scholarly journals Case Report of A Rare Idiosyncratic Hepatotoxicity Induced by Valproic Acid

2021 ◽  
pp. 1-6
Author(s):  
Malek Michael Bouhairie ◽  
Keyword(s):  
Valproic Acid ◽  
Drug Level ◽  
Altered Mental Status ◽  
Ammonia Level ◽  
Normal Serum ◽  
Accurate Information ◽  
Hepatocellular Injury ◽  
Idiosyncratic Reaction ◽  
Acid Therapy ◽  
New Biomarkers

Valproate induced hepatotoxicity is a well-known side effect, which frequently required periodic monitoring of serum drug level. Hepatotoxicity caused by valproate typically occurs at supratherapeutic drug levels. Once in a while, an idiosyncratic reaction is elicited, liver injury might occur despite normal serum valproate level mainly in chronic users. We hereby identify an unusual case of acute idiosyncratic valproate induced hepatotoxicity. We report a case of a 65 years old male with dyslipidemia and history of seizure, on valproic acid therapy, presented with altered mental status and drowsiness. The patient’s home medications include only zenil 10 mg daily and valproate which was started one month ago. At presentation, He was awake, oriented, but lethargic. Laboratory testing reveals hepatocellular injury with elevated transaminase levels, direct hyperbilirubinemia and coagulopathy. The ammonia level was normal and valproate level was within the therapeutic range. Abdomen computed tomography with IV contrast and MRCP results were irrelevant. Idiosyncratic valproate toxicity was diagnosed after exclusion of all other possible etiologies and after a rapid clinical and laboratory improvement once the drug was discontinued. Based on the patient’s clinical context the diagnosis of valproate induced hepatotoxicity was confirmed. This case emphasizes the importance of identifying, diagnosing, and managing valproate toxicity when no alternative clarification for their symptoms. We need further attempts and more researches to improve the detection of adverse hepatic reactions and to obtain reliable information about the discovery of new biomarkers or tools for early prediction of DILI, as well as to obtain accurate information on epidemiology, drug safety, and pathogenesis in order to improve management for better survival.

Case Report of A Rare Idiosyncratic Hepatotoxicity Induced by Valproic Acid

2021 ◽  
Vol 2 (2) ◽  
pp. 1-6
Author(s):  
Malek Michael Bouhairie ◽  
◽  
Sabrina Nasreddine ◽  
Keyword(s):  
Valproic Acid ◽  
Drug Level ◽  
Altered Mental Status ◽  
Ammonia Level ◽  
Normal Serum ◽  
Accurate Information ◽  
Hepatocellular Injury ◽  
Idiosyncratic Reaction ◽  
Acid Therapy ◽  
New Biomarkers

Valproate induced hepatotoxicity is a well-known side effect, which frequently required periodic monitoring of serum drug level. Hepatotoxicity caused by valproate typically occurs at supratherapeutic drug levels. Once in a while, an idiosyncratic reaction is elicited, liver injury might occur despite normal serum valproate level mainly in chronic users. We hereby identify an unusual case of acute idiosyncratic valproate induced hepatotoxicity. We report a case of a 65 years old male with dyslipidemia and history of seizure, on valproic acid therapy, presented with altered mental status and drowsiness. The patient’s home medications include only zenil 10 mg daily and valproate which was started one month ago. At presentation, He was awake, oriented, but lethargic. Laboratory testing reveals hepatocellular injury with elevated transaminase levels, direct hyperbilirubinemia and coagulopathy. The ammonia level was normal and valproate level was within the therapeutic range. Abdomen computed tomography with IV contrast and MRCP results were irrelevant. Idiosyncratic valproate toxicity was diagnosed after exclusion of all other possible etiologies and after a rapid clinical and laboratory improvement once the drug was discontinued. Based on the patient’s clinical context the diagnosis of valproate induced hepatotoxicity was confirmed. This case emphasizes the importance of identifying, diagnosing, and managing valproate toxicity when no alternative clarification for their symptoms. We need further attempts and more researches to improve the detection of adverse hepatic reactions and to obtain reliable information about the discovery of new biomarkers or tools for early prediction of DILI, as well as to obtain accurate information on epidemiology, drug safety, and pathogenesis in order to improve management for better survival.

A Case of Hyperammonemic Encephalopathy Secondary to a Combination of Valproic Acid and Topiramate

2005 ◽  
Vol 40 (3) ◽  
pp. 247-249
Author(s):  
Kurt A. Wargo ◽  
M. Georgia Wavra
Keyword(s):  
Valproic Acid ◽  
Mental Status ◽  
Altered Mental Status ◽  
Clonic Seizure ◽  
Ammonia Level ◽  
Acid Therapy ◽  
Metabolic Encephalopathy ◽  
Hyperammonemic Encephalopathy ◽  
Normal Limits ◽  
Rule Out

Purpose To report a case of hyperammonemic encephalopathy induced by a combination of valproic acid and topiramate. Case Summary A 30-year-old male was admitted to our institution after experiencing headaches, decreasing mental capacity and increasing somnolence over the previous 3 days. Past medical history was significant for generalized tonic-clonic seizure disorder and mild mental retardation for which he had been regularly taking valproic acid, topiramate, and lorazepam. The patient was seizure free for the past 9 months prior to his seizure 2 weeks prior to admission. Upon presentation, an electroencephalogram revealed excessive slowing in the left more than right, with a differential consistent with a metabolic encephalopathy, head injury, or postictal state. Laboratory workup revealed a valproic acid level that was slightly elevated, but still within normal limits, at 92.5 mcg/mL (normal = 50 to 100 mcg/mL). Furthermore, the patient's ammonia level was found to be elevated at 72 mcg/dL (normal = 14.7 to 55.3 mcg/dL). On hospital day 3, after discovering these findings, valproic acid was discontinued and lactulose 20 g three times daily was started. Five days after admission, the patient's mental status changes were resolved, and he was discharged with an ammonia level of 57 mcg/dL. Conclusion Hyperammonemic encephalopathy is rare, but a serious and sometimes fatal disorder can occur in patients receiving valproic acid therapy. The incidence of hyperammonemia may be increased in patients receiving concomitant valproic acid and topiramate therapy. In patients on valproic acid and topiramate who present with altered mental status, an ammonia level in addition to a serum valproate level should be ascertained to rule out this potentially serious adverse drug reaction.

scholarly journals High Blood Ammonia Levels Associated with Long-term Valproic Acids Therapy in Epileptic Children

2020 ◽  
Vol 4 (2) ◽  
pp. 83
Author(s):  
I Gusti Lanang Sidiartha ◽  
I Gusti Ngurah Made Suwarba ◽  
Dyah Kanya Wati ◽  
Ida Bagus Subanada
Keyword(s):  
Valproic Acid ◽  
Combination Therapy ◽  
Ammonia Level ◽  
Blood Ammonia ◽  
Cross Sectional ◽  
Acid Therapy ◽  
Blood Ammonia Level ◽  
Significant Difference ◽  
Epileptic Children

Background: Valproic acid is an effective drug for controlling seizure in children with epilepsy and it is usually used for treatment as long as two years or more. Blood ammonia level often increased in epileptic children who were treated with long-term valproic acid. The study was conducted to determine the relationship between blood ammonia level with valproic acid therapy in epileptic children.Materials and Methods: This is an observational study with cross-sectional approach. The subjects were 64 children with epilepsy, average age of 6.2 years old. Subjects were 33 boys and 31 girls. Blood ammonia level was examined using enzymatic glutamate dehydrogenase. Subjects were divided into 2 therapeutic groups based on the duration, doses and combination therapy of valproic acid. Subjects were recruited from Pediatric Neurology Clinic, Sanglah General Hospital, Bali, Indonesia, from May to December 2017. Comparison of blood ammonia level between groups were analyzed using an Independent t-test with significances if the p<0.05. Results: A significant difference of blood ammonia level was found between subjects who were treated with valproic acid less than 2 years and more than 2 years (45.7±16.4 mmol/L vs. 70.9±43.6 mmol/L; p=0.032). However, significant difference was not found between the groups according to the doses and combination therapy (p=0.450 and p=0.647, respectively).Conclusion: Blood ammonia level was significantly higher in epileptic children who used long-term valproic acid, hence it was recommended to check the blood ammonia level routinely.Keywords: ammonia, epilepsy, valproic, children

scholarly journals Valproic Acid and Topiramate Induced Hyperammonemic Encephalopathy in a Patient With Normal Serum Carnitine

2013 ◽  
Vol 18 (2) ◽  
pp. 128-136 ◽  
Author(s):  
Martha G. Blackford ◽  
Stephanie T. Do ◽  
Thomas C. Enlow ◽  
Michael D. Reed
Keyword(s):  
Valproic Acid ◽  
Mental Status ◽  
Pediatric Intensive Care ◽  
Altered Mental Status ◽  
Ammonia Concentration ◽  
Normal Serum ◽  
Urine Drug Screen ◽  
Blood Ammonia ◽  
Persistent Symptoms ◽  
Hyperammonemic Encephalopathy

A 17-year-old female developed hyperammonemic encephalopathy 2 weeks after valproic acid (VPA), 500 mg twice a day, was added to her regimen of topiramate (TPM), 200 mg twice a day. She presented to the emergency department (ED) with altered mental status, hypotension, bradycardia, and lethargy. Laboratory analysis showed mild non-anion gap hyperchloremic acidosis, serum VPA concentration of 86 mg/L, and urine drug screen result that was positive for marijuana. She was admitted to the pediatric intensive care unit for persistent symptoms, prolonged QTc, and medical history. Blood ammonia concentrations were obtained because of her persistent altered mental status, initially 94 μmol/L and a peak of 252 μmol/L. A serum carnitine profile was obtained at the time of hyperammonemia and was found to be normal (results were available postdischarge). VPA and TPM were discontinued on day 1 and day 2, respectively, as the patient's blood ammonia concentration remained elevated. On day 3, her mental status had returned to baseline, and blood ammonia concentrations trended downward; by day 4 her blood ammonia concentration was 23 μmol/L. VPA has been associated with numerous side effects including hyperammonemia and encephalopathy. Recently, drug interactions with TPM and VPA have been reported; however, serum carnitine concentrations have not been available. We discuss the possible mechanisms that VPA and TPM may affect serum ammonia and carnitine concentrations and the use of levocarnitine for patients or treating toxicity.

Blood Ammonia Level during Valproic Acid Therapy

1986 ◽  
Vol 40 (4) ◽  
pp. 663-668 ◽  
Author(s):  
Toshiaki Kugoh ◽  
Mitsutoshi Yamamoto ◽  
Kiyoshi Hosokawa
Keyword(s):  
Valproic Acid ◽  
Ammonia Level ◽  
Blood Ammonia ◽  
Acid Therapy ◽  
Valproic Acid Therapy ◽  
Blood Ammonia Level

scholarly journals The Effect of Carnitine Supplementation on Blood Ammonia Level in Epilepsy Children Treated with Valproic Acid: A Randomized Controlled Trial

2021 ◽  
Vol 5 (1) ◽  
pp. 18
Author(s):  
I Gusti Lanang Sidiartha ◽  
I Gusti Ngurah Made Suwarba ◽  
Dyah Kanya Wati ◽  
Ida Bagus Subanada
Keyword(s):  
Valproic Acid ◽  
Controlled Trial ◽  
Ammonia Level ◽  
Control Group ◽  
Carnitine Supplementation ◽  
Blood Ammonia ◽  
Acid Therapy ◽  
Blood Ammonia Level ◽  
And Control

Background: Long-term use of valproic acid is associated with a high level of blood ammonia related to carnitine deficiency. This study investigates the effect of carnitine supplementation on blood ammonia levels in children with epilepsy who have been treated with valproic acid for more than six months.Materials and Methods: This was a randomized, double-blind, placebo-controlled trial study where children with epilepsy who were treated with valproic acid were randomly allocated to the carnitine supplementation and control group. All children were followed for month, and then measured for blood ammonia level. Blood ammonia levels of both groups were compared using an Independent t-test with a significant of p<0.05.Results: Total of 32 children with epilepsy were enrolled as subjects in this study, with 16 children in carnitine group, and 16 children in control group. Among the subjects, 50% were male and 50% were female, with a mean age of 6.5 years old. The average duration of epilepsy in the carnitine and control group were 41.7 months and 36.9 months, respectively (p=0.419). The duration of valproic acid therapy in the carnitine and control group were 33.1 months and 27.6 months, respectively (p=0.483). The level of blood ammonia in carnitine and control group were 44.6 mg/dL and 81.4 mg/dL, respectively (p=0.007).Conclusion: The level of blood ammonia in a carnitine group was significantly lower than in a control group. It is recommended to give carnitine supplementation in epileptic children treating with long-term valproic acid.Keywords: ammonia, carnitine, epilepsy, seizure, valproic acid

scholarly journals Acute Pancreatitis as a Complication of Antiepileptic Treatment: Case Series and Review of the Literature

2021 ◽  
Vol 13 (1) ◽  
pp. 98-103
Author(s):  
Agnieszka Pawłowska-Kamieniak ◽  
Paulina Krawiec ◽  
Elżbieta Pac-Kożuchowska
Keyword(s):  
Valproic Acid ◽  
Acute Pancreatitis ◽  
Metabolic Disorders ◽  
Genetic Factors ◽  
Clinical Symptoms ◽  
Gallstone Disease ◽  
Young Patients ◽  
Case Series ◽  
Review Of The Literature ◽  
Acid Therapy

Acute pancreatitis (AP) appears to be rare disease in childhood. In children, it has a different aetiology and course, and requires different management than in adult patients. The diagnosis of AP is based on at least two of the three criteria, which include typical clinical symptoms, abnormalities in laboratory tests and/or imaging studies of the pancreas. There are many known causes leading to AP in children including infections, blunt abdominal trauma, genetic factors, gallstone disease, metabolic disorders, anatomical defects of the pancreas, systemic diseases, as well as drugs, including antiepileptic drugs, and especially preparations of valproic acid. In our study, we present four cases of young patients diagnosed with acute pancreatitis as a complication of valproic acid therapy and we present a review of the literature. We believe that the activity of pancreatic enzymes should be monitored in children treated with valproate preparations in the case of clinical symptoms suggesting AP.

Thyroid Functions in Children on Levetiracetam or Valproic Acid Therapy

2020 ◽  
Author(s):  
Elif Karatoprak ◽  
Samet Paksoy
Keyword(s):  
Valproic Acid ◽  
Subclinical Hypothyroidism ◽  
Control Group ◽  
Thyroid Function Tests ◽  
Healthy Children ◽  
Control Groups ◽  
Acid Therapy ◽  
Significant Difference ◽  
And Control ◽  
Tsh Levels

AbstractThe aim of this study was to investigate the thyroid functions in children receiving levetiracetam or valproate monotherapy. We retrospectively reviewed the records of children with controlled epilepsy receiving valproic acid (VPA group) or levetiracetam monotherapy (LEV group) for at least 6 months. Free thyroxine 4 levels (fT4) and thyroid stimulating hormone (TSH) levels were compared between VPA group, LEV group, and age- and gender-matched healthy children (control group). A total of 190 children were included in the study: 63 were in the VPA, 60 in the LEV, and 67 in the control group. Although there was no significant difference regarding average fT4 levels, higher TSH levels were found in the VPA group when compared with the LEV and control groups (p < 0.001 and p < 0.001, respectively). There was no significant difference in terms of fT4 and TSH values in the LEV group when compared with the control group (p = 0.56 and p = 0.61, respectively). Subclinical hypothyroidism (defined as a TSH level above 5 uIU/mL with a normal fT4 level was detected in 16% of patients in the VPA group, none in the LEV and control groups. Our study found that VPA therapy is associated with an increased risk of subclinical hypothyroidism while LEV had no effect on thyroid function tests.

Association of genetic variants in six candidate genes with valproic acid therapy optimization

2011 ◽  
Vol 12 (8) ◽  
pp. 1107-1117 ◽  
Author(s):  
Chin-Chuan Hung ◽  
Jia-Ling Ho ◽  
Wei-Lun Chang ◽  
John Jen Tai ◽  
Tsung-Jen Hsieh ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Candidate Genes ◽  
Genetic Variants ◽  
Acid Therapy ◽  
Valproic Acid Therapy

scholarly journals Valproic Acid Administration in Management of Status Epilepticus Causing Reye’s Syndrome

2021 ◽  
Vol 07 (01) ◽  
pp. 044-046
Author(s):  
Pooja Prabhakar Kamath
Keyword(s):  
Valproic Acid ◽  
Status Epilepticus ◽  
Hepatic Dysfunction ◽  
Rare Condition ◽  
Normal Serum ◽  
Reye's Syndrome ◽  
Serum Glutamic Oxaloacetic Transaminase ◽  
Viral Illness ◽  
Laboratory Investigations ◽  
Serum Ammonia

Abstract Introduction Valproic acid is commonly used to treat seizures in children. Regular use of valproic acid is known to cause hepatic dysfunction, and in extremely rare cases, it is known to have caused Reye’s syndrome. There are very few reports of Reye’s syndrome caused by valproic acid use. Methods A 2-year asymptomatic girl underwent modified Blalock–Taussig shunt surgery for correction of tetralogy of Fallot. Postoperatively the girl developed status epilepticus, which did not subside with initial use of intravenous midazolam and phenytoin sodium. She eventually responded to two doses of intravenous valproic acid administered 10 minutes apart. She developed depressed sensorium and was put on mechanical ventilation. The following day’s laboratory investigations revealed raised levels of serum ammonia, serum glutamic-oxaloacetic transaminase (SGOT), and serum glutamic-pyruvic transaminase (SGPT) with normal serum bilirubin. Thus, a diagnosis of Reye’s syndrome was established. The patient succumbed to disease 2 days later. Discussion Reye’s syndrome is a rare and a fulminant illness seen typically in children following a viral illness and/or use of salicylates or other medications. There are rare reports of Reye’s syndrome following use of medications like valproic acid. This patient had a noninflammatory encephalopathy with hepatic dysfunction following two doses of valproic acid. Conclusion There are very few reports on Reye’s syndrome in the literature as it is a rare condition and diagnosis is difficult. Knowledge of the presentation of Reye’s syndrome is essential for treatment and management. When using drugs like valproic acid in children, liver enzymes and serum ammonia levels should be monitored.

Sign in / Sign up

Export Citation Format

Share Document