What is the regimen for a loading dose of Depakote (Valproate) 20mg/kg followed by a maintenance dose, with Zyprexa (Olanzapine) 10mg at bedtime?

Valproate Loading and Maintenance Regimen with Olanzapine

Loading Dose Regimen

Administer valproate 20 mg/kg intravenously now as a single loading dose, infused at a maximum rate of 10 mg/kg/min, followed by a maintenance dose of 20 mg/kg/day (divided into 2-3 doses), with olanzapine 10 mg orally at bedtime starting tonight. 1

Immediate Administration (Day 1)

• Loading dose: 20 mg/kg IV valproate administered now 2
• Infusion rate: Maximum 10 mg/kg/min to minimize hypotension risk 1
• Expected therapeutic level: This loading strategy should achieve serum valproate concentrations of approximately 75-93 mg/L within 48-72 hours 2, 3

Maintenance Dosing (Starting Day 2)

Valproate maintenance:

• 20 mg/kg/day divided into 2-3 doses daily 1, 3, 4
• Continue this dose for ongoing seizure control or mood stabilization
• Monitor serum levels at 48-72 hours; target therapeutic range is 50-125 mcg/mL 3, 4

Olanzapine:

• 10 mg orally at bedtime starting tonight and continuing daily 2, 5, 6
• This dose is appropriate for acute management and can be continued as maintenance 2

Critical Monitoring Parameters

Within First 72 Hours

• Vital signs: Monitor blood pressure closely during and after IV loading—hypotension can occur with rapid infusion 2
• Serum valproate level: Check at 48-72 hours post-loading to confirm therapeutic range (target >50 mcg/mL) 3, 4
• Respiratory status: Watch for sedation, especially with the olanzapine-valproate combination 2, 6

Baseline and Ongoing Monitoring

• Before initiating treatment: Obtain liver function tests, complete blood count, and pregnancy test (if applicable) 1
• During maintenance: Monitor hepatic and hematological indices every 3-6 months 1
• Common side effects to monitor: Sedation, gastrointestinal disturbances, tremor, transient liver enzyme elevations, weight gain 1, 6

Important Clinical Considerations

Drug Interaction Alert

• Valproate reduces oral olanzapine concentrations by approximately 18% through a presystemic mechanism 7
• This interaction is clinically significant only with oral olanzapine, not with long-acting injectable formulations 7
• Smokers are at particular risk for subtherapeutic olanzapine levels when combined with valproate (8.7% had levels <10 ng/mL) 7
• Consider monitoring olanzapine levels if inadequate clinical response, especially in smokers 7

Safety Profile

• This loading strategy (30 mg/kg/day × 2 days followed by 20 mg/kg/day) has been shown to be well-tolerated with 84% achieving therapeutic levels by day 3 4
• The combination of olanzapine and valproate shows similar adverse event profiles to monotherapy, with increased drowsiness, weight gain, and dizziness being most common 6
• No increased risk of extrapyramidal symptoms with combination therapy 6

Efficacy Expectations

• Rapid therapeutic effect: The loading strategy achieves therapeutic levels within 48-72 hours versus 7-10 days with standard titration 3, 4
• Combination therapy superiority: Olanzapine-valproate combination shows significantly greater improvement than either agent alone by week 3-4 of treatment 5, 6
• Early response with olanzapine: Expect more rapid symptom improvement in weeks 1-4 when olanzapine is added to valproate 5

Common Pitfalls to Avoid

• Do not infuse faster than 10 mg/kg/min—this increases hypotension risk 1
• Do not assume therapeutic levels without checking—verify serum concentration at 48-72 hours 3, 4
• Do not overlook the valproate-olanzapine interaction in smokers—these patients may need higher olanzapine doses 7
• Do not skip baseline laboratory monitoring—hepatotoxicity and hematologic abnormalities require baseline assessment 1