Phenytoin is an anticonvulsant which may be useful in the treatment of generalized tonic-clonic status epilepticus. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. Possibly by promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient.
This includes the reduction of posttetanic potentiation at synapses. Loss of posttetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas. Phenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of generalized tonic-clonic seizures.
Indications: Management of generalized tonic-clonic (grand mal), complex partial seizures; prevention of seizures following neurosurgery, Prevention of early (within 1 week) post-traumatic seizures (PTS) following traumatic brain injury
Phenytoin base (eg, oral suspension, chewable tablets) contains ~8% more drug than phenytoin sodium (~92 mg base is equivalent to 100 mg phenytoin sodium). Dosage adjustments and closer serum monitoring may be necessary when switching dosage forms.
Status epilepticus: I.V.
Loading dose: Manufacturer recommends 10-15 mg/kg, however, 15-20 mg/kg at a maximum rate of 50 mg/minute is generally recommended (Kalvianines, 2007; Lowenstein, 2005); initial maintenance dose: I.V. or Oral: 100 mg every 6-8 hours
Oral: Loading dose: 15-20 mg/kg; consider prior phenytoin serum concentrations and/or recent dosing history if available; administer oral loading dose in 3 divided doses given every 2-4 hours to decrease GI adverse effects and to ensure complete oral absorption; initial maintenance dose: 300 mg daily in 3 divided doses; may also administer in 1-2 divided doses using extended release formulation; adjust dosage based on individual requirements; usual maintenance dose range: 300-600 mg daily.
Common side effect:
I.V. effects: Hypotension, bradycardia, cardiac arrhythmia, cardiovascular collapse (especially with rapid I.V. use), venous irritation and pain, thrombophlebitis Effects not related to plasma phenytoin concentrations: Hypertrichosis, gingival hypertrophy, thickening of facial features, carbohydrate intolerance, folic acid deficiency, peripheral neuropathy, vitamin D deficiency, osteomalacia, systemic lupus erythematosus
Nystagmus, blurred vision, diplopia, ataxia, slurred speech, dizziness, drowsiness, lethargy, coma, rash, fever, nausea, vomiting, gum tenderness, confusion, mood changes, folic acid depletion, osteomalacia, hyperglycemia
Cardiovascular: Bradycardia, cardiac arrhythmia, cardiovascular collapse, hypotension
Gastrointestinal: Constipation, gingival hyperplasia, enlargement of lips, nausea, taste disturbance, vomiting
Genitourinary: Peyronie’s disease Hematologic: Agranulocytosis, granulocytopenia, leukopenia, pancytopenia, thrombocytopenia
Neuromuscular and skeletal: Paresthesia, peripheral neuropathy, tremor
Ocular: Blurred vision, diplopia, nystagmus
Phenytoin is contraindicated in patients with a history of hypersensitivity to phenytoin, its inactive ingredients, or other hydantoins. Because of its effect on ventricular automaticity, phenytoin is contraindicated in sinus bradycardia, sino-atrial block, second and third degree A-V block, and patients with Adams-Stokes syndrome.
Co-administration of phenytoin is contraindicated with delavirdine due to potential for loss of virologic response and possible resistance to delavirdine or to the class of non-nucleoside reverse transcriptase inhibitors.
Usage in Pregnancy
Pregnancy Category D:
An increase in seizure frequency may occur during pregnancy because of altered phenytoin pharmacokinetics. Periodic measurement of plasma phenytoin concentrations may be valuable in the management of pregnant women as a guide to appropriate adjustment of dosage
If this drug is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be apprised of the potential harm to the fetus.
Prenatal exposure to phenytoin may increase the risks for congenital malformations and other adverse development outcomes. Increased frequencies of major malformations (such as profacial clefts and cardiac defects), minor anomalies (dysmorphic facial features, nail and digit hypoplasia), growth abnormalities (including microcephaly), and mental deficiency have been reported among children born to epileptic women who took phenytoin alone or in combination with other antiepileptic drugs during pregnancy.
There have also been several reported cases of malignancies, including neuroblastoma, in children whose mothers received phenytoin during pregnancy