levetiracetam and Stevens-Johnson-Syndrome

Antiseizure medications (ASMs) can rarely result in severe, sometimes fatal, cutaneous adverse reactions. To date, few studies have reported on the incidence rates (IRs) of severe cutaneous adverse reactions (SCARs) due to ASM use. This study aimed to determine the IRs of SCAR resulting from the use of seven commonly prescribed ASMs, carbamazepine (CBZ), phenytoin (PHT), oxcarbazepine (OXC), lamotrigine (LMT), zonisamide (ZNS), levetiracetam (LVT), and topiramate (TPM), and to compare the associated risks among the drugs.. Using a nationwide health claims database, we selected all the patients prescribed with one of the target ASMs. We defined a SCAR case as the first hospitalization with one of three specific codes provided by the International Classification of Diseases, 10th revision (L511, L512, and L27). We then calculated the IR of SCARs according to each target ASM.. The IR of SCARs for each ASM was as follows: 870/1 000 000 person-years (PYs) for CBZ, 5750/1 000 000 PYs for PHT, 1490/1 000 000 PYs for OXC, 3860/1 000 000 PYs for LMT, 1540/1 000 000 PYs for ZNS, 830/1 000 000 PYs for LVT, and 400/1 000 000 PYs for TPM. Concomitant use of antibiotics and nonsteroidal anti-inflammatory drugs significantly increased the risk of SCARs with OXC, LVT, or TPM use. Comorbid skin disease was associated with a significantly higher IR of SCARs from CBZ, PHT, OXC, LMT, or LVT use.. This is the first study in Asia to determine the IRs of SCARs for various ASMs and compare the rates across drugs using a large dataset. The results from this study should help clinicians select safer ASMs in practice.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Carbamazepine; Child; Drug Hypersensitivity Syndrome; Female; Humans; Incidence; Lamotrigine; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Phenytoin; Republic of Korea; Severity of Illness Index; Stevens-Johnson Syndrome; Topiramate; Young Adult; Zonisamide

Evidence for the risk and incidence of anticonvulsant-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in Japan is scarce.. We conducted a matched case-control study using a large-scale Japanese claims database. SJS/TEN cases were identified using a claims-based algorithm developed in a previous study (sensitivity 76.9%, specificity 99.0%). Conditional logistic regression with Firth's bias correction to address an issue of rare events was used to estimate odds ratios (ORs) for SJS/TEN for each anticonvulsant use (90 days before the index date) versus non-use. 90-day cumulative incidence of SJS/TEN per 100,000 new users was calculated for 33 anticonvulsants. Causality between anticonvulsant use and SJS/TEN in each exposed case was assessed using the algorithm of drug causality for epidermal necrolysis (ALDEN) score.. From 5,114,492 subjects, we selected 71 SJS/TEN cases and 284 controls. We observed significantly increased ORs for SJS/TEN among new users of carbamazepine (OR 68.00) and lamotrigine (OR 36.00) with ALDEN scores of "probable" or higher. Cumulative incidence of SJS/TEN was 93.83 for carbamazepine and 84.33 for lamotrigine. One case newly exposed to phenytoin which developed SJS/TEN was rated "unlikely" in ALDEN causality, resulting in cumulative incidence of 66.27. Cumulative incidence of SJS/TEN was 25.23 for levetiracetam, 7.52 for clonazepam, and 1.23 for diazepam, but their ALDEN scores were "very unlikely".. This study is the first to document the differential risk of SJS/TEN for anticonvulsants in a real-world setting in Japan. Exposure to carbamazepine and lamotrigine was associated with an increased risk of SJS/TEN.

Topics: Adult; Anticonvulsants; Carbamazepine; Case-Control Studies; Clonazepam; Cohort Studies; Diazepam; Female; Humans; Incidence; Japan; Lamotrigine; Levetiracetam; Logistic Models; Male; Middle Aged; Odds Ratio; Phenytoin; Risk Factors; Stevens-Johnson Syndrome

Antiepileptic drugs (AEDs) are among the most common causes of severe delayed-type hypersensitivity reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms(DRESS) in children. These reactions are more commonly seen with aromatic AEDs such as phenytoin and carbamazepine than the non-aromatic or new generation AEDs. However immediate-type hypersensitivity reactions such as urticaria/angioedema, anaphylaxis are very rare with AEDs.. Levetiracetam is an increasingly used new non-aromatic antiepileptic drug and reported to have a better safety profile in daily practice. We present the first adolescent case who developed an anaphylactic reaction with intravenous levetiracetam, not reported in this age group before in the literature.. Hypersensitivity reactions in the form of anaphylaxis can be rarely observed with new generation AEDs. Therefore, when any antiepileptic drug is started on any patient, immediate type serious reactions such as anaphylaxis should be kept in mind, not only focusing on delayed reactions such as SJS, TEN,or DRESS.

Topics: Adolescent; Anaphylaxis; Anticonvulsants; Carbamazepine; Child; Humans; Levetiracetam; Stevens-Johnson Syndrome

Successful management of toxic epidermal necrolysis (TEN) with tumor necrosis factor-α inhibitors has been described in adults, but few cases have been reported in children. To date, only four pediatric cases of TEN treated with infliximab and one with etanercept have been published. We present the case of an 8-year-old boy diagnosed with TEN induced by levetiracetam, successfully treated with etanercept, systemic corticosteroids, and intravenous immunoglobulin.

Topics: Adult; Child; Etanercept; Humans; Immunoglobulins, Intravenous; Infliximab; Levetiracetam; Male; Stevens-Johnson Syndrome; Tumor Necrosis Factor-alpha

Topics: Anticonvulsants; Asian People; Carbamazepine; Female; HLA-B15 Antigen; Humans; Levetiracetam; Stevens-Johnson Syndrome; Young Adult

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are immune-mediated diseases characterized by an extensive loss of the epidermal skin layer, often resulting in death. SJS and TEN are often triggered by certain drugs, including antiepileptic drugs (AEDs). Epilepsy is very difficult to treat and often involves the combination of two or more AEDs. In this study, we quantified not only the risk of SJS or TEN associated with single-AED therapy but also the risk related to concomitant AED treatment using reporting-derived signals.. An analysis of the Japanese Adverse Drug Event Report (JADER) database was performed from the first quarter of 2004 to the fourth quarter of 2018. The single-AED signals were evaluated using the proportional reporting ratio (PRR), and the combination therapy signals were evaluated using Ω shrinkage measure and combination risk ratio (CRR).. SJS signals were associated with 11 AEDs, and TEN signals were related to 12 AEDs. Moreover, the following AED combinations were associated with SJS signals: carbamazepine-lorazepam (Ω. This study identified two AED combinations that increased the SJS signals and seven combinations that increased the TEN signals. Although AED monotherapies require attention for SJS and TEN, some AED combinations require extra caution.

Topics: Anticonvulsants; Carbamazepine; Clobazam; Clonazepam; Databases, Factual; Drug Therapy, Combination; Epilepsy; Gabapentin; Humans; Japan; Lacosamide; Lamotrigine; Levetiracetam; Lorazepam; Pharmacovigilance; Phenytoin; Stevens-Johnson Syndrome; Valproic Acid

Topics: Adult; Anticonvulsants; Humans; Levetiracetam; Male; Neutropenia; Piracetam; Steroids; Stevens-Johnson Syndrome

Topics: Acetaminophen; Analgesics, Opioid; Anti-Inflammatory Agents; Anticonvulsants; Antiemetics; Antineoplastic Agents; Dacarbazine; Dexamethasone; Drug Combinations; Erythema; gamma-Globulins; Glioblastoma; Humans; Immunologic Factors; Levetiracetam; Male; Methylprednisolone; Middle Aged; Omeprazole; Oxycodone; Piperidines; Piracetam; Proton Pump Inhibitors; Quinazolines; Stevens-Johnson Syndrome; Temozolomide; Wound Healing

Toxic epidermal necrolysis (TEN) is rare, life-threatening skin disorder that usually is caused by an adverse drug reaction. The exact pathogenesis of TEN is still unknown. Many treatments including prednisolone, cyclosporine and intravenous immunoglobulin (IVIG) can be used to halt the disease process. We present a 12-year-old girl with epilepsy who developed TEN after about 14 days of lamotrigine treatment. Lamotrigine was immediately discontinued. After receiving systemic corticosteroid treatment, the patient had a complete recovery. Antiepileptic-induced TEN can be mortal in some cases. Thus, we would like to point out the importance of early diagnosis and treatment.

Topics: Anticonvulsants; Child; Drug Combinations; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Piracetam; Stevens-Johnson Syndrome; Triazines

Topics: Adult; Anticonvulsants; Female; Humans; Levetiracetam; Piracetam; Stevens-Johnson Syndrome; United States; United States Food and Drug Administration; Young Adult

Topics: Anticonvulsants; Cardiovascular Surgical Procedures; Child, Preschool; Female; Heart Defects, Congenital; Humans; Levetiracetam; Piracetam; Postoperative Complications; Seizures; Stevens-Johnson Syndrome