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An overdose can cause excessive bleeding. Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

You may still bleed more easily for several days after you stop taking Coumadin. Foods that are high in vitamin K liver, leafy green vegetables, or vegetable oils can make warfarin less effective.

If these foods are part of your diet, eat a consistent amount on a weekly basis. Grapefruit juice, cranberry juice, noni juice, and pomegranate juice may interact with warfarin and lead to unwanted side effects.

Avoid the use of these juice products while taking Coumadin. Ask your doctor before using any medicine for pain, arthritis, fever, or swelling.

This includes aspirin, ibuprofen Advil, Motrin , naproxen Aleve , celecoxib Celebrex , diclofenac, indomethacin, meloxicam, and others. These medicines may affect blood clotting and may also increase your risk of stomach bleeding.

Get emergency medical help if you have signs of an allergic reaction to Coumadin : hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Coumadin increases your risk of bleeding, which can be severe or life-threatening. Call your doctor at once if you have any signs of bleeding such as:.

Clots formed by Coumadin may block normal blood flow, which could lead to tissue death or amputation of the affected body part.

Get medical help at once if you have:. This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

Coumadin side effects in more detail. Many drugs including some over-the-counter medicines and herbal products can affect your INR and may increase the risk of bleeding if you take them with Coumadin.

Not all possible drug interactions are listed in this medication guide. It is very important to ask your doctor and pharmacist before you start or stop using any other medicine, especially:.

John's wort. This list is not complete and many other drugs can interact with warfarin. This includes prescription and over-the-counter medicines, vitamins, and herbal products.

Give a list of all your medicines to any healthcare provider who treats you. Coumadin drug interactions in more detail. Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Coumadin only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances. Other brands: Jantoven.

The easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records. Available for Android and iOS devices.

Subscribe to Drugs. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment.

Skip to Content. See also: Coumadin dosage information in more detail. See also: Coumadin side effects in more detail. See also: Coumadin drug interactions in more detail.

Drug Status Availability Prescription only Rx. Bristol-Myers Squibb Company. Drug Class. Coumarins and indandiones. Related Drugs.

Coumadin Images. Subscribe to our newsletters. FDA Safety Alerts for all medications. Daily MedNews. Weekly Drug News Roundup.

Monthly Newsletter. FWS is characterized mainly by skeletal abnormalities, which include nasal hypoplasia , a depressed or narrowed nasal bridge , scoliosis , and calcifications in the vertebral column , femur , and heel bone , which show a peculiar stippled appearance on X-rays.

Limb abnormalities , such as brachydactyly unusually short fingers and toes or underdeveloped extremities, can also occur.

Warfarin administration in the second and third trimesters is much less commonly associated with birth defects, and when they do occur, are considerably different from fetal warfarin syndrome.

The most common congenital abnormalities associated with warfarin use in late pregnancy are central nervous system disorders, including spasticity and seizures , and eye defects.

Similarly, INR levels should be checked to avoid adverse effects. The only common side effect of warfarin is bleeding.

A number of risk scores exist to predict bleeding in people using warfarin and similar anticoagulants. A commonly used score HAS-BLED includes known predictors of warfarin-related bleeding: uncontrolled high blood pressure H , abnormal kidney function A , previous stroke S , known previous bleeding condition B , previous labile INR when on anticoagulation L , elderly as defined by age over 65 E , and drugs associated with bleeding e.

While their use is recommended in clinical practice guidelines, [35] they are only moderately effective in predicting bleeding risk and do not perform well in predicting hemorrhagic stroke.

A rare but serious complication resulting from treatment with warfarin is warfarin necrosis , which occurs more frequently shortly after commencing treatment in patients with a deficiency of protein C.

Protein C is an innate anticoagulant that, like the procoagulant factors that warfarin inhibits, requires vitamin K-dependent carboxylation for its activity.

Since warfarin initially decreases protein C levels faster than the coagulation factors, it can paradoxically increase the blood's tendency to coagulate when treatment is first begun many patients when starting on warfarin are given heparin in parallel to combat this , leading to massive thrombosis with skin necrosis and gangrene of limbs.

Its natural counterpart, purpura fulminans , occurs in children who are homozygous for certain protein C mutations.

After initial reports that warfarin could reduce bone mineral density , several studies demonstrated a link between warfarin use and osteoporosis -related fracture.

A study in women taking warfarin for deep venous thrombosis , risk of vertebral fracture and rib fracture was increased; other fracture types did not occur more commonly.

The mechanism was thought to be a combination of reduced intake of vitamin K a vitamin necessary for bone health and inhibition by warfarin of vitamin K-mediated carboxylation of certain bone proteins, rendering them nonfunctional.

Another rare complication that may occur early during warfarin treatment usually within 3 to 8 weeks of commencement is purple toe syndrome. This condition is thought to result from small deposits of cholesterol breaking loose and causing embolisms in blood vessels in the skin of the feet, which causes a blueish-purple colour and may be painful.

It is typically thought to affect the big toe , but it affects other parts of the feet as well, including the bottom of the foot plantar surface.

The occurrence of purple toe syndrome may require discontinuation of warfarin. Several studies have also implicated warfarin use in valvular and vascular calcification.

No specific treatment is available, but some modalities are under investigation. The major side effect of warfarin use is bleeding.

Risk of bleeding is increased if the INR is out of range due to accidental or deliberate overdose or due to interactions. For people who need rapid reversal of warfarin — such as due to serious bleeding — or who need emergency surgery, the effects of warfarin can be reversed with vitamin K , prothrombin complex concentrate PCC , or fresh frozen plasma FFP.

Administration of PCCs result in rapid hemostasis, similar to that of FFP; namely, with comparable rates of thromboembolic events, but with reduced rates of volume overload.

Blood products should not be routinely used to reverse warfarin overdose, when vitamin K could work alone. Details on reversing warfarin are provided in clinical practice guidelines from the American College of Chest Physicians.

When warfarin is being given and INR is in therapeutic range, simple discontinuation of the drug for five days is usually enough to reverse the effect and cause INR to drop below 1.

Warfarin interacts with many commonly used drugs, and the metabolism of warfarin varies greatly between patients. When taken with nonsteroidal anti-inflammatory drugs NSAIDs , warfarin increases the risk for gastrointestinal bleeding.

This increased risk is due to the anti-platelet effect of NSAIDs as well as the possible damage to the gastrointestinal mucosa.

Many commonly used antibiotics , such as metronidazole or the macrolides , will greatly increase the effect of warfarin by reducing the metabolism of warfarin in the body.

Other broad-spectrum antibiotics can reduce the amount of the normal bacterial flora in the bowel , which make significant quantities of vitamin K 1 , thus potentiating the effect of warfarin.

Excessive use of alcohol is also known to affect the metabolism of warfarin and can elevate the INR and thus increase the risk of bleeding.

Warfarin also interacts with many herbs and spices, [60] some used in food such as ginger and garlic and others used purely for medicinal purposes such as ginseng and Ginkgo biloba.

All may increase bleeding and bruising in people taking warfarin; similar effects have been reported with borage starflower oil.

John's Wort , sometimes recommended to help with mild to moderate depression, reduces the effectiveness of a given dose of warfarin; it induces the enzymes that break down warfarin in the body, causing a reduced anticoagulant effect.

Between and , the UK Committee on Safety of Medicines received several reports of increased INR and risk of haemorrhage in people taking warfarin and cranberry juice.

X-ray crystallographic studies of warfarin show that it exists in tautomeric form, as the cyclic hemiketal , which is formed from the 4-hydroxycoumarin and the ketone in the 3-position substituent.

Warfarin contains a stereocenter and consists of two enantiomers. This is a racemate , i. Warfarin consists of a racemic mixture of two active enantiomers — R - and S - forms—each of which is cleared by different pathways.

S-warfarin is 2—5 times more potent than the R-isomer in producing an anticoagulant response. Warfarin is slower-acting than the common anticoagulant heparin , though it has a number of advantages.

Heparin must be given by injection, whereas warfarin is available orally. Warfarin has a long half-life and need only be given once a day. Heparin can also cause a prothrombotic condition, heparin-induced thrombocytopenia an antibody -mediated decrease in platelet levels , which increases the risk for thrombosis.

It takes several days for warfarin to reach the therapeutic effect since the circulating coagulation factors are not affected by the drug thrombin has a half-life time of days.

Warfarin's long half-life means that it remains effective for several days after it is stopped. Furthermore, if given initially without additional anticoagulant cover, it can increase thrombosis risk see below.

For these main reasons, hospitalised patients are usually given heparin with warfarin initially, the heparin covering the 3—5-day lag period and being withdrawn after a few days.

While warfarin is one of several drugs popularly referred to as a "blood thinner", this is a misnomer since it does not affect the viscosity of blood.

The precursors of these factors require gamma carboxylation of their glutamic acid residues to allow the coagulation factors to bind to phospholipid surfaces inside blood vessels , on the vascular endothelium.

The enzyme that carries out the carboxylation of glutamic acid is gamma-glutamyl carboxylase. The carboxylation reaction will proceed only if the carboxylase enzyme is able to convert a reduced form of vitamin K vitamin K hydroquinone to vitamin K epoxide at the same time.

Warfarin inhibits epoxide reductase [73] specifically the VKORC1 subunit [74] [75] , thereby diminishing available vitamin K and vitamin K hydroquinone in the tissues, which inhibits the carboxylation activity of the glutamyl carboxylase.

When this occurs, the coagulation factors are no longer carboxylated at certain glutamic acid residues, and are incapable of binding to the endothelial surface of blood vessels, and are thus biologically inactive.

As the body's stores of previously produced active factors degrade over several days and are replaced by inactive factors, the anticoagulation effect becomes apparent.

The end result of warfarin use, therefore, is to diminish blood clotting in the patient. When warfarin is newly started, it may promote clot formation temporarily.

This is because the level of protein C and protein S are also dependent on vitamin K activity. Warfarin causes decline in protein C levels in first 36 hours.

In addition, reduced levels of protein S lead to a reduction in activity of protein C for which it is the co-factor and therefore reduced degradation of factor Va and factor VIIIa.

The haemostasis system becomes temporarily biased towards thrombus formation, leading to a prothrombotic state. Warfarin activity is determined partially by genetic factors.

Despite the promise of pharmacogenomic testing in warfarin dosing, its use in clinical practice is controversial. In the early s, there was an outbreak of a previously unrecognized cattle disease in the northern United States and Canada.

Cattle were haemorrhaging after minor procedures, and on some occasions spontaneously. All of these animals had bled to death.

In , Frank Schofield , a Canadian veterinary pathologist , determined that the cattle were ingesting moldy silage made from sweet clover , and that this was functioning as a potent anticoagulant.

The rabbit that had ingested the good stalks remained well, but the rabbit that had ingested the damaged stalks died from a haemorrhagic illness.

A duplicate experiment with a different sample of clover hay produced the same result. Roderick demonstrated that the condition was due to a lack of functioning prothrombin.

The identity of the anticoagulant substance in spoiled sweet clover remained a mystery until In Karl Paul Link and his lab of chemists working at the University of Wisconsin set out to isolate and characterize the haemorrhagic agent from the spoiled hay.

Next, Link's student Mark A. Stahmann took over the project and initiated a large-scale extraction, isolating 1.

This was enough material for Stahmann and Charles F. Huebner to check their results against Campbell's, and to thoroughly characterize the compound.

Through degradation experiments they established that the anticoagulant was 3,3'-methylenebis- 4-hydroxycoumarin , which they later named dicoumarol.

They confirmed their results by synthesizing dicoumarol and proving in that it was identical to the naturally occurring agent. Dicoumarol was a product of the plant molecule coumarin not to be confused with Couma d in, a later tradename for warfarin.

Coumarin is now known to be present in many plants, and produces the notably sweet smell of freshly cut grass or hay and plants like sweet grass ; in fact, the plant's high content of coumarin is responsible for the original common name of "sweet clover", which is named for its sweet smell, not its bitter taste.

However, coumarins themselves do not influence clotting or warfarin-like action, but must first be metabolized by various fungi into compounds such as 4-hydroxycoumarin , then further in the presence of naturally occurring formaldehyde into dicoumarol , in order to have any anticoagulant properties.

Over the next few years, numerous similar chemicals specifically 4-hydroxycoumarins with a large aromatic substituent at the 3 position were found to have the same anticoagulant properties.

The first drug in the class to be widely commercialized was dicoumarol itself, patented in and later used as a pharmaceutical.

Karl Link continued working on developing more potent coumarin-based anticoagulants for use as rodent poisons , resulting in warfarin in Warfarin was first registered for use as a rodenticide in the US in , and was immediately popular.

Although warfarin was developed by Link, the Wisconsin Alumni Research Foundation financially supported the research and was assigned the patent.

After an incident in , in which an army inductee attempted suicide with multiple doses of warfarin in rodenticide but recovered fully after presenting to a Naval Hospital and being treated with vitamin K by then known as a specific antidote , [89] studies began in the use of warfarin as a therapeutic anticoagulant.

An early recipient of warfarin was US President Dwight Eisenhower , who was prescribed the drug after having a heart attack in The exact mechanism of action remained unknown until it was demonstrated, in , that warfarin inhibits the enzyme epoxide reductase , and hence interferes with vitamin K metabolism.

It has been posited that Lavrenty Beria , Nikita Khrushchev , and others conspired to use warfarin to poison Soviet leader Joseph Stalin.

Warfarin is tasteless and colourless, and produces symptoms similar to those that Stalin exhibited. Coumarins 4-hydroxycoumarin derivatives are used as rodenticides for controlling rats and mice in residential, industrial, and agricultural areas.

It may also be mixed with talc and used as a tracking powder , which accumulates on the animal's skin and fur, and is subsequently consumed during grooming.

The use of warfarin itself as a rat poison is now declining, because many rat populations have developed resistance to it, and poisons of considerably greater potency are now available.

Other 4-hydroxycoumarins used as rodenticides include coumatetralyl and brodifacoum , which is sometimes referred to as "super-warfarin", because it is more potent, longer-acting, and effective even in rat and mouse populations that are resistant to warfarin.

Unlike warfarin, which is readily excreted, newer anticoagulant poisons also accumulate in the liver and kidneys after ingestion. Warfarin is used to cull vampire bat populations in areas where human—wildlife conflict is a concern.

The bat returns to its roost and other members of the roost become poisoned as well by ingesting the warfarin after reciprocal grooming.

People can be exposed to warfarin in the workplace by breathing it in, swallowing it, skin absorption, and eye contact. It is classified as an extremely hazardous substance in the United States as defined in Section of the U.

Warfarin is a derivative of dicoumarol , an anticoagulant originally discovered in spoiled sweet clover.

Dicoumarol, in turn, is from coumarin , a sweet-smelling but coagulation-inactive chemical found in "sweet" clover and tonka beans also known as cumaru from which coumarin's name derives.

The name warfarin stems from its discovery at the University of Wisconsin , incorporating the acronym for the organization that funded the key research, WARF for the Wisconsin Alumni Research Foundation and the ending -arin , indicating its link with coumarin.

Long-term use of vitamin K antagonists as anticoagulation therapy was associated with lower cancer incidence.

From Wikipedia, the free encyclopedia. Medication used as an anticoagulant. This article is about the anticoagulation medication.

For the rodenticide often called "coumarins", see 4-hydroxycoumarins. IUPAC name. Interactive image.

Main article: INR self-monitoring. Further information: Fetal warfarin syndrome and Anticoagulation in pregnancy. Main article: Warfarin necrosis.

See also: Blue toe syndrome. Main article: 4-hydroxycoumarins. Archived from the original on 5 April Retrieved 4 April Retrieved 7 February Understanding the dose-effect relationship".

Clinical Pharmacokinetics. TGA eBusiness Services. Aspen Pharma Pty Ltd. Archived from the original on 17 October Retrieved 11 December Archived from the original on 12 June Retrieved 8 January Archived from the original on 18 September World Health Organization model list of essential medicines: 21st list Geneva: World Health Organization.

BNF 69 69 ed. British Medical Association. Retrieved 11 April Archived from the original on 3 February Retrieved 3 April Journal of the American College of Cardiology.

Journal of Cardiology. Archives of Internal Medicine. British Journal of Haematology. Archived from the original PDF on 20 October Retrieved 27 March American Family Physician.

Archived from the original on 1 February

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If you've been prescribed warfarin Coumadin, Jantoven to prevent blood clots, you probably already know that this powerful drug can save your life if you are at risk of or previously had blood clots.

But it's also important to remember that warfarin can result in serious side effects. The same action of warfarin that prevents blood clotting can result in bleeding.

Warfarin treatment is a careful balance, and certain factors can tip the balance, increasing the risk of bleeding. These include incorrect usage, interactions with certain drugs, supplements or foods, changes in diets, and illnesses.

If your doctor prescribes warfarin for you, make sure you understand what the potential side effects are and how to help prevent them.

The main risk is bleeding. While the risk of major bleeding is low, you need to be aware of potential problems.

For example, you might have trouble stopping the bleeding from a cut on your hand, or you have a nosebleed. More-serious bleeding may be inside the body internal.

Rarely, warfarin can cause the death of skin tissue necrosis. This complication occurs within a few days of starting warfarin treatment. Seek immediate medical care if you notice any sores, changes in skin color or temperature, or severe pain on your skin.

Some studies suggest that the risk of bleeding is generally higher in the first three months of warfarin treatment.

Older adults are generally at greater risk of bleeding, and taking other blood-thinning medication also increases your risk. A number of people who take warfarin are at a higher risk of bleeding because of their genetics make them more sensitive to warfarin.

Your doctor may recommend a genetic test to guide decisions about appropriate dosing of the drug. Like any other medication, warfarin can interact with drugs, foods, vitamins or herbal supplements.

The interaction might lower the effectiveness of warfarin or increase your risk of bleeding. More than drugs and foods that can interact with warfarin have been identified.

It's important to understand the role of vitamin K in warfarin treatment and a healthy diet. Warfarin works by disrupting the role of vitamin K in a complex series of molecular events that cause blood clotting.

But vitamin K is a nutrient essential for heart and bone health. Foods rich in vitamin K are green vegetables, such as lettuce, spinach and broccoli.

If you take warfarin, it's important to have a consistent amount of vitamin K in your diet. If you have little vitamin K in your diet, a sudden spike can increase your risk of bleeding.

This website can be viewed using the vertical display on your mobile device. Full Prescribing Information. Learn about another prescription blood thinner treatment option.

This site is intended for US residents 18 years of age or older. COUMADIN may have been prescribed to help you: Reduce your risk of forming blood clots if you have had a heart-valve replacement or if you have an irregular, rapid heartbeat, called atrial fibrillation.

Lower the risk of death if you've had a heart attack, as well as lowering your risk of having another heart attack, stroke, and having blood clots move to another part of your body.

What Is Atrial Fibrillation? 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 that 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 and talk to your healthcare provider before making any diet changes. Do not eat large amounts of leafy green vegetables, which contain vitamin K.

Certain vegetable oils also contain large amounts of vitamin K. Nonmedicinal ingredients: lactose anhydrous, magnesium stearate, and pregelatinized tapioca starch.

There is no dye in this product. The dose of warfarin is individualized by your doctor according to blood clotting time. Blood clotting time is determined by a laboratory test, called an INR, which should be performed at regular intervals.

It is very important to keep your lab appointments, as there is a narrow range between too much and too little of the medication.

Too much medication may cause you to bleed more. Too little medication may lead to harmful clots forming.

Different circumstances in your life e. Ask your doctor or pharmacist for a list of these foods and medications. It is very important that you take warfarin exactly as prescribed by your doctor.

Take your dose of warfarin at the same time each day. If you miss a dose of warfarin, notify your health care provider right away.

Take the missed dose as soon as possible and continue with your regular schedule. If it is almost time for your next dose, skip the missed dose and continue with your regular dosing schedule.

Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

Store this medication at room temperature, protect it from light and moisture, and keep it out of the reach of children. Do not dispose of medications in wastewater e.

Ask your pharmacist how to dispose of medications that are no longer needed or have expired. Anticoagulation blood thinning should not take place in any situation where the risk of bleeding might be greater than the potential benefits of anticoagulation.

Many medications can cause side-effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

Many of these side effects can be managed, and some may go away on their own over time. Contact your doctor if you experience these side effects and they are severe or bothersome.

Your pharmacist may be able to advise you on managing side effects. Although most of the side effects listed below don't happen very often, they could lead to serious problems if you do not seek medical attention.

Stop taking the medication and seek immediate medical attention if any of the following occur:. Some people may experience side effects other than those listed.

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