Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Pro-Epanutin (Pfizer)
10 mL vials containing 75 mg/mL
Approved indication: epilepsy
Australian Medicines Handbook Section 16.1.3

Phenytoin sometimes has to be given parenterally, for example to stop status epilepticus. Intramuscular injections are not recommended because of local adverse reactions and unpredictable absorption. The injection is not very soluble and can be precipitated if given with other intravenous infusions. Injectable phenytoin is pH 12 so the intravenous line must be flushed with saline to reduce local venous irritation. Fosphenytoin has been developed to try and reduce these practical problems.

Fosphenytoin is a prodrug. It is converted rapidly (half-life15 minutes) to phenytoin. Fosphenytoin is less alkaline than phenytoin and can be given by intramuscular injection. This route is not recommended in status epilepticus as peak plasma concentrations are not reached for 30 minutes.

The pharmacokinetics are complex. Fosphenytoin is highly bound to plasma proteins. It displaces phenytoin from binding sites, increasing the unbound fraction of phenytoin. To reduce confusion about the dose of fosphenytoin it is expressed as phenytoin equivalents. (A fosphenytoin concentration of75 mg/mL is equivalent to 50 mg/mL of phenytoin sodium.)

When the prodrug is converted to phenytoin, formaldehyde and phosphate are also produced. These compounds are not thought to cause adverse reactions, but the phosphate load needs to be considered in patients with renal impairment. Renal and hepatic dysfunction can also result in changes to protein binding. Many drugs can alter phenytoin concentrations, but none are known to affect the conversion of fosphenytoin.

Adverse reactions include hypotension and central nervous system depression. Some patients will complain of itching or paraesthesia. The safety(and effectiveness) of fosphenytoin has not been assessed for longer than five days.

In Australia fosphenytoin has been approved for use in generalised convulsive status epilepticus and the prevention and treatment of seizures occurring in connection with neurosurgery and/or head trauma.