Trick of the Trade: Rapid Oral Phenytoin Loading in the ED
Posted Apr 16 2013 12:00am
A 57 y/o, 75 kg male presents to the ED after a witnessed seizure. He describes a history of seizure disorder and is prescribed phenytoin, but recently ran out. A level is sent and, not surprisingly, results as < 3 mcg/mL (negative). After a complete ED workup, the decision is made to 'load' him with phenytoin 1 gm and discharge him with a prescription to resume phenytoin. An IV was not placed.
Drug references say that an oral loading dose (15-20 mg/kg) of phenytoin should be administered in 3 divided doses given every 2 hours to
decrease GI adverse effects and to ensure complete oral absorption. For a 1 gm dose, that would be 400 mg, then 300 mg, then 300 mg administered every 2 hours (4 hour total administration time). Who has time for three doses spanned over 4+ hours in a busy ED?
Trick of the Trade: Give the oral phenytoin load as a single dose.
Supporting Data for Single Dose
Osborn HH, et al. Single-dose oral phenytoin loading. Ann Emerg Med 1987;16(4):407-12. PMID 3826809
A single 18 mg/kg dose of oral phenytoin capsules or suspension (mean dose, 1.3
g) was given to 44 patients with recent seizures and no detectable serum
Mean serum phenytoin levels after loading for patients
receiving capsules were 6.8 mcg/mL at 2 hours, 9.7 mcg/mL at
3-5 hours, 12.3 mcg/mL at 6-10 hours, and 15.1
mcg/mL at 16-24 hours.
Evens RP, et al. Pheyntoin toxicity and blood levels after a large oral dose. Am J Hosp Pharm 1980;37(2):232-5. PMID 7361796
A single 900 mg dose of oral phenytoin sodium was given to 6 healthy men. Total (bound and free) plasma phenytoin levels were within the therapeutic range
(10-20 mcg/mL) for two subjects and close (not less than 8.39
mcg/mL) for the remaining four.
Peak free drug levels were 1.01-1.60
Time to reach total and free peak plasma levels was 6-14 hours and 2-10 hours, respectively.
Ratanakorn D, et al. Single oral loading dose of phenytoin: a pharmacokinetic study. J Neurol Sci 1997;147(1):89-92. PMID 9094065
A single oral phenytoin dose of 18.7 mg/kg in
males and 24.8 mg/kg in females rapidly produced therapeutic
concentration (10 mcg/mL) within an average of 2 hours in males
and 2.4 hours in females with minimal side-effects.
If you're still uncomfortable giving a large single dose, there is also support for two-dose oral loading (which still cuts 2 hours off the ED stay compared to 3 doses).
Record KE, et al. Oral phenytoin loading in adults: rapid achievement of therapeutic plasma levels. Ann Neurol 1979;5(3):268-70. PMID 443759
20 patients were administered an average
dose of 19 mg/kg of phenytoin divided into 2-4 increments.
The authors found that this regimen (in which no increment of
the loading dose exceeded 600 mg) is sufficient to achieve and maintain
therapeutic plasma concentrations 18-24 hours after initiation of the loading
We frequently give 500 mg now and 500 mg more in two hours at discharge.
Oral phenytoin loading can be achieved in a single dose, obviating the need for an IV while still achieving quick administration, adequate serum levels, and minimal side effects.
Both the immediate release (suspension or chewable tablet) and extended release (phenytoin sodium ER capsule) products have been used successfully.
IV loading does achieve quicker therapeutic level (<1 hour vs. > 3 hours), so there may still be a risk of seizure for a short time after oral loading.