What is the recommended loading dose and administration rate for phenytoin (Dilantin) in a patient with seizures?

From the Guidelines

The recommended loading dose of phenytoin (Dilantin) for seizures is 20 mg/kg divided in maximum doses of 400 mg every 2 h orally, or 18 mg/kg IV at a maximum rate of 50 mg/min. For a typical adult, this translates to approximately 1000-1500 mg total when administered intravenously. The medication should be administered in normal saline (not dextrose solutions, which can cause precipitation) through a large vein using an in-line filter 1. Some key points to consider when administering phenytoin include:

• Continuous cardiac monitoring is necessary during administration due to the risk of hypotension and cardiac arrhythmias.
• Blood pressure should be checked every 5-10 minutes during the infusion.
• Following the loading dose, maintenance therapy typically begins 12 hours later at 4-6 mg/kg/day (usually 300-400 mg/day for adults), divided into 2-3 doses.
• Phenytoin works by blocking voltage-sensitive sodium channels in neurons, which limits repetitive firing of action potentials and prevents seizure propagation.
• Therapeutic drug monitoring is important, with a target serum concentration of 10-20 mcg/mL.
• Patients should be monitored for adverse effects including cardiac complications, hypotension, and infusion site reactions 1. It's also worth noting that fosphenytoin, a pro-drug of phenytoin, can be used as an alternative with a potentially better safety profile, especially regarding local and systemic adverse effects 1.

From the FDA Drug Label

For Status Epilepticus and Non-emergent Loading Dose: Adult loading dose is 10 to 15 mg/kg at a rate not exceeding 50 mg/min. ( 2 SECT 2.2) Pediatric loading dose is 15 to 20 mg/kg at a rate not exceeding 1 to 3 mg/kg/min or 50 mg/min, whichever is slower. ( 2 SECT 2. 8)

The recommended loading dose for phenytoin (Dilantin) in a patient with seizures is:

• Adults: 10 to 15 mg/kg
• Pediatrics: 15 to 20 mg/kg The recommended administration rate is:
• Not exceeding 50 mg/min for adults
• Not exceeding 1 to 3 mg/kg/min or 50 mg/min, whichever is slower, for pediatrics 2

From the Research

Phenytoin Loading Dose

• The recommended loading dose for phenytoin is 18 mg/kg, administered as a solution of 500 mg phenytoin in 50 mL normal saline using a constant infusion pump 3.
• The initial delivery rate can be 40 mg/min, but it may need to be reduced to 20 mg/min in some cases to relieve discomfort at the IV infusion site 3.
• Therapeutic phenytoin blood levels (greater than 10 micrograms/mL) can be achieved in most patients (97%) with this loading dose 3.

Administration Rate

• The administration rate of phenytoin can be adjusted based on the patient's response and tolerance to the medication 3.
• A study compared the effectiveness of three phenytoin-loading techniques, including intravenous phenytoin at an initial infusion rate of 50 mg/min, and found that it was effective in achieving therapeutic drug concentrations quickly 4.
• Another study found that estimating weight in children for the 20 mg/kg intravenous loading dose of phenytoin can be inaccurate, resulting in up to 138% of the expected and recommended dose 5.

Safety and Efficacy

• Phenytoin has been associated with fatal haemodynamic complications and serious reactions at the injection site, including skin necrosis and amputation of extremities 6.
• Fosphenytoin, a phenytoin prodrug, has the same pharmacological properties as phenytoin but none of the injection site and cardiac rhythm complications of intravenous infusions of phenytoin 7, 6.
• The incidence of purple glove syndrome is less frequent with fosphenytoin than with phenytoin 7.
• Supra-therapeutic serum concentrations of phenytoin can occur, especially when estimating weight in children, and can be associated with adverse effects consistent with phenytoin toxicity 5.