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Questions and Answers
When is monitoring recommended?
When is monitoring recommended?
What is one of the monitoring parameters for valproic acid?
What is one of the monitoring parameters for valproic acid?
What is a potential side effect of valproic acid?
What is a potential side effect of valproic acid?
Who may be at a higher risk for valproic acid toxicity?
Who may be at a higher risk for valproic acid toxicity?
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What can be used to monitor valproic acid concentrations?
What can be used to monitor valproic acid concentrations?
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What is a potential adverse reaction of valproic acid?
What is a potential adverse reaction of valproic acid?
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When can hemodialysis/hemoperfusion be considered?
When can hemodialysis/hemoperfusion be considered?
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What is a potential treatment for valproic acid-induced coma?
What is a potential treatment for valproic acid-induced coma?
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What is a monitoring parameter for patients with symptoms of lethargy or mental status change?
What is a monitoring parameter for patients with symptoms of lethargy or mental status change?
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What is a potential side effect of valproic acid that can be monitored?
What is a potential side effect of valproic acid that can be monitored?
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Study Notes
Mechanism
- Valproic acid is used to treat generalized, partial, and absence seizures, as well as migraines and psychiatric disorders.
- It has a wider spectrum of activity than other antiepileptic drugs.
Pharmacokinetic
- Bioavailability: • Intravenous: 100% • Oral: 100% • Sustained Release Tablet: 90% • Extended Release Tablet: 80-90%
- Volume of Distribution (Vd): • Pediatric: 0.22 (+ 0.05) L/kg • Adults: 0.15 (+ 0.10) L/kg
- Therapeutic range: • Seizures: 50-100 mg/L • Psychiatric Disorder: 50-125 mg/L
Volume of Distribution (Vd)
- Valproic acid is highly bound to serum albumin (90-95%).
- Binding becomes saturated within the therapeutic range (above 50 mg/L), leading to nonlinear pharmacokinetics.
- Factors affecting unbound valproic acid fraction: • Hypoalbuminemia • Liver disease • Nephrotic syndrome • Cystic fibrosis • Trauma • Malnourishment • Elderly • Displacement by endogenous or exogenous substances
Metabolism
- Valproic acid metabolism is induced by other drugs that enhance hepatic enzyme activity.
- One metabolite, 4-hydroxy-valproic acid, may be associated with hepatotoxicity.
- Elimination: mostly through hepatic metabolism (>95%) and minimally through renal route (<5%).
- Clearance (CL) correlates better with ideal body weight than total body weight in obese patients.
- Liver dysfunction reduces valproic acid clearance.
Half-Life
- Pediatric: 6-8 hours
- Adult: 12-18 hours
Time to Peak
- Oral: 1-3 hours (before meal), 6-8 hours (after meal)
- Intravenous: at the end of 1 hour infusion
Indication and Therapeutic Range
- Generalized, partial, and absence seizures: 50-100 mg/L
- Mania, anxiety, depression, psychosis, and substance-abuse withdrawal: 50-125 mg/L
Therapeutic Dose
- Initial dose: 10-15 mg/kg/day PO
- Dose increase: 5-10 mg/kg/week to achieve optimal clinical response
- Maximum dose: 60 mg/kg/day
Special Considerations
- Valproic acid concentrations above 100 mg/L may be required in patients with partial seizures.
- IV Valproate is not recommended for post-traumatic seizure prophylaxis in patients with acute head trauma.
- Valproate should be withdrawn gradually to minimize the potential of increased seizure frequency.
Renal and Hepatic Impairment
- Renal impairment: no dosage adjustment necessary, but renal function needs to be monitored closely.
- Hepatic impairment: patients with existing liver disease should be classified according to liver dysfunction index (Child-Pugh score) before initiation of the drug.
Interaction
- Valproic acid is an enzyme inhibitor and is subject to enzyme induction.
Monitoring
- Steady state: 2-4 days
- Sampling time: 30 minutes or just before next dose
- Monitoring is recommended in certain conditions, including: • Initiation of therapy • Change in dosing regimen • Addition of other antiepileptic drugs • Change in patient's clinical course • Claims of valproic acid side effects
Monitoring Parameters
- Liver enzymes
- Full blood count with platelets
- Serum ammonia (with symptoms of lethargy, mental status change)
- Body weight
- Blood pressure
- Heart rate
Adverse Drug Reactions
- Side effects: alopecia, pancreatitis, hyperammonemic encephalopathy, hepatotoxicity, weight gain
- Patients at higher risk: young patients, especially those with hepatic failure
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Description
This quiz covers the use of Valproic Acid in treating various seizure types and psychiatric disorders, including its mechanism, benefits, and comparisons to other antiepileptic drugs.
