A 57-year-old male (75 kg) 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 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.
Can you rapidly load him orally?
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
- Ann Emerg Med 1987;16(4):407-12 
- 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 phenytoin level.
- 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.
- Only 2 patients vomited after loading (one immediately and the other at 2 hours) and were partially or fully reloaded. One of these patients was in frank alcohol withdrawal and may have had other reasons for vomiting.
- Am J Hosp Pharm 1980;37(2):232-5 
- 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 mcg/mL.
- Time to reach total and free peak plasma levels was 6-14 hours and 2-10 hours, respectively.
- J Neurol Sci 1997;147(1):89-92 
- Group 1: 19 medical staff volunteers received a 15 mg/kg oral loading dose of phenytoin. Therapeutic levels (10 mcg/mL) were reached within 2.62 hours of the load.
- Group 2: 14 epileptic patients. A single oral phenytoin dose of 18.7 mg/kg in 7 males and 24.8 mg/kg in 7 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.
- No vomiting was recorded in either group.
Alternative: Two-dose oral loading
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).
- Ann Neurol 1979;5(3):268-70 
- 20 patients admitted to a neurosurgical service 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 dose.
- 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 (3 hours), so there may still be a risk of seizure for a short time after oral loading.
- Osborn HH, et al. Single-dose oral phenytoin loading. Ann Emerg Med 1987;16(4):407-12. [PMID 3826809]
- Evens RP, et al. Phenytoin toxicity and blood levels after a large oral dose. Am J Hosp Pharm 1980;37(2):232-5. [PMID 7361796]
- Ratanakorn D, et al. Single oral loading dose of phenytoin: a pharmacokinetic study. J Neurol Sci 1997;147(1):89-92. [PMID 9094065]
- Record KE, et al. Oral phenytoin loading in adults: rapid achievement of therapeutic plasma levels. Ann Neurol 1979;5(3):268-70. [PMID 443759]