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.
Lactation: Excreted in breast milk; not recommended
Indication
Epilepsy, Tonic-clonic status epilepticus
Contra Indication
Pregnancy. IV admin in sinus bradycardia, heart block, or Stokes-Adams syndrome.
Dose
N/A
Side Effect
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.
Pregnancy Category
Name :
Not Classified
Description
FDA has not yet classified the drug into a specified pregnancy category.
Mode of Action
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.
Interaction
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.
Pregnancy Category Note
Pregnancy
An increased incidence of major malformations (such as orofacial clefts and cardiac defects) and abnormalities characteristic of fetal hydantoin syndrome (dysmorphic skull and facial features, nail and digit hypoplasia, growth abnormalities [including microcephaly], and cognitive deficits) reported among children born to epileptic women who took phenytoin alone or in combination with other antiepileptic drugs during pregnancy
An increase in seizure frequency may occur during pregnancy; periodic measurement of plasma phenytoin concentrations may be valuable to make appropriate dosage adjustments; postpartum restoration of original dosage will probably be indicated
Consider vitamin K supplementation for 1 month before birth
Lactation
Phenytoin is secreted in human milk; developmental and health benefits of breastfeeding should be considered along with mother?s clinical need for therapy and any potential adverse effects on breastfed infant from phenytoin or from underlying maternal condition
Adult Dose
Status epilepticus
Load 10-15 mg/kg or 15-20 mg/kg at 25-50 mg/min, THEN
Maintenance: 100 mg IV q6-8hr PRN
Administer IV slowly; not to exceed 50 mg/min
Child Dose
Status Epilepticus
15-20 mg/kg IV in single or divided dose; if necessary may administer additional dose of 5-10 mg/kg 10 min after loading dose
Maintenance: 4-8 mg/kg/day IV divided twice daily
Renal Dose
N/A
Administration
IV Preparation
Load IV in 250 mL NS; monitor BP
IV/IM Administration
Administer slowly; no more than 50 mg/min in adults and no more than 1-3 mg/kg/min in pediatric patients
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