-
Pediatric Neurology Sep 2019Valproic acid is one of the most commonly used antiseizure medications. Multiple hematologic abnormalities have been reported with the use of valproic acid, which may be... (Review)
Review
BACKGROUND
Valproic acid is one of the most commonly used antiseizure medications. Multiple hematologic abnormalities have been reported with the use of valproic acid, which may be particularly relevant in the perioperative surgical setting. The incidence of these abnormalities and prevalence of periprocedural hemorrhage vary significantly in the published literature. In this article we analyze the prevalence and possible etiology of coagulopathy and hemorrhage in patients receiving valproic acid.
METHODS
A literature search was completed using "VPA," "coagulopathy," and "surgery." The available published data from case reports to large case series were reviewed.
RESULTS
Thrombocytopenia was noted to be the most common laboratory abnormality associated with valproic acid. An association between valproic acid and acquired von Willebrand disease has also been suggested. There are case reports describing bleeding in the setting of hypofibrinogenemia and factor XIII deficiency. Perioperative hemorrhage was reported in pediatric studies of orthopedic procedures, but not in adult cohorts undergoing neurosurgical interventions.
CONCLUSIONS
VPA use can cause thrombocytopenia and other coagulation abnormalities. Rigorous, prospective trials are needed to better assess the association between valproic acid and clinically significant coagulopathy. Until such data are available, physicians need to be aware of the potential risk of bleeding in patients receiving valproic acid. A hemostatic evaluation should be considered in symptomatic patients, and may be considered for patients taking VPA who are scheduled for surgery. If an abnormality is detected, hematologists should be involved to make recommendation on perioperative hemostatic strategy.
Topics: Anticonvulsants; Blood Coagulation Disorders; Hemostasis; Humans; Valproic Acid
PubMed: 31201069
DOI: 10.1016/j.pediatrneurol.2019.04.019 -
Journal of Clinical Pathology Aug 2023Hyperammonaemia (HA) as a consequence of numerous primary or secondary causes, gives rise to clinical manifestations due to its toxic effects on the brain. The... (Review)
Review
Hyperammonaemia (HA) as a consequence of numerous primary or secondary causes, gives rise to clinical manifestations due to its toxic effects on the brain. The neurological consequences broadly reflect the ammonia level, duration and age, with paediatric patients being more susceptible. Drug-induced HA may arise due to either decreased ammonia elimination or increased production. This is associated most frequently with use of valproate and presents a dilemma between ongoing therapeutic need, toxicity and the possibility of an alternative cause. As there is no specific test for drug-induced HA, prompt discussion with a metabolic physician is recommended, as the neurotoxic effects are time-dependent. Specific guidelines for managing drug-induced HA have yet to be published and hence the treatment approach outlined in this review reflects that outlined in relevant urea cycle disorder guidelines.
Topics: Humans; Child; Hyperammonemia; Ammonia; Brain; Valproic Acid
PubMed: 37164630
DOI: 10.1136/jcp-2022-208644 -
Issues in Mental Health Nursing Nov 2022
Topics: Humans; Valproic Acid; Delirium; Brain Injuries, Traumatic
PubMed: 36136610
DOI: 10.1080/01612840.2022.2122431 -
Current Neuropharmacology 2023
Topics: Humans; Valproic Acid; Bipolar Disorder; Lithium; Antimanic Agents; Lithium Compounds
PubMed: 37203193
DOI: 10.2174/1570159X2104230307123319 -
Journal of Human Genetics Dec 2017Valproic acid is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. Adverse effects of valproic acid are rare,... (Review)
Review
Valproic acid is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. Adverse effects of valproic acid are rare, but hepatotoxicity is severe in particular in those younger than 2 years old and polytherapy. During valproic acid treatment, it is difficult for prescribers to predict its individual response. Recent advances in the field of pharmacogenomics have indicated variants of candidate genes that affect valproic acid efficacy and safety. In this review, a large number of candidate genes that influence valproic acid pharmacokinetics and pharmacodynamics are discussed, including metabolic enzymes, drug transporters, neurotransmitters and drug targets. Furthermore, pharmacogenomics is an important tool not only in further understanding of interindividual variability but also to assess the therapeutic potential of such variability in drug individualization and therapeutic optimization.
Topics: Anticonvulsants; Bipolar Disorder; Cytochrome P-450 Enzyme System; Drug Delivery Systems; Epilepsy; Genetic Variation; Humans; Neurotransmitter Agents; Pharmacogenetics; Pharmacokinetics; Precision Medicine; Valproic Acid
PubMed: 28878340
DOI: 10.1038/jhg.2017.91 -
Clinical Medicine (London, England) Apr 2018Antiepileptic medications, and valproate principally, are commonly prescribed teratogens. There is significant concern that we are not doing enough to educate clinicians... (Review)
Review
Antiepileptic medications, and valproate principally, are commonly prescribed teratogens. There is significant concern that we are not doing enough to educate clinicians and potential parents about the risks of valproate in pregnancy. There is clear advice from the Medicines and Healthcare products Regulatory Agency and the International League Against Epilepsy about the risks of valproate exposure Reviews and guidelines that are focused on fetal risk, however, fall short in being able to fully replicate the complexity of a real clinical decision. Valproate is certainly life-changing if your child is one of the 10% with a major malformation or 30-40% with a neurodevelopmental disorder, but valproate is also potentially life-saving in the context of ensuring the best possible seizure control for some mothers with epilepsy. There are significant knowledge gaps regarding the risks to mothers who elect to take another drug, or to mother and baby if she comes off medication entirely. We also should be doing more to reduce rates of sudden unexpected death in epilepsy (SUDEP), which is recognised as a key target when evaluating all maternal deaths.
Topics: Anticonvulsants; England; Epilepsy; Female; Humans; Maternal Exposure; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prescriptions; Teratogens; Treatment Outcome; Valproic Acid
PubMed: 29700085
DOI: 10.7861/clinmedicine.18-2-s1 -
ChemMedChem Feb 2023Paracetamol and valproic acid are standalone drugs with leading position in the world drug market. The phosphonate analogues of these drugs were synthesized and were...
Paracetamol and valproic acid are standalone drugs with leading position in the world drug market. The phosphonate analogues of these drugs were synthesized and were tested in vivo. N-(4-hydroxyphenylcarbamoyl)phosphonic acid was four times more potent than paracetamol in preventing acetic acid-induced writhing. Phosphonate derivative of valproic acid, (2-propylpentanoyl)phosphonic acid, had similar in vivo activity to valproic acid in the pentylenetetrazole-induced kindling mouse model.
Topics: Mice; Animals; Valproic Acid; Acetaminophen; Organophosphonates; Phosphorous Acids
PubMed: 36367256
DOI: 10.1002/cmdc.202200526 -
Advanced Emergency Nursing Journal 2020Migraine headaches can be a disabling condition for patients. Fortunately, most patients can be successfully managed in the outpatient setting, however, there are a... (Review)
Review
Migraine headaches can be a disabling condition for patients. Fortunately, most patients can be successfully managed in the outpatient setting, however, there are a number of patients who may not respond to the abortive treatments that they have been prescribed. These patients often present to the emergency department (ED) for further assistance with the management of their condition. Migraines are the fourth most common cause of ED visits and are associated with an estimated annual cost of $17 billion in the United States. Familiarity with abortive treatments is critical for providers in the ED as are treatments, such as valproic acid, that may be considered in patients who do not respond to other treatment options. Many providers are more familiar with the role of valproic acid in the treatment of mood and seizure disorders, but its tolerability and the successes reported in the primary literature make it a reasonable consideration for patients with migraine who fail to respond to other therapies. This article briefly summarizes the therapies considered first line for abortive treatment in the setting of migraines and provides an overview of the primary literature describing the use of valproic acid in these patients.
Topics: Emergency Service, Hospital; GABA Agents; Humans; Migraine Disorders; Valproic Acid
PubMed: 33105176
DOI: 10.1097/TME.0000000000000319 -
Therapeutic Drug Monitoring Jun 2022This therapeutic drug monitoring (TDM) grand round describes a patient with serious valproic acid intoxication. A total valproic acid level of 844 mg/L and an unbound...
This therapeutic drug monitoring (TDM) grand round describes a patient with serious valproic acid intoxication. A total valproic acid level of 844 mg/L and an unbound valproic acid level of 604 mg/L were observed. Meropenem was administered to enhance the clearance of valproic acid. This off-label usage of meropenem is based on the drug-drug interaction between carbapenems and valproic acid, which reduced the level of valproic acid within 24 hours after administration.
Topics: Anti-Bacterial Agents; Anticonvulsants; Drug Interactions; Humans; Meropenem; Valproic Acid
PubMed: 35170557
DOI: 10.1097/FTD.0000000000000973 -
Current Pharmaceutical Design 2019Valproic acid (VPA) as a widely used primary medication in the treatment of epilepsy is associated with reversible or irreversible hepatotoxicity. Long-term VPA therapy... (Review)
Review
BACKGROUND
Valproic acid (VPA) as a widely used primary medication in the treatment of epilepsy is associated with reversible or irreversible hepatotoxicity. Long-term VPA therapy is also related to increased risk for the development of non-alcoholic fatty liver disease (NAFLD). In this review, metabolic elimination pathways of VPA in the liver and underlying mechanisms of VPA-induced hepatotoxicity are discussed.
METHODS
We searched in PubMed for manuscripts published in English, combining terms such as "Valproic acid", "hepatotoxicity", "liver injury", and "mechanisms". The data of screened papers were analyzed and summarized.
RESULTS
The formation of VPA reactive metabolites, inhibition of fatty acid β-oxidation, excessive oxidative stress and genetic variants of some enzymes, such as CPS1, POLG, GSTs, SOD2, UGTs and CYPs genes, have been reported to be associated with VPA hepatotoxicity. Furthermore, carnitine supplementation and antioxidants administration proved to be positive treatment strategies for VPA-induced hepatotoxicity.
CONCLUSION
Therapeutic drug monitoring (TDM) and routine liver biochemistry monitoring during VPA-therapy, as well as genotype screening for certain patients before VPA administration, could improve the safety profile of this antiepileptic drug.
Topics: Anticonvulsants; Antioxidants; Carnitine; Chemical and Drug Induced Liver Injury; Epilepsy; Humans; Liver; Valproic Acid
PubMed: 30931853
DOI: 10.2174/1381612825666190329145428