Colchicine

1 INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

Colchicine capsules are indicated for prophylaxis of gout flares in adults. Limitations of Use: The safety and effectiveness of colchicine capsules for acute treatment of gout flares during prophylaxis has not been studied. Colchicine capsules are not an analgesic medication and should not be used to treat pain from other causes.

2 DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION SECTION

3 DOSAGE FORMS AND STRENGTHS

DOSAGE FORMS & STRENGTHS SECTION

Colchicine capsules 0.6 mg are light blue cap imprinted with “CO” and light blue body imprinted with “0.6” in black ink filled with white to off-white powder.

4 CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

Patients with renal or hepatic impairment should not be given colchicine capsules with drugs that inhibit both P-glycoprotein and CYP3A4 inhibitors [see Drug Interactions (7) ] . Combining these dual inhibitors with colchicine in patients with renal or hepatic impairment has resulted in life-threatening or fatal colchicine toxicity. Patients with both renal and hepatic impairment should not be given colchicine capsules.

5 WARNINGS AND PRECAUTIONS

WARNINGS AND PRECAUTIONS SECTION

6 ADVERSE REACTIONS

ADVERSE REACTIONS SECTION

Gastrointestinal disorders are the most common adverse reactions with colchicine. They are often the first signs of toxicity and may indicate that the colchicine dosage needs to be reduced or therapy stopped. These include diarrhea, nausea, vomiting, and abdominal pain. Colchicine has been reported to cause neuromuscular toxicity, which may present as muscle pain or weakness [see Warnings and Precautions (5.4) ]. Toxic manifestations associated with colchicine include myelosuppression, disseminated intravascular coagulation, and injury to cells in the renal, hepatic, circulatory, and central nervous system. These most often occur with excessive accumulation or overdosage [see Overdosage (10) ]. The following reactions have been reported with colchicine. These have been generally reversible by interrupting treatment or lowering the dose of colchicine: Digestive : abdominal cramping, abdominal pain, diarrhea, lactose intolerance, nausea, vomiting Neurological : sensory motor neuropathy Dermatological : alopecia, maculopapular rash, purpura, rash 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

DRUG INTERACTIONS SECTION

Colchicine is a substrate of the efflux transporter P-glycoprotein (P-gp), and the CYP3A4 metabolizing enzyme. Fatal drug interactions have been reported when colchicine is administered with clarithromycin, a dual inhibitor of CYP3A4 and P-glycoprotein. Toxicities have also been reported when colchicine is administered with inhibitors of CYP3A4 that may not be potent inhibitors of P-gp (e.g., grapefruit juice, erythromycin, verapamil), or inhibitors of P-gp that may not be potent inhibitors of CYP3A4 (e.g., cyclosporine). Patients with renal or hepatic impairment should not be given colchicine with drugs that inhibit both P-glycoprotein and CYP3A4 [see Contraindications (4) ]. Combining these dual inhibitors with colchicine in patients with renal and hepatic impairment has resulted in life-threatening or fatal colchicine toxicity. Physicians should ensure that patients are suitable candidates for treatment with colchicine and remain alert for signs and symptoms of toxic reactions associated with increased colchicine exposure due to drug interactions. Signs and symptoms of colchicine toxicity should be evaluated promptly and, if toxicity is suspected, colchicine should be discontinued immediately.

8 USE IN SPECIFIC POPULATIONS

USE IN SPECIFIC POPULATIONS SECTION

9 DRUG ABUSE AND DEPENDENCE

DRUG ABUSE AND DEPENDENCE SECTION

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

10 OVERDOSAGE

OVERDOSAGE SECTION

The dose of colchicine that would induce significant toxicity for an individual is unknown. Fatalities have been reported in patients after ingesting a dose as low as 7 mg over a 4-day period, while other patients have reportedly 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 adverse reactions, such as gastrointestinal symptoms, whereas those who ingested from 0.5 to 0.8 mg/kg had more severe adverse reactions, including myelosuppression. There was 100% mortality among patients 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 multi-organ failure and its associated consequences. Death usually results from respiratory depression and cardiovascular collapse. If the patient survives, recovery of multi-organ injury may be accompanied by rebound leukocytosis and alopecia starting about 1 week after the initial ingestion. Treatment of colchicine overdose 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 hemodialysis [see Pharmacokinetics (12.3) ].

11 DESCRIPTION

DESCRIPTION SECTION

Colchicine is an alkaloid obtained from the plant colchicum autumnale . The chemical name for colchicine is ( S)-N- (5,6,7,9- tetrahydro-1,2,3,10-tetramethoxy-9 oxobenzol[a]heptalen-7-yl) acetamide. The structural formula is represented below: Colchicine consists of pale yellow to pale greenish-yellow amorphous scales or powder or crystalline powder; it darkens on exposure to light. Colchicine is soluble in water, freely soluble in alcohol and in chloroform; slightly soluble in ether. Colchicine capsules are supplied for oral administration. Each capsule contains 0.6 mg colchicine, USP and the following inactive ingredients: colloidal silicon dioxide, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The capsule shell contains FD&C Blue No. 1, FD&C Red No. 40, gelatin and titanium dioxide. The capsules are imprinted with black ink containing black iron oxide, potassium hydroxide and shellac.

12 CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

NONCLINICAL TOXICOLOGY SECTION

14 CLINICAL STUDIES

CLINICAL STUDIES SECTION

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.

16 HOW SUPPLIED/STORAGE AND HANDLING

HOW SUPPLIED SECTION

17 PATIENT COUNSELING INFORMATION

INFORMATION FOR PATIENTS SECTION

Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Dosing Instructions If a dose of colchicine is missed, advise the patient to take the dose as soon as possible and then return to the normal dosing schedule. However, if a dose is skipped, the patient should not double the next dose. Fatal Overdose Advise the patient that fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine. Colchicine should be kept out of the reach of children. Blood Dyscrasias Advise patients that bone marrow depression with agranulocytosis, aplastic anemia, and thrombocytopenia may occur with colchicine. Drug and Food Interactions Advise patients that many drugs or other substances may interact with colchicine 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, including short-term medications such as antibiotics. Patients should also be advised to report the use of non-prescription medication or herbal products. Grapefruit and grapefruit juice may also interact and should not be consumed during treatment with colchicine. Neuromuscular Toxicity Advise patients that muscle pain or weakness, tingling or numbness in fingers or toes may occur with colchicine alone or when it is used with certain other drugs. Patients developing any of these signs or symptoms must discontinue colchicine and seek medical evaluation immediately. Infertility Advise males of reproductive potential that colchicine may rarely and transiently impair fertility [see Use in Specific Populations (8.3) ] . Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad–500 032, India Revised: 06/2024 Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides

SPL MEDGUIDE SECTION

SPL MEDGUIDE SECTION

Medication Guide Colchicine ( kol′ chi seen ) Capsules, for oral use 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 capsules are too high in your body. Taking certain medicines with colchicine capsules can cause your level of colchicine capsules 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. if you are a male with a female partner who can become pregnant. Receiving treatment with colchicine capsules may be related to infertility in some men that is reversible when treatment is stopped. Tell your healthcare provider about all the medicines you take, including prescription, over-the-counter 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 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 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 use 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, call Aurobindo Pharma USA, Inc. at 1-866-850-2876. What are the ingredients in colchicine capsules? Active Ingredient: Colchicine Inactive Ingredients: colloidal silicon dioxide, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The capsule shell contains FD&C Blue No. 1, FD&C Red No. 40, gelatin and titanium dioxide. The capsules are imprinted with black ink containing black iron oxide, potassium hydroxide and shellac. Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad–500 032, India This Medication Guide has been approved by the U.S. Food and Drug Administration Revised: 06/2024

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 0.6 mg (30 Capsules Bottle)

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 59651-446-30 Colchicine Capsules 0.6 mg PHARMACIST: Dispense the Medication Guide Provided Separately to each patient. Rx only 30 Capsules AUROBINDO

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 0.6 mg (100 Capsules Bottle)

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 59651-446-01 Colchicine Capsules 0.6 mg PHARMACIST: Dispense the Medication Guide Provided Separately to each patient. Rx only 100 Capsules AUROBINDO