be used to treat pain from other

Sections or subsections omitted from the full prescribing information are not listed.

Prophylaxis of Gout Flares:

Colchicine Tablets, USP are indicated for prophylaxis of gout flares.

Treatment of Gout Flares:

Colchicine Tablets, USP are indicated for treatment of acute gout flares when taken at the first

sign of a flare.

causes.

2.1 Gout Flares

Prophylaxis of Gout Flares

The recommended dosage of Colchicine Tablets, USP 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. Colchicine Tablets, USP are 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 Colchicine Tablets, USP 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. Colchicine Tablets, USP 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.

2.2 FMF

The recommended dosage of Colchicine Tablets, USP for FMF in adults is 1.2 to 2.4 mg daily.

Colchicine Tablets, USP 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 Colchicine Tablets, USP

dose may be administered in one to two divided doses.

2.3 Recommended Pediatric Dosage

Prophylaxis and Treatment of Gout Flares

Colchicine Tablets, USP are not recommended for pediatric use in prophylaxis or treatment of gout

flares.

The recommended dosage of Colchicine Tablets, USP for FMF in pediatric patients four 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 Coadministration of Interacting Drugs

Concomitant Therapy

Coadministration of Colchicine Tablets, USP with drugs known to inhibit CYP3A4 and/or P-

glycoprotein (P-gp) increases the risk of colchicine-induced toxic effects (Table 1). If patients are

taking or have recently completed treatment with drugs listed in Table 1 within the prior 14 days, the

dose adjustments are as shown in the table below [see Drug Interactions (7)].

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

Table 1. Colchicine Tablets, USP 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

Dos age

Adjus ted

Dos e

Original

Intended

Dos age

Adjus ted

Dos e

Original

Intended

Dos age

Adjus ted

Dos e

Atazanavir

Clarithromycin

Darunavir/Ritonavir

Indinavir

Itraconazole

Ketoconazole

Lopinavir/Ritonavir

Nefazodone

Nelfinavir

Ritonavir

Saquinavir

Telithromycin

Tipranavir/Ritonavir

Significant

increase in

colchicine

plasma levels ;

fatal

colchicine

toxicity has

been reported

with

clarithromycin,

a strong

CYP3A4

inhibitor.

Similarly,

significant

increase in

colchicine

plasma levels

is anticipated

with other

strong

CYP3A4

inhibitors.

0.6 mg twice

a day

0.3 mg

once a day

1.2 mg (2

tablets)

followed

by 0.6 mg

(1 tablet)

1 hour

later.

Dose to

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

repeated

no earlier

than 3

days.

Maximum

daily

dose of

1.2 – 2.4

Maximum

daily

dose of

0.6 mg

(may be

given as

0.3 mg

twice a

day)

0.6 mg once

a day

0.3 mg

once every

other day

Moderate CYP3A4 Inhibitors

Drug

Noted or

Anticipated

Outcome

Gout Flares

FMF

Prophylaxis of Gout

Flares

Treatment of Gout

Flares

Original

Intended

Dos age

Adjus ted

Dos e

Original

Intended

Dos age

Adjus ted

Dos e

Original

Intended

Dos age

Adjus ted

Dos e

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

0.3 mg

twice a day

or 0.6 mg

once a day

1.2 mg (2

tablets)

followed

by 0.6 mg

(1 tablet)

1 hour

later.

Dose to

repeated

no earlier

than 3

1.2 mg (2

tablets) ×

1 dose.

Dose to

repeated

no earlier

than 3

days.

Maximum

daily

dose of

1.2 – 2.4

Maximum

daily

dose of

1.2 mg

(may be

given as

0.6 mg

twice a

day)

0.6 mg once

a day

0.3 mg

once a day

*

days.

P-gp Inhibitors

Drug

Noted or

Anticipated

Outcome

Gout Flares

FMF

Prophylaxis of Gout

Flares

Treatment of Gout

Flares

Original

Intended

Dos age

Adjus ted

Dos e

Original

Intended

Dos age

Adjus ted

Dos e

Original

Intended

Dos age

Adjus ted

Dos e

Cyclosporine

Ranolazine

Significant

increase in

colchicine

plasma levels ;

fatal

colchicine

toxicity has

been reported

with

cyclosporine, a

P-gp inhibitor.

Similarly,

significant

increase in

colchicine

plasma levels

is anticipated

with other P-

gp inhibitors.

0.6 mg twice

a day

0.3 mg

once a day

1.2 mg (2

tablets)

followed

by 0.6 mg

(1 tablet)

1 hour

later.

Dose to

repeated

no earlier

than 3

days.

0.6 mg (1

tablet) × 1

dose.

Dose to

repeated

no earlier

than 3

days.

Maximum

daily

dose of

1.2 – 2.4

Maximum

daily

dose of

0.6 mg

(may be

given as

0.3 mg

twice a

day)

0.6 mg once

a day

0.3 mg

once every

other day

Table 2. Colchicine Tablets, USP Dose Adjustment for Coadministration with Protease Inhibitors

Protease Inhibitor

Clinical

Comment

w/Colchicine - Prophylaxis of

Gout Flares

w/Colchicine -

Treatment of

Gout Flares

w/Colchicine

- Treatment

of FMF

Atazanavir sulfate

(Reyataz)

Patients with

renal or hepatic

impairment

should not be

given colchicine

with Reyataz.

Original dose

Adjusted dose 0.6 mg (1

tablet) × 1

dose,

followed by

0.3 mg (1/2

tablet) 1 hour

later. Dose to

be repeated no

earlier than 3

days.

Maximum

daily dose of

0.6 mg (may

be given as

0.3 mg twice

a day)

0.6 mg twice a

0.3 mg once a

0.6 mg once a day 0.3 mg once

every other day

Darunavir

(Prezista)

Patients with

renal or hepatic

impairment

should not be

Original dose

Adjusted dose 0.6 mg (1

tablet) × 1

dose,

followed by

Maximum

daily dose of

0.6 mg (may

be given as

0.6 mg twice a

0.3 mg once a

0.6 mg once a day 0.3 mg once

For magnitude of effect on colchicine plasma concentrations [see Clinical Pharmacology (12.3)]

Patients with renal or hepatic impairment should not be given Colchicine Tablets, USP in conjunction with strong

CYP3A4 or P-gp inhibitors [see Contraindications (4)]

When used in combination with Ritonavir, see dosing recommendations for strong CYP3A4 inhibitors [see

Contraindications (4)]

given colchicine

with

Prezista/ritonavir.

0.6 mg once a day 0.3 mg once

every other day

0.3 mg (1/2

tablet) 1 hour

later. Dose to

be repeated no

earlier than 3

days.

0.3 mg twice

a day)

Fosamprenavir

(Lexiva) with

Ritonavir

Patients with

renal or hepatic

impairment

should not be

given colchicine

with

Lexiva/ritonavir.

Original dose

Adjusted dose 0.6 mg (1

tablet) × 1

dose,

followed by

0.3 mg (1/2

tablet) 1 hour

later. Dose to

be repeated no

earlier than 3

days.

Maximum

daily dose of

0.6 mg (may

be given as

0.3 mg twice

a day)

0.6 mg twice a

0.3 mg once a

0.6 mg once a day 0.3 mg once

every other day

Fosamprenavir

(Lexiva)

Patients with

renal or hepatic

impairment

should not be

given colchicine

with

Lexiva/ritonavir.

Original dose

Adjusted dose 1.2 mg (2

tablets) × 1

dose. Dose to

be repeated no

earlier than 3

days.

Maximum

daily dose of

1.2 mg (may

be given as

0.6 mg twice

a day)

0.6 mg twice a

0.3 mg twice a

day or 0.6 mg

once a day

0.6 mg once a day 0.3 mg once a

Indinavir (Crixivan) Patients with

renal or hepatic

impairment

should not be

given colchicine

with Crixivan.

Original dose

Adjusted dose 0.6 mg (1

tablet) × 1

dose,

followed by

0.3 mg (1/2

tablet) 1 hour

later. Dose to

be repeated no

earlier than 3

days.

Maximum

daily dose of

0.6 mg (may

be given as

0.3 mg twice

a day)

0.6 mg twice a

0.3 mg once a

0.6 mg once a day 0.3 mg once

every other day

Lopinavir/Ritonavir

(Kaletra)

Patients with

renal or hepatic

impairment

should not be

given colchicine

with Kaletra.

Original dose

Adjusted dose 0.6 mg (1

tablet) × 1

dose,

followed by

0.3 mg (1/2

tablet) 1 hour

later. Dose to

be repeated no

earlier than 3

days.

Maximum

daily dose of

0.6 mg (may

be given as

0.3 mg twice

a day)

0.6 mg twice a

0.3 mg once a

0.6 mg once a day 0.3 mg once

every other day

Nelfinavir mesylate

(Viracept)

Patients with

renal or hepatic

impairment

should not be

given colchicine

with Viracept.

Original dose

Adjusted dose 0.6 mg (1

tablet) × 1

dose,

followed by

0.3 mg (1/2

tablet) 1 hour

later. Dose to

be repeated no

earlier than 3

Maximum

daily dose of

0.6 mg (may

be given as

0.3 mg twice

a day)

0.6 mg twice a

0.3 mg once a

0.6 mg once a day 0.3 mg once

every other day

days.

Ritonavir (Norvir)

Patients with

renal or hepatic

impairment

should not be

given colchicine

with Norvir.

Original dose

Adjusted dose 0.6 mg (1

tablet) × 1

dose,

followed by

0.3 mg (1/2

tablet) 1 hour

later. Dose to

be repeated no

earlier than 3

days.

Maximum

daily dose of

0.6 mg (may

be given as

0.3 mg twice

a day)

0.6 mg twice a

0.3 mg once a

0.6 mg once a day 0.3 mg once

every other day

Saquinavir

mesylate (Invirase)

Patients with

renal or hepatic

impairment

should not be

given colchicine

with

Invirase/ritonavir.

Original dose

Adjusted dose 0.6 mg (1

tablet) × 1

dose,

followed by

0.3 mg (1/2

tablet) 1 hour

later. Dose to

be repeated no

earlier than 3

days.

Maximum

daily dose of

0.6 mg (may

be given as

0.3 mg twice

a day)

0.6 mg twice a

0.3 mg once a

0.6 mg once a day 0.3 mg once

every other day

Tipranavir

(Aptivus)

Patients with

renal or hepatic

impairment

should not be

given colchicine

with

Aptivus/ritonavir.

Original dose

Adjusted dose 0.6 mg (1

tablet) × 1

dose,

followed by

0.3 mg (1/2

tablet) 1 hour

later. Dose to

be repeated no

earlier than 3

days.

Maximum

daily dose of

0.6 mg (may

be given as

0.3 mg twice

a day)

0.6 mg twice a

0.3 mg once a

0.6 mg once a day 0.3 mg once

every other day

Treatment of gout flares with Colchicine Tablets, USP is not recommended in patients receiving

prophylactic dose of Colchicine Tablets, USP and CYP3A4 inhibitors.

2.5 Dose Modification in Renal Impairment

Colchicine dosing must be individualized according to the patient's renal function [see Use in Specific

Populations (8.6)].

in mL/minute may be estimated from serum creatinine (mg/dL) determination using the following

formula:

[140-age (years) × weight (kg)]

= 72 × serum creatinine (mg/dL) × 0.85 for female patients

Gout Flares

Prophylaxis of Gout Flares

For prophylaxis of gout flares in patients with mild (estimated creatinine clearance [Cl

] 50 to 80

mL/min) to moderate (Cl

30 to 50 mL/min) renal function impairment, adjustment of the recommended

dose is not required, but patients should be monitored closely for adverse effects of colchicine.

However, in patients with severe impairment, the starting dose should be 0.3 mg/day and any increase in

dose should be done with close monitoring. For the prophylaxis of gout flares in patients undergoing

dialysis, the starting doses should be 0.3 mg given twice a week with close monitoring [see Clinical

Pharmacology (12.3) and Use in Specific Populations (8.6)].

Treatment of Gout Flares

For treatment of gout flares in patients with mild (Cl

50 to 80 mL/min) to moderate (Cl

30 to 50

mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients

should be monitored closely for adverse effects of colchicine. However, in patients with severe

impairment, while the dose does not need to be adjusted for the treatment of gout flares, a treatment

course should be repeated no more than once every two weeks. For patients with gout flares requiring

repeated courses, consideration should be given to alternate therapy. For patients undergoing dialysis,

the total recommended dose for the treatment of gout flares should be reduced to a single dose of 0.6

mg (one tablet). For these patients, the treatment course should not be repeated more than once every

two weeks [see Clinical Pharmacology (12.3) and Use in Specific Populations (8.6)].

Treatment of gout flares with Colchicine Tablets, USP is not recommended in patients with renal

impairment who are receiving Colchicine Tablets, USP for prophylaxis.

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 (Cl

50 to 80 mL/min) and moderate (Cl

30 to 50 mL/min) renal impairment

should be monitored closely for adverse effects of colchicine. Dose reduction may be necessary. For

patients with severe renal failure (Cl

less than 30 mL/min), start with 0.3 mg/day; any increase in dose

should be done with adequate monitoring of the patient for adverse effects of colchicine [see Use in

Specific Populations (8.6)]. For patients undergoing dialysis, the total recommended starting dose should

be 0.3 mg (half tablet) per day. Dosing can be increased with close monitoring. Any increase in dose

should be done with adequate monitoring of the patient for adverse effects of colchicine [see Clinical

Pharmacology (12.3) and Use in Specific Populations (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 colchicine. Dose reduction should be considered for the prophylaxis of gout flares in patients with

severe hepatic impairment [see Use in Specific Populations (8.7)].

Treatment of Gout Flares

For treatment of gout flares in patients with mild to moderate hepatic function impairment, adjustment of

the recommended dose is not required, but patients should be monitored closely for adverse effects of

colchicine. However, for the treatment of gout flares in patients with severe impairment, while the dose

does not need to be adjusted, a treatment course should be repeated no more than once every two weeks.

For these patients, requiring repeated courses for the treatment of gout flares, consideration should be

given to alternate therapy [see Use in Specific Populations (8.7)].

Treatment of gout flares with Colchicine Tablets, USP is not recommended in patients with hepatic

impairment who are receiving Colchicine Tablets, USP for prophylaxis.

Patients with mild to moderate hepatic impairment should be monitored closely for adverse effects of

colchicine. Dose reduction should be considered in patients with severe hepatic impairment [see Use in

Specific Populations (8.7)].

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 Colchicine Tablets, USP 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.

5 WARNINGS AND PRECAUTIONS

5.1 Fatal Overdose

Fatal overdoses, both accidental and intentional, have been reported in adults and children who have

ingested colchicine [see Overdosage (10)]. Colchicine Tablets, USP 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 colchicine used in therapeutic doses.

5.3 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 (7)]. Use of

Colchicine Tablets, USP 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 Colchicine Tablets, USP may potentiate the

development of myopathy [see Drug Interactions (7)]. Once colchicine is stopped, the symptoms

generally resolve within one week to several months.

6 ADVERSE REACTIONS

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 Colchicine Tablets, USP for

treatment of gout flares were diarrhea (23%) and pharyngolaryngeal pain (3%).

Gastrointestinal tract adverse effects are the most frequent side effects in patients initiating Colchicine

Tablets, USP, 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 one hour) of

Colchicine Tablets, USP 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

Colchicine Tablets, USP 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 Colchicine Tablets, USP 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

Colchicine Tablets, USP 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)

Abdominal Discomfort

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

3 (4)

2 (3)

Gout

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)

Pharyngolaryngeal Pain

1 (2)

2 (3)

6.2 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 (10)].

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

7 DRUG INTERACTIONS

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 Colchicine Tablets,

USP are 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 Colchicine Tablets,

USP 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 colchicine toxicity should be evaluated promptly

and, if toxicity is suspected, Colchicine Tablets, USP 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:

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

8 USE IN SPECIFIC POPULATIONS

8.1 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 Colchicine Tablets, USP,

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. Colchicine Tablets, USP 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 colchicine on labor and delivery is unknown.

8.3 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 Colchicine Tablets, USP are administered to a nursing

woman.

8.4 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.

8.5 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 Dosage and Administration (2.4) and Clinical Pharmacology (12.3)].

8.6 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 Cl

50 to 80

mL/min) to moderate (Cl

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 Dosage and

Administration (2.5)].

Treatment of Gout Flares

For treatment of gout flares in patients with mild (Cl

50 to 80 mL/min) to moderate (Cl

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 Dosage and Administration (2.5)].

Although, pharmacokinetics of colchicine in patients with mild (Cl

50 to 80 mL/min) and moderate

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

less than 30 mL/min) and end-stage renal disease requiring dialysis, Colchicine Tablets, USP 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 colchicine [see Clinical Pharmacology (12.3) and Dosage and

Administration (2.5)].

8.7 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 Clinical Pharmacology (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 colchicine. Dose reduction should be considered for the prophylaxis of gout flares in patients with

severe hepatic impairment [see Dosage and Administration (2.6)].

Treatment of Gout Flares

For treatment of gout flares in patients with mild to moderate hepatic function impairment, adjustment of

the recommended Colchicine Tablets, USP 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, 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 Dosage and Administration (2.6)].

In patients with severe hepatic disease, dose reduction should be considered with careful monitoring

[see Clinical Pharmacology (12.3) and Dosage and Administration (2.6)].

9 DRUG ABUSE AND DEPENDENCE

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

10 OVERDOSAGE

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 Clinical Pharmacology (12.3)].

11 DESCRIPTION

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 C

H NO 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.

Colchicine Tablets, USP 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 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.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The mechanism by which Colchicine Tablets, USP exert their beneficial effect in patients with FMF has

not been fully elucidated; however, evidence suggests that colchicine may interfere with the

intracellular assembly of the inflammasome complex present in neutrophils and monocytes that mediates

activation of interleukin-1β. Additionally, colchicine 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, colchicine is absorbed when given orally, reaching a mean C

of 2.5 ng/mL (range

1.1 to 4.4 ng/mL) in one to two hours (range 0.5 to three hours) after a single dose administered under

fasting conditions.

Following oral administration of Colchicine Tablets, USP given as 1.8 mg colchicine over one hour to

healthy, young adults under fasting conditions, colchicine 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 nonrecommended high-dose regimen (4.8 mg over six 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 postdose (range 0.5 to 3.0 hours). Mean pharmacokinetic

parameter values in healthy adults are shown in Table 5.

Table 5. Mean (%CV) Pharmacokinetic Parameters in Healthy Adults

Given Colchicine Tablets, USP

C

(Colchicine ng/mL)

T

(h)

Vd/F

(L)

CL/F

(L/hr)

t

(h)

CL = Dose/AUC

(calculated from mean values)

Vd = CL/Ke (calculated from mean values)

Colchicine Tablets, USP 0.6 mg Single Dose (N=13)

(28.7)

(1.0 – 3.0)

341.5

(54.4)

54.1

(31.0)

Colchicine Tablets, USP 0.6 mg Twice Daily × 10 Days (N=13)

(23.7)

(0.5 – 3.0)

1150

(18.7)

30.3

(19.0)

26.6

(16.3)

In some subjects, secondary colchicine peaks are seen, occurring between three and 36 hours postdose

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 Colchicine Tablets, USP with food has no effect on the rate of colchicine absorption

but does decrease the extent of colchicine by approximately 15%. This is without clinical significance.

Distribution

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

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

Colchicine crosses the placenta (plasma levels in the fetus are reported to be approximately 15% of the

maternal concentration). Colchicine also distributes into breast milk at concentrations similar to those

found in the maternal serum [see Use in Specific Populations (8.1, 8.3)].

Metabolism

Colchicine 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 colchicine to 2- and 3-DMC. Plasma levels of these metabolites are

minimal (less than 5% of parent drug).

Elimination/Excretion

max

max

*

1/2

mean (range)

max

In healthy volunteers (n=12), 40 to 65% of 1 mg orally administered colchicine was recovered

unchanged in urine. Enterohepatic recirculation and biliary excretion are also postulated to play a role

in colchicine 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. Colchicine is a

substrate of P-gp.

Extracorporeal Elimination

Colchicine is not removed by hemodialysis.

Special Populations

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

Pediatric Patients

Pharmacokinetics of colchicine was not evaluated in pediatric patients.

Elderly

A published report described the pharmacokinetics of 1 mg oral colchicine tablet in four elderly

women compared to six young healthy males. The mean age of the four elderly women was 83 years

(range 75 to 93), mean weight was 47 kg (38 to 61 kg) and mean creatinine clearance was 46 mL/min

(range 25 to 75 mL/min). Mean peak plasma levels and AUC of colchicine were two times higher in

elderly subjects compared to young healthy males.

A pharmacokinetic study using a single oral dose of one 0.6 mg colchicine tablet was conducted in

young healthy subjects (n=20) between the ages of 18 and 30 years and elderly subjects (n=18) between

the ages of 60 and 70 years. Elderly subjects in this study had a median age of 62 years and a mean

(±SD) age of 62.83 ± 2.83 years. A statistically significant difference in creatinine clearance (mean ±

SD) was found between the two age groups (132.56 ± 23.16 mL/min for young vs 87.02 ± 17.92 mL/min

for elderly subjects, respectively). The following pharmacokinetic parameter values (mean ± SD) were

observed for colchicine in the young and elderly subjects, respectively: AUC

(ng/hr/mL) 22.39 ±

6.95 and 25.01 ± 6.92; C

(ng/mL) 2.61 ± 0.71 and 2.56 ± 0.97; T

(hr) 1.38 ± 0.42 and 1.25 ± 0.43;

apparent elimination half-life (hr) 24.92 ± 5.34 and 30.06 ± 10.78; and clearance (mL/min) 0.0321 ±

0.0091 and 0.0292 ± 0.0071.

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 than 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 Dosage and Administration (2.4) and Use in Specific Populations (8.5)].

Renal Impairment

Pharmacokinetics of colchicine in patients with mild and moderate renal impairment is not known. A

published report described the disposition of colchicine (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 colchicine 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 Dosage and Administration (2.5) and Use in Specific Populations (8.6)].

Hepatic Impairment

Published reports on the pharmacokinetics of IV colchicine in patients with severe chronic liver

disease, as well as those with alcoholic or primary biliary cirrhosis and normal renal function suggest

wide interpatient variability. In some subjects with mild to moderate cirrhosis, the clearance of

colchicine is significantly reduced and plasma half-life prolonged compared to healthy subjects. In

subjects with primary biliary cirrhosis, no consistent trends were noted [see Dosage and Administration

(2.6) and Use in Specific Populations (8.7)]. No pharmacokinetic data are available for patients with

severe hepatic impairment (Child-Pugh C).

0-inf

Drug Interactions

In Vitro Drug Interactions

In vitro studies in human liver microsomes have shown that colchicine 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 coadministration of other drugs with Colchicine Tablets, USP on C

, AUC and C

are summarized in Table 6 (effect of other drugs on colchicine) and Table 7 (effect of colchicine on

other drugs). For information regarding clinical recommendations, see Table 1 in Dose Modification for

Coadministration of Interacting Drugs [see Dosage and Administration (2.4)].

Table 6. Drug Interactions: Pharmacokinetic Parameters for Colchicine

Tablets, USP in the Presence of the Coadministered Drug

Coadminis tered

Drug

Dose of

Coadminis tered

Drug (mg)

Dose of

Colchicine

T ablets ,

USP (mg)

N

% Change in

Colchicine

Concentrations from

Baseline

(Range: Min - Max)

C

AUC

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 twice

daily, 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 twice

daily, 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 twice

daily, 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 twice

daily, 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) coadministered with Colchicine Tablets, USP (0.6 mg twice daily ×

14 days), hormone concentrations are not affected.

In healthy volunteers given theophylline coadministered with Colchicine Tablets, USP (0.6 mg twice

daily × 14 days), theophylline concentrations were not affected.

max

0 -t

Table 7. Drug Interactions: Pharmacokinetic Parameters for

Coadministration of Drug in the Presence of Colchicine Tablets, USP

Coadminis tered

Drug

Dose of

Coadminis tered

Drug (mg)

Dose of

Colchicine

T ablets ,

USP (mg)

N

% Change in

Coadministered Drug

Concentrations from

Baseline

(Range: Min - Max)

C

AUC

Theophylline

300 mg (elixir)

single dose

0.6 mg

twice daily

× 14 days

(-30.4 to

23.1)

(-28.5 to

27.1)

Ethinyl Estradiol

(Ortho-Novum

1/35)

21-day cycle

(active treatment)

+ 7-day placebo

0.6 mg

twice daily

× 14 days

-6.7

(-40.3 to

44.7)

-3.0

(-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

Two year studies were conducted in mice and rats to assess the carcinogenic potential of colchicine.

No evidence of colchicine-related tumorigenicity was observed in mice or rats at colchicine oral doses

up to 3 and 2 mg/kg/day, respectively (approximately six and eight times, respectively, the maximum

recommended human dose of 2.4 mg on a mg/m basis).

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 Colchicine Tablets, USP. 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

max

0 -t

Conducted in healthy adult females

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.

14 CLINICAL STUDIES

The evidence for the efficacy of colchicine in patients with chronic gout is derived from the published

literature. Two randomized clinical trials assessed the efficacy of colchicine 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 colchicine decreased the frequency of gout flares.

The efficacy of a low-dosage regimen of oral colchicine (total dose 1.8 mg over one hour) for

treatment of gout flares was assessed in a multicenter, randomized, double-blind, placebo-controlled,

parallel group, one week, dose-comparison study. Patients meeting American College of Rheumatology

criteria for gout were randomly assigned to three groups: high-dose colchicine (1.2 mg, then 0.6 mg

hourly × six hours [4.8 mg total]); low-dose colchicine (1.2 mg, then 0.6 mg in one hour [1.8 mg total]

followed by five placebo doses hourly); or placebo (two capsules, then one capsule hourly × six

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 colchicine 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 postdose assessment relative to the pretreatment score and

did not use rescue medication prior to the actual time of 24 hour postdose assessment.

Rates of response were similar for the recommended low-dose treatment group (38%) and the

nonrecommended high-dose group (33%) but were higher as compared to the placebo group (16%) as

shown in Table 8.

Table 8. Number (%) of Responders Based on Target Joint Pain Score

at 24 Hours Post First Dose

Colchicine Tablets, USP

Dose Responders n (%)

% Differences in Proportion

Low-Dose

(n=74)

High-Dose

(n=52)

Placebo n (%)

(n=58)

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 shows the percentage of patients achieving varying degrees of improvement in pain from

baseline at 24 hours.

The evidence for the efficacy of colchicine 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 six month crossover study during which five

patients discontinued due to study noncompliance. The 10 patients completing the study experienced

five attacks over the course of 90 days while treated with colchicine 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 four month crossover study during which nine patients discontinued due to lack of efficacy

while receiving placebo or study noncompliance. The 13 patients completing the study experienced 18

attacks over the course of 60 days while treated with colchicine compared to 68 attacks over the

course of 60 days while treated with placebo. The third study was discontinued after an interim analysis

of six of the 11 patients enrolled had completed the study; results could not be confirmed.

Open-label experience with colchicine 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

colchicine and for dosing recommendations.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Colchicine Tablets, USP 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 71205-310-30

Bottles of 60 71205-310-60

Bottles of 90 71205-310-90

16.2 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.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Dosing Instructions

Patients should be advised to take Colchicine Tablets, USP 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 Colchicine Tablets, USP is missed:

Fatal Overdose

Instruct patient that fatal overdoses, both accidental and intentional, have been reported in adults and

children who have ingested colchicine. Colchicine Tablets, USP 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 Colchicine Tablets, USP.

Drug and Food Interactions

Patients should be advised that many drugs or other substances may interact with Colchicine Tablets,

USP 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 Colchicine Tablets, USP treatment.

Neuromuscular Toxicity

Patients should be informed that muscle pain or weakness, tingling or numbness in fingers or toes may

occur with Colchicine Tablets, USP alone or when it is used with certain other drugs. Patients

developing any of these signs or symptoms must discontinue Colchicine Tablets, USP and seek medical

evaluation immediately.

MEDICATION GUIDE

Colchicine Tablets, USP

Read the Medication Guide that comes with Colchicine Tablets, USP 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 Colchicine Tablets, USP when you start taking it and at regular checkups.

What is the most important information that I should know about Colchicine Tablets, USP?

Colchicine Tablets, USP can cause serious side effects or death if levels of colchicine are too high in

your body.

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.

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 Colchicine Tablets, USP.

What are Colchicine Tablets, USP?

Colchicine Tablets, USP are a prescription medicine used to:

Colchicine Tablets, USP are not a pain medicine, and should not be taken to treat pain related to other

conditions unless specifically prescribed for those conditions.

Who should not take Colchicine Tablets, USP?

Do not take Colchicine Tablets, USP 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 that I should know about Colchicine

Tablets, USP?"

What should I tell my healthcare provider before starting Colchicine Tablets, USP?

See "What is the most important information that I should know about Colchicine Tablets,

USP?"

Taking certain medicines with Colchicine Tablets, USP can cause your level of colchicine to be

too high, especially if you have kidney or liver problems.

Tell your healthcare provider about all your medical conditions, including if you have kidney or

liver problems. Your dose of Colchicine Tablets, USP may need to be changed.

Tell your healthcare provider about all the medicines you take, including prescription and

nonprescription medicines, vitamins and herbal supplements.

Even medicines that you take for a short period of time, such as antibiotics, can interact with

Colchicine Tablets, USP and cause serious side effects or death.

Talk to your healthcare provider or pharmacist before taking any new medicine.

Especially tell your healthcare provider if you take:

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)

Know the medicines you take. Keep a list of them and show it to your healthcare provider and

pharmacist when you get a new medicine.

Keep Colchicine Tablets, USP out of the reach of children.

prevent and treat gout flares in adults

treat familial Mediterranean fever (FMF) in adults and children age 4 or older

Before you take Colchicine Tablets, USP 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 that I

should know about Colchicine Tablets, USP?" Do not start a new medicine without talking to your

healthcare provider.

Using Colchicine Tablets, USP 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 Colchicine Tablets, USP. Talk to your healthcare provider about whether the

medications you are taking might interact with Colchicine Tablets, USP and what side effects to look

for.

How should I take Colchicine Tablets, USP?

What should I avoid while taking Colchicine Tablets, USP?

What are the possible side effects of Colchicine Tablets, USP?

Colchicine Tablets, USP can cause serious side effects or even cause death. See "What is the most

important information that I should know about Colchicine Tablets, USP?"

Get medical help right away if you have:

have liver or kidney problems.

are pregnant or plan to become pregnant. It is not known if Colchicine Tablets, USP will harm

your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become

pregnant.

are breastfeeding or plan to breastfeed. Colchicine passes into your breast milk. You and your

healthcare provider should decide if you will take Colchicine Tablets, USP or breastfeed. If you

take Colchicine Tablets, USP and breastfeed, you should talk to your child's healthcare provider

about how to watch for side effects in your child.

Take Colchicine Tablets, USP exactly as your healthcare provider tells you to take them. If you

are not sure about your dosing, call your healthcare provider.

Colchicine Tablets, USP can be taken with or without food.

If you take too many Colchicine Tablets, USP go to the nearest hospital emergency room right

away.

Do not stop taking Colchicine Tablets, USP even if you start to feel better, unless your healthcare

provider tells you.

Your healthcare provider may do blood tests while you take Colchicine Tablets, USP.

If you take Colchicine Tablets, USP daily and you miss a dose, then take it as soon as you

remember. If it is almost time for your next dose, just skip the missed dose. Take the next dose at

your regular time. Do not take 2 doses at the same time.

If you have a gout flare while taking Colchicine Tablets, USP daily, report this to your healthcare

provider.

Avoid eating grapefruit or drinking grapefruit juice while taking Colchicine Tablets, USP. It can

increase your chances of getting serious side effects.

Muscle weakness or pain

Numbness or tingling in your fingers or toes

Gout Flares: The most common side effect of Colchicine Tablets, USP in people who have gout flares

is diarrhea.

FMF: The most common side effects of Colchicine Tablets, USP 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 Colchicine Tablets, USP. 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 Colchicine Tablets, USP?

Keep Colchicine Tablets, USP and all medicines out of the reach of children.

General Information about Colchicine Tablets, USP

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not

use Colchicine Tablets, USP for a condition for which it was not prescribed. Do not give Colchicine

Tablets, USP 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 Colchicine Tablets, USP. If

you would like more information, talk with your healthcare provider. You can ask your healthcare

provider or pharmacist for information about Colchicine Tablets, USP that is written for healthcare

professionals.

For more information, call 1-877-825-3327.

What are the ingredients in Colchicine Tablets, USP?

Active Ingredient: colchicine

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.

All trademarks are the property of their respective owners.

Distributed by:

Par Pharmaceutical

Chestnut Ridge, NY 10977

Relabeled by:

Proficient Rx LP

Thousand Oaks, CA 91320

OS2008-01-75-01

Unusual bleeding or bruising

Increased infections

Feel weak or tired

Pale or gray color to your lips, tongue or palms of your hands

Severe diarrhea or vomiting

Store Colchicine Tablets, USP at room temperature between 68°F and 77°F (20°C and 25°C).

Keep Colchicine Tablets, USP in a tightly closed container.

Keep Colchicine Tablets, USP out of the light.

COL345 R1

February 2018

PRINCIPAL DISPLAY PANEL - 0.6 mg Tablet Bottle Label

30 TABLETS

NDC 71205-310-30

Colchicine

Tablets, USP

0.6 mg

PHARMACIST:

PLEASE DISPENSE WITH

MEDICATION GUIDE ATTACHED

PAR

PHARMACEUTICAL

Rx only

COLCHICINE

colchicine tablet, film coated

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:7120 5-310 (NDC:0 254-20 0 8 )

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

Co lchicine (UNII: SML2Y3J35T) (Co lchicine - UNII:SML2Y3J35T)

Co lc hic ine

0 .6 mg

Proficient Rx LP

Inactive Ingredients

Ingredient Name

Stre ng th

ca rna uba wa x (UNII: R12CBM0 EIZ)

FD&C blue no . 2 (UNII: L0 6 K8 R7DQK)

FD&C red no . 4 0 (UNII: WZB9 127XOA)

hypro mello se, unspecified (UNII: 3NXW29 V3WO)

la cto se mo no hydra te (UNII: EWQ57Q8 I5X)

ma g nesium stea ra te (UNII: 70 0 9 7M6 I30 )

micro crysta lline cellulo se (UNII: OP1R32D6 1U)

po lydextro se (UNII: VH2XOU12IE)

po lyethylene g lyco l, unspecified (UNII: 3WJQ0 SDW1A)

sta rch, co rn (UNII: O8 232NY3SJ)

so dium sta rch g lyco la te type A po ta to (UNII: 58 56 J3G2A2)

tita nium dio xide (UNII: 15FIX9 V2JP)

tria cetin (UNII: XHX3C3X6 73)

Product Characteristics

Color

PURPLE

S core

2 pieces

S hap e

OVAL (capsule-shaped)

S iz e

8 mm

Flavor

Imprint Code

AR;374

Contains

Packag ing

#

Item Code

Package Description

Marketing Start

Date

Marketing End

Date

1

NDC:7120 5-310 -

30 in 1 BOTTLE, PLASTIC; Type 0 : No t a Co mbinatio n

Pro duc t

0 8 /0 1/20 19

2

NDC:7120 5-310 -

6 0 in 1 BOTTLE, PLASTIC; Type 0 : No t a Co mbinatio n

Pro duc t

0 8 /0 1/20 19

3

NDC:7120 5-310 -

9 0 in 1 BOTTLE, PLASTIC; Type 0 : No t a Co mbinatio n

Pro duc t

0 8 /0 1/20 19

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA autho rized generic

NDA0 22352

0 7/0 1/20 18

Labeler -

Proficient Rx LP (079196022)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Pro ficient Rx LP

0 79 19 6 0 22

RELABEL(7120 5-310 )

Revised: 10/2019

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