Dilantin (Phenytoin) Loading: IV vs. 4 hour oral load, or is there another way?

You have a breakthrough seizure patient on Dilantin whose level came back undetectable (or really low), and you plan to load them and then discharge them.  Reference guidelines for oral phenytoin loading recommend about 1g in 3 divided doses spaced by 2hrs each.  This is usually done with 400mg, waiting 2hrs, 300mg, waiting 2hrs, then a final 300mg, resulting in a total of 1g after 4 hours.  Alternatively, some people will load phenytoin IV while the patient is on a cardiac monitor for 20 minutes (a GIGANTIC waste if the patient can tolerate PO meds).  So, why can’t we give patients 1g orally all at once?  The short answer is that we CAN give 1g oral load all at once.  ALIEM has a nice summary of the research behind this and the link is included below.   The long answer is that the side effects of nausea and vomiting were believed to be less and the absorption higher with the divided dosing, but research shows these effects are minimal.  Several small studies in which patients were given about 1g oral load and then serum levels tested at varying time points after the load have shown that therapeutic range (10 mcg/mL) is reached within 3-5 hours.  Furthermore, there have been only a handful with vomiting or severe nausea. So, go ahead and give them 1g orally, maybe consider a dose of antiemetic, and remember that they won’t be therapeutic for the first few hours with any type of oral loading.  Or, if that makes you nervous, try 2 doses of 500mg and/or more rapid spacing between doses.  Please note that these are small studies, and our DMC reference recommends the 4 hour load, so discuss with your attending.

ALIEM article on single oral load: https://www.aliem.com/2013/04/trick-of-trade-rapid-oral-phenytoin-loading/