What is the role of fosphenytoin in the treatment of epilepsy?

Updated: Jan 28, 2020
  • Author: Juan G Ochoa, MD; Chief Editor: Selim R Benbadis, MD  more...
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Fosphenytoin sodium is a prodrug intended for parenteral administration. Its active metabolite is PHT. It is safer and better tolerated than PHT and can be infused 3 times faster than intravenous (IV) PHT can.

When administered by IV infusion, maximum plasma fosphenytoin concentration is achieved at the end of the infusion. Fosphenytoin is completely bioavailable after intramuscular (IM) administration. Peak concentration occurs at 30 minutes after administration. The half-life is 15 minutes, and the drug is presumed to be metabolized completely by phosphatases to PHT. Fosphenytoin is not excreted in the urine.

The antiepileptic effect of fosphenytoin is attributable to its active metabolite, PHT. It is clearly better tolerated than PHT. One double-blind controlled study compared the infusion tolerance of fosphenytoin at 150 mg/min and PHT 50 mg/min. Local intolerance was reported in 9% of patients after fosphenytoin loading; 21% had infusion disrupted, and the infusion time was 13 minutes. In patients who received PHT, on the other hand, local intolerance was reported in 90%, 67% had infusion disrupted, and infusion time averaged 44 minutes.

Fosphenytoin is indicated for treatment of status epilepticus and for short-term parenteral administration when other routes are not available or inappropriate.

Cardiovascular depression and hypotension may occur with fosphenytoin but to a lesser extent than with PHT. These adverse effects usually are related to the rate of infusion. Slower infusion is recommended in susceptible patients. Severe burning, itching, and/or paresthesia, mainly in the groin area, have been associated with rapid infusion. The discomfort may be improved by lowering the infusion rate or temporary discontinuation. Hepatic or hemopoietic adverse reactions, like those seen with PHT, also may occur.

Fosphenytoin is a better IV preparation than PHT, mainly because of tolerability and safety. It also may allow faster achievement of therapeutic serum PHT levels. However, fosphenytoin is much more expensive than PHT.

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