scholarly journals Lamotrigine-Valproic Acid Interaction Leading to Stevens–Johnson Syndrome

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.

Author(s):  
Rutuja S Nalkar ◽  
Suhas S Siddheshwar ◽  
Mahesh H Kolhe

Lamotrigine is an anticonvulsant drug used in the treatment of epilepsy & bipolar disorder/major affective disorder (manic depression). Lamotrigine is and antiepileptic drug of phenyltriazine class. For epilepsy it is used to treat the partial seizures, primary and secondary tonic-clonic seizures, and seizures associated with the Lennox-Gastuat syndrome and are chemically unrelated to the other anticonvulsants. Lamotrigine is a phenyltriazine that has comparatively few side-effects and it does not requires blood monitoring/observance in monotherapy. It additionally acts as a mood stabilizer. Common side-effects of lamotrigine include, nausea, sleepiness, headache, vomiting, trouble/bother with co-ordination and rash. Serious side-effects include in, lack of red blood cells, accumulated in risk of suicide, Stevens-Johnson syndrome and allergy. It issues that use of lamotrigine throughout pregnancy or breastfeeding it’s going to lead/result in harm/damage.


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.


1992 ◽  
Vol 26 (12) ◽  
pp. 1520-1521 ◽  
Author(s):  
Cato T. Laurencin ◽  
Richard F. Horan ◽  
Patrick B. Senatus ◽  
Clara B. Wheeler ◽  
Stephen J. Lipson

OBJECTIVE: To report a case of Stevens-Johnson syndrome caused by vancomycin. CASE SUMMARY: Stevens-Johnson syndrome is an acute mucocutaneous process characterized by epidermal and mucosal desquamation. Its pathogenesis is poorly understood. Mortality rates have ranged from 30 to 100 percent. We describe a case of Stevens-Johnson syndrome related to the use of vancomycin in a 71-year-old woman with rheumatoid arthritis receiving treatment for an infected cervical fusion site. Classic “target” lesions distributed throughout the trunk and extremities along with erosive lesions involving the oral and vaginal mucosae were observed in this patient. DISCUSSION: A number of agents have been implicated in the etiology of Stevens-Johnson syndrome. Serious cutaneous reactions to vancomycin, however, have been uncommon. Cessation of vancomycin treatment in our patient led to eventual resolution of her symptoms. CONCLUSIONS: Vancomycin is a potential causative agent of Stevens-Johnson syndrome.


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):  
Rodrigo Banegas Ruiz ◽  
Alan I. Valderrama Treviño ◽  
Gómez Mendoza F. F. ◽  
Baca Domínguez C. R. ◽  
Campos Angulo G. ◽  
...  

Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are considered a single entity with variability in the extent of the lesions, characterized by erythema multiforme that may involve mucosa. Severe cutaneous reactions secondary to medications are classified according to the area of epidermal detachment. The activation of cytotoxic T cells and macrophages is mediated mainly by IL-2 and interferon gamma secreted by Th1 lymphocytes, and the activation of eosinophils and B lymphocytes in IgE is mediated by secreted IL-4, IL-5, IL-10 and IL13 by B lymphocytes. The topography of SJS is predominantly central, affecting the trunk and sometimes a generalized dissemination is shown that affects a body surface area of less than 10%, characterized by irregular violaceous erythematous macules of target shooting, which can form confluent blisters. TEN is characterized by a skin detachment greater than 30% of the body surface, whose predominant lesion is diffuse erythema with individual macules, which give rise to detachment surfaces greater than 5 cm. The treatment is symptomatic, nonspecific, and aimed at avoiding complications, carried out in specialized intensive care units, due to ignorance of the pathogenesis. Integral management with different therapeutic alternatives can represent a crucial part in the multisystemic management of SJS and TEN.


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

Sign in / Sign up

Export Citation Format

Share Document