Generic Name

Valproate Sodium

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Classification

FDA Approved Indications

• Prevention and treatment of seizures (including generalized seizures, complex partial seizures, absence seizures)
• Manic episodes associated with bipolar disorder

Mechanism of Action

Valproate increases brain gamma-aminobutyric acid (GABA) levels by inhibiting GABA transaminase and succinate semialdehyde dehydrogenase, leading to enhanced inhibitory neurotransmission.

Dosage and Administration

Adult: Doses vary; initial doses around 600 mg/day divided in multiple doses, titrated up based on response and tolerability.

Pediatric: Dose depends on weight and age; typically starting at 10-15 mg/kg/day, adjusted as needed.

Geriatric: Careful dose titration due to increased risk of side effects.

Renal Impairment: Use with caution; monitor plasma levels, dose adjustments may be necessary.

Hepatic Impairment: Contraindicated in hepatic disease; use caution and monitor liver function during therapy.

Pharmacokinetics

Absorption: Rapid and complete when given orally.

Distribution: Widely distributed; crosses blood-brain barrier.

Metabolism: Metabolized in the liver via glucuronidation and beta-oxidation.

Excretion: Excreted primarily in urine as metabolites.

Half Life: Approximately 9-16 hours in adults; may be longer in children.

Contraindications

• History of hypersensitivity to valproate or other valproic acid derivatives.
• Hepatic disease.

Precautions

• Monitor liver function regularly, especially during the first 6 months of therapy.
• Use with caution in patients with mitochondrial disorders, bleeding disorders, or on other hepatotoxic drugs.
• Pregnancy category D; risk of neural tube defects and developmental issues.

Adverse Reactions - Common

• Gastrointestinal disturbances (nausea, vomiting) (Common)
• Drowsiness, dizziness (Common)
• Weight gain (Common)
• Tremor (Common)

Adverse Reactions - Serious

• Hepatotoxicity (liver failure) (Rare but serious)
• Pancreatitis (Rare)
• Thrombocytopenia, leukopenia, anemia (Rare)
• Neural tube defects in pregnancy (Serious risk; contraindicated in pregnancy unless benefits outweigh risks.)

Drug-Drug Interactions

• Carbapenem antibiotics (may decrease valproate levels)
• Other CNS depressants (potential additive sedation)
• Enzyme-inducing agents (may decrease valproate levels)

Drug-Food Interactions

• None significant

Drug-Herb Interactions

• None well documented

Nursing Implications

Patient/Family Teaching

• Take medication exactly as prescribed.
• Report signs of liver problems (jaundice, abdominal pain), rash, bleeding, or mental status changes.
• Avoid alcohol and CNS depressants.
• Use contraception; do not use during pregnancy unless clearly indicated.

Special Considerations

Black Box Warnings:

• Hepatotoxicity, fatal liver failure
• Teratogenicity, including neural tube defects

Genetic Factors: Patients with mitochondrial disorders may have increased risk.

Lab Test Interference: May interfere with certain lab tests, including ammonia levels.

Overdose Management

Signs/Symptoms: Nausea, vomiting, blurred vision, ataxia, coma, hypotension, respiratory depression.

Treatment: Supportive care, activated charcoal if ingestion is recent, hemodialysis in severe cases, monitor vital signs and organ functions.

Storage and Handling

Storage: Store at room temperature, away from moisture and light.

Stability: Stable under recommended conditions for shelf life specified by manufacturer.