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phenytoin

phenytoin

see also:

introduction

  • phenytoin is a sodium channel blocking anticonvulsant agent with antiarrhythmic properties (and thus potentially pro-arrhythmogenic)
  • many drug interactions (see below)

presentation

  • ampoules for iv use:
    • 100mg in 2ml
    • 250mg in 5ml
  • Dilantin oral:
    • 50mg chewable tablet, spearmint flavour (200 per box)
    • 30mg and 100mg capsules (200 per box)
    • mixture 6mg/ml (red colour) 500ml
  • not for use in hypoglycaemic or metabolic induced seizures
  • ineffective in petit mal seizures
  • other C/I include heart block, PH HS reaction (see below under precautions)
  • pregnancy category D
  • not compatible with dextrose/glucose solutions
  • extravasation may cause tissue necrosis thus administer via large peripheral veins where possible
  • intramuscular administration of phenytoin is unsuitable for the emergency treatment of status epilepticus due to very slow and erratic absorption from the intramuscular site.
  • max. infusion rate is 50mg/min in adults or 1 mg/kg/min in children - more rapid infusions may cause cardiac arrest
  • high risk patients (eg. PH cardiac disease) should have continuous ECG monitoring throughout infusion
  • generally give undiluted as diluted solutions are less stable and may result in precipitation
  • infusion should be completed prior to transfer to a general ward unless the ward is accredited for such infusions

toxicity

  • nystagmus - usually appears at 20 microgram/mL
  • nausea/vomiting
  • sedation
  • slurred speech
  • ataxia - usually appears at 30 microgram/mL
  • dysarthria and lethargy appear when the plasma concentration is over 40 microgram/mL, but as high a concentration as 50 microgram/mL has been reported without evidence of toxicity
  • cardiac conduction disturbances
  • hypotension
  • the lethal oral dose in adults is estimated to be 2 to 5 g

iv loading dose in status epilepticus

adults

  • 10-15mg/kg (max. 1.2g) given over 20-30min via syringe pump at max. rate of 50mg/min with cardiac monitoring

neonates and children

  • phenytoin 18-20 mg/kg1) (max. 1.2g) IV via syringe pump over 30min
    • max. infusion rate 1 mg/kg/min in children with monitoring
    • in status epilepticus, loading dose can be given over 30min, in less urgent situations, give over 60min.

iv dose of phenytoin for certain ventricular arrhythmias

  • may be of use in certain situations such as digoxin toxicity
  • usual slow iv dose 3-5mg/kg (up to 100mg in adults), repeat as needed every 5-10min, up to maximum loading dose (20mg/kg or 1.2g)

usual maintenance dose

  • orally or slow iv every 6-8 hours (although long term oral use can usually be given in 2-3 equally divided doses)
  • although phenytoin has a relatively long plasma half-life, thrice daily dosing may reduce the incidence of gastric irritation since lower doses can be administered with thrice daily dosing as compared with twice daily dosing.
  • blood level monitoring is important with phenytoin, blood samples usually being taken before next dose is due.
    • target serum level 10-20 mcg/mL
  • adults: initially 4-5 mg/kg/day; may incr every 2 wks; max 600 mg/day - usually 100mg 6-8 hrly initially.
    • neurosurgical patients pre and post-op usual adult dose is 250mg by cautious slow IV every 6 - 12 hours until oral dosing possible.
  • children: initially 5 mg/kg/day; maintenance 4-8 mg/kg/day; max 300 mg/day

adverse effects of long term use

  • gum thickening (hyperplasia)
  • excessive hair growth (hirsutism)
  • folate deficiency
  • vit D deficiency, osteomalacia;
  • others:
    • hepatic damage, SLE; haematological abnormality; lymphadenopathy; periarteritis nodosa; taste perversion;

drug interactions

  • CYP3A4, CYP2D6, CYP1A2, CYP2C9, CYP2C19 inhibitors/ inducers;
  • capecitabine, fluorouracil, alcohol;

drugs which may increase phenytoin serum levels

  • acute alcohol intake, amiodarone, amphotericin B, azapropazone, chloramphenicol, chlordiazepoxide, cimetidine, clopidrogel, diazepam, dicumarol, diltiazem, disulfiram, erythromycin, felbamate, fluconazole, fluoxetine, fluvoxamine, H2-antagonists, halothane, isoniazid, itraconazole, ketoconazole, methylphenidate, miconazole, nifedipine, oestrogens, omeprazole, phenothiazines, phenylbutazone, salicylates, sertraline, succinimides (ethosuximide, methsuximide, phensuximide), sulfonamides, ticlopidine, tolbutamide, trazodone, viloxazine

drugs which may decrease phenytoin levels

  • antibacterial agents/ fluoroquinones (e.g. ciprofloxacin, rifampicin), chronic alcohol abuse, diazoxide, folic acid, reserpine, sucralfate, theophylline, vigabatrin and Hypericum perforatum (St John's wort).
  • Calcium ions may interfere with the absorption of phenytoin. Ingestion times of phenytoin and antacid preparations containing calcium should be staggered in patients with low serum phenytoin levels to prevent absorption problems.

drugs which may either increase or decrease phenytoin serum levels

  • antineoplastic agents, carbamazepine, chlordiazepoxide, ciprofloxacin, diazepam, phenobarbitone, sodium valproate and valproic acid.
  • similarly, the effect of phenytoin on carbamazepine, phenobarbitone, valproic acid and sodium valproate serum levels is unpredictable.

drugs which may lower seizure threshold and thus risk seizures in patients on phenytoin

  • although not a pharmacokinetic drug interaction, antidepressants, antipsychotics, tramadol and other seizure threshold lowering drugs may precipitate seizures in susceptible patients by lowering convulsive threshold.
  • phenytoin dosage may need to be adjusted.

drugs whose efficacy is impaired by phenytoin

  • alcuronium, azoles, chlorpropamide, clozapine, corticosteroids, coumarin anticoagulants, cyclosporin, diazoxide, doxycycline, frusemide, glibenclamide, lamotrigine, methadone, nicardipine, nimodipine, oestrogens, oral contraceptives, pancuronium, paroxetine, praziquantel, quinidine, rifampicin, sertraline, teniposide, tetracycline, theophylline, tolbutamide, verapamil, vecuronium, vitamin D.

other precautions

  • PH hypersensitivity to phenytoin or to structurally related compounds
  • Hepatic impairment; diabetes; abrupt withdrawal; porphyria; hypoalbuminaemia; variable rate of metabolism,
  • caps contain 8% w/w less active ingredient than susp or Infatabs (monitor serum level);
  • acute, chronic alcohol intake; enteral feeding; cranial irradiation with corticosteroid dose reduction; prolonged use (monitor FBC); elderly, gravely ill; pregnancy, lactation
  • ideally infusions should use a 0.22 micron filter to remove any residual precipitate
phenytoin.txt · Last modified: 2009/03/21 19:22 (external edit)