Fosphenytoin

What it is used for

Fosphenytoin sodium injection is indicated for the treatment of generalized tonic-clonic status epilepticus and prevention and treatment of seizures occurring during neurosurgery. Fosphenytoin sodium injection can also be substituted, short-term, for oral phenytoin. Fosphenytoin sodium injection should be used only when oral phenytoin administration is not possible.

Side effects, and when to stop

The following serious adverse reactions are described elsewhere in the labeling:

• Cardiovascular Risk Associated with Rapid Infusion
• Withdrawal Precipitated Seizure, Status Epilepticus
• Serious Dermatologic Reactions
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity
• Hypersensitivity
• Angioedema
• Hepatic Injury
• Hematopoietic Complications
• Sensory Disturbances
• Local Toxicity (Including Purple Glove Syndrome)
• Exacerbation of Porphyria
• Teratogenicity and Other Harm to the Newborn
• Hyperglycemia

Who should not take it

Fosphenytoin sodium injection is contraindicated in patients with:

• A history of hypersensitivity to fosphenytoin sodium injection or its inactive ingredients, or to phenytoin or other hydantoins. Reactions have included angioedema.
• Sinus bradycardia, sino-atrial block, second and third degree A-V block, or Adams-Stokes syndrome because of the effect of parenteral phenytoin or fosphenytoin sodium injection on ventricular automaticity.
• A history of prior acute hepatotoxicity attributable to fosphenytoin sodium injection or phenytoin.
• Coadministration with delavirdine because of the potential for loss of virologic response and possible resistance to delavirdine or to the class of non-nucleoside reverse transcriptase inhibitors.

Other medicines and interactions

Fosphenytoin is extensively bound to human plasma proteins. Drugs highly bound to albumin could increase the unbound fraction of fosphenytoin. Although, it is unknown whether this could result in clinically significant effects, caution is advised when administering fosphenytoin sodium injection with other drugs that significantly bind to serum albumin. The most significant drug interactions following administration of fosphenytoin sodium injection are expected to occur with drugs that interact with phenytoin. Phenytoin is extensively bound to serum plasma proteins and is prone to competitive displacement. Phenytoin is primarily metabolized by the hepatic cytochrome P450 enzyme CYP2C9 and to a lesser extent by CYP2C19 and is particularly susceptible to inhibitory drug interactions because it is subject to saturable metabolism. Inhibition of metabolism may produce significant increases in circulating phenytoin concentrations and enhance the risk of drug toxicity. Monitoring of phenytoin serum levels is recommended when a drug interaction is suspected.

Phenytoin or fosphenytoin sodium injection is a potent inducer of hepatic drug-metabolizing enzymes.

Storing it

Store under refrigeration at 2°C to 8°C (36°F to 46°F). The product should not be stored at room temperature for more than 48 hours. Vials that develop particulate matter should not be used.

Injection vials are single-dose only. After opening, any unused product should be discarded.