Colchicine

Colchicine is used to prevent gout attacks (sudden, severe pain in one or more joints caused by abnormally high levels of a substance called uric acid in the blood) in adults, and to relieve the pain of gout attacks when they occur. Colchicine is also used to treat familial Mediterranean fever (FMF; an inborn condition that causes episodes of fever, pain, and swelling of the stomach area, lungs, and joints) in adults and children 4 years of age and older. Colchicine is not a pain reliever and cannot be used to treat pain that is not caused by gout or FMF. Colchicine is in a class of medications called anti-gout agents. It works by stopping the natural processes that cause swelling and other symptoms of gout and FMF.

The recommended dose of colchicine for acute gout is:

• 1.2 mg at the first sign of symptoms followed by 0.6 mg one hour later.
• The maximum dose over a one hour period is 1.8 mg.
• In clinical trials 1.8 mg of colchicine administered over 1 hour was as effective as 4.8 mg administered over 6 hours, and patients experienced fewer side effects.
• The recommended dose for preventing flares of gout in individuals older than 16 years of age is 0.6 mg once or twice daily.

The recommended doses of colchicine for FMF are:

• Children 4-6 years old: 0.3 to 1.8 mg daily
• Children 6-12 years old: 0.6 to 1.8 mg daily
• Adults and adolescents older than 12 years: 1.2 to 2.4 mg daily

Total daily doses may be administered in two divided doses. Doses should be increased by 0.3 mg daily as tolerated until symptoms are controlled or maximum daily doses are reached. Doses should be decreased by 0.3 mg daily if side effects occur.

Tablets: 0.6 mg

Colchicine should be stored between 20 and 25 C (68-77 F)

Colchicine Capsules

What is the most important information I should know about colchicine capsules?

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

• Taking certain medicines with colchicine capsules 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 capsules may need to be changed.
• Even medicines that you take for a short period of time, such as antibiotics, can interact with colchicine capsules and cause serious side effects or death.

What are colchicine capsules?

Colchicine capsules are a prescription medication used to prevent gout flares in adults.

It is not known if colchicine capsules are safe and effective for the treatment of:

• acute gout flares

Colchicine capsules are not a pain medicine and it should not be taken to treat pain related to other conditions unless specifically for those conditions.

It is not known if colchicine capsules are safe and effective in children.

Who should not take colchicine capsules?

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

What should I tell my healthcare provider before taking colchicine capsules?

Before you take colchicine capsules, tell your healthcare provider:

• about all of your medical conditions
• if you have kidney or liver problems
• if you are pregnant or plan to become pregnant. It is not known if colchicine capsules can harm your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant.
• if you are breastfeeding or plan to breastfeed. Colchicine can pass into your breast milk and may harm your baby. Talk to your healthcare provider about the best way to feed your baby if you take colchicine capsules.

Tell your healthcare provider about all the medicines you take, including prescription, over-thecounter medicines, vitamins, or herbal supplements.

• Using colchicine capsules with certain other medicines can affect each other causing serious side effects and/or death.
• Do not take colchicine capsules with other medicines unless your healthcare provider tells you to.
• Know the medicines you take. Keep a list of your medicines with you to show your healthcare provider and pharmacist each time you get a new medicine.
• Especially tell your healthcare provider if you take:
  • medicines that may affect how your liver works (CYP3A4 inhibitors)
  • cyclosporine (Neoral®, Gengraf®, Sandimmune®)
  • cholesterol lowering medicines
  • antibiotics

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 affect colchicine capsules.

How should I take colchicine capsules?

• Take colchicine capsules exactly as your healthcare provider tells you to take it.
• Colchicine capsules can be taken with or without food.
• If you take too much colchicine capsules, call your healthcare provider or go to the nearest hospital emergency room right away.
• Do not stop taking colchicine capsules unless your healthcare provider tells you to.
• If you miss a dose of colchicine capsules, take it as soon as you remember. If it is almost time for your next dose, 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 capsules, tell your healthcare provider.

What should I avoid while taking colchicine capsules?

• Avoid eating grapefruit or drinking grapefruit juice while taking colchicine capsules. It can increase your chances of getting serious side effects.

What are the possible side effects of colchicine capsules?

Colchicine capsules can cause serious side effects or death. See “What is the most important information I should know about colchicine capsules?”

Get medical help right away, if you have:

• unusual bleeding or bruising
• increased infections
• weakness or fatigue
• muscle weakness or pain
• numbness or tingling in your fingers or toes
• pale or gray color to your lips, tongue, or palms of your hands
• severe diarrhea or vomiting

The most common side effects of colchicine capsules include 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 capsules. 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 capsules?

• Store colchicine capsules at room temperature between 68° to 77°F (20° to 25°C).
• Keep colchicine capsules in a tightly closed container.
• Keep colchicine capsules out of the light and away from moisture.

Keep colchicine capsules and all medicines out of the reach of children.

General information about the safe and effective use of colchicine capsules

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not take colchicine capsules for a condition for which it was not prescribed. Do not give colchicine capsules 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 capsules. If you would like more information, talk to your pharmacist or healthcare provider for information about colchicine capsules that is written for health professionals.

For more information, go to www.west-ward.com or call 1-877-233-2001.

What are the ingredients in colchicine capsules?

Active Ingredient: Colchicine

Inactive Ingredients : colloidal silicon dioxide, lactose anhydrous, magnesium stearate, microcrystalline cellulose and sodium starch glycolate. The capsule shell contains gelatin, purified water, titanium dioxide, erythrosine, Brilliant Blue FCF and Quinoline Yellow.

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

Mechanism of Action

Gout: Disruption of cytoskeletal functions through inhibition of β-tubulin polymerization into microtubules; this prevents activation, degranulation, and migration of neutrophils thought to mediate some gout symptoms

FMF: Mechanism not established; may interfere with intracellular assembly of inflammasome complex present in neutrophils and monocytes, which mediates activation of interleukin-1β

Absorption

Bioavailability: 45%

Onset: 18-24 hr

Time to peak effect: 48-72 hr

Peak plasma concentration: 6.2-6.8 ng/mL

Distribution

Protein bound: 34-44%

Vd: 5-8 L/kg

Metabolism

Metabolized by P-gp and CYP3A4

Metabolites: Demethylated to 2 primary metabolites and 1 minor metabolite

Elimination

Half-life: 26.6-31.2 hr

Dialyzable: No (hemodialysis)

Excretion: Feces, urine (65%)

If you take too much colchicine call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If colchicine is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

• Gout (Gouty Arthritis)

You should not use colchicine if you are allergic to it.

Some medicines can cause unwanted or dangerous effects when used with colchicine, especially if you have liver or kidney disease. Your doctor may need to change your treatment plan if you use any of the following drugs:

• cyclosporine;

• nefazodone;

• tipranavir;

• clarithromycin or telithromycin;

• itraconazole or ketoconazole; or

• HIV or AIDS medicine--atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, or saquinavir.

To make sure colchicine is safe for you, tell your doctor if you have:

• liver disease;

• kidney disease; or

• if you take digoxin, or cholesterol-lowering medications.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Colchicine can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

(KOL chi seen)

• Antigout Agent

Concomitant use of a P-glycoprotein (P-gp) or strong CYP3A4 inhibitor in presence of renal or hepatic impairment

Mitigare: Patients with both renal and hepatic impairment.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to colchicine; serious gastrointestinal, hepatic, renal, and cardiac disease

Familial Mediterranean fever (FMF): Oral:

Tablet (eg, Colcrys) only:

Children 4 to 6 years: 0.3 to 1.8 mg daily in 1 to 2 divided doses

Children 6 to 12 years: 0.9 to 1.8 mg daily in 1 to 2 divided doses

Adolescents >12 years: Refer to adult dosing.

Gout prophylaxis/treatment: Oral: Adolescents >16 years: Refer to adult dosing.

CBC, renal and hepatic function tests

Adverse events were observed in animal reproduction studies. Colchicine crosses the human placenta. Use during pregnancy in the treatment of familial Mediterranean fever has not shown an increase in miscarriage, stillbirth, or teratogenic effects (limited data).

Consult your pharmacist.

How to use Colchicine Powder

Consult your pharmacist.

Consult your pharmacist.

Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

Applies to colchicine: oral capsule, oral tablet

Along with its needed effects, colchicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking colchicine:

• Diarrhea
• nausea or vomiting
• stomach pain

• Black, tarry stools
• blood in the urine or stools
• burning, "crawling", or tingling feeling in the skin
• difficulty with breathing when exercising
• fever with or without chills
• headache
• large, hive-like swellings on the face, eyelids, mouth, lips, or tongue
• muscle weakness
• numbness in the fingers or toes (usually mild)
• pain
• peeling of the skin
• pinpoint red spots on the skin
• redness
• skin rash or hives
• sores, ulcers, or white spots on the lips or in the mouth
• sore throat
• swelling
• tenderness
• unusual bleeding or bruising
• unusual tiredness or weakness

Get emergency help immediately if any of the following symptoms of overdose occur while taking colchicine:

• Bleeding
• burning feeling in the stomach, throat, or skin
• convulsions (seizures)
• diarrhea (severe or bloody)
• fast, shallow breathing
• muscle weakness (very severe)
• nausea, stomach pain, or vomiting (severe)

Some side effects of colchicine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Hair loss
• loss of appetite

0.6 mg orally once or twice a day
Maximum dose: 1.2 mg/day

Comments:
-Dose adjustments may be required based on renal function, hepatic function, and use of concomitant medications.
-The safety and effectiveness for the acute treatment of gout flares during prophylaxis has not been studied.

Use: For the prophylaxis of gout flares.

Patients with renal impairment should not take colchicine in conjunction with drugs that inhibit both P-glycoprotein (P-gp) and CYP450 3A4.

Gout Flares:
Mild to moderate renal impairment (CrCl 30 to 80 mL/min): Use caution; no adjustment recommended, but dose reduction may be necessary; monitor closely for adverse effects
Severe renal impairment (CrCl less than 30 mL/min):
-Dose reduction should be considered
-Treatment course should be repeated no more than once every 2 weeks
-For patients requiring repeated courses, consideration should be given to alternate therapy.

Gout Prophylaxis:
Severe renal impairment: Dose reductions or alternatives should be considered

Familial Mediterranean Fever (FMF):
Mild to moderate renal impairment (CrCl 30 to 80 mL/min): Use caution; no adjustment recommended, but dose reduction may be necessary; monitor closely for adverse effects
Severe renal impairment (CrCl less than 30 mL/min):
-Initial dose: 0.3 mg/day; dose increases should be done with adequate monitoring for adverse effects.

• May be used to prevent gout flares in adults.
• There have been no reports regarding tolerance, dependence or abuse associated with colchicine use.

Colchicine is effective for preventing gout flares in adults; however, colchicine may interact with a number of other medications and cause gastrointestinal side effects at higher dosages.

Substance Name

Colchicine

CAS Registry Number

64-86-8

Drug Class

Antigout Agents

Gout Suppressants