From the October 23,1996 Issue
Problem: As noted in a "Safety
Brief" in our last issue, there is a quirky dosing
method for Cerebyx® (fosphenytoin sodium injection), the
recently marketed Parke-Davis prodrug which is replacing Dilantin®
(phenytoin sodium injection)*. FDA and the manufacturer agreed
on labeling that calls for the prodrug to be prescribed in
terms of its phenytoin equivalent (indicated by the abbreviation
"PE" ). Since fosphenytoin sodium 75 mg is equivalent to phenytoin
sodium 50 mg, a 100 mg dose of IV phenytoin is to be ordered
as "fosphenytoin 100 mg PE," rather than conventionally as
"fosphenytoin 150 mg."
In other words, people are being asked to name one drug,
yet refer to the dose of another. As one might expect, this
non-standard dosing method has a built-in error factor. The
"PE" designation may be accidentally omitted when ordering,
transcribing or dispensing (labeling) the drug, leaving room
for ambiguity where it can't be tolerated. The potential for
adverse outcomes is great if too much or too little of this
important medication is administered to a seizure disorder
patient. Reports indicate that some prescribers are, in fact,
dosing the drug by its actual strength (e.g. 150 mg) while
others are using the suggested method (e.g. 100 mg PE). Some
underdoses and overdoses have occurred early in the experience.
Although it may not translate into actual medication errors,
the abbreviation "PE" itself may also cause confusion. For
example, it may be misread as "PO" when poorly handwritten.
In some settings "PE" means "phenylephrine" or "pseudoephedrine."
There is even a product called Robitussin-PE® which contains
pseudoephedrine. Who knows how else "PE" might be interpreted
in medical records (e.g., pulmonary embolism, pulmonary edema,
Safe Practice Recommendation: The
new product has some advantages that make it more likely to
be used in hospitals and perhaps in long term care facilities
and home care. Unlike phenytoin, fosphenytoin is completely
bioavailable by IM injection and can, therefore, be used when
no IV route has been established. It also produces fewer local
reactions when it is given IV. Since IV phenytoin is often
associated with vein irritation and tissue damage if it extravasates,
the new drug will be welcomed by some. It is also compatible
with dextrose solutions. Admixing of phenytoin with dextrose
solutions causes precipitation in IV solutions and administration
sets which increases the risk of vein damage, including upper
extremity phlebitis. With fosphenytoin, similar problems are
unlikely to occur.
The dosing problem has been recognized by the manufacturer
and FDA, and steps are sure to be taken to further increase
awareness of professionals about the need to use phenytoin
equivalent dosing when prescribing fosphenytoin. In the mean-
time, where fosphenytoin is available, unless "PE" accompanies
orders, nurses and pharmacists need to communicate with prescribers.
Otherwise it can't be known for sure whether or not the "PE"
designation was accidentally left off. Formulary decisions
about which phenytoin products will be used should be undertaken
in an orderly fashion, with the above situation in mind and
with an awareness of the need for education. Institutional
development of preprinted orders and protocols should also
be considered as a way to help reduce confusion.
We don't know whether consideration is being given by FDA
or the company for labeling changes that would encourage standard
dosing methods for fosphenytoin. For now, be on your toes,
use teamwork to create an awareness of the situation, and
consider error prevention methods. If you are clever enough
to come up with a fool-proof dosing method or special order
forms, we'd like to hear about it so we can share the information
with readers. [D, N, P, T]
*Note: Only generic forms of phenytoin injection, and oral
Dilantin® will remain after January 1997.