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Graedons’ Guide to Coumadin Interactions Some of our most important medicines have been discovered almost by accident. Coumadin (warfarin) is a classic example. In the early 1900s, Dakota farmers started using sweet clover to feed their cattle because it grew well under difficult conditions. But in the ’20s, cattle that ate spoiled clover silage developed a severe bleeding disease. Scientists tracked the cause of the problem to an ingredient of clover, dicoumarol. They developed a synthetic derivative, warfarin, initially for use as rat poison. In the 1950s doctors realized that this compound could be used to prevent blood clots in humans. Millions of people now take Coumadin regularly to prevent dangerous blood clots in the legs, lungs, heart or brain. This anticoagulant medicine is a life-saver for people prone to such clots, especially those with irregular heart rhythms (atrial fibrillation) or other conditions that predispose them to this kind of problem. Getting the dose right is essential in using Coumadin successfully. Too low a dose and a person can run the risk of thrombophlebitis, pulmonary embolism, heart attack or stroke. But if the dose climbs too high, there is an increasing possibility of hemorrhage, which can also be life-threatening. To help them keep their patients on this tightrope, doctors measure blood clotting potential (called prothrombin time, or PT) periodically. At first, PT should be measured every day or two. But even patients stabilized on Coumadin should have PT monitored every 4 to 6 weeks. Daily monitoring is also desirable any time a new drug is added or an old one dropped. The doctor will use values for the PT and the International Normalized Ratio (INR), calculated from the PT, to adjust the dose of Coumadin if necessary. Although each situation is different, the doctor will usually aim for an INR between 2 and 3. If the INR climbs above 4 there is a risk of serious hemorrhage. Many drugs can affect the activity of Coumadin. Most patients are warned to avoid aspirin, which increases the risk of hemorrhage. As few as four regular strength (325 mg) acetaminophen tablets daily over the course of a week or more can dramatically increase the risk of a high INR (JAMA, March 4, 1998). Since acetaminophen is found in hundreds of OTC and prescription products (Tylenol is best known), anyone on Coumadin must be extremely vigilant. Because the artifical sweetener aspartame (NutraSweet) increases bleeding time on its own (Clin. Pharmacol. Ther., Feb. 1998), it too should be used with caution by people taking Coumadin. Here is a partial list of medications that may alter Coumadin's effectiveness. If you must take one of them, please check with your physician and pharmacist. Never start or stop any medicine without medical supervision. acetaminophen Achromycin V Advil Aleve Alka-Seltzer Anacin Ansaid Antabuse Ascriptin aspirin Bactrim barbiturates Biaxin Cardioquin co-trimoxazole Colestid Cordarone © 1998 Graedon Enterprises, Inc. Danocrine Diflucan Dilantin E-Mycin E.E.S. Ecotrin ERYC EryPed EryTab Erythrocin flu vaccine Feldene Flagyl Ilosone Indocin Lodine Lopid male hormones Mevacor Monistat Motrin Naprosyn Nizoral Nolvadex Nuprin Paxil PCE Pediazole phenytoin Propulsid Protostat Prozac Questran quinidine Quinora Relafen rifampin Septra SMZ-TMP Sporanox Tagamet tamoxifen Tao Tegretol tetracycline thyroid hormone Toradol Vibramycin Voltaren Zithromax Zoloft Many people forget that alcohol is a drug and it can affect Coumadin. Alcohol is complicated, however, because modest intake has a different impact on bleeding time than heavy drinking. Grapefruit or grapefruit juice may also alter PT values. Illness that involves diarrhea or vomiting which can lead to dehydration may increase the potency of Coumadin. Diet is one of the most complicated factors in Coumadin management. Because this drug works by counteracting vitamin K, essential for coagulation, it is important to keep vitamin K intake relatively stable. Too much vitamin K in the diet could reduce the benefits of the drug and lead to a blood clot. People should not avoid vitamin K-rich foods, but they should be careful not to deprive themselves all week and suddenly overindulge. One woman ended up in the hospital with a pulmonary embolism because she binged on collard greens over the weekend. The RDA for normal healthy people is 0.5 to 1 microgram (mcg) of vitamin K per kilogram [2.2 lb] of body weight. This means that appropriate vitamin K intake be at least 25 mcg to 45 mcg of vitamin K daily for a small person of about 100 pounds. A larger person weighing 180 pounds should get a minimum of 40 mcg to 80 mcg vitamin K daily. For a person on Coumadin the most important factor is not to vary vitamin K intake much from day to day. Keeping track of your diet and your PT and INR values will allow you and your physician to adjust your dose of Coumadin properly. For example, a person striving for 75 mcg of vitamin K daily might eat cereal with a glass of milk (10 mcg) for breakfast and have tuna (24 mcg) in a salad with celery (32 mcg) for lunch. The next day, this person might have a serving of cole slaw (52 mcg) at lunch and a half-cup of green peas (24 mcg) at dinner. Unfortunately, the tables we consulted from the manufacturer of Coumadin and Bowes & Church's Food Values of Portions Commonly Used, 17th edition, did not agree in each case. We have indicated discrepancies with an asterisk (*) and given both values. The key to successful anticoagulant therapy is regular blood testing. Too much Coumadin can lead to hemorrhage. Alert your physician immediately if you experience: easy bruising; unusual bleeding, including blood in stool, urine or around the gums; nosebleeds; or excessive menstrual bleeding. FOOD SOURCES OF VITAMIN K Foods Vitamin K in mcg Vegetables: Asparagus (1 spear)* Bean sprouts, raw (1/2 cup) Broccoli, cooked (1/2 cup)* Brussels sprouts (5 sprouts) Cabbage, raw (1/2 cup shredded) Cabbage, cooked (2/3 cup) Cauliflower, raw (1/2 cup) Chick peas, dry uncooked (1 ounce) Celery, raw (2 1/2 stalks) Collards, cooked (1/2 cup) Endive, raw (1 cup) Green beans (3/4 cup) Kale, raw (3 1/2 ounces) Lentils, uncooked (1 ounce) Lettuce, bibb (1 ounce) Lettuce, red leaf (1 ounce) Lettuce, iceberg (5 leaves) Mung beans, uncooked (1 ounce) Okra, sliced and cooked (1/2 cup) Parsley, raw (1/2 cup) Peas, split, uncooked (1 ounce) Peas, green, cooked (1/2 cup) Seaweed, dulse (3 1/2 ounces) 4 or 11 17 63 or 113 289 52 98 96 74 32 440 115 16 817 62 35 60 31 48 40 180 23 24 1700 Foods Scallions, chopped (1/3 cup) Soybeans,uncooked (1 ounce) Spinach, cooked (1/2 cup)* Squash, summer (3 1/2 ounces) Swiss chard, raw (3 1/2 ounces) Turnip greens, raw (1/2 cup) Tomato, raw (one medium)* Fruit: Avocado (1 small) Kiwi (1 1/4) Pumpkin (1/2 cup) Strawberries (1 cup)* Nuts: Mixed nuts (3 1/2 ounces) Pistachios (3 1/2 ounces) Meat and Fish: Abalone (3 1/2 ounces) Tuna canned in oil (3 1/2 ounces) Beef liver (3 1/2 ounces) Chicken liver (3 1/2 ounces) Other: Egg (1 large)* Milk (8 ounces) Soybean oil (1 Tablespoon) Vitamin K in mcg 104 53 131 or 360 80 830 182 3 or 28 14 25 16 2.3 or 21 13 70 23 24 104 80 0.15 or 25 10 76