Delving into the Latest Updates on Sodium Valproate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

SV, Valproate Sodium, VPA-Na

+ [16]

Target

GABA transaminase

Mechanism

GABA transaminase inhibitors(Gamma-amino-N-butyrate transaminase inhibitors)

Therapeutic Areas

Nervous System DiseasesOther Diseases

Active Indication

Nervous System DiseasesBipolar DisorderMigraine Disorders+ [1]

Inactive Indication

Epilepsies, PartialEpilepsy, Absence

Originator Organization

Kyowa Kirin Co., Ltd.

Active Organization

Sumitomo Pharma Co., Ltd.

Kyowa Kirin Co., Ltd.

Kowa Co., Ltd.

+ [2]

Inactive Organization

AbbVie, Inc.

Drug Highest PhaseApproved

First Approval Date

JP (24 May 1974),

Epilepsy

RegulationOrphan Drug (US), Orphan Drug (EU)

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Structure

Molecular FormulaC8H16NaO2

InChIKeyRGZUPIWJTSGERU-UHFFFAOYSA-N

CAS Registry1069-66-5

Epilepsy is one of the most common serious chronic brain disorders of childhood. The causes of epilepsy include :acquired brain damage, altered metabolic states, inborn brain malformations, and genetic causes. At present, antiepileptic drugs (AEDs) are the first line therapy for resistant epilepsy (RE) , and the second line is surgery , and vagus nerve stimulation . Sodium valproate (SV) is a first line anti epileptic drug that can be applied to various seizure types in children . SV has anticonvulsant activity through regulation of neuronal pathways . It has a molecular structure similar to neurotransmitter γ aminobutyric acid (GABA) resulting in GABA synergism , A serious adverse effect of the valproic acid (VPA) : is its effect on liver function with resultant drug-induced hepatotoxicity, hyperammonemia . Lamotrigine (LTG) is a second generation AED
. LTG belongs to the sodium channel blocking class of antiseizure medications (ASMs). Lamortigine side effects include severe rash, fever, lymphadenopathy, hepatic dysfunction, blood disorder,and disseminated intravascular coagulation and Stevens-Johnson syndrome (SJS) . the aim : Evaluation of the efficacy and safety of adding lamotrigine to sodium valproate in epileptic children not responding to SV alone for 6 months. Moreover, the investigators will evaluate the effects of this addition ,appearance of side effects,laboratory evaluation and EEG changes 50 epileptic patients receive SV for 6 months without complete remission for participants, the investigators will add lamotrigine for 6 months.

Start Date29 Jul 2024

Sponsor / Collaborator

Assiut University

100 Clinical Results associated with Sodium Valproate

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100 Translational Medicine associated with Sodium Valproate

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100 Patents (Medical) associated with Sodium Valproate

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4,099

Literatures (Medical) associated with Sodium Valproate

30 Dec 2024·Acta neurologica Taiwanica

Taste Disorder and Tongue Numbness After Lithium Overdose.

Article

Author: Chu, Si-Yu ; Wang, Huang-Chi ; Hsieh, Ming-Hong ; Chang, Cheng-Chen

PURPOSE:

Drug-induced taste disturbances are prevalent in clinical practice, with dysgeusia being a frequent manifestation. This study aims to present a case of taste disorders and tongue numbness induced by a lithium overdose.

CASE REPORT:

A 33-year-old woman with bipolar II disorder attempted suicide by ingesting multiple drugs, including lithium and benzodiazepines. She exhibited weakness but was conscious after admission. Laboratory analyses indicated elevated serum lithium and urine benzodiazepine levels. Admitted to a psychiatric ward, her symptoms included diarrhea, poor appetite, and postprandial nausea. Two weeks later, she reported altered taste sensations and tongue numbness following the overdose. Her ongoing medication included venlafaxine, valproate sodium, and clozapine. Symptoms improved over time without specific treatment, aligning with increased appetite and weight gain.

CONCLUSION:

Drug-induced taste disturbances have a substantial impact on patients' quality of life and medication adherence. This case brings attention to taste disorders induced by lithium and suggests potential mechanisms that could contribute to taste alterations. It underscores the importance of conducting thorough assessments in patients experiencing gustatory symptoms, particularly during the ongoing pandemic.

01 Dec 2024·IBRO Neuroscience Reports

Challenges of status epilepticus management in a resource-limited setting: A review

Article

Author: Fong, Si-Lei ; Thuy Le, Minh-An ; Lim, Kheng-Seang ; Yahaya, Siti Nasrina ; Khosama, Herlyani

Status epilepticus (SE) is a life-threatening neurological condition with significant mortality. Rapid management is essential to minimize the mortality and disability of SE. Two recent trials provided evidence to guide SE management in early and established stages. The Rapid Anticonvulsant Medication Prior To Arrival Trial (RAMPART, 2011) showed that intramuscular midazolam is a better alternative for early convulsive SE in prehospital settings. The Established Status Epilepticus Treatment Trial (ESETT, 2020) supported the use of sodium valproate and levetiracetam as second-line treatment for its efficacy and shorter administration time. However, there are challenges to revising the status epilepticus management in resource-limited settings, in pre-hospital, first- and second-line treatment, as well as management of refractory and super-refractory SE. These challenges included restrictions or lack of training in the administration of benzodiazepine in the prehospital setting, limited availability and accessibility of newer antiseizure medications (ASMs) in emergency departments and smaller hospitals, and low clinicians' awareness of the latest evidence. A collaborative effort to educate, improve awareness, and make certain ASMs more readily available is recommended to achieve a better clinical outcome in SE.

01 Dec 2024·Child psychiatry and human development

An Overview of Pharmacotherapy in the Management of Children with Autism Spectrum Disorder at a Public Hospital in KwaZulu-Natal

Article

Author: Karrim, Saira B S ; Oosthuizen, Frasia ; Maniram, Jennal

Abstract:

This study presents an overview of prescribing patterns and provides insight into the current management practice for the core symptoms and comorbidities of ASD in children. A quantitative retrospective study was conducted at a public hospital in KwaZulu-Natal, South Africa by reviewing patient files of children diagnosed with ASD and meeting the inclusion criteria for the study. A descriptive analysis of data was done to identify treatment trends and patient therapeutic outcomes. A total of 181 children met the inclusion criteria of the study. Risperidone was the most frequently prescribed drug (88%) for the management of comorbidities and/or core symptoms of ASD. Drugs prescribed to manage ASD comorbidities included methylphenidate, melatonin, sodium valproate, risperidone, oxybutynin, carbamazepine, and others. Except for risperidone, there were no additional drugs that targeted the core symptoms of ASD. Non-pharmacological therapies were often used collaboratively with medication to manage ASD symptoms. In 41% of patients, there were improvements in their symptoms.

6

News (Medical) associated with Sodium Valproate

06 Sep 2024

·www.pharmaceutical-technology.com

Men taking valproate and their partners warned to use contraception by MHRA

The guidance tells patients and their partners that they should take effective measures during treatment with valproate and three months after stopping the drug. Credit: Prostock-studio via Shutterstock. The UK’s Medicines and Healthcare Regulatory Agency (MHRA) has warned men taking epilepsy medication valproate and their partners to use effective contraception, due to risks associated with neurodevelopmental disorders in children. The guidance tells patients and their partners that they should take effective measures during treatment with valproate and three months after stopping the drug. Patients should not donate sperm during valproate use and three months after treatment either. Valproate is prescribed under various brand names, including Sanofi ’s Depakine (sodium valproate), and Abbott ’s Depakote (divalproex sodium). It is mainly prescribed for the treatment of epilepsy; however, it can also be used to treat bipolar disorder. This announcement comes a few months after a study, commissioned by the European Medicines Agency, raised flags regarding a potential heightened risk of neurodevelopmental disorders in children fathered by men on valproate around conception. The data from the study indicate d that approximately five out of 100 children born to fathers treated with valproate during conception were diagnosed with a neurodevelopmental disorder, in contrast to three out of 100 children whose fathers were on Lamictal (lamotrigine) or Keppra (levetiracetam), two other anti-seizure medicines. See Also: FDA grants ODD to Abdera’s neuroendocrine carcinoma treatment Lilly partners with Haya for lncRNA obesity target deal worth $1bn The MHRA previously published guidance on medicines containing valproate in October 2023. Following this, the original pack dispensing medicines containing valproate was designed to inform patients about the risks to an unborn baby. Additionally, since January 2024, new measures recommended that valproate must not be started in new male or female patients younger than 55 years of age unless two specialists independently consider and document that there is no other effective or tolerated treatment, or unless there are compelling reasons that the reproductive risks do not apply. The heightened risk of neurodevelopmental disorders is an issue that has previously landed Sanofi in court . The drugmaker was ordered to pay more than $400,000 in damages in May 2022 after a French court ruled Sanofi at fault due to inadequate labelling information for Depakine. The damages were paid to a family that was not made aware of the potential for birth defects related to its drug Depakine. In the announcement accompanying the latest guidance, MHRA’s chief safety officer Alison Cave said: “While the risk to a child is lower than the risk associated with a mother taking valproate in pregnancy, we recommend that men taking valproate and their partners follow the updated guidance and use effective contraception.” This content was updated on 25 January 2024

Drug ApprovalPatent Infringement

16 Jan 2024

·www.pharmaceutical-technology.com

UK MHRA announces new data flagging potential valproate risks

A new study highlights that 5 out of 100 children born to fathers treated with valproate during conception were diagnosed with a neurodevelopmental disorder. Credit: luchschenF via Shutterstock. A recent study, commissioned by the European Medicines Agency, has raised flags regarding potential heightened risks of neurodevelopmental disorders in children fathered by men on valproate around conception. The study indicates that approximately five out of 100 children born to fathers treated with valproate during conception were diagnosed with a neurodevelopmental disorder, in contrast to three out of 100 children whose fathers were on Lamictal (lamotrigine) or Keppra (levetiracetam), two other anti-seizure medicines. The study was resubmitted in August after the trial sponsor, Sanofi , revealed errors that could impact the results. The regulatory authorities are scrutinising the revised study results with forthcoming guidance for patients and healthcare professionals in the pipeline from the Commission on Human Medicines. UK regulators initially recommended strengthened safety measures for valproate, setting them for implementation in January 2024. These measures include restrictions on initiating valproate in new patients under the age of 55 unless there are no other effective treatments or compelling reasons to justify its use. The UK Medicines and Healthcare products Regulatory Agency (MHRA) published guidance in October 2023, introducing original pack dispensing on medicines containing valproate, informing patients about the risks to an unborn baby. Sanofi’s Depakine (sodium valproate) is a drug used to treat conditions such as epilepsy, migraine, and bi-polar disorder. The drug works by affecting certain neurotransmitters in the brain, helping to control seizures. The drug has been linked to an increased risk of birth defects and developmental issues in children when taken by pregnant individuals. In May 2022, a French court ordered Sanofi to pay more than $400,000 in damages to a family that were not made aware about the potential for birth defects related to its drug Depakine. The case involved a child whose autism was said to be linked to the mother taking the drug during pregnancy. The court ruled Sanofi at fault due to inadequate labelling information for Depakine. In 2020, Sanofi was hit with a formal investigation regarding manslaughter charges for the death of four babies, whose mothers took Depakine during their pregnancies. The company denied the charges at the time and said it would challenge the findings of the investigation.

Clinical ResultPatent Infringement

12 Dec 2023

·www.fiercepharma.com

After leak of neurotoxin, Sanofi plant in France is under scrutiny again

A Sanofi plant in France, which was closed down in 2018 for emitting a dangerous neurotoxin, is under scrutiny again after a leak last month. A Sanofi manufacturing facility in France, which was temporarily closed five years ago for emitting dangerous emissions, is under the microscope again after a recent leak caused the release of the same neurotoxin, bromopropane. The plant, which produces epilepsy drug Depakine (sodium valproate), released 75 times the allowable amount of bromopropane in mid-November, according to a report in the French news outlet Le Monde. The facility, located in Mourenx, stopped production “immediately" after noting “inconsistent measurements” of bromopropane emissions, according to a Sanofi spokesperson. “We quickly identified that this isolated and very brief event was linked to the degradation of the treatment unit’s activated carbons following the bad weather and heavy rains that had affected the region in the preceding days,” Sanofi said. “The coals were replaced and bromopropane emissions returned to normal, enabling production to resume after approval from the authorities.” Bromopropane—which is used in the production of Depakine—is classified as a possible carcinogen by the World Health Organization. Manufacturers using bromopropane are required to self-monitor their emissions of the neurotoxin. The drug itself, Depakine, has been under the microscope in France for years. In 2020, France launched an investigation into alleged safety risks for babies when valproate is taken by pregnant mothers. The company has denied the charges. Last month, Le Monde reported that a woman in France, who never took Depakine but has worked next door to the plant since 2011, filed a complaint against Sanofi, saying that her two epileptic children—who were born in 2014 and 2016—have disorders similar to those shown in children whose mothers took the drug during pregnancy. In 2018, after the plant was shut down, French officials continued their scrutiny of the Mourenx facility. In August 2022, a public health investigation was launched, ramping up pressure on the site to remain compliant.

Clinical StudyDrug Approval

100 Deals associated with Sodium Valproate

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Sodium Valproate	N03AG01	DBSALT001257

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Epilepsies, Partial	US	AbbVie, Inc.	30 Dec 1996
Epilepsy, Absence	US	AbbVie, Inc.	30 Dec 1996
Nervous System Diseases	CN	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	01 Jan 1982
Bipolar Disorder	JP	Sumitomo Pharma Co., Ltd.	01 Sep 1981
Migraine Disorders	JP	Sumitomo Pharma Co., Ltd.	01 Sep 1981
Epilepsy	JP	Kyowa Kirin Co., Ltd.	24 May 1974

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05224531 (CS1-003, PipelineReview) Manual	Phase 2	Pulmonary Arterial Hypertension	21	CS1	nkzqtunifx(xeojfioobx) = lijorzvkmq pwbxdeztgs (ffsifasyjl ) View more	Positive	29 Sep 2024
EADV2023	Not Applicable	Alopecia Areata beta catenin	66	Topical Sodium Valproate (SV) -loaded nanospanlastics	bfjscyfoqo(knccdyzklq) = Baseline beta catenin was found to significantly negatively correlate with improvement in the representative patch in patients with baseline level above 0.42 ng/ml wvqghsaosc (loajlwgktz ) View more	-	11 Oct 2023
				Topical Mometasone Furoate Lotion
IEC2023	Not Applicable	Epilepsy, Generalized	225	Sodium valproate (VPA) up to 700 mg	vkhmijvrzd(mquewvmqto) = ebsvvjdaor djccqvdicl (moktffsnmq )	Positive	04 Sep 2023
NCT04698525 (CTgov)	Phase 3	Migraine Disorders	33	Valproate Sodium (Valproate Group)	poysgkgmdp(nfosvgqqoc) = ohoelvpire sdrkwljylt (leuwbjjynw, cltzkipnhc - wlddimvajo) View more	-	17 May 2023
				memantine (Memantine)	poysgkgmdp(nfosvgqqoc) = fgeuifbkbi sdrkwljylt (leuwbjjynw, ugodwwdsvo - mdmgwmvrsd) View more
CTRI/2020/01/022781 (ESMO_ASIA2022)	Phase 2	Platinum-Resistant Ovarian Carcinoma	27	Oral etoposide + Sodium valproic acid (VPA)	tevgsatbfq(mdsylcmfib) = oncreddfbk owwtdwzwwn (ubdubligch ) View more	-	03 Dec 2022
IEC2017	Not Applicable	Status Epilepticus	100	Sodium Valproate	uacwabvcal(miyqsyziog) = mecnzfenzu vbqdleoheu (nkstyzbmdt ) View more	Positive	03 Sep 2017
				Levetiracetam	erxqhqwkix(cpfkaokfyf) = gqlbocrhpj fisfbpswgp (kylcnatoua )
IEC2015	Not Applicable	Epilepsy antioxidant parameters	66	Vitamin E	yxiujzuaqb(tuimcnipfh) = malondialdehyde decreased but was not statistically significant in case (p = 0.1),but in control don ’ t decreased(p = 0.53) rhzihshtnd (beebtqpfgd )	Positive	08 Sep 2015
				Sodium valproate (Placebo)
IRCT201202199014N1 (Pubmed \| J Biol Chem)	Phase 3	Migraine Disorders	104	Intravenous sodium valproate	gjeqxwfcik(pjmqxrpoee) = nywgxyypkh rxeejqbysv (idjxbdxcdd )	-	01 Jan 2015
				Intravenous dexamethasone	gjeqxwfcik(pjmqxrpoee) = kxxoschbto rxeejqbysv (idjxbdxcdd )
IEC2011	Not Applicable	Epilepsy	-	Sodium valproate (VPA)	oqmlnavjoc(evkeiueeqa) = eohowcjghg nrsrkvlapp (vldirxoztp ) View more	Positive	31 Aug 2011
NCT00203242 (CTgov)	Not Applicable	Cluster Headache	15	Depakote+Depacon IV	nwoyxglmvo(mfxxbbmizf) = vktqskikdh cqckvymysq (qjuktuudyt, jgauefcbpi - vvobpqthxa) View more	-	06 Jul 2011