Neurology 4: Phenytoin and Fosphenytoin Loading Portal
Phenytoin is a safe, effective anti-convulsive agent. However, because it is lipid soluble and poorly soluble in water, it is provided in a diluent containing propylene glycol and alcohol additives. The pH of this diluent is 12. Phenytoin also precipitates in any glucose-containing solution, such as D5W. The diluent causes the phenytoin solution to be inflammatory and painful when there is extravasation from an IV. Tissue necrosis can occur with extravasation. In its extreme form, the phenytoin extravasation may result in the formation of the purple glove syndrome. For that reason, phenytoin must not be given IM. Even without extravasation, there is often painful irritation of the veins themselves. Phenytoin may be given by the intraosseous route.
The diluent causes side effects (hypotension and occasionally, heart block and bradycardia) when phenytoin is administered too rapidly. The side effects are reversible and respond to slowing the rate of infusion. ECG monitoring of patients undergoing IV loading is advisable.
The rate of IV loading of phenytoin is 20 to 50 mg/min in adults and (PEDS:) a maximum of 1 mg/kg/min in children. Use an IV pump to deliver the phenytoin. Give through a filter. Administer the drug to geriatric patients at 20 mg/min. This regimen results in a therapeutic level in 30 minutes. The therapeutic window is large for phenytoin. Some neurologists use 25 to 30 mg/kg before switching to another anti-convulsant.
Phenytoin acts by decreasing the firing of neurons and inhibiting membrane depolarization. A great advantage is that phenytoin does not cause a depressed LOC as benzodiazepines and barbiturates do. However, phenytoin is not as lipid soluble as these agents, so it does not work as rapidly. Phenytoin is most effective for epileptic seizures but is also effective for seizures of many causes ranging from encephalopathy to trauma. Phenytoin is least effective for alcohol withdrawal seizures and for the seizures of drug ingestions such as isoniazide, cocaine, and tricyclics. Because phenytoin is so well tolerated, however, it continues to be recommended for almost all seizures.
Patients who are toxic with too much phenytoin display nystagmus and ataxia. Patients may exhibit confusion, dizziness, agitation, and involuntary movements. Sometimes these findings appear immediately after the completion of an IV loading dose but disappear within a few minutes.
Fosphenytoin is a water-soluble ester of phenytoin. When injected, fosphenytoin is converted rapidly (within a few minutes) to phenytoin by plasma phosphatases. The net effect is that, even though the fosphenytoin is injected rapidly, therapeutic levels of phenytoin are reached in about the same time. Once converted to phenytoin, fosphenytoin acts in the same way. Fosphenytoin may be given with any IV solution and is not tissue toxic. Fosphenytoin may even be given IM, but the volume of the injection usually makes this impractical. The IM route is not recommended for status seizures unless IV access is not available. The drug is measured in PE (phenytoin equivalents) so the drug dosaging is the same. Fosphenytoin is administered at a rate of 150 mg/minute IV. The calculated dose may generally be administered in 10 minutes for adults. PEDS: The same is true for infants and children.
IV Loading Doses of Phenytoin:
PEDS:
(age 5 years or
older) 15 to 20 mg/kg IV
Adults: (< 65 years) 18 to 20 mg/kg IV
Geriatric: (> 65 years) 15 mg/kg IV
IV Loading Doses of Fosphenytoin is the same as above in phenytoin equivalents (PE).
Oral Loading of Phenytoin:
Oral loading of phenytoin is not necessary in many cases, but it can be
useful in some situations such as in a patient in whom phenytoin is
prescribed but who has run out of drug and had a seizure earlier in the
day. The oral load is not only much more cost effective than an IV
load and does not require ECG monitoring, but also results in a steady
state much faster than the 5 days needed when just the maintenance dose
of phenytoin is given orally each day.
If the patient’s serum level is down to zero, the oral loading dose of phenytoin for children (> 5 years) and adults (< 65 years) is 18 to 20 mg/kg. The total dose is divided into 3 or 4 portions with each dose given 3 to 4 hours apart.
Maintenance Doses of Phenytoin:
Maintenance doses of
phenytoin should be given once a day and should be based on body weight
and age for adults and children. For children and adults < 65
years, start with 5 mg/kg. For adults > 65 years, start with 3 mg/kg.
Adjust doses from this amount based on serum levels and
clinical
response.
Checking Phenytoin Levels:
Checking phenytoin levels after an IV load is usually not necessary unless the patient
continues to seize. Pharmacokinetic research has established that a
full load of phenytoin (18 to 20 mg/kg) yields a therapeutic level (1
to 2 @g/mL of free phenytoin or 10 to 20 μg/mL of total phenytoin) 24
hours after the load.
Steady state levels are reached after 5 days of a maintenance dose. Therefore, levels should be checked 5 days after starting the maintenance dose to see if the initial dose (eg, 5 mg/kg in adults) is correct.