Valproate Toxicity Medication

  • Author: Timothy J Wiegand, MD; Chief Editor: Asim Tarabar, MD   more...
 
Updated: Nov 4, 2010
 

Medication Summary

Despite favorable reviews and outcomes in case reports, it remains to be seen, prospectively, whether the use of L-carnitine in valproic acid (VPA) overdose impacts clinical outcome. Despite this lack of evidence, however, some groups advocate use when the VPA levels exceed 450 mg/L, VPA-associated hepatotoxicity and/or encephalopathy occurs and in any case of primary carnitine deficiency (particularly relevant in the pediatric population). Specific recommendations regarding the optimal dose, frequency, or route of administration are limited (some recommendations are given above). L-carnitine should be administered in consultation with a medical toxicologist or a poison control center certified by the American Association of Poison Control Centers.

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Antidotes

Class Summary

These agents are used in the emergency treatment of poisoning caused by drugs and chemicals.

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Naloxone (Narcan)

 

Pure competitive opioid antagonist used for reversal of respiratory depression after opioid exposure.

Reversal in VPA exposure may be due to nonspecific action of naloxone or due to reversal of the effect of undetected opioid (coingestant).

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Activated charcoal (Liqui-Char, Actidose-Aqua, Insta-Char)

 

Has network of pores present that absorbs 100-1000 mg drug per gram charcoal. Does not dissolve in water. For maximum effect, administer within 0.5-1 h of poison ingestion.

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Levocarnitine

 

Levocarnitine is endogenous carboxylic acid involved in fatty-acid metabolism. Carnitine deficiency can result from dietary deficiency, inborn errors of metabolism, therapy with many anticonvulsants, and VPA toxicity. VPA may interrupt fatty-acid metabolism, impairing mitochondrial function and ultimately urea metabolism, leading to hyperammonemia. Carnitine deficiency may allow for production of hepatotoxic VPA metabolites by increasing alternate routes of metabolism (gamma oxidation). Effectively treats hyperammonemia associated with chronic VPA toxicity. Carnitine also improves outcome in hepatotoxicity and coma associated with acute VPA ingestion.

No consensus on dose, frequency, and route in VPA overdose. Supplementation appears to be well tolerated; few adverse reactions reported.

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Contributor Information and Disclosures
Author

Timothy J Wiegand, MD  Director, Ruth A Lawrence Poison and Drug Information Center, Associate Clinical Professor of Medicine and Emergency Medicine, University of Rochester Medical Center and Strong Memorial Hospital

Timothy J Wiegand, MD, is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Medical Toxicology, and American College of Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Kent R Olson, MD, FACEP  Clinical Professor of Medicine and Pharmacy, University of California, San Francisco, School of Medicine; Medical Director, San Francisco Division, California Poison Control System

Kent R Olson, MD, FACEP is a member of the following medical societies: American Academy of Clinical Toxicology and American College of Medical Toxicology

Disclosure: Nothing to disclose.

Herbert E Hern Jr, MD  Assistant Clinical Professor, Department of Emergency Medicine, University of California, San Francisco; Residency Director, Department of Emergency Medicine, Highland General Hospital

Herbert E Hern Jr, MD is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Lance W Kreplick, MD, FAAEM, MMM  Medical Director of Hyperbaric Medicine, Fawcett Wound Management and Hyperbaric Medicine; Consulting Staff in Occupational Health and Rehabilitation, Company Care Occupational Health Services; President and Chief Executive Officer, QED Medical Solutions, LLC

Lance W Kreplick, MD, FAAEM, MMM, is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physician Executives

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.

Fred Harchelroad, MD, FACMT, FAAEM, FACEP  Director of Medical Toxicology, Allegheny General Hospital

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.

Additional Contributors

The staff, faculty, and fellows of the San Francisco Bay Area Regional Poison Control Center contributed insight, review, and encouragement for this review.

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