For the use of Registered Medical Practitioner or Hospital or Laboratory only (June-2025)

VALPROT* ORAL SOLUTION

(Sodium Valproate Oral Solution IP)

COMPOSITION:

Each 5 mL contains: Sodium Valproate IP 200 mg

CLINICAL PHARMACOLOGY:

Mechanism of action

Valproate exerts antiepileptic effects via GABAergic enhancement (increased GABA synthesis/reduced degradation), sodium channel blockade, and modulation of calcium currents.

PHARMACOKINETICS

Absorption: Valproic acid is rapidly and almost completely absorbed in fasting patients following oral dosing as syrup and sugar-free liquid, with peak blood levels occurring within 1 to 4 hours. Local gastric irritation may occur with the plain tablets, sugar-free liquid or syrup when administered on an empty stomach, due to transformation of sodium valproate into valproic acid.

Distribution: Distribution of sodium valproate/valproic acid is rapid and most likely restricted to the circulation and rapidly exchangeable extracellular water. CSF and breast milk levels were found to be 5 to 15% and about 1 to 10% of plasma levels, respectively. Valproic acid shows non-linear kinetics, due to concentration-dependent plasma protein binding as well as a relatively short half-life. The half-life of sodium valproate/valproic acid is usually reported to be within the range 8-20 hours. It is usually shorter in children.

Metabolism: Its metabolism is complex; the major elimination pathway is via glucuronidation (40-60%). The remainder is largely metabolized via oxidation pathways, β-oxidation accounting for 30-40% and w-oxidation (cytochrome P450 dependent), and the remaining fraction. Only 1 to 3% of the ingested dose is found to be excreted unchanged in the urine.

Elimination: Sodium valproate and valproic acid are almost completely metabolized prior to excretion. Plasma half-life is variable but generally appears to be 8 to 12 hours (range 3.84 to 15.77 hours) in adults. It may be shorter in patients receiving other anticonvulsants and patients receiving the medicine for long periods. In cases of overdose, long half-lives up to 30 hours have been reported.

 INDICATIONS AND USAGE:

Oral solution is administered for the treatment of generalized, partial or other epilepsy and in treatment of mania where other therapy has proved inadequate or is inappropriate.

DOSAGE AND ADMINISTRATION:

Daily dosage requirements vary according to age and body weight.

Adult: Dosage should start at 600mg daily increasing by 200mg at three-day intervals until control is achieved in epilepsy. This is generally within the dosage range 1000mg to 2000mg per day.

For children: Weight over 20kg, initial dosage should be 20-30mg/kg/day while for children under 20kg, 20mg/kg/day is recommended.

 WARNINGS AND PRECAUTIONS:

Hepatotoxicity: Monitor LFTs (high risk in children <2 years).

Teratogenicity: Neural tube defects, neurodevelopmental disorders.

Pancreatitis: Discontinue if severe abdominal pain/vomiting occurs.

Hyperammonemia: Monitor ammonia levels (especially with topiramate).

Hematologic: Thrombocytopenia, bleeding risk (monitor platelets).

DRESS syndrome: Discontinue if multiorgan hypersensitivity occurs.

ADVERSE REACTIONS:

Common (≥5%): Abdominal pain, alopecia, amblyopia/blurred vision, amnesia, anorexia, asthenia, ataxia, bronchitis, constipation, depression, diarrhea, diplopia, dizziness, dyspepsia, dyspnea, ecchymosis, emotional lability, fever, flu syndrome, headache, infection, insomnia, nausea, nervousness, nystagmus, peripheral edema, pharyngitis, rhinitis, somnolence, thinking abnormal, thrombocytopenia, tinnitus, tremor, vomiting, weight gain, weight loss

Serious (<0.05%): Chest pain, euphoria, hypesthesia

USE IN SPECIFIC POPULATIONS:

Pregnancy: Valproate sodium can cause congenital malformations including neural tube defects, decreased IQ, and neurodevelopmental disorders.

Pediatric: Children under the age of two years are at considerably higher risk of fatal hepatotoxicity.

Geriatric: Reduce starting dose, increase dosage more slowly; monitor fluid and nutritional intake.

 OVERDOSAGE:

Overdosage with valproate may result in somnolence, heart block, deep coma, and hypernatremia. Fatalities have been reported; however patients have recovered from valproate serum concentrations as high as 2120 mcg/mL. Naloxone has been reported to reverse the CNS depressant effects of valproate overdosage.

PRESENTATION: Carton containing 1 bottle of 200 ml.