Lateral gaze nystagmus usually appears at 20 µg/mL, ataxia at 30 µg/mL, and dysarthria and lethargy appear when the serum concentration is over 40 µg/mL. Sodium channels are: 1) Closed 2) Open 3) Inactive (phenytoin effect) Phenytoin is believed to protect against seizures by causing voltage-dependent block of voltage gated sodium channels. Attention to these details may prevent some Fosphenytoin Sodium Injection medication errors from occurring.Prior to intravenous (IV) infusion, dilute Fosphenytoin Sodium Injection in 5% dextrose or 0.9% saline solution for injection to a concentration ranging from 1.5 to 25 mg PE/mL. Fosphenytoin Sodium Injection, USP is a clear, colorless to pale yellow, sterile solution.The chemical name of Fosphenytoin is 5,5-diphenyl-3-[(phosphonooxy)methyl]-2,4-imidazolidinedione disodium salt. For this reason, serum phenytoin concentrations may increase modestly when IM or IV Fosphenytoin Sodium Injection is substituted for oral phenytoin sodium therapy. Other signs include tremor, hyperreflexia, lethargy, slurred speech, nausea, vomiting, coma, and hypotension. Malformations (including craniofacial, cardiovascular, neural, limb, and digit abnormalities) were observed in rats, rabbits, and mice at doses as low as 100, 75, and 12.5 mg/kg, respectively.It is not known whether Fosphenytoin is secreted in human milk. 1 Advice to Patients Advise women of childbearing potential who are not planning a pregnancy to use effective contraception while using Fosphenytoin Sodium Injection, keeping in mind that there is a potential for decreased hormonal contraceptive efficacy Instruct patients to notify their physician if they become pregnant or intend to become pregnant during therapy, and to notify their physician if they are breastfeeding or intend to breastfeed during therapy Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. In a separate cohort of 16 normal volunteers (taken from 2 other studies) who were administered IV Fosphenytoin Sodium Injection at a dose of 1200 mg PE at the maximum rate of administration (150 mg PE/min), none experienced severe disturbances, but most experienced mild to moderate itching or tingling. When, in the judgment of the clinician, the need for dosage reduction, discontinuation, or substitution of alternative antiepileptic medication arises, this should be done gradually. Mean plasma unbound phenytoin concentrations following IV administration of 1200 mg PE Fosphenytoin Sodium Injection infused at 100 mg PE/min (triangles) or 150 mg PE/min (squares) and 1200 mg Dilantin infused at 50 mg/min (diamonds) to healthy subjects (N = 12). Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring in greater than 1/100 individuals; infrequent adverse events are those occurring in 1/100 to 1/1000 individuals.The following adverse reactions have been identified during post-approval use of Fosphenytoin. Fosphenytoin Sodium Injection should normally be gradually withdrawn to reduce the potential for increased seizure frequency and status epilepticus Advise patients of the early toxic signs and symptoms of potential hematologic, dermatologic, hypersensitivity, or hepatic reactions. Periodic measurement of serum phenytoin concentrations may be valuable in the management of pregnant women as a guide to appropriate adjustment of dosage A potentially life-threatening bleeding disorder related to decreased levels of vitamin K-dependent clotting factors may occur in newborns exposed to phenytoin Meta-analyses using data from published observational studies and registries have estimated an approximately 2.4-fold increased risk for any major malformation in children with prenatal phenytoin exposure compared to controls.