see also:

• seizures

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

• 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

• 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
• ventricular fibrillation (VF)
• the lethal oral dose in adults is estimated to be 2 to 5 g

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

• 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.

• 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)

• 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

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

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

• 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

• 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.

• 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.

• 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.

• 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.

• 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