Anticancer Section / Case Report

Moussouni M.a· Graff V.a· Couturier F.a· Herrscher H.b

Author affiliations

aPharmacy, Clinique Sainte Anne, Groupe Hospitalier Saint Vincent, Strasbourg, France
bOncology, Strasbourg Oncologie Libérale, Strasbourg, France

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Article / Publication Details

First-Page Preview

Received: July 29, 2022
Accepted: November 09, 2022
Published online: November 29, 2022

Number of Print Pages: 4
Number of Figures: 0
Number of Tables: 0

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

For additional information: https://www.karger.com/CHE

Abstract

Mistletoe, Viscum album, is a medicinal plant used in complementary medicine in oncology. Patients do not necessarily mention to their oncologist this phytotherapeutic treatment which may be responsible for unsuspected drug interactions. Some patients are adept at taking medicinal plants, a practice often unknown to health professionals who take care of them. This case reports drug interactions leading to bleeding secondary to warfarin overdose. A patient over 75 years of age was treated with nab-paclitaxel and gemcitabine as a first course for metastatic pancreatic adenocarcinoma (day 0). He was also treated with warfarin for atrial fibrillation. At day 3, he reported faintness and melena. At day 5, the biological assessment revealed anemia with hemoglobinemia of 5.1 g/dL and an international normalized ratio of 7.3, indicating vitamin K antagonist (VKA) overdose. Warfarin was discontinued and the patient received vitamin K supplementation and transfusions. The final diagnosis was an anemic syndrome due to gastrointestinal bleeding secondary to VKA overdose. Based on the chronology, a drug interaction between chemotherapy and warfarin was first suspected. Then, the patient interview found out that he self-medicated with subcutaneous injections of mistletoe extracts: 10 mg on day 0 and on day 2. Nab-paclitaxel can displace warfarin from its albumin binding sites and increase the free and active concentration of warfarin. Mistletoe extracts (V. album) are used as complementary medicine in oncology. Warfarin is predominantly metabolized in the liver by 1A2, 2C9, and 3A4 cytochrome P450 (CYP) isoforms. An inhibitor of these cytochromes prevents the degradation of warfarin into inactive metabolites, leading to accumulation or even overdose of this narrow therapeutic index VKA. Nab-paclitaxel and gemcitabine do not act on these cytochromes. V. album is a cytochrome P450 3A4 inhibitor which therefore probably led to an increase in exposure to warfarin. Thus, there are two pharmacokinetic hypotheses that may explain warfarin overdose: the displacement of warfarin from its albumin binding sites or the inhibition of CYP3A4 by mistletoe. This adverse drug event was reported to the Regional Pharmacovigilance Center of Strasbourg on June 30, 2021, and registered under the number ST20212767.

© 2022 S. Karger AG, Basel

References Béliard A, Girard C, Chaumont JP, et al. Viscum Album L., Le gui : passé magique, avenir prometteur. La phytothérapie européenne. 2007 Décembre. Kovacs E. Effects of Viscum album extract therapy in patients with cancer: relation with interleukin-6, soluble interleukin-6 receptor, and soluble gp130. J Altern Complement Med. 2004;10(2):241–6. Bantel H, Engels IH, Voelter W, Schulze-Osthoff K, Wesselborg S. Mistletoe lectin activates caspase-8/FLICE independently of death receptor signaling and enhances anticancer drug-induced apoptosis. Cancer Res. 1999;59(9):2083–90. Kienle GS, Kiene H. Review article: influence of Viscum album L (European mistletoe) extracts on quality of life in cancer patients: a systematic review of controlled clinical studies. Integr Cancer Ther. 2010;9(2):142–57. Gentric A, Estivin S. [Use of anticoagulant treatments in the elderly]. Rev Med Interne. 2006;27(6):458–64. Spiller HA. Warfarin. Encyclopedia of toxicology. 2nd; 2005. p. 461–3. Trynda-Lemiesz L. Paclitaxel-HSA interaction. Binding sites on HSA molecule. Bioorg Med Chem. 2004;12(12):3269–75. Moore N, Berdaï D, Blin P, Droz C. Pharmacovigilance-the next chapter. Therapie. 2019 Dec;74(6):557–67. Thompson ME, Highley MS. Interaction between paclitaxel and warfarin. Ann Oncol. 2003;14(3):500. Saif MW. Interaction between gemcitabine and warfarin causing gastrointestinal bleeding in a patient with pancreatic cancer. J Appl Res. 2005;5(3):434–7. Hôpitaux Universitaires de Genève. Interactions médicamenteuses, cytochromes P450 et P-glycoprotéine (Pgp). Available on: https://www.hug.ch/sites/interhug/files/structures/pharmacologie_et_toxicologie_cliniques/a5_cytochromes_6_2.pdf. Weissenstein U, Kunz M, Urech K, Baumgartner S. Interaction of standardized mistletoe (Viscum album) extracts with chemotherapeutic drugs regarding cytostatic and cytotoxic effects in vitro. BMC Complement Altern Med. 2014;14:6. Article / Publication Details

First-Page Preview

Received: July 29, 2022
Accepted: November 09, 2022
Published online: November 29, 2022

Number of Print Pages: 4
Number of Figures: 0
Number of Tables: 0

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

For additional information: https://www.karger.com/CHE

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