PHENYTOIN

PHENYTOIN
(fen'i-toy-in)
Dilantin-125, Dilantin
PHENYTOIN SODIUM EXTENDED
Dilantin Kapseals, Phentek
PHENYTOIN SODIUM PROMPT
Dilantin
Classifications: anticonvulsant; hydantoin;
Therapeutic: anticonvulsant

Pregnancy Category: D

Availability

100 mg capsule; 100 mg, 200 mg, 300 mg sustained release capsule; 50 mg chewable tablet; 125 mg/5 mL suspension; 50 mg/mL injection

Action

Anticonvulsant action elevates the seizure threshold and/or limits the spread of seizure discharge. Phenytoin is accompanied by reduced voltage, frequency, and spread of electrical discharges within the motor cortex. Has class IB antiarrhythmic properties.

Therapeutic Effect

Inhibits seizure activity. Effective in treating arrhythmias associated with QT prolongation.

Uses

To control tonic-clonic (grand mal) seizures, psychomotor and nonepileptic seizures (e.g., Reye's syndrome, after head trauma). Also used to prevent or treat seizures occurring during or after neurosurgery. Is not effective for absence seizures.

Unlabeled Uses

Antiarrhythmic agent (phenytoin IV) especially in treatment of digitalis-induced arrhythmias; treatment of trigeminal neuralgia (tic douloureux).

Contraindications

Hypersensitivity to hydantoin products; rash; seizures due to hypoglycemia; sinus bradycardia, complete or incomplete heart block; Adams-Stokes syndrome; pregnancy (category D).

Cautious Use

Impaired liver or kidney function; alcoholism; blood dyscrasias; hypotension, severe myocardial insufficiency, impending or frank heart failure; older adult, debilitated, gravely ill patients; pancreatic adenoma; diabetes mellitus, hyperglycemia; respiratory depression; acute intermittent porphyria.

Route & Dosage

Anticonvulsant
Adult: PO 15–20 mg/kg loading dose, then 300 mg/d in 1–3 divided doses, may be gradually increased by 100 mg/wk until seizures are controlled IV 10–15 mg/kg then 300 mg/d in divided doses
Child: PO/IV 15–20 mg/kg loading dose, then 5 mg/kg in 2 divided doses

Administration

Oral
  • Ensure that sustained release form is not chewed or crushed. Must be swallowed whole.
  • Do not give within 2–3 h of antacid ingestion.
  • Shake suspension vigorously before pouring to ensure uniform distribution of drug.
  • Note: Prompt release capsules and chewable tablets are not intended for once-a-day dosage since drug is too quickly bioavailable and can therefore lead to toxic serum levels.
  • Use sustained release capsules ONLY for once-a-day dosage regimens.
Intravenous
  • Note: Verify correct rate of IV injection for administration to infants or children with physician.
  • Inspect solution prior to use. May use a slightly yellowed injectable solution safely. Precipitation may be caused by refrigeration, but slow warming to room temperature restores clarity.

PREPARE: Direct: Give undiluted. Use only when clear without precipitate.  

ADMINISTER: Direct for Adult: ??Give 50 mg or fraction thereof over 1 min (25 mg/min in older adult or when used as antiarrhythmic). ??Follow with an injection of sterile saline through the same in-place catheter or needle. DO NOT use solutions containing dextrose. Direct for Child/Neonate: ??Give 1 mg/kg/min. ??Follow with an injection of sterile saline through the same in-place catheter or needle. DO NOT use solutions containing dextrose. 

INCOMPATIBILITIES Solution/additive: 5% dextrose, lactated Ringer's, fat emulsion, sodium chloride, amikacin, aminophylline, bretylium, cephalothin, cephapirin, chloramphenicol, chlordiazepoxide, clindamycin, codeine phosphate, diphenhydramine, dobutamine, hydromorphone, insulin, levorphanol, lidocaine, lincomycin, meperidine, metaraminol, metha-done, morphine, nitroglycerin, norepinephrine, penicillin G, pentobarbital, phenylephedrine, phytonadione, procaine, prochlorperazine, secobarbital, streptomycin, warfarin. Y-site: Amikacin, amphotericin B cholesteryl complex, bretylium, cimetidine, ciprofloxacin, clarithromycin, clindamycin, diltiazem, dobutamine, enalaprilat, fenoldopam, gatifloxacin, heparin, hydromorphone, lidocaine, linezolid, methadone, morphine, ondansetron, potassium chloride, propofol, sufentanil, tacrolimus, theophylline, TPN, vitamin B complex with C.

  • Observe injection site frequently during administration to prevent infiltration. Local soft tissue irritation may be serious, leading to erosion of tissues.

Adverse Effects (≥1%)

CNS: Usually dose-related: Nystagmus, drowsiness, ataxia, dizziness, mental confusion, tremors, insomnia, headache, seizures. CV: Bradycardia, hypotension, cardiovascular collapse, ventricular fibrillation, phlebitis. Special Senses: Photophobia, conjunctivitis, diplopia, blurred vision. GI: Gingival hyperplasia, nausea, vomiting, constipation, epigastric pain, dysphagia, loss of taste, weight loss, hepatitis, liver necrosis. Hematologic: Thrombocytopenia, leukopenia, leukocytosis, agranulocytosis, pancytopenia, eosinophilia; megaloblastic, hemolytic, or aplastic anemias. Metabolic: Fever, hyperglycemia, glycosuria, weight gain, edema, transient increase in serum thyrotropic (TSH) level, osteomalacia or rickets associated with hypocalcemia and elevated alkaline phosphatase activity. Skin: Alopecia, hirsutism (especially in young female); rash: scarlatiniform, maculopapular, urticaria, morbilliform; bullous, exfoliative, or purpuric dermatitis; Stevens-Johnson syndrome, toxic epidermal necrolysis, keratosis, neonatal hemorrhage. Urogenital: Acute renal failure, Peyronie's disease. Respiratory: Acute pneumonitis, pulmonary fibrosis. Body as a Whole: Periarteritis nodosum, acute systemic lupus erythematosus, craniofacial abnormalities (with enlargement of lips); lymphadenopathy.

Diagnostic Test Interference

Phenytoin (hydantoins) may produce lower than normal values for dexamethasone or metyrapone tests; may increase serum levels of glucose, BSP, and alkaline phosphatase and may decrease PBI and urinary steroid levels.

Interactions

Drug: Alcohol decreases phenytoin effects; other anticonvulsants may increase or decrease phenytoin levels; phenytoin may decrease absorption and increase metabolism of oral anticoagulants; phenytoin increases metabolism of corticosteroids, oral contraceptives, and nisoldipine, decreasing their effectiveness; amiodarone, chloramphenicol, omeprazole, and ticlopidine increase phenytoin levels; antituberculosis agents decrease phenytoin levels. Food: Folic acid, calcium, and vitamin D absorption may be decreased by phenytoin; phenytoin absorption may be decreased by enteral nutrition supplements. Herbal: Ginkgo may decrease anticonvulsant effectiveness.

Pharmacokinetics

Absorption: Completely from GI tract. Peak: 1.5–3 h prompt release; 4–12 h sustained release. Distribution: 95% protein bound; crosses placenta; small amount in breast milk. Metabolism: Oxidized in liver to inactive metabolites. Elimination: By kidneys. Half-Life: 22 h.

Nursing Implications

Assessment & Drug Effects

  • Monitor infusion site closely as extravasation may cause tissue necrosis.
  • Continuously monitor vital signs and symptoms during IV infusion and for an hour afterward. Watch for respiratory depression. Constant observation and a cardiac monitor are necessary with older adults or patients with cardiac disease. Margin between toxic and therapeutic IV doses is relatively small.
  • Be aware of therapeutic serum concentration: 10–20 mcg/mL; toxic level: 30–50 mcg/mL; lethal level: 100 mcg/mL. Steady-state therapeutic levels are not achieved for at least 7–10 d.
  • Lab tests: Periodic serum phenytoin concentration; CBC with differential, platelet count, and Hct and Hgb; serum glucose, serum calcium, and serum magnesium; and liver funtion tests.
  • Observe patient closely for neurologic adverse effects following IV administration. Have on hand oxygen, atropine, vasopressor, assisted ventilation, seizure precaution equipment (mouth gag, nonmetal airway, suction apparatus).
  • Be aware that gingival hyperplasia appears most commonly in children and adolescents and never occurs in patients without teeth.
  • Make sure patients on prolonged therapy have adequate intake of vitamin D-containing foods and sufficient exposure to sunlight.
  • Monitor diabetics for loss of glycemic control.
  • Check periodically for decrease in serum calcium levels. Particularly susceptible: patients receiving other anticonvulsants concurrently, as well as those who are inactive, have limited exposure to sun, or whose dietary intake is inadequate.
  • Observe for symptoms of folic acid deficiency: neuropathy, mental dysfunction.
  • Be alert to symptoms of hypomagnesemia (see Appendix F); neuromuscular symptoms: tetany, positive Chvostek's and Trousseau's signs, seizures, tremors, ataxia, vertigo, nystagmus, muscular fasciculations.

Patient & Family Education

  • Be aware that drug may make urine pink or red to red-brown.
  • Report symptoms of fatigue, dry skin, deepening voice when receiving long-term therapy because phenytoin can unmask a low thyroid reserve.
  • Do not alter prescribed drug regimen. Stopping drug abruptly may precipitate seizures and status epilepticus.
  • Do not to request/accept change in drug brand when refilling prescription without consulting physician.
  • Understand the effects of alcohol: Alcohol intake may increase phenytoin serum levels, leading to phenytoin toxicity.
  • Discontinue drug immediately if a measles-like skin rash or jaundice appears and notify physician.
  • Be aware that influenza vaccine during phenytoin treatment may increase seizure activity. Understand that a change in dose may be necessary.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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