Phenytoin

Disclaimer to the Online Edition

This Manual has been designed for use in the NICU at London Health Sciences Centre (LHSC), London, Ontario, Canada, and represents clinical practice at this institution. The information contained within the Manual may not be applicable to other centres. If users of this Manual are not familiar with a drug, it is recommended that the official monograph be consulted before it is prescribed and administered. Any user of this information is advised that the contributors, Editor and LHSC are not responsible for any errors or omissions, and / or any consequences arising from the use of the information in this Manual.

Phenytoin

Indication

  • Treatment of seizures which are unresponsive to phenobarbital
  • An antiarrhythmic agent, which has been useful in the treatment of ventricular arrhythmias, associated with digoxin toxicity

Pharmacology

  • Phenytoin acts as an anticonvulsant by limiting the development and spread of seizure activity. More effective than phenobarbital in stopping the spread of seizure activity; less active than phenobarbital in suppressing focal activity
  • Phenytoin acts as an antiarrhythmic agent by decreasing cardiac automaticity and prolonging the refractory period
  • Because phenytoin exhibits "zero order" kinetics, a small change in dose may result in an unexpectedly large increase in serum concentration
  • Bilirubin can displace phenytoin from albumin binding sites; this will create difficulty in the interpretation of serum concentrations, which are normally measured and reported as total drug (ie. free + bound)

Side Effects

  • Actute, following IV administration: hypotension, bradycardia, ventricular fibrillation, vasodilation; venous irritation; pain, thrombophlebitis, skin rash. Observe IV site carefully. Extravasation may cause tissue inflammation and necrosis.
    If extravasation does occur; Hyaluronidase may be used as follows: Dilute the 150 units/mL concentration to 15 units/mL with 0.9% NaCl. Inject the 15 units/mL dilution at 5 separate sites (0.2 mL per site) around the periphery of the extravasation
  • GI side effects: vomiting, constipation
  • Other side effects that may be seen with chronic use include toxic hepatitis, gingival hyperplasia, hyperglycemia and osteoporosis

Precautions and Nursing Implications

  • Monitor IV site closely; to avoid local tissue injury use dilute solutions of phenytoin, flush the IV catheter with 0.9% NaCl before and after phenytoin administration and try to avoid small hand, wrist or foot veins
  • Do not stop phenytoin abruptly, this may precipitate seizures (withdrawal)
  • Do not mix phenytoin with any solution containing dextrose because it will precipitate
  • Clear IV butterfly or angiocath tubing with saline 0.5 mL before and after drug administration
  • Recommended blood serum levels: 40-80 micromol/L (10-20 micrograms/mL)
  • Observe ECG tracings for cardiac arrhythmias, (eg. ventricular fibrillation) while administering phenytoin
  • Do not give IM
  • Oral absorption is poor in neonates
  • Use with caution in asphyxiated infants because of increased risk of cardiac arrest
  • Drug interaction with Phenobarbital - levels of phenytoin may increase or decrease (usually decrease); therefore monitor Phenytoin levels closely
  • Also likely to interact with other medications which are metabolized in the liver (eg. may decrease serum concentrations of theophylline)

Dose

  • A 0.22 Micron in-line filter is required due to the protentional of drug interactions
As an anticonvulsant:
  • Stat Dose: 10-20 mg/kg IV
    • A stat dose may be given in this manner: Phenytoin must be administered slowly. In neonates phenytoin should be administered at a rate not exceeding 1 to 3 mg/kg/min. The administration of the drug may be made easier by dilution (must be with saline solution e.g. NaCl 0.9 %) to 5 mg/mL. See last page for instructions.
Maintenance Dose:
  • 2 to 4 mg/kg IV q12h
  • Administered by slow IV infusion at a concentration of 5 mg/mL
  • IV solution must be saline
  • Do not give IM
Oral Maintenance Dose:
  • 2 to 4 mg/kg po q12h
  • Absorption of phenytoin is highly variable and often very poor in infants. Doses up to 15 mg/kg/day have been used; anecdotal reports show that even higher doses have been required in certain cases. If these doses are used, the increases should occur slowly and serum levels monitored very closely
  • If an infant has a feeding tube, the tube should be flushed with 0.9% NaCl before and after administration of phenytoin to minimize adsorption to the tube; to minimize poor absorption hold feedings for 2 hours before and after phenytoin administration, if possible
As an antiarrhythmic:
  • 5 to 10 mg/kg IV, for ventricular tachycardia, especially if due to digoxin toxicity
  • Note that phenytoin is rarely used in neonates for this purpose

Supplied As

  • 25 mg/mL suspension for oral use (keep at room temperature; shake well prior to each use)
  • 50 mg/mL, 2 mL ampoule for IV use
  • The IV solution may be diluted to 5 mg/mL as follows:
    • ADD 1mL OF PHENYTOIN 50 mg/mL
    • TO 9mL OF SODIUM CHLORIDE 0.9%
    • TO PRODUCE FINAL CONCENTRATION OF
    • 50 mg/10mL (5mg/mL)
    • DOSE =_______mg
    • =_______mL of 5mg/mL SOL'N
  • Note that saline solution (E.G NaCl 0.9%) must be used the dilution should be used within 1 hour after preparation
  • The IV solution may be further diluted to as low as 1mg/mL
References
  1. Cloherty JP and Stark AR (eds): Manual of Neonatal Intensive Care, Little, Brown and Company, 1991.
  2. Roberts, RJ: Drug Therapy in Infants, W.B. Saunders, Toronto, 1984.
  3. Drugs Dex, Denver, Colorado, 1992.
  4. Trissel L.A.: Handbook on Injectable Drugs, American Society of Hospital Pharmacists 1988.
  5. Krogh CME et al (ed): Compendium of Pharmaceuticals and Specialties, Canadian Pharmaceutical Association, 1992.
  6. Gomella TL (Ed): Neonatology - Management, Procedures, On-Call Problems, Diseases, Drugs, 1992, Appleton and Lange, Norwalk, Connecticut.
  7. Personal Communication with John Kettlewell, Department of Pharmacy, The Hospital for Sick Children, Toronto, 1 March 1990.
  8. Volpe JJ: Neurology of the Newborn, Sanders, Toronto, 1987.
  9. Taketomo CK, Hodding JH and Kraus DM: Pediatric Dosage Handbook, Lexi-Comp Inc., Cleveland, 1992.
  10. Young TE and Mangum OB: Neofax - A Manual of Drugs Used in Neonatal Care, Columbus, Ohio: Ross Laboratories, 1992.