EPIPROATE CR 500 500MG TABLET

Indications

• Epilepsy
• Bipolar disorder
• Migraine prophylaxis

Dosage

Children: For children, the initial dosage typically starts at 10-15 mg/kg/day, divided into two or three doses. The dose may be increased by 5-10 mg/kg/week

Adults: The usual starting dose for adults is 600 mg daily in divided doses, which can be gradually increased based on clinical response and tolerability. The maximum recommended dose is generally around 2,500 mg per day, but this can vary based on individual patient factors.

Mechanism of action

Valproate primarily enhances the levels of GABA in the brain by inhibiting its degradation and increasing its synthesis. It also modulates voltage-gated sodium channels, stabilizing the neuronal membrane and preventing excessive neuronal firing. Additionally, valproate may influence various signaling pathways, including histone deacetylase inhibition, contributing to its neuroprotective effects.

Pharmacodynamics

Valproate exhibits dose-dependent pharmacological effects, leading to increased GABAergic activity and reduced excitatory neurotransmission. This results in its anticonvulsant, mood-stabilizing, and migraine-preventive properties. The therapeutic effect is often accompanied by a predictable side effect profile, including sedation, weight gain, and potential hepatotoxicity.

Pharmacokinetics

Valproate is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1 to 4 hours after oral administration. It is extensively protein-bound, primarily to albumin. The drug undergoes hepatic metabolism, primarily through glucuronidation and beta-oxidation, producing several metabolites. The elimination half-life ranges from 9 to 16 hours. It is excreted in the urine as metabolites, and dosage adjustments may be necessary in cases of hepatic impairment.

Contra-indications

• Hypersensitivity to valproate or any of its components
• Severe liver impairment
• Urea cycle disorders
• Pregnancy in women with epilepsy unless no alternative treatment is appropriate

Adverse effects

• Nausea
• Vomiting
• Drowsiness
• Tremor
• Weight gain
• Hepatotoxicity
• Pancreatitis
• Thrombocytopenia
• Cognitive impairment
• Hair loss

Interactions

• valproate+penicillins: Severe (increases risk of adverse effects)
• valproate+pivmecillinam: Severe (increases risk of adverse effects)
• valproate+antipsychotics, second generation: Moderate (increases exposure)
• valproate+paliperidone: Moderate (increases exposure)
• valproate+calcium channel blockers: Moderate (increases exposure)
• valproate+nimodipine: Moderate (increases exposure)
• cannabidiol+valproate: Moderate (increases risk of increased alt concentrations)
• guanfacine+valproate: Moderate (increases concentration)
• valproate+propofol: Moderate (increases concentration)
• apalutamide+valproate: Unknown (decreases exposure)

Precautions

• Monitor liver function tests prior to and during treatment
• Use with caution in patients with hepatic impairment
• Assess for potential drug interactions
• Consider risk of teratogenic effects in women of childbearing age

Pregnancy

Valproate is contraindicated in pregnancy for the treatment of epilepsy unless no alternative treatment is appropriate, as it is associated with a high risk of teratogenic effects.

Breast-feeding

Valproate is excreted in breast milk. Caution is advised when administering to breastfeeding mothers, considering potential effects on the infant.

Storage

Store below 25°C. Protect from light. Keep out of reach of children.

Formulations

• Tablets
• Oral solution
• Capsules
• Sustained-release tablets