Depakote ER Dosing and Laboratory Monitoring
Initial Dosing
Start Depakote ER at 10-15 mg/kg/day and titrate by 5-10 mg/kg/week to achieve therapeutic serum levels of 50-100 μg/mL for seizures or 40-90 μg/mL for bipolar disorder. 1
Specific Starting Regimens by Indication
For Bipolar Disorder:
- Begin at 125 mg twice daily (250 mg/day total) 2, 3
- Increase gradually based on clinical response and serum levels 2
- Target therapeutic range: 40-90 μg/mL 2, 3
- Optimal dosing typically falls between 750-3000 mg/day for most adults 2
For Seizure Disorders:
- Start at 15 mg/kg/day 1
- Increase at weekly intervals by 5-10 mg/kg/day 1
- Target therapeutic range: 50-100 μg/mL 1
- Maximum recommended dose: 60 mg/kg/day 1
Dosing Conversion: Regular Divalproex to Depakote ER
When converting from regular divalproex to Depakote ER, increase the total daily dose by 8-20% due to lower bioavailability of the ER formulation. 4
- Convert immediately (12 hours after last regular dose) rather than using delayed or stepwise strategies 5
- The ER formulation maintains more stable plasma levels with less fluctuation 4, 6
- Once-daily dosing is appropriate for Depakote ER across all dose ranges 6
Critical caveat: Regular enteric-coated divalproex should NOT be dosed once-daily at high doses (≥2000 mg/day) due to risk of excessive peak concentrations (>125 mg/L) and potential toxicity 6
Dose Adjustments for Subtherapeutic Levels
For subtherapeutic levels, increase the dose by 250-500 mg daily. 2
- Recheck valproate levels in 3-5 days after dose adjustment 2
- Aim for mid-range therapeutic levels (65-85 μg/mL for bipolar disorder) to balance efficacy and tolerability 2
Maximum Dosing and Safety Thresholds
Optimal clinical response is ordinarily achieved at daily doses below 60 mg/kg/day; no recommendation can be made for doses above this threshold. 1
Critical Safety Thresholds:
- Thrombocytopenia risk increases significantly at trough levels >110 μg/mL in females and >135 μg/mL in males 1
- Weigh benefits of higher doses against increased adverse event risk 1
- For doses approaching or exceeding 3000 mg/day, document clearly that lower doses failed and that no dose-related side effects are present 2
Laboratory Monitoring Requirements
Baseline Labs (Before Initiation):
- Liver function tests (AST, ALT) 2, 3, 1
- Complete blood count with platelets 2, 3, 1
- Prothrombin time (PT) and partial thromboplastin time (PTT) 3, 1
- Pregnancy test in females of reproductive age 2
Ongoing Monitoring During Titration:
- Valproate serum levels: Check 3-5 days after each dose adjustment 2
- Monitor for drug interactions if on concomitant antiepileptic drugs 1
Maintenance Monitoring (Once Stable):
- Valproate serum levels: Every 3-6 months 2
- Liver function tests: Every 3-6 months 2
- Complete blood count with platelets: Every 3-6 months 2
- PT/PTT: As clinically indicated 3, 1
- Screen for polycystic ovary disease in females 2
Important monitoring caveat: Do not rely solely on periodic laboratory values; educate patients to report symptoms of hepatotoxicity (nausea, vomiting, abdominal pain, jaundice), thrombocytopenia (easy bruising, bleeding), or other adverse effects 2
Special Population Considerations
Elderly Patients:
- Start at lower doses (e.g., 125 mg twice daily) 1
- Titrate more slowly with regular monitoring for somnolence, dehydration, and decreased food/fluid intake 1
- Consider dose reduction or discontinuation if excessive somnolence or decreased intake occurs 1
Hepatic or Renal Impairment:
Women of Childbearing Potential:
- Avoid valproate if possible due to teratogenicity risk 7
- If used, prescribe as monotherapy at minimum effective dose 7
- Supplement with folic acid 7