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Drug dosage identifier

Phenytoin Sodium

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Dose and administration

  1. Loading dose: 20 mg/kg by slow IV infusion over 60 minutes5.
  2. Maintenance dose: 2-4 mg/kg/dose twice a day by slow IV infusion, or PO6.
    Administer at a rate not faster than 1.0 mg/kg/minute6.
    The maintenance dose needs to be monitored and adjusted according to blood levels.

Indication

Seizures refractory to phenobarbitone therapy alone.

Contraindications

Sinus rhythm bradycardia, sinoatrial or atrioventricular block.

Precautions

  1. Known hypersensitivity to phenytoin.
  2. Neonates with jaundice, respiratory failure, hypotension or heart failure.
  3. Preterm infants, especially extreme immaturity.
  4. Neonates and infants with hepatic or renal impairment.

Drug interactions

  • Phenytoin may increase the levels of: Phenobarbitone.
  • Phenytoin may decrease the levels or activity of: Paracetamol, caffeine, corticosteroids, diazoxide, digoxin, dopamine, fentanyl, furosemide, theophylline.
  • Phenytoin levels may be decreased by: Phenobarbitone, rifampicin, theophylline.
  • Phenytoin levels may be increased by: Fluconazole, ranitidine.
  • Phenytoin levels may be altered by: Chlorpromazine, benzodiazepines.
  • Phenytoin levels may be altered by: Interfere with thyroid function tests, and produce lower than normal values for metyrapone suppression tests.

Clinical pharmacology

Phenytoin is an anticonvulsant with a primary site of action in the motor cortex. Environmental changes or excessive stimulation can cause a reduction in membrane sodium gradient. Phenytoin causes an efflux of sodium from neurons and therefore stabilises the threshold against over-activity in those brain stem centres responsible for the tonic phase of grand mal seizures9. Absorption from gastrointestinal tract and intramuscular injection sites erratic. Phenytoin has high binding (85-90%) to plasma protein. Bilirubin displaces phenytoin from albumin binding sites resulting in higher percentage of unbound drug in plasma. Elimination via the kidney. Pharmacokinetics are dose-dependent over the therapeutic range and unpredictable in the neonate. Relatively small margin between full therapeutic effect and a minimally toxic dose of phenytoin.

Possible adverse effects

  1. Injection is very alkaline -therefore may result in venous irritation and phlebitis. Avoid extravasation.
  2. Observe diluted solution, for crystal formation.
  3. Rapid administration may result in hypotension, CNS depression, cardiac arrhythmias, and impaired cardiac conduction.
  4. Gastrointestinal disturbances (nausea, vomiting, constipation).
  5. Overdosage may result in hypotension, coma, respiratory depression. Nystagmus may be an indication of toxicity.
  6. Possible interference of Vitamin D and folate metabolism. Megaloblastic anaemia.
  7. Hypersensitivity reactions eg. skin rashes. Bullous or purpuric rashes are indicators to withdraw therapy as they may be symptoms of rare but severe reactions eg. toxic epidermal necrolysis.
  8. Hyperglycaemia.

Special considerations

  1. DO NOT administer phenytoin intramuscularly. Crystallisation in muscle results in erratic absorption and severe pain.
  2. If used for maintenance therapy:
    1. Monitor: Liver function and full blood count.
    2. Therapeutic Drug Monitoring (TDM)6: Time to steady state: 1 to 2 weeks (variable).
      Serum level (neonate): 40-80 μmol/L8.
      Measure serum phenytoin levels at least 12 - 24 hours after IV loading dose and at regular intervals during maintenance therapy.
  3. Management of phenytoin overdose and/or toxicity: stop phenytoin, supportive therapy (ventilation, volume expansion, inotropes, and/or anti-arrhythmic agents).

Management of Phenytoin administration

Description

IV preparation

  • Clear colourless solution 50 mg/ml in 2 ml ampoules.
  • Contains propylene glycol 0.4 ml/ml, ethanol 0.1 ml/ml.
  • pH 10-12.3.

Oral preparation

  • Flavoured syrup 30 mg/5 ml. Preservative sodium benzoate 5 mg/ml.
  • Note: there is a Dilantin Forte Suspension containing phenytoin 100mg/5ml

Prescription

  • Loading doses are charted in mg/dose on stat page of prescription chart.
  • Maintenance doses are charted on prescription chart in mg/dose.

Administration

Slow IV Infusion (Avoid administration via central lines)

  1. Dilute immediately prior to use to 5 mg/ml by adding to sodium chloride 0.9%5. No other diluent is acceptable.
  2. Use a Pall 0.2 micron in-line filter during administration.
  3. Administer at a rate not faster than 1.0 mg/kg/minute6 using a syringe pump. Diluted solution must be administered within one hour of preparation5. Observe diluted solution for the formation of crystals.
  4. Flush line with sodium chloride 0.9% before and after administration of phenytoin.
  5. Do NOT mix with other drugs, IV solutions, blood or blood products.

Oral

  1. Enteral feeding decreases the absorption of oral phenytoin. Do not give oral feeds for 30 minutes before and after phenytoin dose. Give oral dose with water to increase absorption6.
  2. As oral phenytoin tends to adhere to the PVC tubing, flush naso-gastric tube with 2ml of water after administration.

Observation and documentation

  1. Monitor for adverse effects.
  2. Assess for signs of toxicity.
  3. Monitor BP closely. ECG monitor during intravenous therapy.
  4. Assess for and document any seizure activity.
  5. Observe administration site closely. Extravasation may cause tissue inflammation and necrosis.

Storage

IV preparation: Store below 25°C. Protect from light

Oral preparation: Follow manufacturers guidelines

Selected references

  1. Roberts RJ. Drug therapy in infants: Pharmacologic principles and clinical experience. Philadelphia, WB Saunders 1984: p104-110.
  2. Painter MI, Pippenger C, Wasterlain C, et al. Phenobarbitol and phenytoin in neonatal seizures; Metabolism and tissue distribution. Neurology 1981; 31:110-7
  3. Loughnan PM, Greenwald A, Purton WW, et al. Pharmacokinetic observations of phenytoin disposition in the newborn and young infant. Arch Dis Child 1977; 52:302.
  4. Young TE, Mangum OB. Neofax. A Manual of drugs used in neonatal care. Ross Laboratories 5th Ed 1992; p50-51.
  5. Loe E. et al. Paediatric Pharmacopoeia, Royal Children's Hospital Melbourne and Leicester Royal Infirmary Children's Hospital. WB Saunders Co. Ltd; 1998: London
  6. Paediatric Formulary. (4th ed. ) Guy's, St. Thomas' and Lewisham Hospitals.
  7. Stockley I. Drug Interactions 4th ed. The Pharmaceutical Press; 1996: London
  8. Kemp C, McDowell J (eds). Paediatric Pharmacopoeia 12th ed. Pharmacy Dept. Royal Children's Hospital; 1997: Melbourne
  9. Phenytoin Injection (DBL) Data Sheet. Baxter Healthcare Ltd.;1996:Auckland.

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Document Control

  • Date last published: 30 July 1999
  • Document type: Drug Dosage Guideline
  • Services responsible: ADHB Pharmacy, Neonatology
  • Editor: Sarah Bellhouse
  • Review frequency: 2 years