Phenytoin

Indications
 Oral
Epilepsy
Adult: Initially, 3-4 mg/kg daily as single dose or in divided doses. Alternatively, 150-300 mg daily increased gradually to 600 mg daily if necessary. Maintenance: 200-500 mg daily.
Child: Initially, 5 mg/kg daily in 2-3 divided doses. Maintenance: 4-8 mg/kg daily in divided doses. Max dose: 300 mg daily.
Intravenous
Tonic-clonic status epilepticus
Adult: Adjunctive therapy with a benzodiazepine (e.g. diazepam): 10-15 mg/kg by slow inj or intermittent infusion at a max rate of 50 mg/min. Maintenance: 100 mg IV (or orally) given every 6-8 hr.
Child: Neonates: 20 mg/kg as a loading dose, then 2.5-5 mg/kg bid; 1 mth-12 yr: 18 mg/kg as a loading dose, then 2.5-5 mg/kg bid; >12 yr: 18 mg/kg as a loading dose, then up to 100 mg 3-4 times daily.
Contraindications
 Pregnancy. IV admin in sinus bradycardia, heart block, or Stokes-Adams syndrome.
Warnings / Precautions
 Cardiovascular disease, e.g. sinus bradycardia, heart blocks; DM; hepatic impairment; hypoalbuminemia; porphyria; seizures (may increase frequency of petit mal seizures); debilitated patients; elderly. Caution in IV admin in hypotension, heart failure or MI, monitor BP and ECG during therapy. IV must be given slowly (too rapid admin may cause hypotension, CNS depression, cardiac arrhythmias and impaired heart conduction). Extravasation and intra-arterial admin must be avoided. Do not discontinue abruptly (may increase seizure frequency), unless safety concerns require a more rapid withdrawal. May impair ability to drive or operate machinery.
Adverse Reactions
 Hypersensitivity, lack of appetite, headache, dizziness, tremor, transient nervousness, insomnia, GI disturbances (e.g. nausea, vomiting, constipation), tenderness and hyperplasia of the gums, acne, hirsutism, coarsening of the facial features, rashes, osteomalacia. Phenytoin toxicity as manifested as a syndrome of cerebellar, vestibular, ocular effects, notably nystagmus, diplopia, slurred speech, and ataxia; also with mental confusion, dyskinesias, exacerbations of seizure frequency, hyperglycaemia. Solutions for inj may cause local irritation or phlebitis. Prolonged use may produce subtle effects on mental function and cognition, especially in children.
Potentially Fatal: Toxic epidermal necrolysis, Stevens-Johnson syndrome.
Overdose Reactions
 Unsteady gait, slurred speech, confusion, nausea, hypothermia, fever, hypotension, respiratory depression, coma. Treatment is symptomatic.
Drug Interactions
 Effects with other sedative drugs or ethanol may be potentiated. Enhances toxic effects of paracetamol, lithium. Increased risk of osteomalacia with acetazolamide. Decreased serum levels/effects with acyclovir, antineoplastics, benzodiazeines, ciprofloxacin, CYP2C9 inducers (e.g. carbamazepine), CYP2C19 inducers (e.g. rifampin), folic acid, vigabatrin. Increased serum concentrations with allopurinol, capecitabine, cimetidine, CYP2C9 inhibitors (e.g. fluconazole), CYP2C19 inhibitors (e.g. delavirdine), disulfiram, methylphenidate, metronidazole, omeprazole, SSRI, trazodone, trimethoprim. Increases metabolism of antiarrhythmics, anticonvulsants, antipsychotics, beta-blockers, calcium channel blockers, chloramphenicol, corticosteroids, doxycycline, oestrogens, HMG-CoA reductase inhibitors, methadone, theophylline, TCAs. Decreases levels/effects of clozapine, ciclosporin, tacrolimus, CYP2B6 substrates (e.g. bupropion, selegiline), CYP2C8 substrates (e.g. amiodarone), CYP2C9 substrates (e.g. celecoxib), CYP2C19 substrates (e.g. citalopram), CYP3A4 substrates (e.g. benzodiazepines), digoxin, itraconazole, levodopa, neuromuscular-blocking agents, thyroid hormones, topiramate. Increases levels/effect of dopamine, ticlopidine. Valproic acid may displace phenytoin from binding sites; and affect phenytoin serum concentrations. Transiently increases the hypothrombinaemia response to warfarin initially, followed by an inhibition of the response.
Potentially Fatal: Enhances the hypotensive properties of dopamine and the cardiac depressant properties of lidocaine.
See Below for More phenytoin Drug Interactions
Lab Interactions
 Thyroid function tests; dexamethasone and metyrapone tests.
Food Interactions
 Avoid or limit ethanol (interferes with metabolism of phenytoin). Serum concentrations may be altered if taken with food. May decrease calcium, folic acid, and vitamin D levels. Avoid evening primrose (seizure threshold decreased); valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
Mechanism of Actions
 Phenytoin acts as an anticonvulsant by increasing efflux or decreasing influx of sodium ions across cell membranes in the motor cortex during generation of nerve impulses; thus stabilising neuronal membranes and decreasing seizure activity. It acts as an antiarrhythmic by extending the effective refractory period and suppressing ventricular pacemaker automaticity, shortening action potential in the heart.
Absorption: Slow but almost complete from the GI tract (oral); much slower absorption (IM).
Distribution: Widely distributed. Protein-binding: 90%.
Metabolism: Extensively hepatic; converted to inactive metabolites.
Excretion: Via urine as hydroxylated metabolite; elimination half life at steady state: 22 hr.
Administration
 Should be taken with food. (When administering to patients on nasogastric or other enteral feeds, do not administer feeds 2 hr before or after a dose. Be consistent throughout therapy in relation to feed times. Do not switch dosage forms/brands w/o prior consideration.)
Storage Conditions
 Intravenous: Solution for inj: Store at room temperature of 15-30°C. Oral: Cap, tab: Store below 30°C. Protect from light and moisture; Oral suspension: Store at room temperature of 20-25°C, do not freeze, protect from light.
ATC Classification
 N03AB02 - phenytoin ; Belongs to the class of hydantoin derivatives antiepileptics.
Storage
 Intravenous: Solution for inj: Store at room temperature of 15-30°C. Oral: Cap, tab: Store below 30°C. Protect from light and moisture; Oral suspension: Store at room temperature of 20-25°C, do not freeze, protect from light.
Available As
  • Phenytoin Sodium 100 mg
  • Phenytoin 100 mg
  • Phenytoin Sodium 100 mg.
  • Phenytoin 150 mg
  • Phenytoin 200 mg
  • Phenytoin Sodium 25 mg
  • Phenytoin 250 mg
  • Phenytoin Sodium 30 mg
  • Phenytoin Sodium 300 mg
  • Phenytoin 300 mg
  • Phenytoin Sodium 50 mg
  • Phenytoin 50 mg
  • Fosphenytoin 75 mg

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