Basic Information
ID DDInter1951 and DDInter371
Interaction A case report suggests that chondroitin and/or glucosamine may potentiate the hypoprothrombinemic effect of warfarin. The mechanism of interaction is unknown. Glucosamine is a chemical component of heparin, while chondroitin is a minor component of danaparoid and has been shown in vitro and in animals to prolong prothrombin time.
Management Patients should consult a healthcare provider before taking any herbal or alternative medicine. In patients treated with warfarin, the INR should be closely monitored following addition or discontinuation of chondroitin and glucosamine, and the warfarin dosage adjusted as necessary. The same precaution may be applicable during therapy with other oral anticoagulants, although clinical data are lacking. 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.
References [1] Rozenfeld V, Crain JL, Callahan AK "Possible augmentation of warfarin effect by glucosamine-chondroitin." Am J Health Syst Pharm 61 (2004): 306-7 [2] Scott GN "Interaction of warfarin with glucosamine--chondroitin." Am J Health Syst Pharm 61 (2004): 1186; author reply 1186 [3] Guo LQ, Yamazoe Y "Inhibition of cytochrome P450 by furanocoumarins in grapefruit juice and herbal medicines." Acta Pharmacol Sin 25 (2004): 129-36 [4] 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 [5] Suvarna R, Pirmohamed M, Henderson L "Possible interaction between warfarin and cranberry juice." BMJ 327 (2003): 1454 [6] Lee M, Schwartz RN, Sharifi R "Warfarin resistance and vitamin K." Ann Intern Med 94 (1981): 140-1 [7] 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 [8] 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 [9] Kempin SJ "Warfarin resistance caused by broccoli." N Engl J Med 308 (1983): 1229-30 [10] Westfall LK "An unrecognized cause of warfarin resistance." Drug Intell Clin Pharm 15 (1981): 131 [11] Kuykendall JR, Houle MD, Rhodes RS "Possible warfarin failure due to interaction with smokeless tobacco." Ann Pharmacother 38 (2004): 595-7 [12] Walker FB "Myocardial infarction after diet-induced warfarin resistance." Arch Intern Med 144 (1984): 2089-90 [13] 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 [14] 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 [15] 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 [16] Wells PS, Holbrook AM, Crowther NR, Hirsh J "Interactions of warfarin with drugs and food." Ann Intern Med 121 (1994): 676-83 [17] MHRA. Mediciines and Healthcare products Regulatory Agency. Committee on Safety of Medicines "Possible interaction between warfarin and cranberry juice. Available from: URL: http://medicines.mhra.gov.uk/ourwork/monitorsafequalmed/currentproblems/currentproblems.htm." ([2003 Sept]): [18] Agencia Española de Medicamentos y Productos Sanitarios Healthcare "Centro de información online de medicamentos de la AEMPS - CIMA. Available from: URL: https://cima.aemps.es/cima/publico/home.html." ([2018]): [19] 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 [20] O'Reilly RA, Rytand DA ""Resistance" to warfarin due to unrecognized vitamin K supplementation." N Engl J Med 303 (1980): 160-1 [21] Kazmier FJ, Spittell JA Jr "Coumarin drug interactions." Mayo Clin Proc 45 (1970): 249-55 [22] Cambria-Kiely JA "Effect of soy milk on warfarin efficacy." Ann Pharmacother 36 (2002): 1893-6 [23] 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 [24] Hamann GL, Campbell JD, George CM "Warfarin-cranberry juice interaction." Ann Pharmacother 45 (2011): e17 [25] Monterrey-Rodriguez J "Interaction between warfarin and mango fruit." Ann Pharmacother 36 (2002): 940-1 [26] 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 [27] Roberts D, Flanagan P "Case report: Cranberry juice and warfarin." Home Healthc Nurse 29 (2011): 92-7 [28] MacLeod SM, Sellers EM "Pharmacodynamic and pharmacokinetic drug interactions with coumarin anticoagulants." Drugs 11 (1976): 461-70 [29] Jarvis S, Li C, Bogle RG "Possible interaction between pomegranate juice and warfarin." Emerg Med J 27 (2010): 74-5 [30] Parr MD, Record KE, Griffith GL, et al "Effect of enteral nutrition on warfarin therapy." Clin Pharm 1 (1982): 274-6 [31] Sullivan DM, Ford MA, Boyden TW "Grapefruit juice and the response to warfarin." Am J Health Syst Pharm 55 (1998): 1581-3 [32] Howard PA, Hannaman KN "Warfarin resistance linked to enteral nutrition products." J Am Diet Assoc 85 (1985): 713-5 [33] Rindone JP, Murphy TW "Warfarin-cranberry juice interaction resulting in profound hypoprothrombinemia and bleeding." Am J Ther 13 (2006): 283-4 [34] Harrell CC, Kline SS "Vitamin K-supplemented snacks containing olestra: Implication for patients taking warfarin." Jama J Am Med Assn 282 (1999): 1133-4 [35] Grant P "Warfarin and cranberry juice: an interaction?" J Heart Valve Dis 13 (2004): 25-6 [36] Ge B, Zhang Z, Zuo Z "Updates on the clinical evidenced herb-warfarin interactions." Evid Based Complement Alternat Med 2014 (2014): 957362 [37] Zallman JA, Lee DP, Jeffrey PL "Liquid nutrition as a cause of warfarin resistance." Am J Hosp Pharm 38 (1981): 1174 [38] Watson AJ, Pegg M, Green JR "Enteral feeds may antagonise warfarin." Br Med J 288 (1984): 557 [39] Andersen P, Godal HC "Predictable reduction in anticoagulant activity of warfarin by small amounts of vitamin K." Acta Med Scand 198 (1975): 269-70
Alternative for Warfarin B01A
Ticagrelor Betrixaban Rivaroxaban Cilostazol Apixaban Clopidogrel
Iloprost Lepirudin Acenocoumarol Urokinase Cangrelor
More
Alternative for Chondroitin sulfate -
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.