Fosphenytoin

Drug Information: Fosphenytoin

Fosphenytoin is a water-soluble prodrug of phenytoin, an anticonvulsant medication used to control certain types of seizures. Because it is water-soluble, fosphenytoin can be administered intravenously or intramuscularly without the risk of precipitation at the injection site, a common issue with phenytoin. Once administered, fosphenytoin is rapidly converted to phenytoin by phosphatases in the body, providing anticonvulsant effects similar to its parent drug but with improved administration properties. It is often preferred in emergency situations where rapid achievement of therapeutic phenytoin levels is desired, particularly when intravenous administration is necessary.

Category

Neurological Drugs – Anticonvulsant

Mechanism of Action

Fosphenytoin’s mechanism of action relies on its rapid conversion to phenytoin within the body. Once administered, phosphatases, enzymes abundant throughout the body, quickly hydrolyze fosphenytoin, cleaving off the phosphate groups and releasing the active drug, phenytoin. Phenytoin primarily exerts its anticonvulsant effects by modulating neuronal voltage-gated sodium channels. Specifically, it prolongs the inactive state of these channels, effectively reducing the ability of neurons to fire high-frequency action potentials. This stabilization of neuronal membranes is particularly important in controlling the spread of seizure activity. By reducing sodium influx into neurons, phenytoin decreases the excessive neuronal excitability that characterizes seizures, thereby preventing or stopping seizure propagation. The pro-drug nature of fosphenytoin allows for faster and more reliable achievement of therapeutic phenytoin levels, especially when intravenous administration is required, due to its superior solubility and reduced risk of injection site complications compared to phenytoin.

Clinical Uses

Fosphenytoin is primarily indicated for the treatment and prevention of seizures, particularly in situations where rapid intravenous or intramuscular administration is necessary. Its clinical uses include:

• Status Epilepticus: Management of generalized tonic-clonic status epilepticus, providing rapid control of prolonged seizure activity.
• Seizures during Neurosurgery: Prevention and treatment of seizures during or following neurosurgical procedures.
• Short-term Substitution for Oral Phenytoin: When oral phenytoin administration is not feasible, such as in patients who are NPO (nothing by mouth) or have difficulty swallowing.
• Treatment of Seizures: Controlling various types of seizures, including partial and generalized seizures, when rapid therapeutic levels are required.

Dosage

Dosage is expressed in phenytoin equivalents (PE).

Adults:

• Loading Dose: 15-20 mg PE/kg, administered intravenously at a rate not exceeding 150 mg PE/min.
• Maintenance Dose: 4-6 mg PE/kg/day, intravenously or intramuscularly, typically divided into one to three doses.

Pediatrics:

• Loading Dose: 15-20 mg PE/kg, administered intravenously at a rate not exceeding 3 mg PE/kg/min.
• Maintenance Dose: 4-8 mg PE/kg/day, intravenously or intramuscularly, typically divided into one to three doses.

Important Considerations:

• Monitor serum phenytoin levels to guide dosage adjustments.
• Dosage adjustments may be necessary based on individual patient response, age, hepatic function, and concurrent medications.

Indications

Common indications for Fosphenytoin include:

• Status epilepticus
• Seizure prophylaxis in neurosurgery
• Short-term replacement for oral phenytoin therapy
• Treatment of generalized tonic-clonic and partial seizures

Contraindications

Fosphenytoin is contraindicated in the following conditions:

• Hypersensitivity to phenytoin or other hydantoins
• Sinus bradycardia, sino-atrial block, 2nd and 3rd degree AV block
• Acute intermittent porphyria
• Concomitant use with delavirdine

FAQ

Q: What is Fosphenytoin used for?

A: Fosphenytoin is used to treat and prevent seizures, especially in emergency situations like status epilepticus and during or after neurosurgery.

Q: How does Fosphenytoin work?

A: Fosphenytoin is a prodrug that is converted into phenytoin in the body. Phenytoin stabilizes neuronal membranes by modulating sodium channels, reducing the excessive excitability that causes seizures.

Q: How is Fosphenytoin administered?

A: Fosphenytoin can be administered intravenously (IV) or intramuscularly (IM).

Q: What are the common side effects of Fosphenytoin?

A: Common side effects include dizziness, drowsiness, incoordination, nausea, and nystagmus. More serious side effects can include cardiac arrhythmias and severe skin reactions.

Q: Is Fosphenytoin safe during pregnancy?

A: Fosphenytoin should be used during pregnancy only if the potential benefit justifies the risk to the fetus. It can cause harm to the developing baby. Discuss the risks and benefits with your doctor.

Q: What medications should I avoid while taking Fosphenytoin?

A: Avoid taking other medications that can interact with phenytoin or fosphenytoin. Consult your doctor or pharmacist about potential drug interactions.

Q: How often should phenytoin levels be monitored when taking Fosphenytoin?

A: Phenytoin levels should be monitored regularly, especially during initial therapy and when dosage adjustments are made, to ensure the drug is within the therapeutic range.

Q: What is the difference between Fosphenytoin and Phenytoin?

A: Fosphenytoin is a prodrug of phenytoin, meaning it is converted to phenytoin in the body. Fosphenytoin is water-soluble and easier to administer intravenously than phenytoin, reducing the risk of injection site reactions.