Fosphenytoin

Excreted Unchanged %
2
Half-Life (Normalesrd) Hours
7-24/Unchanged
Plasma Protein Binding %
90
Volume Of Distribution L/Kg
0.7
Dose For Normal Renal Function
15-20 mg PE/kg at 100-150 mg PE/min
Adjustment For Renal Failure Gfr, Ml/Min >50 [Recommended Level]
100% [B]
Adjustment For Renal Failure Gfr, Ml/Min 10-50 [Recommended Level]
100% [B]
Adjustment For Renal Failure Gfr, Ml/Min <10 [Recommended Level]
100% [B]
Supplement For Dialysis [Recommendation Level]: Ihd
IHD: None, [A]
Supplement For Dialysis [Recommendation Level]: Pd
PD: None, [B]
Supplement For Dialysis [Recommendation Level]: Crrt
CRRT: 100%, [B]
References
Borg&#229; O, Hoppel C, Odar-Cederl&#246; f I, Garle M. Plasma levels and renal excretion of phenytoin and its metabolites in patients with renal failure. Clin Pharmacol Ther. 1979; 26: 306-14. [PMID: 466924] / Frenchie D, Bastani B. Significant removal of phenytoin during high flux dialysis with cellulose triacetate dialyzer [Letter]. Nephrol Dial Transplant. 1998; 13: 817-8. [PMID: 9550689] / Hays DP, Primack WA, Abroms IF. Phenytoin clearance by continuous ambulatory peritoneal dialysis. Drug Intell Clin Pharm. 1985; 19: 429-31. [PMID: 4006737] / Lau AH, Kronfol NO. Effect of continuous hemofiltration on phenytoin elimination. Ther Drug Monit. 1994; 16: 53-7. [PMID: 8160256] / Liponi DF, Winter ME, Tozer TN. Renal function and therapeutic concentrations of phenytoin. Neurology. 1984; 34: 395-7. [PMID: 6538287] / Martin E, Gambertoglio JG, Adler DS, Tozer TN, Roman LA, Grausz H. Removal of phenytoin by hemodialysis in uremic patients. JAMA. 1977; 238: 1750-3. [PMID: 578272] / Reeves JH, Butt WW. A comparison of solute clearance during continuous hemofiltration, hemodiafiltration, and hemodialysis using a polysulfone hemofilter. ASAIO J. 1995; 41: 100-4. [PMID: 7727810] / Tiula E, Tallgren LG, Neuvonen PJ. Serum protein binding of phenytoin, diazepam and propranolol in chronic renal diseases. Int J Clin Pharmacol Ther Toxicol. 1987; 25: 545-52. [PMID: 3429058]
Toxicity Notes
Fosphenytoin is a prodrug of phenytoin (q.v.) and is completely converted to phenytoin with a half-life of 15 minutes. The dose, concentration in dosing solutions, and infusion rate of IV fosphenytoin is expressed as phenytoin sodium equivalents (PE). Fosphenytoin sodium 750 mg is equivalent to 500 mg of phenytoin sodium. Pharmacokinetic data are for phenytoin. Dosage should be individualized. Measure free levels. Seven to ten days may be required to achieve steady-state blood levels. Protein binding decreased and distribution volume increased in renal failure.