Warfarin

Generic name: warfarin sodium · Brand names: Coumadin, Jantoven

Quick facts

Drug class
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95, Highlights, Indications and Usage
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Also
MedlinePlus: Warfarin is in a class of medications called anticoagulants ('blood thinners').
Also url
https://medlineplus.gov/druginfo/meds/a682277.html
Source text (exact source wording)
Warfarin sodium tablets are a vitamin K antagonist indicated for:
Rx or otc
Rx (label is a prescribing-information label; MedlinePlus: 'Your doctor or pharmacist will give you the Medication Guide.')
Forms and strengths
  • Scored tablets: 1, 2, 2.5, 3, 4, 5, 6, 7.5, or 10 mg (Highlights, section 3)
  • 1 mg pink; 2 mg lavender; 2.5 mg green; 3 mg tan; 4 mg blue; 5 mg peach; 6 mg teal; 7.5 mg yellow; 10 mg white, capsule-shaped, biconvex scored tablets (section 3)
Generic available
Value
Yes. This is a generic (ANDA) label from Teva; MedlinePlus lists Coumadin and Jantoven as brand names.
Source
DailyMed spls.json list and label page (marketing category ANDA seen on drugInfo page); https://medlineplus.gov/druginfo/meds/a682277.html
Common use one line
Blood thinner used to prevent and treat blood clots (MedlinePlus: 'prevent and treat blood clots').

What it is used for

Warfarin is used to prevent and treat blood clots in veins and in the lungs. It also helps prevent clot problems in people with atrial fibrillation or a heart valve replacement, and lowers the risk of death, another heart attack, and stroke-type clots after a heart attack. It does not dissolve a clot that has already formed and does not reverse tissue damage.
Section
1 INDICATIONS AND USAGE
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Confidence
high
Source text (exact source wording)
Warfarin sodium tablets are 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: Warfarin sodium tablets have 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.

How it works

Warfarin lowers the amount of several clotting proteins that the body makes with the help of vitamin K (Factors II, VII, IX, and X, and proteins C and S). It is thought to do this by blocking an enzyme complex called VKORC1.
Section
12.1 Mechanism of Action
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Confidence
high
Source text (exact source wording)
Warfarin acts by inhibiting the synthesis of vitamin K-dependent clotting factors, which include Factors II, VII, IX, and X, and the anticoagulant proteins C and S. Vitamin K is an essential cofactor for the post ribosomal synthesis of the vitamin K-dependent clotting factors. Vitamin K promotes the biosynthesis of γ-carboxyglutamic acid residues in the proteins that are essential for biological activity. Warfarin is thought to interfere with clotting factor synthesis by inhibition of the C1 subunit of vitamin K epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K1 epoxide [see Clinical Pharmacology (12.5)].

Dosage: adults

The dose is set for each person using blood tests called INR. For most clot conditions the target INR is 2.5 (range 2 to 3). If genetic test results are not known, the starting dose is usually 2 to 5 mg once daily, and usual maintenance doses are 2 to 10 mg once daily. INR is checked daily after the first dose until it is steady, then usually every 1 to 4 weeks. Loading doses are not recommended. Other heart valve and heart attack targets are in the full label (section 2.2).
Section
2.1, 2.2, 2.3, 2.4 (Dosage and Administration)
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Confidence
high
Source text (exact source wording)
2.1: The dosage and administration of warfarin sodium tablets must be individualized for each patient according to the patient’s International Normalized Ratio (INR) response to the drug. Adjust the dose based on the patient’s INR and the condition being treated. 2.2: An INR of greater than 4 appears to provide no additional therapeutic benefit in most patients and is associated with a higher risk of bleeding. Venous Thromboembolism: Adjust the warfarin dose to maintain a target INR of 2.5 (INR range, 2 to 3) for all treatment durations. Atrial Fibrillation: In patients with non-valvular AF, anticoagulate with warfarin to target INR of 2.5 (range, 2 to 3). 2.3: If the patient’s CYP2C9 and VKORC1 genotypes are not known, the initial dose of warfarin sodium tablets is usually 2 to 5 mg once daily. Determine each patient’s dosing needs by close monitoring of the INR response and consideration of the indication being treated. Typical maintenance doses are 2 to 10 mg once daily. Routine use of loading doses is not recommended as this practice may increase hemorrhagic and other complications and does not offer more rapid protection against clot formation. 2.4: Determine the INR daily after the administration of the initial dose until INR results stabilize in the therapeutic range. After stabilization, maintain dosing within the therapeutic range by performing periodic INRs. The frequency of performing INR should be based on the clinical situation but generally acceptable intervals for INR determinations are 1 to 4 weeks.

Dosage: children

Good studies in children have not been done, so the best dose, safety, and benefit in children are not known. Pediatric use relies on adult data and limited observational data. Children taking warfarin should avoid activities or sports that could cause injury.
Section
8.4 Pediatric Use
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Confidence
high
Source text (exact source wording)
Adequate and well-controlled studies with warfarin sodium have not been conducted in any pediatric population, and the optimum dosing, safety, and efficacy in pediatric patients is unknown. Pediatric use of warfarin sodium is based on adult data and recommendations, and available limited pediatric data from observational studies and patient registries. Pediatric patients administered warfarin sodium should avoid any activity or sport that may result in traumatic injury.

Dosage adjustments

Drug interaction caps
The label does not give fixed dose caps for drug interactions. It says to check INR more often whenever other drugs, including herbal products and short-term antibiotics, antifungals, or corticosteroids, are started, stopped, or changed.
Section
7.1 General Information; 2.4
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Confidence
high
Source text (exact source wording)
More frequent INR monitoring should be performed when starting or stopping other drugs, including botanicals, or when changing dosages of other drugs, including drugs intended for short-term use (e.g., antibiotics, antifungals, corticosteroids) [see Boxed Warning]. Closely monitor INR if a concomitant drug is a CYP2C9, 1A2, and/or 3A4 inhibitor or inducer. (7.2)
Kidney
No dose change is needed for kidney problems, but INR should be checked more often.
Section
2.5 Renal Impairment; 8.6
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Confidence
high
Source text (exact source wording)
No dosage adjustment is necessary for patients with renal failure. Monitor INR more frequently in patients with compromised renal function to maintain INR within the therapeutic range [see Warnings and Precautions (5.4) and Use in Specific Populations (8.6)].
Liver
Liver problems can make warfarin work more strongly. More frequent monitoring for bleeding is advised.
Section
8.7 Hepatic Impairment
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Confidence
high
Source text (exact source wording)
Hepatic impairment can potentiate the response to warfarin through impaired synthesis of clotting factors and decreased metabolism of warfarin. Conduct more frequent monitoring for bleeding when using warfarin sodium in these patients.
Elderly
People 60 years or older can respond more strongly than expected. The label says to monitor older patients for bleeding more often and to consider lower starting and maintenance doses.
Section
8.5 Geriatric Use
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Confidence
high
Source text (exact source wording)
Patients 60 years or older appear to exhibit greater than expected INR response to the anticoagulant effects of warfarin [see Clinical Pharmacology (12.3)]. Warfarin sodium is contraindicated in any unsupervised patient with senility. Conduct more frequent monitoring for bleeding with administration of warfarin sodium 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 warfarin sodium in elderly patients [see Dosage and Administration (2.2, 2.3)].

Missed dose

If you miss a dose, take it as soon as possible on the same day. Do not double the dose the next day.
Section
2.6 Missed Dose
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Confidence
high
Source text (exact source wording)
The anticoagulant effect of warfarin sodium tablets persists beyond 24 hours. If a patient misses a dose of warfarin sodium tablets at the intended time of day, the patient should take the dose as soon as possible on the same day. The patient should not double the dose the next day to make up for a missed dose.

Overdose

Too much warfarin shows up as bleeding, such as blood in stool or urine, heavy periods, or easy bruising. Treatment depends on the INR and whether there is bleeding, and may include stopping warfarin and giving vitamin K1. For overdose, call poison control at 1-800-222-1222 (MedlinePlus lists this number); call 911 if the person collapsed or has trouble breathing.
Section
10.1 Signs and Symptoms; 10.2 Treatment
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Confidence
high
Source text (exact source wording)
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. The treatment of excessive anticoagulation is based on the level of the INR, the presence or absence of bleeding, and clinical circumstances. Reversal of warfarin sodium anticoagulation may be obtained by discontinuing warfarin sodium therapy and, if necessary, by administration of oral or parenteral vitamin K1.
Medlineplus source text (exact source wording)
In case of overdose, call the poison control helpline at 1-800-222-1222. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911. (MedlinePlus, In case of emergency/overdose)

Storage

Store at 20° to 25°C (68° to 77°F), protected from light, with the container tightly closed, and keep out of reach of children. This text is from the Teva label; other labelers may differ.
Section
16 HOW SUPPLIED/STORAGE AND HANDLING
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Confidence
high
Source text (exact source wording)
Protect from light. Keep tightly closed. Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Keep this and all medications out of the reach of children.

Boxed warning

Warfarin can cause serious or deadly bleeding. Regular INR blood tests are required. Other drugs, diet changes, and other factors change INR. Patients should be taught how to lower bleeding risk and to report signs of bleeding.
Section
BOXED WARNING
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Confidence
high
Source text (exact source wording)
WARNING: BLEEDING RISK. Warfarin sodium can cause major or fatal bleeding [see Warnings and Precautions (5.1)]. Perform regular monitoring of INR in all treated patients [see Dosage and Administration (2.1)]. Drugs, dietary changes, and other factors affect INR levels achieved with warfarin sodium therapy [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)].

Contraindications

Not for use in pregnancy, except in pregnant women with mechanical heart valves at high risk of clots.
Section
4 CONTRAINDICATIONS
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Pregnancy: Warfarin sodium is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism [see Warnings and Precautions (5.7) and Use in Specific Populations (8.1)].
Not for people with a tendency to bleed or with blood disorders.
Section
4 CONTRAINDICATIONS
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Hemorrhagic tendencies or blood dyscrasias
Not for recent or planned surgery of the brain, spine, or eye, or surgery that leaves large open surfaces.
Section
4 CONTRAINDICATIONS
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Recent or contemplated surgery of the central nervous system or eye, or traumatic surgery resulting in large open surfaces [see Warnings and Precautions (5.8)]
Not for people with active bleeding or ulcers in the gut, urinary, or breathing tract, bleeding in the brain or spinal cord, brain aneurysm or dissecting aorta, pericarditis with fluid, or bacterial endocarditis.
Section
4 CONTRAINDICATIONS
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Bleeding tendencies associated with: Active ulceration or overt bleeding of the gastrointestinal, genitourinary, or respiratory tract; Central nervous system hemorrhage; Cerebral aneurysms, dissecting aorta; Pericarditis and pericardial effusions; Bacterial endocarditis
Not for threatened miscarriage, eclampsia, or preeclampsia.
Section
4 CONTRAINDICATIONS
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Threatened abortion, eclampsia, and preeclampsia
Not for unsupervised patients who are likely not to follow directions.
Section
4 CONTRAINDICATIONS
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Unsupervised patients with conditions associated with potential high level of non-compliance
Not with spinal puncture or other procedures that could cause uncontrollable bleeding.
Section
4 CONTRAINDICATIONS
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding
Not for people allergic to warfarin or its ingredients.
Section
4 CONTRAINDICATIONS
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Hypersensitivity to warfarin or to any other components of this product (e.g., anaphylaxis) [see Adverse Reactions (6)]
Not with major regional or lumbar block anesthesia.
Section
4 CONTRAINDICATIONS
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Major regional or lumbar block anesthesia
Not for malignant hypertension.
Section
4 CONTRAINDICATIONS
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Malignant hypertension

Warnings and precautions

Warfarin can cause major or fatal bleeding, most likely in the first month. Risk is higher with INR above 4, age 65 or older, past stomach or gut bleeding, high blood pressure, stroke disease, anemia, cancer, injury, kidney problems, and long treatment. Regular INR checks are needed, and a normal INR does not remove the risk.
Heading
5.1 Hemorrhage
Section
5.1 Hemorrhage
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Warfarin sodium 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), 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.
Warfarin can rarely (<0.1%) cause death of skin or other tissue, usually within a few days of starting. Severe cases have needed surgery or amputation. Warfarin is stopped if this happens.
Heading
5.2 Tissue Necrosis
Section
5.2 Tissue Necrosis
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Warfarin sodium can cause necrosis and/or gangrene of skin and other tissues, which 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 warfarin sodium therapy. In severe cases of necrosis, treatment through debridement or amputation of the affected tissue, limb, breast, or penis has been reported. Discontinue warfarin sodium therapy if necrosis occurs. Consider alternative drugs if continued anticoagulation therapy is necessary.
Warfarin can cause a serious, sometimes fatal condition called calciphylaxis, in people with or without end-stage kidney disease. Warfarin is stopped if it is diagnosed.
Heading
5.3 Calciphylaxis
Section
5.3 Calciphylaxis
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Warfarin sodium can cause fatal and serious calciphylaxis or calcium uremic arteriolopathy, which has been reported in patients with and without end-stage renal disease. When calciphylaxis is diagnosed in these patients, discontinue warfarin sodium and treat calciphylaxis as appropriate. Consider alternative anticoagulation therapy.
People with kidney disease may get acute kidney injury, possibly with too much anticoagulation and blood in the urine. More frequent monitoring is advised.
Heading
5.4 Acute Kidney Injury
Section
5.4 Acute Kidney Injury
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
In patients with altered glomerular integrity or with a history of kidney disease, acute kidney injury may occur with warfarin sodium, possibly in relation to episodes of excessive anticoagulation and hematuria. More frequent monitoring of anticoagulation is advised in patients with compromised renal function.
Warfarin may release plaque pieces that block small vessels, most often in the kidneys, and a foot problem called purple toes syndrome can occur. Some cases led to tissue death or death. Warfarin is stopped if this is seen.
Heading
5.5 Systemic Atheroemboli and Cholesterol Microemboli
Section
5.5 Systemic Atheroemboli and Cholesterol Microemboli
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Anticoagulation therapy with warfarin sodium 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 warfarin sodium therapy if such phenomena are observed. Consider alternative drugs if continued anticoagulation therapy is necessary.
Warfarin should not be the first treatment for HIT or HITTS. Limb damage, amputation, and death have occurred. It may be considered after the platelet count returns to normal.
Heading
5.6 Limb Ischemia, Necrosis, and Gangrene in Patients with HIT and HITTS
Section
5.6 Limb Ischemia, Necrosis, and Gangrene in Patients with HIT and HITTS
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Do not use warfarin sodium 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 warfarin sodium may be considered after the platelet count has normalized.
Warfarin can harm an unborn baby. For pregnant women with mechanical heart valves at high clot risk, benefits may outweigh risks, and the choice is reviewed with the patient.
Heading
5.7 Use in Pregnant Women with Mechanical Heart Valves
Section
5.7 Use in Pregnant Women with Mechanical Heart Valves
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Warfarin sodium can cause fetal harm when administered to a pregnant woman. While warfarin sodium is contraindicated during pregnancy, the potential benefits of using warfarin sodium 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 warfarin sodium 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.
Risks may be higher with moderate to severe liver problems, infections or gut flora problems, an indwelling catheter, high blood pressure, protein C deficiency, eye surgery, polycythemia vera, vasculitis, and diabetes.
Heading
5.8 Other Clinical Settings with Increased Risks
Section
5.8 Other Clinical Settings with Increased Risks
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
In the following clinical settings, the risks of warfarin sodium 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; Eye surgery; Polycythemia vera; Vasculitis; Diabetes mellitus
Diarrhea, liver disorders, poor nutrition, steatorrhea, or low vitamin K can raise the INR response. More vitamin K intake or inherited resistance can lower it.
Heading
5.9 Endogenous Factors Affecting INR
Section
5.9 Endogenous Factors Affecting INR
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
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 and breastfeeding

Section
8.1 Pregnancy; 8.2 Lactation; 8.3 Females and Males of Reproductive Potential
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Confidence
high
Source text (exact source wording)
8.1: Warfarin sodium 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 warfarin sodium may outweigh the risks [see Warnings and Precautions (5.7)]. Warfarin sodium 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. 8.2: Warfarin was not present in human milk from mothers treated with warfarin from a limited published study. Monitor breastfeeding infants for bruising or bleeding. Based on published data in 15 nursing mothers, warfarin was not detected in human milk. 8.3: Verify the pregnancy status of females of reproductive potential prior to initiating warfarin sodium therapy. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the final dose of warfarin sodium.

Side effects

Common
The most common side effect is bleeding, which can be fatal or non-fatal and can happen in any tissue or organ.
Threshold
The label does not give an incidence threshold or percentage list; it states the most common adverse reactions in Highlights.
Section
Highlights, Adverse Reactions
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Most common adverse reactions to warfarin sodium are fatal and nonfatal hemorrhage from any tissue or organ.
Less common
The label lists other reactions without how often they happen: allergic reactions, vasculitis, hepatitis and high liver enzymes, stomach and gut upset, taste change, rash and hair loss, calcification of the windpipe, and chills.
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Serious
Label
Serious effects named in the label are bleeding, tissue death, calciphylaxis, acute kidney injury, plaque emboli, limb damage with HIT, and other settings with higher risk.
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Section
6 ADVERSE REACTIONS
Source text (exact source wording)
The following serious adverse reactions to warfarin sodium are discussed in greater detail in other sections of the labeling: Hemorrhage [see Boxed Warning, Warnings and Precautions (5.1), and Overdosage (10)]; Tissue Necrosis [see Warnings and Precautions (5.2)]; Calciphylaxis [see Warnings and Precautions (5.3)]; Acute Kidney Injury [see Warnings and Precautions (5.4)]; Systemic Atheroemboli and Cholesterol Microemboli [see Warnings and Precautions (5.5)]; Limb Ischemia, Necrosis, and Gangrene in Patients with HIT and HITTS [see Warnings and Precautions (5.6)]; Other Clinical Settings with Increased Risks [see Warnings and Precautions (5.8)]
Medlineplus
MedlinePlus says to call your doctor right away for allergic signs, breathing or swallowing trouble, chest pain, swelling, fever, severe stomach or liver symptoms, yellow skin or eyes, dark or purple skin, or painful or purple toes.
Source
MedlinePlus Warfarin
Url
https://medlineplus.gov/druginfo/meds/a682277.html
Source text (exact source wording)
If you experience any of the following symptoms, or those listed in the IMPORTANT WARNING section, call your doctor immediately: hives, rash, itching; difficulty breathing or swallowing; swelling of the face, throat, tongue, lips, or eyes; hoarseness; chest pain or pressure; swelling of the hands, feet, ankles, or lower legs; fever, infection; nausea, vomiting, diarrhea; extreme tiredness, loss of energy; loss of appetite; pain in the upper right part of the stomach; yellowing of the skin or eyes; flu-like symptoms. Call your doctor immediately if you notice dark or purple skin, ulcers, any unusual problem on your skin or body, sudden severe pain, or color or temperature change on your body. Call your doctor immediately if your toes hurt or turn purple or dark.

Interactions

Drugs
Other blood thinners, antiplatelet drugs, NSAIDs, and SSRI/SNRI antidepressants raise bleeding risk with warfarin and need close monitoring.
Name
Drugs that increase bleeding risk
Section
7.3 Drugs that Increase Bleeding Risk
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Examples of drugs known to increase the risk of bleeding are presented in Table 3. Because bleeding risk is increased when these drugs are used concomitantly with warfarin, closely monitor patients receiving any such drug with warfarin. Table 3: Anticoagulants: argatroban, dabigatran, bivalirudin, desirudin, heparin, lepirudin. Antiplatelet Agents: aspirin, cilostazol, clopidogrel, dipyridamole, prasugrel, ticlopidine. Non-steroidal Anti-Inflammatory Agents: celecoxib, diclofenac, diflunisal, fenoprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, mefenamic acid, naproxen, oxaprozin, piroxicam, sulindac. Serotonin Reuptake Inhibitors: citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, paroxetine, sertraline, venlafaxine, vilazodone.
Drugs that block these liver enzymes can raise INR, and drugs that speed them up can lower INR. Check INR closely. The full lists are in Table 2 of the label.
Name
CYP450 inhibitors and inducers
Section
7.2 CYP450 Interactions
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Inhibitors of CYP2C9, 1A2, and/or 3A4 have the potential to increase the effect (increase INR) of warfarin by increasing the exposure of warfarin. Inducers of CYP2C9, 1A2, and/or 3A4 have the potential to decrease the effect (decrease INR) of warfarin by decreasing the exposure of warfarin. Examples are in Table 2 of the label (CYP2C9 inhibitors: amiodarone, capecitabine, cotrimoxazole, etravirine, fluconazole, fluvastatin, fluvoxamine, metronidazole, miconazole, oxandrolone, sulfinpyrazone, tigecycline, voriconazole, zafirlukast; CYP2C9 inducers: aprepitant, bosentan, carbamazepine, phenobarbital, rifampin). Closely monitor INR if a concomitant drug is a CYP2C9, 1A2, and/or 3A4 inhibitor or inducer.
INR can change with antibiotics or antifungals, so INR should be checked closely when one is started or stopped.
Name
Antibiotics and antifungals
Section
7.4 Antibiotics and Antifungals
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
There have been reports of changes in INR in patients taking warfarin and antibiotics or antifungals, but clinical pharmacokinetic studies have not shown consistent effects of these agents on plasma concentrations of warfarin. Closely monitor INR when starting or stopping any antibiotic or antifungal in patients taking warfarin.
Food and alcohol
Keep vitamin K intake steady and avoid big diet changes, such as large amounts of leafy green vegetables.
Name
Vitamin K in food
Section
7.5 Botanical (Herbal) Products and Foods
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
The amount of vitamin K in food may affect therapy with warfarin sodium. Advise patients taking warfarin sodium to eat a normal, balanced diet maintaining a consistent amount of vitamin K. Patients taking warfarin sodium should avoid drastic changes in dietary habits, such as eating large amounts of green leafy vegetables.
Grapefruit juice is named as a food that can interact with warfarin.
Name
Grapefruit juice
Section
7.5 Botanical (Herbal) Products and Foods
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Some botanicals and foods can interact with warfarin sodium through CYP450 interactions (e.g., echinacea, grapefruit juice, ginkgo, goldenseal, St. John’s wort).
Ask your doctor whether alcohol is safe with warfarin.
Name
Alcohol (MedlinePlus)
Section
What special precautions should I follow?
Source
MedlinePlus Warfarin
Url
https://medlineplus.gov/druginfo/meds/a682277.html
Source text (exact source wording)
ask your doctor about the safe use of alcoholic beverages while you are taking warfarin.
Other
Garlic and ginkgo can add to bleeding. Coenzyme Q10, St. John's wort, and ginseng may weaken warfarin.
Name
Botanical (herbal) products
Section
7.5 Botanical (Herbal) Products and Foods
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Some botanicals may cause bleeding events when taken alone (e.g., garlic and Ginkgo biloba) and may have anticoagulant, antiplatelet, and/or fibrinolytic properties. These effects would be expected to be additive to the anticoagulant effects of warfarin sodium. Conversely, some botanicals may decrease the effects of warfarin sodium (e.g., co-enzyme Q10, St. John’s wort, ginseng).
Smoking may make warfarin work less well.
Name
Tobacco (MedlinePlus)
Section
What special precautions should I follow?
Source
MedlinePlus Warfarin
Url
https://medlineplus.gov/druginfo/meds/a682277.html
Source text (exact source wording)
Cigarette smoking may decrease the effectiveness of this medication.

Patient tips

Medlineplus
Take warfarin once a day at about the same time, with or without food, and keep taking it even if you feel well. Do not stop without your doctor. Avoid injury-prone activities, carry a warfarin ID card or bracelet, never take two warfarin products together, and call your doctor right away if you take too much.
Source
MedlinePlus Warfarin
Url
https://medlineplus.gov/druginfo/meds/a682277.html
Source text (exact source wording)
Take once a day with or without food. Take warfarin at around the same time every day. Continue to take warfarin even if you feel well. Do not stop taking warfarin without talking to your doctor. Avoid activities or sports where you could get injured. Carry an identification card or wear a bracelet stating that you take warfarin. Do not take two or more medications that contain warfarin at the same time. Call your doctor immediately if you take more than your prescribed dose of warfarin.
Confidence
medium

Alternatives

Pharmacologic class
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95 Highlights
Url
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0cbce382-9c88-4f58-ae0f-532a841e8f95&type=display
Source text (exact source wording)
Warfarin sodium tablets are a vitamin K antagonist indicated for:
Note
No recommendation is made.

Frequently asked questions

Question
What is warfarin used for?
Answer
Warfarin is used to prevent and treat blood clots, and to help prevent clot problems in people with certain irregular heartbeats, prosthetic heart valves, or after a heart attack or stroke.
Source section
1 INDICATIONS AND USAGE; MedlinePlus Why is this medication prescribed?
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Question
Should I take warfarin with food?
Answer
Warfarin can be taken once a day with or without food, at around the same time every day.
Source section
How should this medicine be used?
Source
MedlinePlus Warfarin
Question
What if I miss a dose?
Answer
Take it as soon as possible on the same day. Do not double the dose the next day.
Source section
2.6 Missed Dose
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Question
Can I eat leafy greens or drink grapefruit juice or alcohol?
Answer
Keep the amount of vitamin K in your diet steady and avoid drastic changes, such as large amounts of green leafy vegetables. Grapefruit juice is named as a food that can interact with warfarin. Ask your doctor whether alcohol is safe.
Source section
7.5; MedlinePlus special precautions
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95; MedlinePlus Warfarin
Question
What is the most common side effect?
Answer
The label says the most common adverse reactions are fatal and nonfatal hemorrhage (bleeding) from any tissue or organ.
Source section
Highlights, Adverse Reactions
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Question
Can I take warfarin while pregnant or breastfeeding?
Answer
Warfarin is not for use in pregnancy except for women with mechanical heart valves at high clot risk. In a limited study of 15 nursing mothers, warfarin was not detected in human milk, and breastfed infants should be monitored for bruising or bleeding. Talk to your doctor.
Source section
4; 8.1; 8.2
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95
Question
What should I not combine with warfarin?
Answer
Do not take two products that contain warfarin. Other blood thinners, antiplatelet drugs, NSAIDs such as ibuprofen or naproxen, and some antidepressants increase bleeding risk. Tell your doctor about all medicines, vitamins, and herbal products.
Source section
7.3; MedlinePlus special precautions
Source
DailyMed label, Teva Pharmaceuticals USA, Inc., set ID 0cbce382-9c88-4f58-ae0f-532a841e8f95; MedlinePlus Warfarin
Question
Should I stop warfarin when I feel well?
Answer
No. Continue to take warfarin even if you feel well, and do not stop without talking to your doctor.
Source section
How should this medicine be used?
Source
MedlinePlus Warfarin

Sources

Information is taken from the cited sources and is for general reference only. It is not medical advice. Report side effects to FDA MedWatch at 1-800-FDA-1088. For a poison emergency call 1-800-222-1222. See prices for this drug