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      Adding Herbal Products to Direct-Acting Oral Anticoagulants Can Be Fatal

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          Abstract

          Direct-acting oral anticoagulants (DOACs) are used to prevent and treat systemic and cerebral embolisms in patients with non-valvular atrial fibrillation (NV-AF). The use of DOACs with herbal products without consulting healthcare professionals increases the possibility of drug–herb interactions and their adverse effects. An 80-year-old man on dabigatran with a known history of NV-AF presented with a 1-day history of haematemesis and black stool which began 3 days after he had started taking a boiled mixture of ginger and cinnamon. The patient was hypotensive and treated as a case of gastrointestinal bleeding and haemorrhagic shock. Despite continuous aggressive resuscitation measures including administration of a reversal agent for dabigatran, we were unable to control bleeding and the patient died within 24 hours. The interaction of ginger and cinnamon with dabigatran led to fatal bleeding.

          LEARNING POINTS
          • Direct-acting oral anticoagulants (DOACs) are frequently prescribed for patients with non-valvular atrial fibrillation.

          • Combining herbal products (ginger and cinnamon) with DOACs can be fatal.

          • Physicians should alert patients and caregivers about dangerous combinations and interactions.

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          Most cited references5

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          Old and new oral anticoagulants: Food, herbal medicines and drug interactions.

          The most commonly prescribed oral anticoagulants worldwide are the vitamin K antagonists (VKAs) such as warfarin. Factors affecting the pharmacokinetics of VKAs are important because deviations from their narrow therapeutic window can result in bleedings due to over-anticoagulation or thrombosis because of under-anticoagulation. In addition to pharmacodynamic interactions (e.g., augmented bleeding risk for concomitant use of NSAIDs), interactions with drugs, foods, herbs, and over-the-counter medications may affect the risk/benefit ratio of VKAs. Direct oral anticoagulants (DOACs) including Factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and thrombin inhibitor (dabigatran) are poised to replace warfarin. Phase-3 studies and real-world evaluations have established that the safety profile of DOACs is superior to those of VKAs. However, some pharmacokinetic and pharmacodynamic interactions are expected. Herein we present a critical review of VKAs and DOACs with focus on their potential for interactions with drugs, foods, herbs and over-the-counter medications.
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            Drug interactions with herbal medicines.

            S. Shi, U Klotz (2012)
            In recent years, the issue of herbal medicine-drug interactions has generated significant concern. Such interactions can increase the risk for an individual patient, especially with regard to drugs with a narrow therapeutic index (e.g. warfarin, ciclosporin and digoxin). The present article summarizes herbal medicine-drug interactions involving mainly inhibition or induction of cytochrome P450 enzymes and/or drug transporters. An increasing number of in vitro and animal studies, case reports and clinical trials evaluating such interactions have been reported, and the majority of the interactions may be difficult to predict. Potential pharmacodynamic and/or pharmacokinetic interactions of commonly used herbal medicines (black cohosh, garlic, Ginkgo, goldenseal, kava, milk thistle, Panax ginseng, Panax quinquefolius, saw palmetto and St John's wort) with conventional drugs are presented, and sometimes the results are contradictory. Clinical implications of herbal medicine-drug interactions depend on a variety of factors, such as the co-administered drugs, the patient characteristics, the origin of the herbal medicines, the composition of their constituents and the applied dosage regimens. To optimize the use of herbal medicines, further controlled studies are urgently needed to explore their potential for interactions with conventional drugs and to delineate the underlying mechanisms.
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              Quantification of flavoring constituents in cinnamon: high variation of coumarin in cassia bark from the German retail market and in authentic samples from indonesia.

              Coumarin is a flavoring which can cause hepatotoxicity in experimental animals and in a proportion of the human population. The tolerable daily intake (TDI) may be exceeded in consumers with high intake of cinnamon containing high levels of coumarin. The objective of this study was to determine these levels in cinnamon samples and to identify possible factors influencing them. A HPLC method to quantify coumarin and related constituents (cinnamaldehyde, cinnamic acid, cinnamyl alcohol, eugenol) in a single run was used. Results found in 47 cinnamon powder samples obtained from the German retail market confirmed high levels of coumarin in cassia cinnamon. A huge variation was observed in stick samples from two packages (range from below the limit of detection to about 10000 mg/kg). Cassia bark samples of five trees received directly from Indonesia were analyzed additionally. Interestingly, a high variation was observed in one of the trees, whereas no coumarin was detected in the samples of two other trees. In conclusion, coumarin levels in cassia cinnamon can vary widely even within a single tree.
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                Author and article information

                Journal
                Eur J Case Rep Intern Med
                European Journal of Case Reports in Internal Medicine
                SMC Media Srl
                2284-2594
                2019
                19 July 2019
                : 6
                : 8
                : 001190
                Affiliations
                Internal Medicine Department, Ahmadi Hospital-Kuwait Oil Company, Al Ahmadi, Kuwait
                Article
                1190-1-8536-1-10-20190715
                10.12890/2019_001190
                6726349
                a2b39f30-9fee-4ab8-a26b-aab05ff81c45
                © EFIM 2019

                This article is licensed under a Commons Attribution Non-Commercial 4.0 License

                History
                : 25 June 2019
                : 01 July 2019
                Categories
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                ginger,cinnamon,dabigatran
                ginger, cinnamon, dabigatran

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