Warfarin Sodium interactions

Food & lifestyle

• alcohol

  Moderate

  Synergy

  Enhanced hypoprothrombinemic response to warfarin has been reported in patients with acute alcohol intoxication and/or liver disease. The proposed mechanisms are inhibition of warfarin metabolism and decreased synthesis of clotting factors. Binge drinking may exacerbate liver impairment and its metabolic ability in patients with liver dysfunction.

  What to do: Patients taking oral anticoagulants should be counseled to avoid large amounts of ethanol, but moderate consumption (one to two drinks per day) are not likely to affect the response to the anticoagulant in patients with normal liver function. Frequent INR/PT monitoring is recommended, especially if alcohol intake changes considerably. It may be advisable to avoid oral anticoagulant therapy in patients with uncontrollable drinking problems. Patients should be advised to promptly report any signs of bleeding to their doctor, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

  8 sources

  1. Breckenridge A "Clinical implications of enzyme induction." Basic Life Sci 6 (1975): 273-301
  2. Karlson B, Leijd B, Hellstrom K "On the influence of vitamin K-rich vegetables and wine on the effectiveness of warfarin treatment." Acta Med Scand 220 (1986): 347-50
  3. Udall JA "Drug interference with warfarin therapy." Clin Med 77 (1970): 20-5
  4. "Product Information. Coumadin (warfarin)." DuPont Pharmaceuticals (2001):
  5. Havrda DE, Mai T, Chonlahan J "Enhanced antithrombotic effect of warfarin associated with low-dose alcohol consumption." Pharmacotherapy 25 (2005): 303-7
  6. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  7. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  8. Pharmaceutical Society of Australia "APPGuide online. Australian prescription products guide online. http://www.appco.com.au/appguide/default.asp" (2006):

• food high in vitamin K

  Moderate

  Antagonism

  Vitamin K may antagonize the hypoprothrombinemic effect of oral anticoagulants. Vitamin K is a cofactor in the synthesis of blood clotting factors that are inhibited by oral anticoagulants, thus intake of vitamin K through supplements or diet can reverse the action of oral anticoagulants. Resistance to oral anticoagulants has been associated with consumption of foods or enteral feedings high in vitamin K content. Likewise, a reduction of vitamin K intake following stabilization of anticoagulant therapy may result in elevation of the INR and bleeding complications. Foods rich in vitamin K include beef liver, broccoli, Brussels sprouts, cabbage, collard greens, endive, kale, lettuce, mustard greens, parsley, soy beans, spinach, Swiss chard, turnip greens, watercress, and other green leafy vegetables. Moderate to high levels of vitamin K are also found in other foods such as asparagus, avocados, dill pickles, green peas, green tea, canola oil, margarine, mayonnaise, olive oil, and soybean oil. Snack foods containing the fat substitute, olestra, are fortified with 80 mcg of vitamin K per each one ounce serving so as to offset any depletion of vitamin K that may occur due to olestra interference with its absorption. Whether these foods can alter the effect of oral anticoagulants has not been extensively studied. One small study found that moderate consumption (1.5 servings/day) does not significantly affect the INR after one week in patients receiving long-term anticoagulation.

  What to do: Intake of vitamin K through supplements or diet should not vary significantly during oral anticoagulant therapy. The diet in general should remain consistent, as other foods containing little or no vitamin K such as mangos and soy milk have been reported to interact with warfarin. Some experts recommend that continuous enteral nutrition should be interrupted for one hour before and one hour after administration of the anticoagulant dose and that enteral formulas containing soy protein should be avoided. Patients should also consider avoiding or limiting the consumption of cranberry juice or other cranberry formulations (e.g., encapsulated dried cranberry powder), pomegranate juice, black currant juice, and black currant seed oil.

  37 sources

  1. Andersen P, Godal HC "Predictable reduction in anticoagulant activity of warfarin by small amounts of vitamin K." Acta Med Scand 198 (1975): 269-70
  2. Westfall LK "An unrecognized cause of warfarin resistance." Drug Intell Clin Pharm 15 (1981): 131
  3. Lee M, Schwartz RN, Sharifi R "Warfarin resistance and vitamin K." Ann Intern Med 94 (1981): 140-1
  4. Zallman JA, Lee DP, Jeffrey PL "Liquid nutrition as a cause of warfarin resistance." Am J Hosp Pharm 38 (1981): 1174
  5. Griffith LD, Olvey SE, Triplett WC "Increasing prothrombin times in a warfarin-treated patient upon withdrawal of ensure plus." Crit Care Med 10 (1982): 799-800
  6. Kempin SJ "Warfarin resistance caused by broccoli." N Engl J Med 308 (1983): 1229-30
  7. Watson AJ, Pegg M, Green JR "Enteral feeds may antagonise warfarin." Br Med J 288 (1984): 557
  8. Walker FB "Myocardial infarction after diet-induced warfarin resistance." Arch Intern Med 144 (1984): 2089-90

  Show all 37 sourcesShow fewer sources

  9. Howard PA, Hannaman KN "Warfarin resistance linked to enteral nutrition products." J Am Diet Assoc 85 (1985): 713-5
  10. Karlson B, Leijd B, Hellstrom K "On the influence of vitamin K-rich vegetables and wine on the effectiveness of warfarin treatment." Acta Med Scand 220 (1986): 347-50
  11. Pedersen FM, Hamberg O, Hess K, Ovesen L "The effect of dietary vitamin K on warfarin-induced anticoagulation." J Intern Med 229 (1991): 517-20
  12. Parr MD, Record KE, Griffith GL, et al. "Effect of enteral nutrition on warfarin therapy." Clin Pharm 1 (1982): 274-6
  13. Wells PS, Holbrook AM, Crowther NR, Hirsh J "Interactions of warfarin with drugs and food." Ann Intern Med 121 (1994): 676-83
  14. O'Reilly RA, Rytand DA ""Resistance" to warfarin due to unrecognized vitamin K supplementation." N Engl J Med 303 (1980): 160-1
  15. Kazmier FJ, Spittell JA Jr "Coumarin drug interactions." Mayo Clin Proc 45 (1970): 249-55
  16. Chow WH, Chow TC, Tse TM, Tai YT, Lee WT "Anticoagulation instability with life-threatening complication after dietary modification." Postgrad Med J 66 (1990): 855-7
  17. MacLeod SM, Sellers EM "Pharmacodynamic and pharmacokinetic drug interactions with coumarin anticoagulants." Drugs 11 (1976): 461-70
  18. Sullivan DM, Ford MA, Boyden TW "Grapefruit juice and the response to warfarin." Am J Health Syst Pharm 55 (1998): 1581-3
  19. Harrell CC, Kline SS "Vitamin K-supplemented snacks containing olestra: Implication for patients taking warfarin." Jama J Am Med Assn 282 (1999): 1133-4
  20. Beckey NP, Korman LB, Parra D "Effect of the moderate consumption of olestra in patients receiving long-term warfarin therapy." Pharmacotherapy 19 (1999): 1075-9
  21. Monterrey-Rodriguez J "Interaction between warfarin and mango fruit." Ann Pharmacother 36 (2002): 940-1
  22. Cambria-Kiely JA "Effect of soy milk on warfarin efficacy." Ann Pharmacother 36 (2002): 1893-6
  23. MHRA. Mediciines and Healthcare products Regulatory Agency. Committee on Safety of Medicines "Possible interaction between warfarin and cranberry juice. http://medicines.mhra.gov.uk/ourwork/monitorsafequalmed/currentproblems/currentproblems.htm" (2003):
  24. Suvarna R, Pirmohamed M, Henderson L "Possible interaction between warfarin and cranberry juice." BMJ 327 (2003): 1454
  25. Kuykendall JR, Houle MD, Rhodes RS "Possible warfarin failure due to interaction with smokeless tobacco." Ann Pharmacother 38 (2004): 595-7
  26. Grant P "Warfarin and cranberry juice: an interaction?" J Heart Valve Dis 13 (2004): 25-6
  27. Rindone JP, Murphy TW "Warfarin-cranberry juice interaction resulting in profound hypoprothrombinemia and bleeding." Am J Ther 13 (2006): 283-4
  28. Brandin H, Myrberg O, Rundlof T, Arvidsson AK, Brenning G "Adverse effects by artificial grapefruit seed extract products in patients on warfarin therapy." Eur J Clin Pharmacol 63 (2007): 565-70
  29. Agencia Espa?ola de Medicamentos y Productos Sanitarios Healthcare "Centro de informaci��n online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html" (2008):
  30. Griffiths AP, Beddall A, Pegler S "Fatal haemopericardium and gastrointestinal haemorrhage due to possible interaction of cranberry juice with warfarin." J R Soc Health 128 (2008): 324-6
  31. Guo LQ, Yamazoe Y "Inhibition of cytochrome P450 by furanocoumarins in grapefruit juice and herbal medicines." Acta Pharmacol Sin 25 (2004): 129-36
  32. Hamann GL, Campbell JD, George CM "Warfarin-cranberry juice interaction." Ann Pharmacother 45 (2011): e17
  33. Jarvis S, Li C, Bogle RG "Possible interaction between pomegranate juice and warfarin." Emerg Med J 27 (2010): 74-5
  34. Roberts D, Flanagan P "Case report: Cranberry juice and warfarin." Home Healthc Nurse 29 (2011): 92-7
  35. Ge B, Zhang Z, Zuo Z "Updates on the clinical evidenced herb-warfarin interactions." Evid Based Complement Alternat Med 2014 (2014): 957362
  36. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67
  37. Bodiford AB, Kessler FO, Fermo JD, Ragucci KR "Elevated international normalized ratio with the consumption of grapefruit and use of warfarin." SAGE Open Med Case Rep 0 (2013): 1-3

Conditions

Conditions in which Warfarin Sodium needs care, as documented in this source.

• Diabetes Mellitus

  Major

  Therapy with oral anticoagulants should be administered cautiously in patients with severe diabetes because they may be at increased risk for hemorrhage. The INR should be monitored closely, and patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

  1 source

  1. "Product Information. Coumadin (warfarin)." DuPont Pharmaceuticals (2001):

• Hemorrhage

  Major

  In general, the use of oral anticoagulants is contraindicated in patients with active bleeding or a hemorrhagic diathesis or other significant risks for bleeding, including hemostatic and/or coagulation defects associated with hemophilia, hypoprothrombinemia, thrombocytopenia, thrombocytopathy, severe hepatic impairment, and myeloproliferative disorders such as leukemia or polycythemia vera. Additionally, oral anticoagulants are usually contraindicated in the presence of any active ulceration of the gastrointestinal, respiratory, or genitourinary tracts; cerebrovascular hemorrhage; aneurysms (cerebral, dissecting aortic); pericarditis and pericardial effusions; bacterial endocarditis; and eclampsia, preeclampsia, or threatened abortion. These patients may be at increased risk for uncontrollable hemorrhage or bleeding complications during therapy with oral anticoagulants. Other potential contraindications include diverticulitis, vasculitis, malnutrition, and vitamin C or vitamin K deficiency. The decision to administer anticoagulants must be based upon clinical judgment in which the risks are weighed against the benefits in each patient.

  13 sources

  1. Dajani YF "Hematuria in patients on anticoagulants." N Engl J Med 297 (1977): 222
  2. Levine MN, Hirsh J "Hemorrhagic complications of anticoagulant therapy." Semin Thromb Hemost 12 (1986): 39-57
  3. Landfeld CS, Goldman L "Major bleeding in outpatients treated with warfarin: incidence and prediction by factors known at the start of outpatient therapy." Am J Med 87 (1989): 144-52
  4. Lee KS, Marwick T "Hemopericardium and cardiac tamponade associated with warfarin therapy." Cleve Clin J Med 60 (1993): 336-8
  5. Landefeld CS, Rosenblatt MW, Goldman L "Bleeding in outpatients treated with warfarin: relation to the prothrombin time and important remediable lesions." Am J Med 87 (1989): 153-9
  6. Landefeld CS, Cook EF, Flatley M, Weisberg M, Goldman L "Identification and preliminary validation of predictors of major bleeding in hospitalized patients starting anticoagulant therapy." Am J Med 82 (1987): 703-13
  7. Hylek EM, Singer DE "Risk factors for intracranial hemorrhage in outpatients taking warfarin." Ann Intern Med 120 (1994): 897-902
  8. "Product Information. Coumadin (warfarin)." DuPont Pharmaceuticals (2001):

  Show all 13 sourcesShow fewer sources

  9. Brigden ML "When bleeding complicates oral anticoagulant therapy: how to anticipate, investigate, and treat." Postgrad Med 98 (1995): 153
  10. White RH, McKittrick T, Takakuwa J, Callahan C, McDonell M, Fihn S "Management and prognosis of life-threatening bleeding during warfarin therapy." Arch Intern Med 156 (1996): 1197-201
  11. Palareti G, Leali N, Coccheri S, Poggi M, Manotti C, Dangelo A, Pengo V, Erba N, Moia M, Ciavarella N, Devote G, Berrettini M, "Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT)." Lancet 348 (1996): 423-8
  12. Morgan RJ, Bristol JB "Unusual findings in a patient taking warfarin - Retroperitoneal haematoma." Postgrad Med J 75 (1999): 299-300
  13. Jimenez J "Abdominal pain in a patient using warfarin - Intramural haematoma of the small bowel in the setting of the warfarin anticoagulation." Postgrad Med J 75 (1999): 747-8

• Hypertension

  Major

  In general, the use of oral anticoagulants is contraindicated in patients with malignant or severe, uncontrolled hypertension. These patients may be at increased risk for cerebral hemorrhage. Therapy with oral anticoagulants should be administered cautiously in patients with moderate hypertension.

  2 sources

  1. Hylek EM, Singer DE "Risk factors for intracranial hemorrhage in outpatients taking warfarin." Ann Intern Med 120 (1994): 897-902
  2. "Product Information. Coumadin (warfarin)." DuPont Pharmaceuticals (2001):

• Liver Diseases

  Major

  Oral anticoagulants (coumarin and indandione derivatives) are primarily metabolized by the liver. Patients with hepatic impairment may have a heightened response to these agents due to decreased clearance of the drugs as well as defective hemostasis associated with impaired synthesis of clotting factors by the liver. Therapy with oral anticoagulants should be administered cautiously in patients with severe or moderate liver disease. The INR should be monitored closely, and patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools

  5 sources

  1. Shetty HG, Fennerty AG, Routledge PA "Clinical pharmacokinetic considerations in the control of oral anticoagulant therapy." Clin Pharmacokinet 16 (1989): 238-53
  2. Williams RL, Schary WL, Blaschke TF, et al. "Influence of acute viral hepatitis on disposition and pharmacologic effect of warfarin." Clin Pharmacol Ther 20 (1976): 90-7
  3. Landefeld CS, Cook EF, Flatley M, Weisberg M, Goldman L "Identification and preliminary validation of predictors of major bleeding in hospitalized patients starting anticoagulant therapy." Am J Med 82 (1987): 703-13
  4. "Product Information. Coumadin (warfarin)." DuPont Pharmaceuticals (2001):
  5. Demirkan K, Stephens MA, Newman KP, Self TH "Response to warfarin and other oral anticoagulants: effects of disease states." South Med J 93 (2000): 448-54; quiz 455

• Protein C Deficiency

  Major

  Tissue necrosis is a rare complication that develops during the initiation of oral anticoagulant therapy due to thrombotic occlusion of venules in the dermis and subcutaneous tissues. Hereditary, familial, or clinical deficiencies of protein C or its cofactor, protein S, may be associated with a hypercoagulable state and an increased risk of the complication. Therapy with oral anticoagulants should be administered cautiously in patients with known or suspected deficiency in protein C-mediated anticoagulant response. Concomitant administration with heparin for the first 5 to 7 days of oral anticoagulant therapy may minimize the risk. If tissue necrosis develops, oral anticoagulant therapy should be discontinued promptly and vitamin K or frozen plasma administered at once. Heparin should then be considered for anticoagulation.

  14 sources

  1. Cole MS, Minifee PK, Wolma FJ "Coumarin necrosis: a review of the literature." Surgery 103 (1988): 271-7
  2. Humphries JE, Gardner JH, Connelly JE "Warfarin skin necrosis: recurrence in the absence of anticoagulant therapy." Am J Hematol 37 (1991): 197-200
  3. Horn JR, Danziger LH, Davis RJ "Warfarin-induced skin necrosis: report of four cases." Am J Hosp Pharm 38 (1981): 1763-8
  4. Kandrotas RJ, Deterding J "Genital necrosis secondary to warfarin therapy." Pharmacotherapy 8 (1988): 351-4
  5. Locht H, Lindstrom FD "Severe skin necrosis following warfarin therapy in a patient with protein C deficiency." J Intern Med 233 (1993): 287-9
  6. Colman RW, Rao AK, Rubin RN "Warfarin skin necrosis in a 33-year-old woman." Am J Hematol 43 (1993): 300-3
  7. LaPrade RF, Fowler BL, Ryan TG "Skin necrosis with minidose warfarin used for prophylaxis against thromboembolic disease after hip surgery." Orthopedics 16 (1993): 703-4
  8. Eby CS "Warfarin-induced skin necrosis." Hematol Oncol Clin North Am 7 (1993): 1291-300

  Show all 14 sourcesShow fewer sources

  9. Griffin JP "Anticoagulants and skin necrosis." Adverse Drug React Toxicol Rev 13 (1994): 157-67
  10. "Product Information. Coumadin (warfarin)." DuPont Pharmaceuticals (2001):
  11. Stewart AJ, Penman ID, Cook MK, Ludlam CA "Warfarin-induced skin necrosis." Postgrad Med J 75 (1999): 233-5
  12. Zimbelman J, Lefkowitz J, Schaeffer C, Hays T, MancoJohnson M, Manhalter C, Nuss R "Unusual complications of warfarin therapy: Skin necrosis and priapism." J Pediat 137 (2000): 266-8
  13. Cheng A, Scheinfeld NS, McDowell B, Dokras AA "Warfarin skin necrosis in a postpartum woman with protein S deficiency." Obstet Gynecol 90(4 Pt 2) (1997): 671-2
  14. Mehta RL, Scott G, Sloand JA, Francis CW "Skin necrosis associated with acquired protein C deficiency in patients with renal failure and calciphylaxis." Am J Med 88 (1990): 252-7

• Coumarin Resistance

  Moderate

  Patients with edema, hereditary coumarin resistance, hyperlipidemia, hypothyroidism, or nephrotic syndrome may exhibit lower than expected hypoprothrombinemic response to oral anticoagulants. Thus, more frequent laboratory (PT/INR) monitoring and dosage adjustment of anticoagulant may be required based on changes in the patient's condition.

  6 sources

  1. Ganeval D, Fischer AM, Barre J, et al. "Pharmacokinetics of warfarin in the nephrotic syndrome and effect on vitamin K-dependent clotting factors." Clin Nephrol 25 (1986): 75-80
  2. Rice AJ, McIntosh TJ, Fouts JR, et al. "Decrease sensitivity to warfarin in patients with myxedema." Am J Med Sci 262 (1971): 211-5
  3. Walters MB "The relationship between thyroid function and anticoagulant therapy." Am J Cardiol 11 (1963): 112-4
  4. "Product Information. Coumadin (warfarin)." DuPont Pharmaceuticals (2001):
  5. Demirkan K, Stephens MA, Newman KP, Self TH "Response to warfarin and other oral anticoagulants: effects of disease states." South Med J 93 (2000): 448-54; quiz 455
  6. Stephens MA, Self TH, Lancaster D, Nash T "Hypothyroidism: effect on warfarin anticoagulation." South Med J 82 (1989): 1585-6

• Coumarin Sensitivity

  Moderate

  Patients with a collagen vascular disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, scleroderma), congestive heart failure (especially decompensated disease), severe or prolonged diarrhea, fever, hyperthyroidism, malabsorption, or steatorrhea may exhibit greater than expected hypoprothrombinemic response to oral anticoagulants. Thus, more frequent laboratory (PT/INR) monitoring and dosage adjustment of anticoagulant may be required based on changes in the patient's condition. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

  10 sources

  1. Vagenakis AG, Cote R, Miller ME, et al. "Enhancement of warfarin-induced hypoprothrombinemia by thyrotoxicosis." Johns Hopkins Med J 131 (1972): 69-73
  2. Owens JC, Neely WB, Owen WR "Effect of sodium dextrothyroxine in patients receiving anticoagulants." N Engl J Med 266 (1962): 76-9
  3. Self T, Weisburst M, Wooten E, Straughn A, Oliver J "Warfarin-induced hypoprothrombinemia: potentiation by hyperthyroidism." JAMA 231 (1975): 1165-6
  4. Landefeld CS, Cook EF, Flatley M, Weisberg M, Goldman L "Identification and preliminary validation of predictors of major bleeding in hospitalized patients starting anticoagulant therapy." Am J Med 82 (1987): 703-13
  5. Black JA "Diarrhoea, vitamin k, and warfarin." Lancet 344 (1994): 1373
  6. "Product Information. Coumadin (warfarin)." DuPont Pharmaceuticals (2001):
  7. Demirkan K, Stephens MA, Newman KP, Self TH "Response to warfarin and other oral anticoagulants: effects of disease states." South Med J 93 (2000): 448-54; quiz 455
  8. Smith JK, Aljazairi A, Fuller SH "INR elevation associated with diarrhea in a patient receiving warfarin." Ann Pharmacother 33 (1999): 301-4

  Show all 10 sourcesShow fewer sources

  9. Kellett HA, Sawers JS, Boulton FE, Cholerton S, Park BK, Toft AD "Problems of anticoagulation with warfarin in hyperthyroidism." Q J Med 58 (1986): 43-51
  10. Self TH, Straughn AB, Weisburst MR "Effect of hyperthryroidism on hypoprothrombinemic response to warfarin." Am J Hosp Pharm 33 (1976): 387-9

• Kidney Diseases

  Moderate

  There is no evidence that hypoprothrombinemic response to oral anticoagulants (coumarin and indandione derivatives) is altered in renal impairment due to decreased plasma protein binding, thus dosage adjustments are generally not necessary. However, patients with renal impairment may demonstrate platelet defects and may be at increased risk for bleeding. Therapy with oral anticoagulants should be administered cautiously in patients with severe or moderate renal dysfunction. The INR should be monitored closely, and patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

  8 sources

  1. Bachmann K, Shapiro R, Mackiewicz J "Influence of renal dysfunction on warfarin plasma protein binding." J Clin Pharmacol 16 (1976): 468-72
  2. Yacobi A, Udall JA, Levy G "Serum protein binding as a determinant of warfarin body clearance and anticoagulant effect." Clin Pharmacol Ther 19 (1976): 552-8
  3. Bachmann K, Shapiro R, Mackiewicz J "Warfarin elimination and responsiveness in patients with renal dysfunction." J Clin Pharmacol 17 (1977): 292-9
  4. Shetty HG, Fennerty AG, Routledge PA "Clinical pharmacokinetic considerations in the control of oral anticoagulant therapy." Clin Pharmacokinet 16 (1989): 238-53
  5. Landfeld CS, Goldman L "Major bleeding in outpatients treated with warfarin: incidence and prediction by factors known at the start of outpatient therapy." Am J Med 87 (1989): 144-52
  6. Landefeld CS, Cook EF, Flatley M, Weisberg M, Goldman L "Identification and preliminary validation of predictors of major bleeding in hospitalized patients starting anticoagulant therapy." Am J Med 82 (1987): 703-13
  7. "Product Information. Coumadin (warfarin)." DuPont Pharmaceuticals (2001):
  8. Demirkan K, Stephens MA, Newman KP, Self TH "Response to warfarin and other oral anticoagulants: effects of disease states." South Med J 93 (2000): 448-54; quiz 455