Warfarin-gıda etkileşmesi: olgu sunumu ve literatürün gözden geçirilmesi

Warfarin, arteriyel ve venöz trombozların önlenmesinde kullanılan antitrombotik etkili bir ilaçtır. Beslenme ile alınan K vitamini karaciğerde sitokrom P450 enzimini inhibe ederek ilaç-gıda etkileşimine girerek warfarinin metabolizmasını etkileyebilir. Elli iki yaşında kadın hasta, akut proksimal derin ven trombozu nedeniyle warfarin tedavisi alıyordu. 7.5 mg/gün warfarin ile terapötik INR (International normalized ratio) seviyeleri sağlanmıştı. Yapılan INR kontrolünde warfarin tedavisinin etkisiz olduğu görülünce doz kademeli olarak artırılarak 20 mg/güne çıkıldı ancak INR değerinde yükselme görülmeyince öyküsünde, warfarin etkileşimi oluşturabilecek ilaç veya gıda araştırıldı. Son iki haftadır bol miktarda roka (Eruca Sativa L.) tüketti ği saptandı. Rokada bulunan yüksek oranda K vitamininin warfarinin metabolizmasını etkilediği düşünülerek roka alımı kesildi. Daha sonra, 5 mg/gün dozunda warfarin ile INR değeri 2.1 olarak saptandı. Tekrarlanan kontrollerde, 7.5 mg/gün warfarin ile INR'nin terapötik düzeyde seyrettiği gözlendi.

Warfarin-food interaction: a case report and review of the literature

Warfarin is an antithrombotic agent which is used in the prevention of arterial and venous thrombosis. Dietary vitamin K can inhibit hepatic cytochrome P450 isoenzymes, exhibit drug-food interactions and thus affect the metabolism of warfarin. Fifty two year-old female patient was on warfarin treatment due to acute proximal deep vein thrombosis. Desirable INR (International normalized ratio) was maintained by 7.5 mg/day warfarin treatment. The warfarin dose was gradually increased to 20 mg/day after INR controls exhibiting insufficient doses of warfarin. Since INR was not elevated by this dose, the possibility of a food or drug interaction was considered. The patient had consumed substantial amounts of garden rocket (Eruca Sativa L.) in the last two weeks. The patient was asked to cease the consumption of this food, considering its high content of vitamin K might affect the metabolism of warfarin. Subsequently, her INR value was 2.1 with a warfarin dose of 5mg/day. Her INR was maintained within therapeutic levels with a dose of 7.5 mg/day in the repeated evaluations.

PDF

___

1) Wells PS, Holbrook AM, Crowther NR, Hirsh J. Interactions of warfarin with drugs and food. Ann Intern Med 1994; 121:676-83.
2) Hirsh J, Fuster V, Ansell J, Halperin JL. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Circulation 2003;107:1692-711.
3) Palareti G, Legnani C. Warfarin withdrawal. Pharmacokineticpharmacodynamic considerations. Clin Pharmacokinet 1996; 30:300-13.
4) Booth SL, Centurelli MA. Vitamin K: a practical guide to the dietary management of patients on warfarin. Nutr Rev 1999; 57(9 Pt 1):288-96.
5) Hirsh J, Dalen J, Anderson DR, Poller L, Bussey H, Ansell J, et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 2001; 119(1 Suppl):8S-21S.
6) Ginsberg JS, Crowther MA, White RA, Ortel TL. Anticoagulation therapy. Hematology Am Soc Hematol Educ Program 2001;:339-57.
7) Lam AY, Elmer GW, Mohutsky MA. Possible interaction between warfarin and Lycium barbarum L. Ann Pharmacother 2001;35:1199-201.
8) Bartle WR. Grapefruit juice might still be factor in warfarin response. Am J Health Syst Pharm 1999;56:676.
9) Shetty HG, Backhouse G, Bentley DP, Routledge PA. Effective reversal of warfarin-induced excessive anticoagulation with low dose vitamin K1. Thromb Haemost 1992; 67:13-5.
10) Booth SL, Sokoll LJ, O�Brien ME, Tucker K, Dawson- Hughes B, Sadowski JA. Assessment of dietary phylloquinone intake and vitamin K status in postmenopausal women. Eur J Clin Nutr 1995;49:832-41.
11) Franco V, Polanczyk CA, Clausell N, Rohde LE. Role of dietary vitamin K intake in chronic oral anticoagulation: prospective evidence from observational and randomized protocols. Am J Med 2004;116:651-6.
12) Pedersen FM, Hamberg O, Hess K, Ovesen L. The effect of dietary vitamin K on warfarin-induced anticoagulation. J Intern Med 1991;229:517-20.
13) Ovesen L, Lyduch S, Idorn ML. The effect of a diet rich in brussels sprouts on warfarin pharmacokinetics. Eur J Clin Pharmacol 1988;34:521-3.
14) 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 1986;220:347-50.
15) Bailey DG, Malcolm J, Arnold O, Spence JD. Grapefruit juice-drug interactions. 1998. Br J Clin Pharmacol 2004; 58:S831-40.
16) Lilja JJ, Kivisto KT, Backman JT, Neuvonen PJ. Effect of grapefruit juice dose on grapefruit juice-triazolam interaction: repeated consumption prolongs triazolam half-life. Eur J Clin Pharmacol 2000;56:411-5.
17) Wong AL, Chan TY. Interaction between warfarin and the herbal product quilinggao. Ann Pharmacother 2003;37:836-8.
18) Carr ME, Klotz J, Bergeron M. Coumadin resistance and the vitamin supplement 'Noni'. Am J Hematol 2004;77:103.
19) Camilo ME, Jatoi A, O'Brien M, Davidson K, Sokoll L, Sadowski JA, et al. Bioavailability of phylloquinone from an intravenous lipid emulsion. Am J Clin Nutr 1998;67:716-21.
20) Penrod LE, Allen JB, Cabacungan LR. Warfarin resistance and enteral feedings: 2 case reports and a supporting in vitro study. Arch Phys Med Rehabil 2001;82:1270-3.
21) Couris RR, Tataronis GR, Dallal GE, Blumberg JB, Dwyer JT. Assessment of healthcare professionals' knowledge about warfarin-vitamin K drug-nutrient interactions. J Am Coll Nutr 2000;19:439-45.