Coumarin Plant Poisoning Medication

  • Author: Arasi Thangavelu, MD; Chief Editor: Asim Tarabar, MD   more...
 
Updated: Apr 30, 2012
 

Medication Summary

For severe or continued bleeding, only vitamin K-1 (phytonadione) (not any other vitamin K derivatives) can be used as an effective antidote. Usual dose is 5-10 mg administered PO/SC. Intravenous injections, even in emergencies, carry substantial risk of anaphylaxis (fatalities have been reported) — Black Box warnings. Intravenous vitamin K should be used very cautiously in emergent conditions, should be diluted, and should be infused very slowly. If immediate hemostatic effect is necessary, adequate concentrations of vitamin K-dependent coagulation factors can be restored by transfusion of fresh frozen plasma (10-20 mL/kg). Since reversal of anticoagulant by vitamin K-1 requires synthesis of fully carboxylated coagulation proteins, significant improvement in homeostasis does not occur for several hours; more than 24 hours may be needed for maximal effect.

Small ingestions of plant material (equivalent to 10-20 mg warfarin) do not cause serious intoxication in adults, yet repeated or long-term ingestion of even smaller amounts (equivalent to 2 mg/d warfarin) can produce significant anticoagulation.

Recommendations from the Seventh ACCP Conference on antithrombotic and thrombolytic therapy:[2]

  • In patients with mild to moderately elevated INRs without major bleeding, vitamin K, when given, should be administered orally rather that subcutaneously (Grade 1 A).
  • For the management of patients with a low risk of thromboembolism, warfarin therapy should be stopped approximately 4 days prior to surgery (Grade 2C).
  • For patients with a high risk of thromboembolism, warfarin therapy should be stopped approximately 4 days before surgery, to allow the INR to return to normal, and therapy with full-dose unfractionated heparin or full dose low-molecular-weight heparin should begin as the INR falls (Grade 2C).
  • In patients undergoing dental procedures, tranexamic acid mouthwash (Grade 2B) or epsilon amino caproic acid mouthwash should be used without interrupting anticoagulant therapy (Grade 2B) if there is concern for local bleeding.

Grading: Grade 1 recommendations are strong, and indicate that the benefits do, or do not, outweigh the risks, burdens, and costs. Grade 2 suggest that individual patient's values may lead to different choices.

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GI decontaminants

Class Summary

Preferred GI decontamination method when decontamination is desired. Generally mixed and given with a cathartic (eg, 70% sorbitol) except in young pediatric patients in whom electrolyte disturbances may be of concern.

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Activated charcoal (Liqui-Char)

 

Emergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water.

For maximum effect, administer within 30 min after ingesting poison.

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Elimination enhancement

Class Summary

Cholestyramine forms a nonabsorbable complex with bile acids in the intestine that inhibits enterohepatic reuptake of intestinal bile salts. Rifampin is used to speed up metabolism of warfarin by induction of hepatic cytochrome P-450 mixed function oxidases.

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Cholestyramine (Questran)

 

Binds bile salts carrying warfarin and its metabolites, thus interfering with enterohepatic recycling.

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Rifampin (Rifadin, Rimactane)

 

Hepatic P-450 enzyme inducer that results in increased metabolism of warfarin and decreased drug half-life.

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Pharmacologic antidote

Class Summary

Promotes liver synthesis of clotting factors that, in turn, inhibit warfarin effects.

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Vitamin K-1 (Phytonadione, AquaMEPHYTON)

 

Overcomes block produced by hydroxycoumarin in production of vitamin K dependent clotting factors; vitamin K-3 (menadione) is not effective for this purpose.

Dose needed varies with clinical situation, including amount of anticoagulant ingested and whether it is a short- or long-acting anticoagulant. Daily doses of 50-200 mg have been required.

Use extreme caution if considering IV administration. Complications of IV use include flushing, diaphoresis, hypotension, dyspnea, and anaphylactoid reactions. SC is preferable to IV administration, which carries a strong box warning against IV administration by the manufacturer. In the patient on chronic anticoagulation for medical reasons, reversal should be performed only very carefully if clinically indicated. Re-anticoagulation can be very difficult in this situation.

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Contributor Information and Disclosures
Author

Arasi Thangavelu, MD  Consulting Staff, Department of Emergency Medicine, Phoebe Putney Memorial Hospital

Arasi Thangavelu, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Emergency Medicine Residents Association

Disclosure: Nothing to disclose.

Coauthor(s)

Lisandro Irizarry, MD, MPH, FAAEM  Chair, Department of Emergency Medicine, Brooklyn Hospital Center; Assistant Professor, Department of Emergency Medicine, Weill Cornell School of Medicine

Lisandro Irizarry, MD, MPH, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

B Zane Horowitz, MD, FACMT  Professor, Department of Emergency Medicine, Oregon Health and Sciences University; Medical Director, Oregon Poison Center; Medical Director, Alaska Poison Control System

B Zane Horowitz, MD, FACMT is a member of the following medical societies: American Academy of Clinical Toxicology and American College of Medical Toxicology

Disclosure: Nothing to disclose.

John T VanDeVoort, PharmD  Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Michael Hodgman, MD  Assistant Clinical Professor of Medicine, Department of Emergency Medicine, Bassett Healthcare

Michael Hodgman, MD is a member of the following medical societies: American College of Medical Toxicology, American College of Physicians, Medical Society of the State of New York, and Wilderness Medical Society

Disclosure: Nothing to disclose.

John D Halamka, MD, MS  Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center

John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD  Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

References

  1. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Giffin SL. 2008 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 26th Annual Report. Clin Toxicol (Phila). Dec 2009;47(10):911-1084. [Medline].

  2. Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. Sep 2004;126(3 Suppl):204S-233S. [Medline].

  3. Jackevicius CA, Ton MN. Enhanced Interaction between Warfarin and High-Dose Ketoconazole: A Case Report. Case Report Med. 2009;2009:315687. [Medline]. [Full Text].

  4. Mercadal Orfila G, Gracia Garcia B, Leiva Badosa E, Perayre Badía M, Reynaldo Martínez C, Jodar Masanes R. Retrospective assessment of potential interaction between levofloxacin and warfarin. Pharm World Sci. Apr 2009;31(2):224-9. [Medline].

  5. Mergenhagen KA, Sherman O. Elevated International Normalized Ratio after concurrent ingestion of cranberry sauce and warfarin. Am J Health Syst Pharm. Nov 15 2008;65(22):2113-6. [Medline].

  6. Fulco PP, Zingone MM, Higginson RT. Possible antiretroviral therapy-warfarin drug interaction. Pharmacotherapy. Jul 2008;28(7):945-9. [Medline].

  7. Berry RG, Morrison JA, Watts JW, Anagnost JW, Gonzalez JJ. Surreptitious superwarfarin ingestion with brodifacoum. South Med J. Jan 2000;93(1):74-5. [Medline].

  8. Chen IS, Chang CT, Sheen WS, et al. Coumarins and antiplatelet aggregation constituents from Formosan Peucedanum japonicum. Phytochemistry. Feb 1996;41(2):525-30. [Medline].

  9. Collins Abrams A. Clinical Drug Therapy. 5th ed. Lippincott; 1997.

  10. Hahn A, Oertreich S, Barkin R. Mosby's Pharmacology in Nursing. 16th ed. 1986.

  11. Hardman JG, et al. Goodman and Gilman's the Pharmacological Basis of Therapeutics. 9th ed. Macmillan; 1996.

  12. Hoult JR, Paya M. Pharmacological and biochemical actions of simple coumarins: natural products with therapeutic potential. Gen Pharmacol. Jun 1996;27(4):713-22. [Medline].

  13. Klassen C, Amdur M, Doull J. Casarett and Doull's Toxicology. 3rd ed. Macmillan; 1986.

  14. Kruse JA, Carlson RW. Fatal rodenticide poisoning with brodifacoum. Ann Emerg Med. Mar 1992;21(3):331-6. [Medline].

  15. La Rosa FG, Clarke SH, Lefkowitz JB. Brodifacoum intoxication with marijuana smoking. Arch Pathol Lab Med. Jan 1997;121(1):67-9. [Medline].

  16. Martin EW, et al. Remington's Pharmaceutical Sciences. 13th ed. Mack Publishing Co; 1965.

  17. Ministry of Agriculture, Fisheries and Food (MAFF). Food Surveillance Information Sheets. Survey of biologically active principles in mint products and herbal teas. November 1996. Available at http://archive.food.gov.uk/maff/archive/food/infsheet/1996/no99/99bap.htm. Accessed December 10, 2004.

  18. Morgan BW, Tomaszewski C, Rotker I. Spontaneous hemoperitoneum from brodifacoum overdose. Am J Emerg Med. Nov 1996;14(7):656-9. [Medline].

  19. Mullins ME, Brands CL, Daya MR. Unintentional pediatric superwarfarin exposures: do we really need a prothrombin time?. Pediatrics. Feb 2000;105(2):402-4. [Medline].

  20. Olsen KR. Poisoning and Drug Overdose. San Francisco Bay Area Regional Poison Control Center. Norwalk, Conn: Appleton and Lange; 1990.

  21. Pengsuparp T, Serit M, Hughes SH, Soejarto DD, Pezzuto JM. Specific inhibition of human immunodeficiency virus type 1 reverse transcriptase mediated by soulattrolide, a coumarin isolated from the latex of calophyllum teysmannii. J Nat Prod. Sep 1996;59(9):839-42. [Medline].

  22. Renowden S, Westmoreland D, White JP, Routledge PA. Oral cholestyramine increases elimination of warfarin after overdose. Br Med J (Clin Res Ed). Aug 24 1985;291(6494):513-4. [Medline]. [Full Text].

  23. Rosen P. Emergency Medicine Concepts and Clinical Practice. 4th ed. Mosby; 1997.

  24. Rund D, Barkin R, Rosen P. Essentials of Emergency Medicine. 2nd ed. Mosby Lifeline; 1996.

  25. Tintinalli J, Krome R, Ruiz E. Emergency Medicine; A Comprehensive Study Guide. 4th ed. McGraw-Hill; 1995.

  26. Travis SF, Warfield W, Greenbaum BH, Molokisher M, Siegel JE. Spontaneous hemorrhage associated with accidental brodifacoum poisoning in a child. J Pediatr. Jun 1993;122(6):982-4. [Medline].

  27. Whyte AC, Gloer JB, Scott JA, Malloch D. Cercophorins A-C: novel antifungal and cytotoxic metabolites from the coprophilous fungus Cercophora areolata. J Nat Prod. Aug 1996;59(8):765-9. [Medline].

  28. Williams CA, Goldstone F, Greenham J. Flavonoids, cinnamic acids and coumarins from the different tissues and medicinal preparations of Taraxacum officinale. Phytochemistry. May 1996;42(1):121-7. [Medline].

 
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