Sodium Valproate

Introduction

Sodium valproate or valproic acid is an anticonvulsant medication used primarily in the treatment of epilepsy. It has been used both alone and as an add-on therapy for absence seizures, partial seizures, and generalized tonic-clonic seizures. It's also used to prevent migraine headaches and help with manic episodes in bipolar disorder.

Generic Name 藥名	HA Code 藥物代碼	Classification藥物分類
Sodium valproate Solution	VALP03	P1S1S3
Enteric-coated tablet	VALP02	P1S1S3
CR tablet 200 mg	VALP06	P1S1S3
CR tablet 300 mg	VALP07	P1S1S3
CR tablet 500 mg	VALP05	P1S1S3

Mechanism of Action

Anticonvulsant medication. It blocks voltage-gated sodium channels and increased brain levels of gamma-aminobutyric acid.

Dosage

1. Epilepsy

Oral: Initially 600 mg daily in 1-2 divided doses increase in steps of 150 -300 mg every 3 days maintenance 1-2g daily, maximum 2.5g daily

Administration in child:

Child 1 month-11 years: initially 10-15 mg/kg daily in 1-2 divided doses, (max per dose 600mg.) maintenance 25-30mg/kg daily in 2 divided doses, doses up to 60mg/kg daily may be used. Monitor hematological parameters if dose exceed 40mg/kg

Child 12-17 years: initially 600 mg daily in 1-2 divided doses increase in steps of 150 -300 mg every 3 days maintenance 1-2g daily, maximum 2.5g daily

2. Migraine prophylaxis:

Oral: initially 200mg twice daily, increased if needed to 1.2-2.5g daily in divided dose.

3. Mania

Initially 750mg daily in 1-2 divided doses, usually dose 1-2g daily in 1-2 divided doses. Carefully monitor if dose exceed 45mg/kg

Side Effects

Common side effects include: Aggression behaviour, anaemia, confusion, convulsion, deafness, diarrhoea, extrapyramidal disorder, gastric irritation, haemorrhage, headache,hyponatremia , memory impairment, menstrual disturbance, nausea, nystagmus, sedation, stupor, thrombocytopenia, transient hair loss, tremor, weight gain.

More serious side effect include:

• Acute hepatic failure.
• Acute pancreatitis.

Discontinue immediately if persistent vomiting and abdominal pain, anorexia, jaundice, oedema, malaise, or loss of seizures control.

Pharmacokinetics

Oral bioavailability	Sodium valproate is rapidly absorbed from the gastrointestinal tract
Onset of action	Peak concentrations being attained 1 to 2 hours after administration
Metabolism	Peak concentrations being attained 1 to 2 hours after administration
Elimination half-life	Elimination half-life approximately 9-16 hours

Drug Management

Monitoring:

• Monitor liver function before therapy and during the first 6 month of treatment, espesically patient with risk.
• Measure full blood count including platelet to make sure no potential bleeding risk.

Drug interaction:

Drugs given with sodium valproate	Potential Effect
Aspirin	Enhance sodium valproate effect
Antibiotics: Erythromycin Carbapenems	May reduce plasma-carbamazepine concentration
Analgesic: Tramadol	Carbamazepine reduces effect of tramadol
Anticoagulants: Apixaban, dabigatran, rivaroxaban, coumarins (warfarin)	Carbamazepine possibly reduces their plasma concentration, Advises avoid concomitant use and monitor signs of thrombosis
Antipsychotics: aripiprazole clozapine Haloperidol Olanzapine Paliperidone Quetiapine risperidone	Carbamazepine accelerates their metabolism and reduced their plasma concentration. Avoid concomitant use or increase the dose
Anxiolytics: Clonazepam midazolam	Carbamazepine reduces their plasma concentration
Diuretics: frusemide	Increased risk of hyponatraemia when carbamazepine given with diuretics
Oestrogens	Carbamazepine accelerates metabolism oestrogens, and reduced contraceptive effect
Theophylline	Carbamazepine accelerates metabolism of theophylline (reduced effect)
Thyroid hormones	Carbamazepine accelerates metabolism of thyroid hormones (may increase thyroxine dosage in hypothyroidism)