Valproic Acid-Induced Stevens-Johnson Syndrome

1998 ◽  
Vol 18 (5) ◽  
pp. 420 ◽  
Author(s):  
Shih-Jen Tsai ◽  
Ying-Sheue Chen
2015 ◽  
Vol 7 (6) ◽  
pp. 756 ◽  
Author(s):  
S Kavitha ◽  
T Anbuchelvan ◽  
V Mahalakshmi ◽  
R Sathya ◽  
TR Sabarinath ◽  
...  

1997 ◽  
Vol 31 (6) ◽  
pp. 720-723 ◽  
Author(s):  
Julie J Chaffin ◽  
Steven M Davis

OBJECTIVE: To describe a patient who developed toxic epidermal necrolysis (TEN) possibly secondary to lamotrigine use. CASE SUMMARY: A 74-year-old white man with a history of probable complex partial seizures was admitted to the neurology service for a prolonged postictal state. His antiepileptic regimen was changed while he was in the hospital to include lamotrigine. After 19 days of hospitalization and 14 days of lamotrigine therapy, the patient became febrile. The next day he developed a rash which progressed within 4 days to TEN, diagnosed by skin biopsy. All suspected drugs were discontinued, including lamotrigine. The patient was treated with hydrotherapy in the burn unit. His symptoms improved and he was discharged from the hospital 26 days after the rash developed. DISCUSSION: During lamotrigine's premarketing clinical trials, the manufacturer reported several cases of Stevens-Johnson syndrome and TEN. There are several published case reports of lamotrigine-induced severe skin reactions. All of these reports included patients being treated with both valproic acid and lamotrigine. Our patient was exposed to phenytoin, carbamazepine, clindamycin, and lamotrigine, but not valproic acid. The patient reported prior use of phenytoin with no skin rash. Carbamazepine was the antiepileptic drug the patient was maintained on prior to his hospital admission, and the symptoms of TEN resolved while he was still receiving carbamazepine. The patient received only two doses of clindamycin, which makes this agent an unlikely cause of TEN. CONCLUSIONS: Because of the temporal relationship of the onset of the patient's rash and several drugs that are known to cause severe rashes, it is not certain which drug was the definite culprit. However, based on the evidence from the literature, lamotrigine appears to be the causative agent.


Author(s):  
John A. Messenheimer

ABSTRACT:Data from clinical trials with lamotrigine indicate that the risk of serious rash in pediatric patients is higher than in adults. The incidence of rash associated with hospitalization among adults treated with lamotrigine is 0.3% and among pediatric patients 1.0%. The incidence of cases reported as possible Stevens-Johnson syndrome is 0.1% for adult patients and 0.5% for pediatric patients. These rates reflect lamotrigine dosing and concomitant AEDs used in these trials, both of which are risk factors for rash. Since many of the trials were conducted prior to the establishment of the current dosing recommendations, the incidence of serious rash in clinical trials does not necessarily reflect the incidence to be expected with use of current dosing recommendations. The higher incidence of serious rash in pediatric patients may at least partially be accounted for by the differential effects of the risk factors of dosing and concomitant use of valproic acid in these patients.


Author(s):  
Kristen K. Barbour ◽  
Christian P. Umfrid ◽  
Benjamin A. Brinton ◽  
Jonathan D. Avery ◽  
Caitlin E. Snow

2019 ◽  
Vol 58 (9) ◽  
pp. 1014-1022 ◽  
Author(s):  
Muhammed Rashid ◽  
Ananth Kashyap ◽  
Krishna Undela

2007 ◽  
Vol 8 (2) ◽  
pp. 107-111 ◽  
Author(s):  
Sedat Kocak ◽  
Sadik A Girisgin ◽  
Mehmet Gul ◽  
Basar Cander ◽  
Halil Kaya ◽  
...  

2018 ◽  
Vol 8 (5) ◽  
pp. 247-249 ◽  
Author(s):  
Jennifer Houser ◽  
Ashley Graham

Abstract Lamotrigine (LTG) is associated with the potential for a life-threatening rash (eg, Stevens-Johnson syndrome or toxic epidermal necrolysis). The incidence has been linked to rapid titration and an interaction with valproic acid that can increase the level of LTG. Providers often have difficulty discriminating between serious versus benign rashes, and the package insert recommends discontinuing the medication at the first sign of a rash. Therefore, many patients end up being taken off LTG when it may have been effective for them. We present a case where LTG is reintroduced with a faster initial titration than what is noted in the literature after development of a rash. This case is also unique in that the patient had been on LTG for years prior to emergence of the rash and demonstrates that retrials can be successful.


2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Marta Vázquez ◽  
Cecilia Maldonado ◽  
Natalia Guevara ◽  
Andrea Rey ◽  
Pietro Fagiolino ◽  
...  

Lamotrigine (LTG) is currently indicated as adjunctive therapy for focal and generalized tonic-clonic seizures and for treatment of bipolar disorder and neuropathic pain. A common concern with LTG in children is the frequency of appearance of skin rash. The intensity of this adverse effect can vary from transient mild rash to Stevens–Johnson syndrome (SJS), which can be fatal mainly when LTG is coadministered with valproic acid (VPA). Hereby, we present the case of an 8-year-old boy who suffered from SJS and other complications two weeks after LTG was added to his VPA treatment in order to control his seizures. VPA is known to decrease LTG clearance via reduced glucuronidation. In this case, the minor elimination pathway of LTG would play a more important role, and the formation of an arene oxide metabolite would be enhanced. As this reactive metabolite is detoxified mainly by enzymatic reactions, involving microsomal epoxide hydrolase and/or GSH-S-transferases and these enzymes are polymorphically expressed in humans, arene oxide toxicity is increased when epoxide hydrolase or GSH-S-transferases is either defective or inhibited or a depletion of intracellular glutathione levels is taking place. VPA can cause inhibition of epoxide hydrolase enzymes and/or depletion of glutathione levels leading to adverse cutaneous reactions.


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