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| Intravenous Phenytoin vs
Fosphenytoin |
 | Fosphenytoin is a water-soluble prodrug of phenytoin. |
| It is rapidly converted into phenytoin in vivo by phosphatase enzymes. |
| The half-life of this conversion is 8-15 min and is independent of the plasma concentrations of either fosphenytoin or phenytoin. |
| Phenytoin has very poor water solubility. |
| To make it available for intravenous use, it must be dissolved in 40% propylene glycol and
10% ethanol at pH 12. |
| It requires slow infusion in glucose free solutions to avoid precipitation. |
| Fosphenytoin is supplied in phenytoin equivalents (PE) to obviate the need for learning new dosage schedules or calculating equivalent dosages. |
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| Characteristics |
Fosphenytoin |
Phenytoin |
| Routes of administration |
i.v. or i.m |
i.v. only |
Maximum i.v. infusion rate
|
150 mg PE/min |
50mg/min |
| Time to max serum level |
20 min |
20 min |
| IV solution compatibility |
Dextrose or saline |
Saline |
| Side effect |
Fosphenytoin |
Phenytoin |
| Local pain or burning |
1% |
37% |
| Hypotension |
2% |
13% |
| Systemic itching / burning (transient, lasting minutes, no
serious risks) |
9% |
0% |
| Purple glove syndrome (see below) |
none reported |
3 to 7% |
| 1000-mg IV loading dose |
$90.00 |
$6.72 |
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| Purple Glove Syndrome (PGS) |
| Study |
| Pharmacologic records of Mayo Foundation hospitals reviewed: 179
consecutive patients received IV phenytoin during a 3-month period. |
| 152 patients: nine (5.9%) developed PGS. |
| There is very little information regarding PGS associated with IV
phenytoin usage. |
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| Signs & symptoms |
| Progressive distal limb edema, discoloration, and pain. |
| Severe form: skin necrosis and limb ischemia |
| Distinguished from simple IV infiltration by:
 | presence of discoloration |
| progression of the clinical condition after the discontinuation of
phenytoin infusion |
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| Distinguish from IV site infections and cellulitis by
| the time course, commencing within 24 hours after IV phenytoin infusion. |
| the characteristic purple or blue discoloration, and lack of a purulent
discharge or fever. |
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| Possible mechanism |
| Believed to be a reaction of the interstitial tissues to extravasation of
the highly alkaline IV phenytoin solution. |
| Phenytoin is weakly acidic and poorly soluble at neutral pH, sodium
hydroxide is added to raise the pH of the solution. Propylene glycol and ethanol are added to enhance solubility. |
| Propylene glycol, ethanol, and sodium hydroxide are
known irritant to soft tissues. |
| Fosphenytoin is highly water soluble at a neutral pH. |
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| Possible Risk factors |
| Higher dose: greater median initial dose of phenytoin, total 24-hour
dose, and total number of doses. |
| Median age older |
| Infusion was more often given for acute seizures |
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| Outcome |
| Length of their hospital stay was longer |
| One patient required surgical therapy, and all other patients resolved
within 3 weeks with conservative management. |
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