Abstract
Several case reports have associated the combined use of thyroid drugs and oral anticoagulants, like coumarin, with overanticoagulation. However, this effect has never been described for phenprocoumon, a coumarin derivate that is widely prescribed in continental European countries and in Latin America. We describe a 62-year-old female who had an unexpectedly labile anticoagulation profile when levothyroxine (Puran T4®) was added to her drug therapy regimen, which included phenprocoumon (Marcoumar®). This resulted in an elevated international normalized ratio (INR) that was unrecordable and bleeding (macroscopic hematuria) that required hospitalization and treatment with vitamin K. The patient had been taking phenprocoumon for almost ten years for systemic embolism prophylaxis because of her history of mechanical bileaflet mitral valve prosthesis. One month before the events described, the patient was prescribed sodium levothyroxine (50 mcg daily) to treat hypothyroidism (TSH = 40 µU/mL; reference range, 0.40–4.0 µU/mL). Approximately 3 weeks prior to initiation of levothyroxine treatment, her INR was 2.8. A drug interaction was therefore suspected. The Horn Drug Interaction Probability Scale (DIPS) indicated a probable interaction between oral phenprocoumon and levothyroxine in this case. Clinicians should be aware that levothyroxine may interact with oral phenprocoumon, resulting in overanticoagulation.
Similar content being viewed by others
References
Gadisseur AP, van der Meer FJ, Adriaansen HJ, Fihn SD, Rosendaal FR. Therapeutic quality control of oral anticoagulant therapy comparing the short-acting acenocoumarol and the long-acting phenprocoumon. Br J Haematol 2002;117:940–946
Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:160S–198S
Beinema M, Brouwers JR, Schalekamp T, Wilffert B. Pharmacogenetic differences between warfarin, acenocoumarol and phenprocoumon. Thromb Haemost 2008;100:1052–1057
Cadamuro J, Dieplinger B, Felder T, Kedenko I, Mueller T, Haltmayer M, et al. Genetic determinants of acenocoumarol and phenprocoumon maintenance dose requirements. Eur J Clin Pharmacol 2010;66:253–260
Leiria TL, Pellanda L, Miglioranza MH, Sant’anna RT, Becker LS, Magalhães E, et al. Warfarin and phenprocoumon: experience of an outpatient anticoagulation clinic. Arq Bras Cardiol 2010;94:41–45
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;119:8S–21S
Ufer M, Svensson JO, Krausz KW, Gelboin HV, Rane A, Tybring G. Identification of cytochromes P450 2C9 and 3A4 as the major catalysts of phenprocoumon hydroxylation in vitro. Eur J Clin Pharmacol 2004;60:173–182
Ufer M. Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet 2005;44:1227–1246
Gavronski M, Hartikainen S, Zharkivsky A. Analysis of potential interactions between warfarin and prescriptions in Estonian outpatients aged 50 years or more. Pharmacy Practice 2012;10:9–16
Brunton L, Parker K, Blumenthal D, Buxton I. Goodman & Gilman. Manual of Pharmacology and Therapeutics. New York: The McGraw-Hill Companies, 2008
British Medical Association and the Royal Pharmaceutical Society of Great Britain. British National Formulary. London: BMJ Publishing Group, 2009
Drugs.com. Drug interactions between coumadin and levothyroxine from Drugs.com. Available from: http://www.drugs.com/drug-interactions/coumadin-with-levothyroxine-2311-1529-1463-0.html. Accessed: 2011 October
Horn JR, Hansten PD, Chan LN. Proposal for a new tool to evaluate drug interaction cases. Ann Pharmacother 2007;41:674–680
Freedman MD, Olatidoye AG. Clinically significant drug interactions with the oral anticoagulants. Drug Saf 1994;10:381–394
Owens JC, Neely WB, Owen WR. Effect of sodium dextrothyroxine in patients receiving anticoagulants. N Engl J Med. 1962;266:76–79
Bubber P, Bubber N, Bansal DD. Effect of thyroxine on plasminogen activator and inhibitor activity in rat. Indian J Exp Biol 2009;47:147–150
Negrev N, Tashev R, Radev R, Anogeianaki A, Ivanova M. Hormones of hypothalamic-pituitarythyroid axis are significant regulators of synthesis and secretion of vitamin K-dependent plasma coagulation factors. J Biol Regul Homeost Agents 2011;25:21–26
Walters MB. The relationship between thyroid function and anticoagulant therapy. Am J Cardiol 1963;11:112–114
Food and Drug Administration. Unithroid (levothyroxine sodium tablets, USP). Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21210lbl.pdf. Accessed: 2011 October
Harder S, Thürmann P. Clinically important drug interactions with anticoagulants. An update. Clin Pharmacokinet 1996;30:416–444
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Gaeti, W.P., Obreli-Neto, P.R. & Cuman, R.K.N. Interaction between Levothyroxine and Phenprocoumon: a case report. cent.eur.j.med 9, 231–234 (2014). https://doi.org/10.2478/s11536-013-0260-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.2478/s11536-013-0260-8