Handbook of clinical drug data.pdf - Me and My Life

422 CENTRAL NERVOUS SYSTEM DRUGSPE/kg in 1 or more injection sites. IV or IM maintenance dosage 4–6 mgPE/kg/day in 1 or 2 divided doses. Safety and effectiveness have not been establishedfor therapy lasting more than 5 days. IV or IM substitution for oralphenytoin therapy use same total daily dosage in PEs.Special Populations. Pediatric Dosage. Safety and efficacy not established.Geriatric Dosage. Advanced age has no effect on fosphenytoin pharmacokinetics,but phenytoin clearance and protein binding might be reduced. (See Phenytoin.)Other Conditions. In patients with renal or hepatic disease, fosphenytoin conversionto phenytoin might be increased because of protein binding changes. 25 Becauseof an increased fraction of unbound phenytoin in patients with renal or hepaticdiseases or hypoalbuminemia, dosage adjustments should be guided bypatient status and measurement of unbound phenytoin concentrations.Dosage Forms. Inj 50 mg PE/mL.Patient Instructions. Itching or tingling can occur during intravenous infusion,particularly in the facial and groin areas. These sensations are usually mild anddisappear within minutes of stopping the infusion. These symptoms do not indicatean allergic reaction to fosphenytoin or phenytoin.Pharmacokinetics. Onset and Duration. Therapeutic concentrations of unboundphenytoin (≥1 g/mL) are attained within 8–10 min after the start of an IV infusionof fosphenytoin (administered at a rate of 100–150 mg PE/min) and are similarto those attained after an equivalent dose of phenytoin administered at 50mg/min. Therapeutic concentrations of unbound phenytoin are attained within 30min after IM injection of fosphenytoin.Serum Levels. Monitoring fosphenytoin serum concentration is not clinically useful.Phenytoin serum concentrations correlate with efficacy and toxicity. (SeePhenytoin.)Fate. Fosphenytoin is completely converted to phenytoin by phosphatases. Peakfreephenytoin concentrations occur 30 min after completion of fosphenytoin infusionadministered at rates of 100–150 mg PE/min and occur 3 hr after an IM doseof fosphenytoin. (See Onset and Duration.) Fosphenytoin is 95–99% bound toplasma proteins, primarily albumin. Fosphenytoin binding is saturable and the V dof fosphenytoin is 4.3–10.8 L depending on plasma concentration. Fosphenytoindisplaces phenytoin from protein binding sites. The free (unbound) fraction ofphenytoin ranges from 0.30 (in the presence of fosphenytoin) to 0.12 (after completeconversion of fosphenytoin to phenytoin). 26,27 (See Phenytoin.)t ¹⁄₂. (Conversion to phenytoin) 15 min.Adverse Reactions. Fosphenytoin commonly causes burning, itching, or paresthesiasduring IV infusion, particularly in the groin and facial areas. These symptomsusually disappear within minutes and can be minimized by slowing or stoppingthe infusion. The frequency and severity of these symptoms increase withfosphenytoin dose and infusion rate and might be related to the phosphate load.Venous irritation including pain, erythema, swelling, tenderness, and cording(hardening of the vessel) occurs less often than with phenytoin. 28 IM fosphenytoin