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
- As per nurse, patient has not had a seizure during hospital stay.
- All doses given appropriately and on time.
- Phenytoin trough concentration drawn appropriately (12 hours post-dose)
- 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)
- Using IBW (as patient is obese), maintenance dose should be 365-512 mg/day
- 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
- As divalproex dose is being increased to pre-admission dose, total phenytoin levels may not accurately indicate that patient is on a therapeutic dose.
- Continue current phenytoin dose, and monitor patient closely for seizures
- Monitor phenytoin concentrations weekly. Level next week will reflect a concentrations closer to steady state.
- Consider doing free phenytoin levels to assess efficacy and safety, if levels continue to remain subtherapeutic.
- Monitor AEs of phenytoin: ataxia, confusion, dizziness, somnolence, headache, slurred speech, N/V, nystagmus