C3.1 R4(e): Perform & document a phenytoin pharmacokinetic interpretation

Clinical Pharmacy Note RE: Phenytoin Levels

ID: 47 yo male with history of seizure disorders (?type of seizure ?unclear history)
(As per nurse, patient reports that last seizure, which was a petit mal seizure, was 2 months ago)

wt = 105.9kg, ht = 5 ft 10 inches, BMI = 33.4 kg/m2

Current regular medications:

  • Phenytoin 200mg extended release capsules PO BID (800hr, 2200hr)
    • Started on Sept 23, 2016 at HS
    • Was on same dose PTA but as per team care binder, did not take it on Sept 21/22
    • As per nurse, no issue swallowing capsules
  • Divalproex EC 250mg PO BID
    • Started on Sept 28, 2016 at HS
    • Dose ↑ on Sept 29, 2016 (today) to 250mg AM (same )and 500mg HS (↑)
  • Paliperidone 100mg IM q 4 weeks
  • Olanzapine 15mg PO HS
  • Nicotine Replacement Therapy

Phenytoin Levels (Target: 40-80 umol/L):

  • Sept 23, 2016: 5 umol/L (prior to 1st dose in hospital)
  • Sept 29, 2016: 11 umol/L at 1000hr (prior to Sept 29 AM dose)

Sept 29, 2016: Alb: 37 g/L        Sept 23, 2016:  sCr: 89umol/L,  eGFR: 92 mL/min


  1. As per nurse, patient has not had a seizure during hospital stay.
  2. All doses given appropriately and on time.
  3. Phenytoin trough concentration drawn appropriately (12 hours post-dose)
  4. Level is likely not at steady state but trending upwards (average half-life: ~22 hrs, but can range from 7 to 42 hrs due to saturation kinetics. Time to steady state can range from 3 to 50 days)
  5. Using IBW (as patient is obese), maintenance dose should be 365-512 mg/day
  6. Drug interactions with phenytoin (Lexicomp):
    – Divalproex may ↓ the protein binding of phenytoin (as both compete for binding to albumin). This may lead to an initial ↑ in free phenytoin and to a ↓ in total phenytoin concentrations. With long-term concurrent use, total phenytoin concentrations may ↑.
    – Phenytoin may ↓ the serum concentration of divalproex. There is also a potential for hepatotoxicity due to the ↑ concentration of a hepatotoxic valproic metabolite if phenytoin dose is increased.
    – Phenytoin may ↓ the concentration of paliperidone and trazodone
    – Trazodone may ↑ the concentration of phenytoin
  7. As divalproex dose is being increased to pre-admission dose, total phenytoin levels may not accurately indicate that patient is on a therapeutic dose.

P: Suggest

  1. Continue current phenytoin dose, and monitor patient closely for seizures
  2. Monitor phenytoin concentrations weekly. Level next week will reflect a concentrations closer to steady state.
  3. Consider doing free phenytoin levels to assess efficacy and safety, if levels continue to remain subtherapeutic.
  4. Monitor AEs of phenytoin: ataxia, confusion, dizziness, somnolence, headache, slurred speech, N/V, nystagmus