Trick of the Trade: Rapid Oral Phenytoin Loading in the ED

Trick of the Trade: Rapid Oral Phenytoin Loading in the ED

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.

Can you rapidly load him orally?

The Problem

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. [1]

    • 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. [2]

    • 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. [3]

    • 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. [4]

    • 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.
We frequently give 500 mg now and 500 mg more in two hours at discharge.

Conclusions

  1. 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.
  2. Both the immediate release (suspension or chewable tablet) and extended release (phenytoin sodium ER capsule) products have been used successfully.
  3. 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.

References

  1. Osborn HH, et al. Single-dose oral phenytoin loading. Ann Emerg Med 1987;16(4):407-12. [PMID 3826809]
  2. 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]
  3. Ratanakorn D, et al. Single oral loading dose of phenytoin: a pharmacokinetic study. J Neurol Sci 1997;147(1):89-92. [PMID 9094065]
  4. Record KE, et al. Oral phenytoin loading in adults: rapid achievement of therapeutic plasma levels. Ann Neurol 1979;5(3):268-70. [PMID 443759]

Bryan D. Hayes, PharmD, FAACT, FASHP

Bryan D. Hayes, PharmD, FAACT, FASHP

Chief Science Officer, ALiEM
Creator and Lead Editor, Capsules series, ALiEMU
Attending Pharmacist, EM and Toxicology, MGH
Assistant Professor of EM, Harvard Medical School
  • Great post on oral PHT loading in the ED. I had a discussion with one of our ED attendings a few months ago regarding this and possibly using a mixed approach to loading PHT using both the oral and IV routes (that is, loading with 500 mg IV and 500 mg PO) to get the patient out of the ED sooner. His rationale was that there would be some PHT in the system immediately after the IV to minimize the risk of seizure breakthrough by just uing a single PO load. In addition, using half of the IV load would minimize the risk of ADRs associated with the IV. Also, administering half of the load as PO would ensure that PHT would be gradually absorbed and remain in the system for quite some time by the time the patient obtains the prescription after discharge from the ED. I thought it was somewhat reasonable, though we actually have not used this approach in any of our patients. I will definitely be providing our ED attendings with information from this post, especially since it has proven to be safe and effective and eliminates the need for IV access. Thank you!

    • Interesting hybrid approach. Thanks for sharing.

      • Seth Trueger

        Funny how much regional/institutional variation there is. 500mg IV + 500mg PO has been standard at a bunch of places I’ve worked.

        • Bryan D. Hayes

          Definitely true Seth. If an IV line is in place, some like to do the 500 IV and 500 PO to ensure adequate levels. If no line, can do the full amount PO. If you have a line already, I’m not sure what the advantages it over just giving the whole amount IV.

  • Great post. I’ll definitely be giving this a go!

  • Kit

    Has anyone found that GI symptoms limit this approach?

    • The studies show limited GI side effects and the quick therapeutic levels show that minimal vomiting must have occurred. In practice, we have not seen many GI side effects from this approach (or the 500 mg now, 500 mg in 2 hours). Thanks for your question.

  • Thanks so much for this. Now to convince the residents (and everyone else).

  • GJ

    Used to do this routinely without a problem, but only issue becomes the occasional patient who seizes before getting out the door (or shortly after discharge). Then do you keep them in the ED for 16 hours, waiting for GI absorption? After that happened a couple of times, decided that unless IV access was a problem, it was easier to just load them IV and send them on their way.