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Fosphenytoin and Phenytoin - Adult/Pediatric - Inpatient Clinical Practice Guideline
Fosphenytoin and Phenytoin - Adult/Pediatric - Inpatient Clinical Practice Guideline
Fosphenytoin and Phenytoin - Adult/Pediatric - Inpatient Clinical Practice Guideline
– Adult/Pediatric – Inpatient
Clinical Practice Guideline
Table of Contents
SCOPE ...................................................................................................................................... 4
METHODOLOGY ...................................................................................................................... 4
DEFINITIONS: ........................................................................................................................... 5
INTRODUCTION ....................................................................................................................... 5
RECOMMENDATIONS .............................................................................................................. 6
UW HEALTH IMPLEMENTATION............................................................................................14
INTERNAL REFERENCES.......................................................................................................14
EXTERNAL REFERENCES .....................................................................................................14
Review Individuals/Bodies:
MUE Subcommittee – May 2015
P&T Committee
Committee Approvals/Dates:
P&T Committee/March 2002
P&T Committee/December 2007
P&T Committee/May 2012
Intended Users:
This guideline is intended to be used by physicians, pharmacists, and nurses.
CPG objective:
The objective of this guideline is to improve the use of phenytoin and fosphenytoin
through improved dosing, administration, and monitoring to improve patient safety,
tolerance and efficacy.
Target Population:
All adult and pediatric inpatients requiring treatment of new onset or previously
controlled seizures, including status epilepticus
Guideline Metrics:
Adequate control or prevention of seizures. Maintenance of therapeutic drug levels.
Methodology
Methods Used to Collect/Select the Evidence:
A review of PubMed database, International Pharmaceutical Abstracts database, and
Google Scholar was conducted with the keywords: fosphenytoin, phenytoin,
administration, monitoring, seizure, and antiepileptic. Also, expert opinions were
consulted throughout UWHC during the construction of the CPG.
Definitions:
1. Fosphenytoin is dosed in phenytoin equivalents (PE) 1 PE fosphenytoin = 1 mg
phenytoin sodium = 1.5 mg fosphenytoin sodium
2. Total body weight (TBW) is defined as the actual total mass of the patient in
kilograms
Introduction
Fosphenytoin is a water soluble prodrug of phenytoin which is rapidly converted to
phenytoin after intravenous (IV) or intramuscular (IM) administration. Fosphenytoin
does not require propylene glycol or alcohol as organic solvents to keep it in solution;
therefore, it is less irritating to tissues and presents a lesser risk of causing hypotension.
Pediatrics:
Loading dose: 18 to 20 mg PE/kg IV
Maintenance dose: 2 to 3 mg PE/kg IV dosed two times daily (4 to 6 mg
PE/kg/day), though significantly higher dosing may be needed based upon
levels.
Route IV or IM administered in 1 to 4 injection sites (maximum volume for IM
injection is 3 mL)
Rate To decrease the risk of adverse reactions such as paresthesias, pruritus,
and hypotension.
Adults:
For indications other than status epilepticus, fosphenytoin should be
administered at a rate less than 150 mg PE/min; (25 to 100 mg PE/min is
suggested).
Pediatrics:
Administer at a rate of 1 to 3 mg PE/kg/min with a maximum of 50 mg
PE/min.
Monitoring Continuous cardiac monitoring (rate, rhythm, and blood pressure) and
(for doses >300 mg observation throughout the period when maximum blood phenytoin
PE) concentrations occur (approximately 10 to 20 minutes after the end of
fosphenytoin infusions)
Dosing weight (kg) = ideal body weight (IBW) + [1.33 x (measured weight – IBW)]
2.2. Adults
2.2.1. Loading dose: 18 to 20 mg/kg x one dose IV; administer at a rate not to
exceed 50 mg/min in adults. If seizures continue after the loading dose,
then an additional 10 mg/kg IV may be given in divided doses of 5 mg/kg
IV. 2 (Class I Level A)
2.2.2. The loading dose for obese patients may be calculated using an adjusted
body weight based on the following formula:
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Dosing weight (kg) = ideal body weight (IBW) + [1.33 x (measured weight – IBW)]
Partial loading dose mg = (desired concentration – actual concentration) x 0.7 L/kg (Vd) x
TBW in kg.
(Vd = volume of distribution; TBW = total body weight)
3.2.3. The bioavailability of enteral phenytoin (liquid, chewable tablets, and
extended-release capsules) is approximately 90%. When given orally,
divide the total dose as calculated and give no more than 6 mg/kg (or 400
mg) per dose every 2 to 4 hours. Use of chewable tablets or suspension
may maximize the amount of drug absorbed, provide more rapid increase
in blood concentrations, and minimize gastrointestinal side effects. (Class
IIa, Level C)
3.2.4. Give the loading dose in addition to the patient’s maintenance dose(s) for
that day. (Class IIA Level C)
3.3. Administration of phenytoin suspension and tube feedings (Class I, Level C)
3.3.1. Turn off tube feedings one hour prior to administration of phenytoin
suspension.
3.3.2. Before administration, shake the suspension well.
3.3.3. Draw the drug up in an appropriate syringe (catheter-tipped) for the tube
and administer via tube.
3.3.4. Draw up approximately 30 to 60 mL of water in the syringe and flush the
tube.
3.3.5. Turn tube feedings on one hour after the administration of the phenytoin
suspension after checking tube placement.
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Fosphenytoin: 18 to 24 hr post-load; however, Divide the total dose and give no more than 6
if given IV may draw 2 hr post-load, if IM may mg/kg (or 400 mg) per dose every 2 to 4 hours
draw 4 hr post-load. Draw trough (non-steady as chewable tablets or suspension.
state) in 3 to 5 days and steady state at day If patient has had recent phenytoin therapy,
10 to 14. If phenytoin given orally, may draw obtain baseline phenytoin concentration. Dose
trough in 18 to 24 hours. on total body weight (TBW) in kilograms.
The therapeutic concentration is 10 to 20
mcg/mL for bound/total phenytoin and 1 to 2 Partial IV Load: give in addition to daily
mcg/mL for unbound phenytoin. In patients dose(s)
with renal impairment (CrCl < 10 mL/min), use (Cdesired* - Cobserved)X Vd= mg/kg/dose**
the HPLC unbound method for phenytoin
concentrations. (Class I, Level A) *Recommend using 20 for desired level as
formula tends to under predict.
Unbound phenytoin concentration: Draw
unbound concentration if: CrCl <10 mL/min*, Vd=volume of distribution=0.7 L/kg (TBW)
albumin <3.2 gm/dL, using valproic acid or TBW= total body weight
high dose aspirin, neonate, pregnant, end
stage liver disease, burn patient or **If given orally, increase dose by 10%.
unexplained toxicity.
Usual maintenance dose = 2 to 3 mg PE/kg/dose
If albumin <3.2 gm/dL and only total two times daily (4 to 6 mg PE/kg/day)
concentration is available, may ESTIMATE:
In geriatric patients consider 1.5 to 2
Ccorrected = Cobserved________ mg/PE/kg/dose tow times daily(3 to 4 mg
(0.25 X albumin PE/kg/day)
concentration)+0.1
Start maintenance dose 18 to 24 hours post
In patients treated with phenytoin and valproic load, or at next dosing interval
acid (VPA) then ESTIMATE:
Cunbound phenytoin = Cphenytoin [0.095 + To increase phenytoin maintenance dose
0.001(Cvalproic acid)] (steady state concentration):
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UW Health Implementation
Potential Benefits/Harms:
The dosing, administration, and monitoring instructions for fosphenytoin and phenytoin
are complex. Implementation of this clinical practice guideline will provide a consistent
approach to ensuring the safe and efficacious use of these agents.
Implementation Tools/Plan
This clinical practice guideline will be posted on UConnect and associated with
medication order records for fosphenytoin and phenytoin.
Disclaimer
CPGs are described to assist clinicians by providing a framework for the evaluation and
treatment of patients. This Clinical Practice Guideline outlines the preferred approach
for most patients. It is not intended to replace a clinician’s judgment or to establish a
protocol for all patients. It is understood that some patients will not fit the clinical
condition contemplated by a guideline and that a guideline will rarely establish the only
appropriate approach to a problem.
Internal References
UW Health Guidelines for the Dosing of Medications in Patients Receiving Continuous Enteral
Feedings
UW Health Guidelines for the Intravenous Administration of Formulary Drugs in Adults
UW Health Guidelines for the Intravenous Administration of Formulary Drugs in Pediatrics
UW Health Drug Concentration Monitoring Protocol
UW Health Guideline for Non-chemotherapeutic Agents: Prevention and Treatment of Chemical
Phlebitis and Extravasation of Peripherally Administered Non-chemotherapeutic Agents
External References
1. Tricoci P, Allen J, Kramer J, Califf R, Smith S. Scientific evidence underlying
the ACC/AHA Clinical Practice Guidelines. JAMA. 2009;301(8):831-841.
2. Meek PD, Davis SN, Collins DM, et al. Guidelines for nonemergency use of
parenteral phenytoin products: proceedings of. Arch Intern Med. Dec 13-27
1999;159(22):2639-2644.
3. Treiman DM, Meyers PD, Walton NY, et al. A comparison of four treatments
for generalized convulsive status epilepticus. N Engl J Med. Sep 17
1998;339(12):792-798.
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