Colchicine is an alkaloid prepared from the dried corns and seeds of Colchicum autumnale, the autumn crocus or meadow saffron. It is a pale yellow powder soluble in water in 1:25 dilution.

Colchicine Tablets, USP are oral anti-inflammatory agents supplied in two dosage strengths 0.5 mg (l/120 gr) and 0.6 mg (l/100 gr). The chemical name for colchicine is (S) N-(5,6,7,9-tetrahydro- 1,2,3, IO-tetramethoxy-9-oxobenzo [alpha] heptaien-7-yl) acetamide.

Inactive Ingredients

0.5 mg tablet: Calcium carbonate, confectioner†s sugar (contains corn starch), D& C Yellow No. 10, dextrin, stearic acid, sucrose and talc.

0.6 mg tablet: Acacia, corn starch, D& C Yellow No. 10, lactose, stearic acid and talc.

Colchicine is specifically indicated for treatment and relief of pain in attacks of acute gouty arthritis. It is also recommended for regular use between attacks as a prophylactic measure, and is often effective in aborting an attack when taken at the first sign of articular discomfort.

Colchicine is administered orally.

For Acute Gouty Arthritis - The usual dose to relieve or abort an attack is 1 to 1.2 mg (two 0.5 mg granules or two 0.6 mg tablets). This dose may be followed by one unit of either preparation (granule or tablet) every hour, or two units every two hours, until pain is relieved or until diarrhea ensues. Each patient should learn the dose needed and should keep the drug at hand for use at the first sign of an attack. After the initial dose, it is sometimes sufficient to take 0.5 or 0.6 mg every two or three hours. The drug should be stopped if there is gastrointestinal discomfort or diarrhea. (Opiates may be needed to control diarrhea.) In subsequent attacks, the patient should be able to judge his medication requirement accurately enough to stop short of his "diarrheal dose." The total amount of colchicine needed to control pain and inflammation during an attack usually ranges from 4 to 8 mg. Articular pain and swelling typically abate within 12 hours and are usually gone in 24 to 48 hours, An interval of three days between colchicine courses is advised in order to minimize the possibility of cumulative toxicity.

If corticotropin (ACTH) is administered for treatment of an attack of gouty arthritis, it is recommended that colchicine also be given in doses of at least 1 mg per day, and that the latter be continued for a few days after the hormone is withdrawn.

For Prophlaxis During Intercritical Periods- To reduce the frequency of paroxysms and lessen their severity, colchicine may be administered continuously. In patients who have less than one attack per year, the usual dose is 0.5 or 0.6 mg per day, three or four days a week. For cases involving more than one attack per year, the usual dose is 0.5 or 0.6 mg daily; severe cases may require two or three 0.5 mg granules or 0.6 mg tablets daily.

For Prophylaxis Against Attacks of Gout in Patients Undergoing Surgery - In patients with gout, an attack may be precipitated by even a minor surgical procedure. Colchicine, one 0.5 mg granule three times a day or one 0.6 mg tablet three times daily, should be administered for three days before and three days after surgery.

Colchicine Tablets, USP are supplied as yellow sugar-coated granules each containing 0.5 mg (1/l20 gr), packaged in bottles of 100 (NDC 0074-0074-02); and as yellow tablets each containing 0.6 mg (l/100 gr), packaged in bottles of 100 (NDC 0074-3781-01).

Dispense in a USP tight, light-resistant container. Recommended Storage: Store below 86° F (30° C ).

Adverse reactions in decreasing order of severity are: bone marrow depression, with aplastic anemia, with agranulocytosis or with thrombocytopenia may occur in patients receiving long-term therapy. Peripheral neuritis, purpura, myopathy, loss of hair, and reversible azoospermia have also been reported.

Vomiting, diarrhea, and nausea may occur with colchicine therapy, especially when maximal doses are necessary for a therapeutic effect. To avoid more serious toxicity, the drug should be discontinued when these symptoms appear, regardless of whether or not joint pain has been relieved.

Dermatoses have been reported. Hypersensitivity reactions may occur infrequently.

Colchicine is inhibited by acidifying agents. The action of colchicine is potentiated by alkalinizing agents.

Colchicine may increase sensitivity to the CNS depressants.

Response to sympathomimetic agents' may be enhanced by colchicine.

Colchicine arrests cell division in animals and plants. It has adversely affected spermatogenesis in humans and in some animal species under certain conditions.

General

Colchicine should be administered with caution to aged or debilitated patients, and to those with early manifestations of gastrointestinal, renal, hepatic, cardiac, or hematological disorders. (see CONTRAINDICATIONS).

If nausea, vomiting, or diarrhea occurs, the drug should be discontinued,

Laboratory Tests

In patients receiving longterm therapy, periodic blood counts should be done.

Drug Interactions

Colchicine is inhibited by acidifying agents. The action of colchicine is potentiated by alkalinizing agents.

Colchicine may increase sensitivity to the CNS depressants.

Response to sympathomimetic agentsmay be enhanced by colchicine.

Laboratory Test Interactions

Colchicine therapy may cause elevated alkaline phosphatase and SGOT values.

Decreased thrombocyte values may be obtained during colchicine therapy.

Colchicine may cause false positive results when testing urine for RBC or hemoglobin.

Carcinogenesis

Data in the literature does not indicate colchicine as a carcinogenic agent.

Fertility

See

WARNINGS

Pregnancy

Pregnancy Category C. Colchicine has been shown to be teratogenic in mice when given doses of 1.25 and 1.5 mg/kg and in hamsters when given 10 mg/kg. There are no adequate and well-controlled studies in pregnant women. Colchicine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when colchicine is administered to a nursing woman.

The onset of toxic effects is usually delayed for several hours or more after the ingestion of an acute overdose. Nausea, vomiting, abdominal pain, and diarrhea occur first. The diarrhea may be bloody due to hemorrhagic gastroenteritis. Burning sensations of the throat, stomach, and skin may be prominent symptoms. Extensive vascular damage may result in shock. Kidney damage, evidenced by hematuria and oliguria, may occur. Muscular weakness may be marked, and ascending paralysis of the central nervous system may develop; the patient usually remains conscious. Delirium and convulsions may occur. Death due to respiratory arrest may result.

Although death from the ingestion of as little as 7 mg has been reported, much larger doses have been survived .

Treatment of colchicine poisoning should begin with gastric lavage and measures to prevent shock. Recent studies appear to support the use of hemodialysis or peritoneal dialysis as proof of the treatment of acute overdosage in addition to gastric lavage. Symptomatic and supportive treatment may include atropine and morphine for the relief of abdominal pain, and artificial respiration with oxygen to combat respiratory distress. No specific antidote is known.

Colchicine is contraindicated in patients with a known hypersensitivity to the drug, in those with serious gastrointestinal, renal, hepatic, or cardiac disorders, and in those with blood dyscrasias.

The exact mechanism of action of colchicine in gout is not completely known, but it involves (1) a reduction in lactic acid production by leukocytes, which results in a decrease in uric acid deposition, and (2) a reduction in phagocytosis, with abatement of the inflammatory response.

Colchicine is not an analgesic, though it relieves pain in acute attacks of gout. It is not a uricosuric agent and will not prevent progression of gout to chronic gouty arthritis. It does have a prophylactic, suppressive effect that helps to reduce the incidence of acute attacks and to relieve the residual pain and mild discomfort that patients with gout occasionally feel.

In man and certain other animals, colchicine can produce a temporary leukopenia that is followed by leukocytosis.

Colchicine has other pharmacologic actions in animals: it alters neuromuscular function, intensifies gastrointestinal activity by neurogenic stimulation, increases sensitivity to central depressants, heightens response to sympathomimetic compounds, depresses the respiratory center, constricts blood vessels, causes hypertension by central vasomotor stimulation, and lowers body temperature.

Colchicine is rapidly absorbed after oral administration. Large amounts of the drug and metabolites enter the intestinal tract in bile and intestinal secretions. High concentrations of colchicine are found in the kidney, liver, and spleen, as well. Colchicine does not appear to be tightly bound to serum protein, hence the drug rapidly leaves the blood stream. Excretion occurs primarily by biliary and renal routes.

See WARNINGS, CONTRAINDICATIONS, and PRECAUTIONS.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

COLCHICINE - ORAL

(COAL-cheh-seen)

USES: This medication is used to treat gout. Colchicine, when used regularly, can help prevent a gout attack (e.g., gouty arthritis). Though not a true pain reliever, colchicine relieves the pain that occurs with a gout attack. It is believed to act by decreasing the amount of swelling in the affected joint.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This drug may also be used for other types of arthritis and certain liver conditions, and to prevent the aches and pains of a certain inherited disease (familial Mediterranean fever).

HOW TO USE: If your doctor has directed you to take this medication to treat gout pain when it occurs, take it exactly as directed. Colchicine controls gout pain best when you take it at the beginning of an attack. At the first sign of an attack, take 1 or 2 tablets by mouth as directed. Your doctor will tell you how soon you can take another dose, how long to wait between doses, and how many tablets you can take for each gout attack. Taking too much colchicine can lead to serious side effects. Never take more of this drug or take more doses than your doctor prescribes. Stop taking this medication when the pain is gone, when you have upset stomach/diarrhea, or when you reach the limit on the number of tablets you should take.

Unless your doctor directs you otherwise, do not take more than 3 or 4 tablets in the first 24 hours. Do not take more than 10 tablets for each gout attack. Do not take more than 5 tablets for each attack if you are elderly, if you weigh less than 110 pounds (50 kilograms), or if you have liver or kidney disease.

Tell your doctor if joint pain persists, if it worsens 12 hours after the beginning of the attack, or if it is not completely gone in 2 days.

If your doctor has directed you to use this drug to treat each gout attack when it occurs, you must wait at least 3 days after your last dose of this drug before using it again to treat the next attack. Talk to your doctor about other ways to relieve gout pain during the days when you cannot use this drug.

To prevent or lessen the number of gout attacks per year, your doctor may direct you to take colchicine on a regular schedule. Dosage will be based on your medical condition, the number of gout attacks you have each year, and your response to treatment. If your doctor directs you to take colchicine regularly, take it at the same time each day to help you remember.

Before you have any surgery (including dental surgery), your dose may need to be increased a few days in advance and remain increased until a few days after surgery. Ask your doctor for details.

SIDE EFFECTS: Stomach upset, vomiting, diarrhea, and nausea may occur. To avoid severe side effects, stop taking colchicine if any of these symptoms occur, and contact your doctor immediately.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: hair loss, decreased appetite, mouth sores, difficulty urinating/incontinence (bladder spasms), constipation.

Tell your doctor immediately if any of these rare but very serious side effects occur: signs of infection (e.g., fever, persistent sore throat), easy bruising/bleeding, yellowing of eyes/skin, fatigue, dark urine, change in the amount of urine, pink/red urine, fatigue, muscle tenderness/pain, numbness/tingling of arms or legs.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking colchicine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: severe liver disease, stomach problems (e.g., bleeding ulcer), severe kidney disease.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: heart problems, kidney problems, blood disorders, alcohol dependence.

Alcohol can decrease this drug's effectiveness. Limit alcohol consumption while taking this drug.

Kidney function declines as you grow older. This medication is removed by the kidneys. Therefore, elderly people may be at greater risk for side effects while using this drug, especially muscle problems.

Colchicine can affect sperm production, which may lower male fertility. Consult your doctor for more information.

This medication is not recommended for use during pregnancy. Consult your doctor for more details.

This medication passes into breast milk. While there have been no reports of harm to nursing infants, consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: certain macrolide antibiotics (e.g., clarithromycin, erythromycin), cyclosporine, fluvastatin, interferon-alpha, vitamin B12 (cyanocobalamin).

This medication may interfere with certain laboratory tests (e.g., test for blood in the urine), possibly causing false test results. Make sure laboratory personnel and your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include: bloody diarrhea, blood in the urine, change in the amount of urine, muscle weakness, seizures, confusion.

NOTES: Do not share this medication with others.

Colchicine relieves only pain due to gout. It should not be used for any other type of pain.

Laboratory and/or medical tests (e.g., liver function, kidney function, and blood counts) should be performed from time to time to monitor your progress or check for side effects.

MISSED DOSE: If you are taking colchicine regularly and miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.