Fatal Seizures Due to Potential Herb-Drug Interactions with Ginkgo Biloba

Abstract

Alternative therapy including herbal drugs and complementary medicine is becoming increasingly popular. However, the rise in the incidence of herb-drug interactions is causing concern, especially in the absence of warning labels addressing potential adverse effects. We present the case of a 55-year-old male who suffered a fatal breakthrough seizure, with no evidence of non-compliance with his anticonvulsant medications. The autopsy report revealed subtherapeutic serum levels for both anticonvulsants Depakote and Dilantin. Concomitant with his prescribed medications, the decedent was also self-medicating with a cornucopia of herbal supplements and nutraceuticals, prominent among which was Ginkgo biloba. Ginkgo, an herbal extract from the leaves of the Ginkgo biloba tree, has been used medicinally for centuries and has been touted as a cure for a variety of medical conditions. The induction of Cytochrome P450 enzymes by components of herbal drugs has been known to affect the metabolism of various drugs. Dilantin is primarily metabolized by CYP2C9, and secondarily metabolized by CYP2C19. Valproate metabolism is also modulated in part by CYP2C9 and CYP2C19. A recent study revealed significant inductive effect of ginkgo on CYP2C19 activity. CYP2C19 induction by ginkgo could be a plausible explanation for the subtherapeutic levels of Dilantin and Depakote. Additionally, ginkgo nuts contain a potent neurotoxin, which is known to induce seizure activity. Evidence of other herbal drugs diminishing the efficacy of anticonvulsant medication does exist; however, there has been only one other documented instance of ginkgo potentiating seizure activity in the presence of anticonvulsant therapy. Highlighting the potential adverse effects and drug interactions of ginkgo on the packaging of the drug may help prevent inadvertent use in vulnerable individuals.

Effects of Herbal Supplements on Drug Glucuronidation. Review of Clinical, Animal, andIn VitroStudies

“…At least 30 clinically proven herb-drug interactions mediated through CYP enzymes have been described [19][20][21]. Induction of CYP2C19, for example, by Ginkgo biloba resulted in subtherapeutic levels of anticonvulsant drugs, which precipitated fatal seizures [22]. St. Johnʼs wort has the most documented evidence of pharmacokinetic drug interactions with more than 100 publications in the last 10 years on its interactions with prescription drugs [20].…”

Bitkisel Ürünlerin ve Gıda Destek Ürünlerinin İçeriklerinin Adli ve Hukuki Boyutu

“…faktörlerin yanı sıra, kullanan bireye özgü yaş, cinsiyet, genetik özellikler, hastalıklar vb. faktörler de söz konusu maddenin vücutta meydana getirdiği değişiklikler de etkilidir (1). Farmasötik bir preperat için söz konusu olan kontaminasyon, katkı maddeleri, toksisite ve etkin doz hataları veya yanlış etiketleme gibi tüm sorunlar bu ürünler için de gündeme gelmektedir.…”

A Comparison Between Lignans from Creosote Bush and Flaxseed and Their Potential to Inhibit Cytochrome P450 Enzyme Activity

“…Several examples exist of natural products undergoing P450-mediated bioactivation and irreversible P450 enzyme inhibition and hepatotoxicity (Johnson et al, 2003;Zhou et al, 2004;Surh & Lee 1995;He et al, 1998;Kent et al, 2002). Furthermore, natural products are known to result in significant interactions with coadministered therapeutic agents resulting in adverse effects or therapeutic failures (Dietz & Bolton 2007;Yuan et al, 2004;Kupiec & Raj 2005). With the growing interest in lignans for their health and wellness or therapeutic values, assessments of their safety are necessary to support their use.…”