Coumadin Injection

COUMADIN® is indicated for:

• Prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism (PE). • Prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation (AF) and/or cardiac valve replacement. • Reduction in the risk of death, recurrent myocardial infarction (MI), and thromboembolic events such as stroke or systemic embolization after myocardial infarction.

Limitations of Use

COUMADIN has no direct effect on an established thrombus, nor does it reverse ischemic tissue damage. Once a thrombus has occurred, however, the goals of anticoagulant treatment are to prevent further extension of the formed clot and to prevent secondary thromboembolic complications that may result in serious and possibly fatal sequelae.

Hemorrhage

COUMADIN can cause major or fatal bleeding. Bleeding is more likely to occur within the first month. Risk factors for bleeding include high intensity of anticoagulation (INR >4.0), age greater than or equal to 65, history of highly variable INRs, history of gastrointestinal bleeding, hypertension, cerebrovascular disease, anemia, malignancy, trauma, renal impairment, certain genetic factors [see Clinical Pharmacology (12.5)], certain concomitant drugs [see Drug Interactions (7)], and long duration of warfarin therapy.

Perform regular monitoring of INR in all treated patients. Those at high risk of bleeding may benefit from more frequent INR monitoring, careful dose adjustment to desired INR, and a shortest duration of therapy appropriate for the clinical condition. However, maintenance of INR in the therapeutic range does not eliminate the risk of bleeding.

Drugs, dietary changes, and other factors affect INR levels achieved with COUMADIN therapy. Perform more frequent INR monitoring when starting or stopping other drugs, including botanicals, or when changing dosages of other drugs [see Drug Interactions (7)].

Instruct patients about prevention measures to minimize risk of bleeding and to report signs and symptoms of bleeding [see Patient Counseling Information (17)].

Tissue Necrosis

Necrosis and/or gangrene of skin and other tissues is an uncommon but serious risk (<0.1%). Necrosis may be associated with local thrombosis and usually appears within a few days of the start of COUMADIN therapy. In severe cases of necrosis, treatment through debridement or amputation of the affected tissue, limb, breast, or penis has been reported.

Careful clinical evaluation is required to determine whether necrosis is caused by an underlying disease. Although various treatments have been attempted, no treatment for necrosis has been considered uniformly effective. Discontinue COUMADIN therapy if necrosis occurs. Consider alternative drugs if continued anticoagulation therapy is necessary.

Calciphylaxis

Fatal and serious calciphylaxis or calcium uremic arteriolopathy has been reported in patients with and without end-stage renal disease. When calciphylaxis is diagnosed in these patients, discontinue COUMADIN and treat calciphylaxis as appropriate. Consider alternative anticoagulation therapy.

Systemic Atheroemboli and Cholesterol Microemboli

Anticoagulation therapy with COUMADIN may enhance the release of atheromatous plaque emboli. Systemic atheroemboli and cholesterol microemboli can present with a variety of signs and symptoms depending on the site of embolization. The most commonly involved visceral organs are the kidneys followed by the pancreas, spleen, and liver. Some cases have progressed to necrosis or death. A distinct syndrome resulting from microemboli to the feet is known as “purple toes syndrome.” Discontinue COUMADIN therapy if such phenomena are observed. Consider alternative drugs if continued anticoagulation therapy is necessary.

Limb Ischemia, Necrosis, and Gangrene in Patients with HIT and HITTS

Do not use COUMADIN as initial therapy in patients with heparin-induced thrombocytopenia (HIT) and with heparin-induced thrombocytopenia with thrombosis syndrome (HITTS). Cases of limb ischemia, necrosis, and gangrene have occurred in patients with HIT and HITTS when heparin treatment was discontinued and warfarin therapy was started or continued. In some patients, sequelae have included amputation of the involved area and/or death. Treatment with COUMADIN may be considered after the platelet count has normalized.

Use in Pregnant Women with Mechanical Heart Valves

COUMADIN can cause fetal harm when administered to a pregnant woman. While COUMADIN is contraindicated during pregnancy, the potential benefits of using COUMADIN may outweigh the risks for pregnant women with mechanical heart valves at high risk of thromboembolism. In those individual situations, the decision to initiate or continue COUMADIN should be reviewed with the patient, taking into consideration the specific risks and benefits pertaining to the individual patient’s medical situation, as well as the most current medical guidelines. COUMADIN exposure during pregnancy causes a recognized pattern of major congenital malformations (warfarin embryopathy and fetotoxicity), fatal fetal hemorrhage, and an increased risk of spontaneous abortion and fetal mortality. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use in Specific Populations (8.1)].

Other Clinical Settings with Increased Risks

In the following clinical settings, the risks of COUMADIN therapy may be increased:

• Moderate to severe hepatic impairment • Infectious diseases or disturbances of intestinal flora (e.g., sprue, antibiotic therapy) • Use of an indwelling catheter • Severe to moderate hypertension • Deficiency in protein C-mediated anticoagulant response: COUMADIN reduces the synthesis of the naturally occurring anticoagulants, protein C and protein S. Hereditary or acquired deficiencies of protein C or its cofactor, protein S, have been associated with tissue necrosis following warfarin administration. Concomitant anticoagulation therapy with heparin for 5 to 7 days during initiation of therapy with COUMADIN may minimize the incidence of tissue necrosis in these patients. • Eye surgery: In cataract surgery, COUMADIN use was associated with a significant increase in minor complications of sharp needle and local anesthesia block but not associated with potentially sight-threatening operative hemorrhagic complications. As COUMADIN cessation or reduction may lead to serious thromboembolic complications, the decision to discontinue COUMADIN before a relatively less invasive and complex eye surgery, such as lens surgery, should be based upon the risks of anticoagulant therapy weighed against the benefits. • Polycythemia vera • Vasculitis • Diabetes mellitus

Endogenous Factors Affecting INR

The following factors may be responsible for increased INR response: diarrhea, hepatic disorders, poor nutritional state, steatorrhea, or vitamin K deficiency.

The following factors may be responsible for decreased INR response: increased vitamin K intake or hereditary warfarin resistance.

Pregnancy

Risk Summary

COUMADIN is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism, and for whom the benefits of COUMADIN may outweigh the risks [see Warnings and Precautions (5.5)]. COUMADIN can cause fetal harm. Exposure to warfarin during the first trimester of pregnancy caused a pattern of congenital malformations in about 5% of exposed offspring. Because these data were not collected in adequate and well-controlled studies, this incidence of major birth defects is not an adequate basis for comparison to the estimated incidences in the control group or the U.S. general population and may not reflect the incidences observed in practice. Consider the benefits and risks of COUMADIN and possible risks to the fetus when prescribing COUMADIN to a pregnant woman.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

In humans, warfarin crosses the placenta, and concentrations in fetal plasma approach the maternal values. Exposure to warfarin during the first trimester of pregnancy caused a pattern of congenital malformations in about 5% of exposed offspring. Warfarin embryopathy is characterized by nasal hypoplasia with or without stippled epiphyses (chondrodysplasia punctata) and growth retardation (including low birth weight). Central nervous system and eye abnormalities have also been reported, including dorsal midline dysplasia characterized by agenesis of the corpus callosum, Dandy-Walker malformation, midline cerebellar atrophy, and ventral midline dysplasia characterized by optic atrophy. Mental retardation, blindness, schizencephaly, microcephaly, hydrocephalus, and other adverse pregnancy outcomes have been reported following warfarin exposure during the second and third trimesters of pregnancy [see Contraindications (4)].

Lactation

Risk Summary

Warfarin was not present in human milk from mothers treated with warfarin from a limited published study. Because of the potential for serious adverse reactions, including bleeding in a breastfed infant, consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for COUMADIN and any potential adverse effects on the breastfed infant from COUMADIN or from the underlying maternal condition before prescribing COUMADIN to a lactating woman.

Clinical Considerations

Monitor breastfeeding infants for bruising or bleeding.

Data

Human Data

Based on published data in 15 nursing mothers, warfarin was not detected in human milk. Among the 15 full-term newborns, 6 nursing infants had documented prothrombin times within the expected range. Prothrombin times were not obtained for the other 9 nursing infants. Effects in premature infants have not been evaluated.

Females and Males of Reproductive Potential

Pregnancy Testing

COUMADIN can cause fetal harm [see Use in Specific Populations (8.1)].

Verify the pregnancy status of females of reproductive potential prior to initiating COUMADIN therapy.

Contraception

Females

Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the final dose of COUMADIN.

Pediatric Use

Adequate and well-controlled studies with COUMADIN have not been conducted in any pediatric population, and the optimum dosing, safety, and efficacy in pediatric patients is unknown. Pediatric use of COUMADIN is based on adult data and recommendations, and available limited pediatric data from observational studies and patient registries. Pediatric patients administered COUMADIN should avoid any activity or sport that may result in traumatic injury.

The developing hemostatic system in infants and children results in a changing physiology of thrombosis and response to anticoagulants. Dosing of warfarin in the pediatric population varies by patient age, with infants generally having the highest, and adolescents having the lowest milligram per kilogram dose requirements to maintain target INRs. Because of changing warfarin requirements due to age, concomitant medications, diet, and existing medical condition, target INR ranges may be difficult to achieve and maintain in pediatric patients, and more frequent INR determinations are recommended. Bleeding rates varied by patient population and clinical care center in pediatric observational studies and patient registries.

Infants and children receiving vitamin K-supplemented nutrition, including infant formulas, may be resistant to warfarin therapy, while human milk-fed infants may be sensitive to warfarin therapy.

Geriatric Use

Of the total number of patients receiving warfarin sodium in controlled clinical trials for which data were available for analysis, 1885 patients (24.4%) were 65 years and older, while 185 patients (2.4%) were 75 years and older. No overall differences in effectiveness or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Patients 60 years or older appear to exhibit greater than expected INR response to the anticoagulant effects of warfarin [see Clinical Pharmacology (12.3)]. COUMADIN is contraindicated in any unsupervised patient with senility. Observe caution with administration of COUMADIN to elderly patients in any situation or with any physical condition where added risk of hemorrhage is present. Consider lower initiation and maintenance doses of COUMADIN in elderly patients [see Dosage and Administration (2.2, 2.3)].

Renal Impairment

Renal clearance is considered to be a minor determinant of anticoagulant response to warfarin. No dosage adjustment is necessary for patients with renal impairment.

Hepatic Impairment

Hepatic impairment can potentiate the response to warfarin through impaired synthesis of clotting factors and decreased metabolism of warfarin. Use caution when using COUMADIN in these patients.

Signs and Symptoms

Bleeding (e.g., appearance of blood in stools or urine, hematuria, excessive menstrual bleeding, melena, petechiae, excessive bruising or persistent oozing from superficial injuries, unexplained fall in hemoglobin) is a manifestation of excessive anticoagulation.

Treatment

The treatment of excessive anticoagulation is based on the level of the INR, the presence or absence of bleeding, and clinical circumstances. Reversal of COUMADIN anticoagulation may be obtained by discontinuing COUMADIN therapy and, if necessary, by administration of oral or parenteral vitamin K1.

The use of vitamin K1 reduces response to subsequent COUMADIN therapy and patients may return to a pretreatment thrombotic status following the rapid reversal of a prolonged INR. Resumption of COUMADIN administration reverses the effect of vitamin K, and a therapeutic INR can again be obtained by careful dosage adjustment. If rapid re-anticoagulation is indicated, heparin may be preferable for initial therapy.

Prothrombin complex concentrate (PCC), fresh frozen plasma, or activated Factor VII treatment may be considered if the requirement to reverse the effects of COUMADIN is urgent. A risk of hepatitis and other viral diseases is associated with the use of blood products; PCC and activated Factor VII are also associated with an increased risk of thrombosis. Therefore, these preparations should be used only in exceptional or life-threatening bleeding episodes secondary to COUMADIN overdosage.

Tablets

COUMADIN tablets are single-scored with one face imprinted numerically with 1, 2, 2-1/2, 3, 4, 5, 6, 7-1/2, or 10 superimposed and inscribed with “COUMADIN” and with the opposite face plain. COUMADIN is available in bottles and hospital unit-dose blister packages with potencies and colors as follows:

	Bottles of 100	Bottles of 1000	Hospital Unit-Dose Blister Package of 100
1 mg pink	NDC 0056-0169-70	NDC 0056-0169-90	NDC 0056-0169-75
2 mg lavender	NDC 0056-0170-70	NDC 0056-0170-90	NDC 0056-0170-75
2-1/2 mg green	NDC 0056-0176-70	NDC 0056-0176-90	NDC 0056-0176-75
3 mg tan	NDC 0056-0188-70		NDC 0056-0188-75
4 mg blue	NDC 0056-0168-70		NDC 0056-0168-75
5 mg peach	NDC 0056-0172-70	NDC 0056-0172-90	NDC 0056-0172-75
6 mg teal	NDC 0056-0189-70	NDC 0056-0189-90	NDC 0056-0189-75
7-1/2 mg yellow	NDC 0056-0173-70		NDC 0056-0173-75
10 mg white      (dye-free)	NDC 0056-0174-70		NDC 0056-0174-75

Protect from light and moisture. Store at controlled room temperature (59°-86°F, 15°-30°C). Dispense in a tight, light-resistant container as defined in the USP.

Store the hospital unit-dose blister packages in the carton until contents have been used.

Injection

COUMADIN for injection vials yield 5 mg of warfarin after reconstitution with 2.7 mL of Sterile Water for Injection (maximum yield is 2.5 mL of a 2 mg/mL solution). Net content of vial is 5.4 mg lyophilized powder.

5-mg vial (box of 6)      NDC 0590-0324-35

Protect from light. Keep vial in box until used. Store at controlled room temperature (59°-86°F, 15°-30°C).

After reconstitution, store at controlled room temperature (59°-86°F, 15°-30°C) and use within 4 hours. Do not refrigerate. Discard any unused solution.

Special Handling

Procedures for proper handling and disposal of potentially hazardous drugs should be considered. Guidelines on this subject have been published [see References (15)].

Pharmacy and clinical personnel who are pregnant should avoid exposure to crushed or broken tablets [see Use in Specific Populations (8.1)].

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

Instructions for Patients

Advise patients to:

• Strictly adhere to the prescribed dosage schedule [see Dosage and Administration (2.1)].
• If the prescribed dose of COUMADIN is missed, take the dose as soon as possible on the same day but do not take a double dose of COUMADIN the next day to make up for missed doses [see Dosage and Administration (2.5)].
• Obtain prothrombin time tests and make regular visits to their physician or clinic to monitor therapy [see Dosage and Administration (2.1)].
• Be aware that if therapy with COUMADIN is discontinued, the anticoagulant effects of COUMADIN may persist for about 2 to 5 days [see Clinical Pharmacology (12.2)].
• Avoid any activity or sport that may result in traumatic injury. [see Use in Special Populations (8.4)]. And to tell their physician if they fall often as this may increase their risk for complications.
• Eat a normal, balanced diet to maintain a consistent intake of vitamin K. Avoid drastic changes in dietary habits, such as eating large amounts of leafy, green vegetables [see Drug Interactions (7.4)].
• Contact their physician to report any serious illness, such as severe diarrhea, infection, or fever [see Warnings and Precautions (5) and Adverse Reactions (6)].
• Carry identification stating that they are taking COUMADIN.

Bleeding Risks

Advise patients to:

• Notify their physician immediately if any unusual bleeding or symptoms occur. Signs and symptoms of bleeding include: pain, swelling or discomfort, prolonged bleeding from cuts, increased menstrual flow or vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or dark brown urine, red or tar black stools, headache, dizziness, or weakness [see Box Warning and Warnings and Precautions (5.1)].

Concomitant Medications and Botanicals (Herbals)

Advise patients to:

• Not take or discontinue any other drug, including salicylates (e.g., aspirin and topical analgesics), other over-the-counter drugs, and botanical (herbal) products except on advice of your physician [see Drug Interactions (7)].

Pregnancy and Nursing

Advise patients to:

• Contact their doctor

-        immediately if they think they are pregnant [see Use in Special Populations (8.1)],

-        to discuss pregnancy planning [see Use in Special Populations (8.3)],

-        if they are considering breastfeeding [see Use in Special Populations (8.2)].

Distributed by:
Bristol-Myers Squibb Company
Princeton, New Jersey 08543 USA

COUMADIN® is a trademark of Bristol-Myers Squibb Pharma Company.

Copyright © Bristol-Myers Squibb Company 2016

Printed in USA

Rev September 2016

MEDICATION GUIDE COUMADIN® (COU-ma-din) (warfarin sodium)
Read this Medication Guide before you start taking COUMADIN (warfarin sodium) 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 COUMADIN when you start taking it and at regular checkups.
What is the most important information I should know about COUMADIN? COUMADIN can cause bleeding which can be serious and sometimes lead to death.This is because COUMADIN is a blood thinner medicine that lowers the chance of blood clots forming in your body. You may have a higher risk of bleeding if you take COUMADIN and: are 65 years of age or older have a history of stomach or intestinal bleeding have high blood pressure (hypertension) have a history of stroke, or “mini-stroke” (transient ischemic attack or TIA) have serious heart disease have a low blood count or cancer have had trauma, such as an accident or surgery have kidney problems take other medicines that increase your risk of bleeding, including: a medicine that contains heparin other medicines to prevent or treat blood clots nonsteroidal anti-inflammatory drugs (NSAIDs) take warfarin sodium for a long time. Warfarin sodium is the active ingredient in COUMADIN. Tell your healthcare provider if you take any of these medicines. Ask your healthcare provider if you are not sure if your medicine is one listed above. Many other medicines can interact with COUMADIN and affect the dose you need or increase COUMADIN side effects. Do not change or stop any of your medicines or start any new medicines before you talk to your healthcare provider. Do not take other medicines that contain warfarin sodium while taking COUMADIN. Get your regular blood test to check for your response to COUMADIN. This blood test is called an INR test. The INR test checks to see how fast your blood clots. Your healthcare provider will decide what INR numbers are best for you. Your dose of COUMADIN will be adjusted to keep your INR in a target range for you. Call your healthcare provider right away if you get any of the following signs or symptoms of bleeding problems: pain, swelling, or discomfort headaches, dizziness, or weakness unusual bruising (bruises that develop without known cause or grow in size) nosebleeds bleeding gums bleeding from cuts takes a long time to stop menstrual bleeding or vaginal bleeding that is heavier than normal pink or brown urine red or black stools coughing up blood vomiting blood or material that looks like coffee grounds Some foods and beverages can interact with COUMADIN and affect your treatment and dose. Eat a normal, balanced diet. Talk to your healthcare provider before you make any diet changes. Do not eat large amounts of leafy, green vegetables. Leafy, green vegetables contain vitamin K. Certain vegetable oils also contain large amounts of vitamin K. Too much vitamin K can lower the effect of COUMADIN. Always tell all of your healthcare providers that you take COUMADIN. Wear or carry information that you take COUMADIN. See “What are the possible side effects of COUMADIN?” for more information about side effects.
What is COUMADIN? COUMADIN is prescription medicine used to treat blood clots and to lower the chance of blood clots forming in your body. Blood clots can cause a stroke, heart attack, or other serious conditions if they form in the legs or lungs.
Who should not take COUMADIN? Do not take COUMADIN if: •your chance of having bleeding problems is higher than the possible benefit of treatment. Your healthcare provider will decide if COUMADIN is right for you. Talk to your healthcare provider about all of your health conditions.•you are pregnant unless you have a mechanical heart valve. COUMADIN may cause birth defects, miscarriage, or death of your unborn baby.•you are allergic to warfarin or any of the other ingredients in COUMADIN. See the end of this leaflet for a complete list of ingredients in COUMADIN.
What should I tell my healthcare provider before taking COUMADIN? Before you take COUMADIN, tell your healthcare provider if you: have bleeding problems fall often have liver problems have kidney problems or are undergoing dialysis have high blood pressure have a heart problem called congestive heart failure have diabetes plan to have any surgery or a dental procedure have any other medical conditions are pregnant or plan to become pregnant. See “Who should not take COUMADIN?” Your healthcare provider will do a pregnancy test before you start treatment with COUMADIN. Females who can become pregnant should use effective birth control during treatment, and for at least 1 month after the last dose of COUMADIN. are breastfeeding. You and your healthcare provider should decide if you will take COUMADIN and breastfeed. Check your baby for bruising or bleeding if you take COUMADIN and breastfeed. Tell all of your healthcare providers and dentists that you are taking COUMADIN. They should talk to the healthcare provider who prescribed COUMADIN for you before you have any surgery or dental procedure. Your COUMADIN may need to be stopped for a short time or you may need your dose adjusted. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some of your other medicines may affect the way COUMADIN works. Certain medicines may increase your risk of bleeding. See “What is the most important information I should know about COUMADIN?” Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
How should I take COUMADIN? •Take COUMADIN exactly as prescribed. Your healthcare provider will adjust your dose from time to time depending on your response to COUMADIN.•You must have regular blood tests and visits with your healthcare provider to monitor your condition.•If you miss a dose of COUMADIN, call your healthcare provider. Take the dose as soon as possible on the same day. Do not take a double dose of COUMADIN the next day to make up for a missed dose.•Call your healthcare provider right away if you:otake too much COUMADINoare sick with diarrhea, an infection, or have a feverofall or injure yourself, especially if you hit your head. Your healthcare provider may need to check you.
What should I avoid while taking COUMADIN? •Do not do any activity or sport that may cause a serious injury.
What are the possible side effects of COUMADIN? COUMADIN may cause serious side effects including: •See “What is the most important information I should know about COUMADIN?”•Death of skin tissue (skin necrosis or gangrene). This can happen soon after starting COUMADIN. It happens because blood clots form and block blood flow to an area of your body. Call your healthcare provider right away if you have pain, color, or temperature change to any area of your body. You may need medical care right away to prevent death or loss (amputation) of your affected body part.•“Purple toes syndrome.”Call your healthcare provider right away if you have pain in your toes and they look purple in color or dark in color. Tell your healthcare provider if you have any side effect that bothers you or does not go away. These are not all of the side effects of COUMADIN. 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 COUMADIN? •Store COUMADIN at 59°F to 86°F (15°C to 30°C).•Keep COUMADIN in a tightly closed container, and keep COUMADIN out of the light and moisture.•Follow your healthcare provider or pharmacist instructions about the right way to throw away outdated or unused COUMADIN.•Females who are pregnant should not handle crushed or broken COUMADIN tablets. Keep COUMADIN and all medicines out of the reach of children.
General information about COUMADIN. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use COUMADIN for a condition for which it was not prescribed. Do not give COUMADIN 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 COUMADIN. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about COUMADIN that is written for health professionals. If you would like more information, go to www.coumadin.com or call 1‑800-321-1335.
What are the ingredients in COUMADIN? Active ingredient: warfarin sodium Inactive ingredients: COUMADIN tablets also contain lactose, starch, and magnesium stearate, in addition:
1 mg:	D&C Red No. 6 Barium Lake
2 mg:	FD&C Blue No. 2 Aluminum Lake and FD&C Red No. 40 Aluminum Lake
2.5 mg:	D&C Yellow No. 10 Aluminum Lake and FD&C Blue No. 1 Aluminum Lake
3 mg:	FD&C Yellow No. 6 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake, and FD&C Red No. 40 Aluminum Lake
4 mg:	FD&C Blue No. 1 Aluminum Lake
5 mg:	FD&C Yellow No. 6 Aluminum Lake
6 mg:	FD&C Yellow No. 6 Aluminum Lake and FD&C Blue No. 1 Aluminum Lake
7.5 mg:	D&C Yellow No. 10 Aluminum Lake and FD&C Yellow No. 6 Aluminum Lake
COUMADIN is distributed by: Bristol-Myers Squibb Company, Princeton, New Jersey 08543 USA COUMADIN® is a registered trademark of Bristol-Myers Squibb Pharma Company.

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

Revised 09/2016

REPRESENTATIVE PACKAGING

See How Supplied section for a complete list of available packages of COUMADIN.

COUMADIN® FOR INJECTION
(Warfarin Sodium for Injection, USP)
5 mg Single Use Vial*
Reconstitute with 2.7 mL of sterile Water for Injection to yield 2 mg/mL.

COUMADIN  warfarin sodium injection, powder, lyophilized, for solution

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0590-0324 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength warfarin sodium (warfarin) warfarin sodium 2 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength sodium phosphate, dibasic, heptahydrate 4.98 mg  in 1 mL sodium phosphate, monobasic, monohydrate 0.194 mg  in 1 mL sodium chloride 0.1 mg  in 1 mL mannitol 38 mg  in 1 mL sodium hydroxide

Packaging # Item Code Package Description 1 NDC:0590-0324-96 1 VIAL in 1 CARTON 1 2.5 mL in 1 VIAL 2 NDC:0590-0324-35 6 CARTON in 1 CARTON 2 1 VIAL in 1 CARTON 2 2.5 mL in 1 VIAL

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA009218 01/01/2009 11/30/2016

Labeler - Bristol-Myers Squibb Holdings Pharma, Ltd. Liability Company (090413568)

Revised: 09/2016   Bristol-Myers Squibb Holdings Pharma, Ltd. Liability Company