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INTRODUCTION

  1. Pharmacology. The neuronal membrane-stabilizing actions of phenytoin through sodium channel blockade make this drug popular for sustained control of acute and chronic seizure disorders and useful for certain cardiac arrhythmias. Because of the relatively slow onset of anticonvulsant action, phenytoin usually is administered after diazepam. At serum concentrations considered therapeutic for seizure control, phenytoin acts similarly to lidocaine to reduce ventricular premature depolarization and suppress ventricular tachycardia. After intravenous administration, peak therapeutic effects are attained within 1 hour. The therapeutic serum concentration for seizure control is 10–20 mg/L. Elimination is nonlinear, with an apparent half-life averaging 22 hours. Fosphenytoin, a prodrug of phenytoin for intravenous use, is converted to phenytoin after injection, with a conversion half-life of 8–32 minutes.

  2. Indications

    1. Control of generalized tonic-clonic seizures or status epilepticus. However, benzodiazepines and phenobarbital are more effective for treating drug-induced seizures.

    2. Control of cardiac arrhythmias, particularly those associated with digitalis intoxication.

  3. Contraindications. Known hypersensitivity to phenytoin or other hydantoins.

  4. Adverse effects

    1. Rapid intravenous administration of phenytoin (>50 mg/min in adults or 1 mg/kg/min in children) may produce hypotension, AV block, and cardiovascular collapse, probably owing to the propylene glycol diluent. Fosphenytoin is readily soluble and does not contain propylene glycol, and, therefore, a hypotensive response is not expected. However, a few cases of bradycardia and asystole have been reported after very large IV doses of fosphenytoin.

    2. Extravasation of phenytoin may result in local tissue necrosis and sloughing. Phenytoin may induce the "purple glove" syndrome (edema, discoloration, and pain) after peripheral IV administration. This can occur hours after infusion, in the absence of clinical signs of extravasation, and can lead to limb ischemia and necrosis from a compartment syndrome. Elderly patients receiving large multiple doses are at risk; other risk factors include use of small IV catheters, high infusion rates, and use of the same catheter site for two or more IV push doses. Extravasation problems have not been observed with fosphenytoin.

    3. Drowsiness, ataxia, nystagmus, and nausea may occur.

    4. Use in pregnancy. FDA category D. Congenital malformations (fetal hydantoin syndrome) and hemorrhagic disease of the newborn have occurred with chronic use. However, this does not preclude acute, short-term use in a seriously symptomatic patient (Introduction).

  5. Drug or laboratory interactions

    1. The various drug interactions associated with chronic phenytoin dosing (ie, accelerated metabolism of other drugs) are not applicable to its acute emergency use.

    2. Extracorporeal removal methods (eg, hemoperfusion and repeat-dose activated charcoal) will enhance phenytoin clearance. Supplemental dosing may be required during such procedures to maintain therapeutic levels.

  6. Dosage and method of administration

    1. Parenteral

      1. Phenytoin. Administer a loading dose of 15–20 mg/kg IV slowly at a rate not to exceed 50 mg/min.

        1. Highly sensitive patients (elderly, patients with preexisting cardiovascular conditions) should receive phenytoin more slowly (20 mg/min), and children at 1 mg/kg/min.

        2. Phenytoin may be diluted in 50–150 mL of normal saline with the use of an in-line 0.22-0.5 micron filter. Further dilution to 5 mg/mL may help reduce the risk of ...

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