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Dose and administration
- Loading dose: 20 mg/kg by slow IV infusion over 60 minutes5.
- 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.
Seizures refractory to phenobarbitone therapy alone.
Sinus rhythm bradycardia, sinoatrial or atrioventricular block.
- Known hypersensitivity to phenytoin.
- Neonates with jaundice, respiratory failure, hypotension or heart failure.
- Preterm infants, especially extreme immaturity.
- Neonates and infants with hepatic or renal impairment.
- 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.
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
- Injection is very alkaline -therefore may result in venous irritation and phlebitis. Avoid extravasation.
- Observe diluted solution, for crystal formation.
- Rapid administration may result in hypotension, CNS depression, cardiac arrhythmias, and impaired cardiac conduction.
- Gastrointestinal disturbances (nausea, vomiting, constipation).
- Overdosage may result in hypotension, coma, respiratory depression. Nystagmus may be an indication of toxicity.
- Possible interference of Vitamin D and folate metabolism. Megaloblastic anaemia.
- 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.
- DO NOT administer phenytoin intramuscularly. Crystallisation in muscle results in erratic absorption and severe pain.
- If used for maintenance therapy:
- Monitor: Liver function and full blood count.
- 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.
- Management of phenytoin overdose and/or toxicity: stop phenytoin, supportive therapy (ventilation, volume expansion, inotropes, and/or anti-arrhythmic agents).
Management of Phenytoin administration
- 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.
- Flavoured syrup 30 mg/5 ml. Preservative sodium benzoate 5 mg/ml.
- Note: there is a Dilantin Forte Suspension containing phenytoin 100mg/5ml
- Loading doses are charted in mg/dose on stat page of prescription chart.
- Maintenance doses are charted on prescription chart in mg/dose.
Slow IV Infusion (Avoid administration via central lines)
- Dilute immediately prior to use to 5 mg/ml by adding to sodium chloride 0.9%5. No other diluent is acceptable.
- Use a Pall 0.2 micron in-line filter during administration.
- 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.
- Flush line with sodium chloride 0.9% before and after administration of phenytoin.
- Do NOT mix with other drugs, IV solutions, blood or blood products.
- 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.
- As oral phenytoin tends to adhere to the PVC tubing, flush naso-gastric tube with 2ml of water after administration.
Observation and documentation
- Monitor for adverse effects.
- Assess for signs of toxicity.
- Monitor BP closely. ECG monitor during intravenous therapy.
- Assess for and document any seizure activity.
- Observe administration site closely. Extravasation may cause tissue inflammation and necrosis.
IV preparation: Store below 25°C. Protect from light
Oral preparation: Follow manufacturers guidelines
- Roberts RJ. Drug therapy in infants: Pharmacologic principles and clinical experience. Philadelphia, WB Saunders 1984: p104-110.
- Painter MI, Pippenger C, Wasterlain C, et al. Phenobarbitol and phenytoin in neonatal seizures; Metabolism and tissue distribution. Neurology 1981; 31:110-7
- 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.
- Young TE, Mangum OB. Neofax. A Manual of drugs used in neonatal care. Ross Laboratories 5th Ed 1992; p50-51.
- Loe E. et al. Paediatric Pharmacopoeia, Royal Children's Hospital Melbourne and Leicester Royal Infirmary Children's Hospital. WB Saunders Co. Ltd; 1998: London
- Paediatric Formulary. (4th ed. ) Guy's, St. Thomas' and Lewisham Hospitals.
- Stockley I. Drug Interactions 4th ed. The Pharmaceutical Press; 1996: London
- Kemp C, McDowell J (eds). Paediatric Pharmacopoeia 12th ed. Pharmacy Dept. Royal Children's Hospital; 1997: Melbourne
- Phenytoin Injection (DBL) Data Sheet. Baxter Healthcare Ltd.;1996:Auckland.
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- Date last published: 30 July 1999
- Document type: Drug Dosage Guideline
- Services responsible: ADHB Pharmacy, Neonatology
- Editor: Sarah Bellhouse
- Review frequency: 2 years