JANTOVEN

Warfarin Sodium 5mg, Oral tablet

Tobacco

· Severity: Moderate

· Notes for Consumers: Tobacco smoke contains substances that may speed the removal of Warfarin from the body; if you start smoking, Warfarin may become less effective at thinning the blood and preventing blood clots. Just the opposite occurs when someone stops smoking tobacco; if you stop smoking this may increase the amount of Warfarin in the blood and side effects from Warfarin may get worse, if you are not closely watched. Too much Warfarin might cause bleeding (like nosebleeds, easy bruising, bleeding gums or blood in urine or stool). Not everyone might experience these effects. Notify your prescriber if any of these effects occur. Your prescriber may need to closely monitor the blood thinning effect of Warfarin whenever a change in tobacco smoking occurs, so inform your prescriber if you are a smoker or if you are going to stop smoking.

· Notes for Professionals: Tobacco smoke contains polycyclic aromatic hydrocarbons that induce hepatic CYP450 microsomal enzymes: e.g., CYP1A1, CYP1A2, CYP2E1. R-warfarin is partially metabolized by CYP1A2; induction by tobacco smoking can make warfarin less effective. Conversely, the sudden cessation of tobacco smoking may result in a reduced clearance of warfarin, despite the initiation of a nicotine replacement product. However, changes in warfarin clearance may not always result in a clinically significant change in the PT or INR; monitor the patient's INR to assess the need for warfarin dosage adjustment when changes in smoking status occur.

Warfarin Sodium 5mg, Oral tablet

Cranberry-containing Foods/Beverages

· Severity: Major

· Notes for Consumers: Drinking cranberry juice may increase the effects of warfarin, which may make bleeding more likely. Use caution until more is known about this potential interaction.

· Notes for Professionals: Interactions with warfarin and cranberry juice (cranberry, Vaccinium macrocarpon Ait.) have been reported, but the data are controversial. Some case reports have reported increased INR or other clinically significant events, while limited and small controlled clinical research data do not support an interaction. It is not clear if warfarin would interact with cranberry supplements (e.g., dried extracts); caution is advised until further data are available; patients should likely have consistent cranberry intake, including intake of cranberry capsules and concentrates, if on warfarin therapy.

Warfarin Sodium 5mg, Oral tablet

Enteral Feedings

· Severity: Major

· Notes for Consumers: Some enteral feedings (examples: Ensure, Boost, Sustical) contain vitamin K, which can decrease the action of Warfarin if taken in large amounts. In some cases, enteral feedings have reduced the effectiveness of Warfarin. However, not all persons experience this interaction. Closely read labels and before taking any meal or food supplements - get your health care professionals approval before use. Your health care professional will help determine the right feeding supplement for you so that you maintain consistency in your vitamin K intake and so your Warfarin and 'blood thinning' remain in the right 'balance'. Report any new or unusual side effects such as swelling or pain in your lower legs or shortness of breath immediately.

· Notes for Professionals: Phytonadione, vitamin K1, is a pharmacologic antagonist of warfarin. Occult sources of vitamin K may decrease or reverse the activity of warfarin. Occult sources of vitamin K may include selected enteral feedings. In general, it is recommended that patients avoid large servings or frequent intake of foods that contain substantial amounts of vitamin K. Patients should aim for a stable and non-excessive intake of vitamin K in the diet to ensure stable INRs and appropriate clinical response to warfarin treatment.

Warfarin Sodium 5mg, Oral tablet

Marijuana

· Severity: Major

· Notes for Consumers: Marijuana may cause you to bruise or bleed more easily while you are receiving Warfarin. Contact your health care provider if you notice any new or unusual bleeding. Signs of bleeding may include bloody or black, tarry stools; red or dark-brown urine; spitting up blood or brown material that looks like coffee grounds; red spots on the skin; unusual bruising or bleeding from the eye, gums, or nose.

· Notes for Professionals: Patients should use caution in combining marijuana use with warfarin. Marijuana may increase warfarin anticoagulant effect by inhibiting its metabolism, and to a lesser extent, displacing warfarin from protein-binding sites. This may lead to an increased risk for bleeding events. CYP2C9 is the principle enzyme that metabolizes S-warfarin and modulates the in vivo activity of warfarin. Certain cannabinoids in marijuana may inhibit CYP2C metabolism. A case report has described a potential interaction in a patient previously stabilized on long-term warfarin therapy who experienced 2 hospitalizations due to bleeding and increased international normalized ratio (INR) after smoking marijuana; the INR normalized and remained stable once the patient quit using marijuana. Other causes for the potential change in INR were ruled out. In patients who report marijuana use while on warfarin therapy, the international normalized ratio (INR) should be carefully monitored.

Warfarin Sodium 5mg, Oral tablet

Chamomile-containing Beverages

· Severity: Moderate

· Notes for Consumers: Do not use excessive amounts of Chamomile tea or other Chamomile products while taking warfarin. Chamomile is found in teas and herbal supplements. Using Chamomile may increase the risk that you will bruise or bleed more easily. Signs of bleeding include, but are not limited to, increased bruising, pinpoint red spots on your skin, nosebleeds, bleeding gums, or black tarry stools. Report any of these effects to your health care provider immediately.

· Notes for Professionals: The regular use of chamomile teas or other chamomile products should be approaced with caution in patients taking warfarin. A case report noted an enhanced effect of warfarin, resulting in an elevated international normalized ratio (INR) and associated bleeding, when a patient increased her ingestion of chamomile tea (chamomile, Matricaria recutita); this is the only known formal report of an interaction. Various chamomile species are known to contain coumarin related compounds that may have an additive effect with warfarin. No pharmacokinetic alterations in warfarin were evident from this case report. The authors recommend that patients limit and not greatly alter their Chamomile use while taking warfarin therapy. Educate patients on the potential risks of the ingestion of nutritional supplements and herbal remedies, and the importance of dietary intake. Monitor the patient clinically for adverse events and regularly monitor the patient's INR.

Warfarin Sodium 5mg, Oral tablet

Vitamin K-containing foods

· Severity: Major

· Notes for Consumers: You must pay close attention to your diet during Warfarin therapy. Try to keep a consistent diet. Certain foods may decrease the effect of warfarin because they contain high amounts of vitamin K or other ingredients that can decrease the effect of warfarin. These foods include green tea, brussel sprouts, kale, asparagus, avocado, broccoli, cabbage, cauliflower, collard greens, lettuce, liver, soybeans or soybean oil, lentils, peas, mustard greens, turnip greens, parsley, green scallions, and spinach. Some enteral feedings (nutritional shakes like Ensure and many others) also can have this effect. If you eat any of these foods regularly, try to have the same number of servings each week as this will allow your warfarin dose to remain more stable. Avoid large servings when possible.

· Notes for Professionals: Phytonadione, vitamin K1, is a pharmacologic antagonist of warfarin; it is often administered to reverse elevated INR from warfarin overdose. Exogenous administration or occult sources of vitamin K may decrease or reverse the activity of warfarin. Response to warfarin usually returns after stopping the vitamin K-containing product. Occult sources of vitamin K include enteral feedings, certain multivitamins, and many food products. Foods that contain large amounts of vitamin K include green tea, brussel sprouts, and kale. Other foods that contain moderate-high quantities of vitamin K include asparagus, avocado, broccoli, cabbage, cauliflower, collard greens, lettuce, liver, soy products (including soy milk, soybeans or soybean oil), lentils, peas, mustard greens, turnip greens, parsley, green scallions, and spinach. Medical products that contain soybean oil such as intravenous lipid emulsions or propofol, may decrease warfarin anticoagulation. Intravenous lipids may interfere with warfarin anticoagulation in many ways including enhancing the production of clotting factors, facilitating platelet aggregation, supplying vitamin K, and enhancing warfarin binding to albumin. In general, it is recommended that patients avoid large servings or frequent intake of foods that contain substantial amounts of vitamin K.

Warfarin Sodium 5mg, Oral tablet

Alcohol

· Severity: Moderate

· Notes for Consumers: If you drink alcohol-containing drinks while taking warfarin, you may bruise or bleed more easily. Avoid alcohol-containing drinks or at least limit to no more than 2 drinks per day while taking warfarin. While you are taking warfarin, watch for signs of bruising or bleeding, which may occur at any time but especially after drinking large amounts of alcohol or with daily drinking. Signs of bleeding include, but are not limited to, increased bruising, pinpoint red spots on your skin, or black, tarry stools.

· Notes for Professionals: In controlled studies of patients or healthy subjects anticoagulated with warfarin, small to moderate amounts of wine do not alter INR values or warfarin levels. However, acute intoxication resulting from large amounts of ethanol may enhance the hypoprothrombinemic response to oral anticoagulants due to inhibition of warfarin's metabolism.

Warfarin Sodium 5mg, Oral tablet

Grapefruit juice

· Severity: Moderate

· Notes for Consumers: These drugs may be taken together only under close supervision from your prescriber. Taking these drugs together may increase your risk to bruise or bleed. Call your doctor or health care professional if you notice any unusual bleeding. Signs of bleeding may include bloody or black, tarry stools; red or dark-brown urine; spitting up blood or brown material that looks like coffee grounds; red spots on the skin; unusual bruising or bleeding from the eye, gums, or nose.

· Notes for Professionals: Closely monitor the INR if coadministration of warfarin with grapefruit/grapefruit juice is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Grapefruit/grapefruit juice is a strong CYP3A4 and moderate CYP2C9 inhibitor and the R-enantiomer of warfarin is a CYP3A4/CYP2C9 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.

<b>DISCLAIMER:</b><em> This drug information content is provided for informational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Patients should always consult their physician with any questions regarding a medical condition and to obtain medical advice and treatment. Drug information is sourced from GSDD (Gold Standard Drug Database ) provided by Elsevier.</em>