Phenytoin (Epanutin, Epilog) is one of the most difficult drugs to dose. This is because phenytoin metabolism depends on the dose. Higher doses take longer to metabolize, so doubling the dose can more than double the serum concentration. Follow these steps...
Loading doses help get to therapeutic levels faster. Give 15 to 20 mg/kg PO or IV, about 1000 mg for most adults. An adjusted body weight should be used to calculate the loading dose of phenytoin for patients who are more than 30% over ideal body weight. The loading dose of phenytoin can be given either orally (PO) or intravenously (IV). Divide the dose if it's given orally. Lower doses are absorbed better and cause less stomach upset. For example, give 400, 300, then 300 mg, separating each dose by 2 to 3 hours. When the loading dose of phenytoin is given IV, it should be administered at a rate not exceeding 50 mg/minute, to avoid hypotension.
Maintenance doses should start at 4 to 7 mg/kg, usually 300 to 400 mg/day then adjust depending on response and serum levels. Ideal body weight is usually recommended for calculating the maintenance dose of phenytoin. Use a lower dose for the elderly or patients with liver failure. Phenytoin tablets and suspension are absorbed more rapidly than the extended-release capsules. Once-daily dosing may not be possible with these products for some patients. For special considerations for dosing phenytoin, see note 1.
-
Serum levels can be drawn after steady-state is reached. This takes about 5 to 7 days for a dose of 300 mg/day, 10 to 14 days for 400 mg/day and about 21 to 28 days for 500 mg/day. To get a trough level, recommend drawing it about 30 min before the next regularly scheduled dose is due.
Phenytoin is about 90% bound to albumin. A regular phenytoin level will measure bound and unbound phenytoin. But in some situations it's more accurate to measure only unbound or FREE phenytoin. Ask for a free phenytoin level when albumin is low or binding is affected due to liver disease, kidney failure, burns, trauma, or malnourishment. Also get a free phenytoin level for patients on other drugs that can displace phenytoin from albumin such as valproic acid (Depakine), warfarin (Marevan), and some NSAIDs. Dose adjustments should be made to aim for a total phenytoin level between 10 to 20 mcg/mL. Increase the dose by no more than 50 to 100 mg to avoid large swings in levels. This is because a dose increase will NOT give a proportionate increase in levels.
Monitoring will depend on the patient. Check another level if the patient has a seizure, the albumin level changes substantially or when starting or stopping an interacting drug. Also watch for symptoms of toxicity such as nystagmus, drowsiness, slurred speech, unsteady gait, and confusion.
REFERENCES
-
von Winckelmann SL, Spriet I, Willems L. Therapeutic drug monitoring of phenytoin in critically ill patients. Pharmacotherapy. 2008 Nov;28(11):1391-400. Available at: https://accpjournals.onlinelibrary.wiley.com/doi/abs/10.1592/phco.28.11.1391
Gold Standard, Inc. Phenytoin. Clinical Pharmacology [database online]. Available at: http://www.clinicalpharmacology.com
Patsalos PN, Berry DJ, Bourgeois BF, et al. Antiepileptic drugs-best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia 2008;49:1239-76. Available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=18397299&dopt=Abstract