Phenytoin

Phenytoin

[100mg IV $13.85; 100mg PO 8 cents]

ADMINISTRATION ROUTES:

  • IV, PO

ALTERNATIVE NAMES:

  • Dilantin, Phenytoin

ICU INDICATIONS:

  1. seizures and seizure prophylaxis

PRESENTATION AND ADMINISTRATION:

  • IV:
    100mg/2ml and 250mg/5ml

    Direct IV injection:
    Inject undiluted into a large vein at a rate not exceeding 50mg/min and for children and neonates not exceeding 3mg/kg/min.
    A slower rate of administration (e.g. not exceeding 25mg/min and if necessary as slow as 5-10mg/min) is recommended in patients with cardiovascular disease and the elderly in order to reduce cardiovascular side effects.
    Follow injection into a vein with 20ml of normal saline to reduce the irritation caused by the alkalinity of the solution (if administering via a peripheral vein)

    Intermittent infusion:
    Dilute phenytoin in 50-100ml of normal saline immediately before use (final concentration not to exceed 6.7mg/ml).
    Infuse within 1 hour.
    Infuse via an in-line filter (0.22-0.5 micron) at a rate not exceeding 50mg/min (children and neonates, give at a rate of 1-3mg/kg/min).
    Inspect closely for appearance of precipitate during infusion.
    Note that intermittent infusion, although widely used, is not recommended by the manufacturer due to the risk of precipitation.
    Compatible with normal saline ONLY.

  • PO:
    Dilantin infatabs 50mg tablets (yellow)
    Dilantin 30mg capsules (white), 100mg capsules (white/orange)
  • Dilantin paediatric suspension 30mg/5ml

DOSAGE:

  • IV:
    Loading dose in an emergency: 15-20mg/kg (max 1.5gm) IV over 1 hour. Maintenance, 100mg three times daily IV or PO. 300mg once daily can also be used for maintenance therapy.
  • PO / NG:
    For NG use, stop feed for 2 hours before and 2 hours after administration of oral phenytoin dose. 300mg once daily can also be used for maintenance therapy.
  • Note: Oral Capsules, IV medication & liquid are NOT bioequivalent dose adjustment is needed

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

  • Dose as in normal renal function

DOSAGE IN PAEDIATRICS:

  • Loading dose in an emergency:
    15-20mg/kg (max 1.5gm) IV over 1 hour.
  • Initial maintenance, oral or IV:
    2mg/kg 12 hourly (preterm); 3mg/kg 12 hourly (1st week of life), 8 hourly (2wk-4yr), 12 hourly (5-12 yr); 2mg/kg (usual max 100mg) 8 hourly (12 yrs)

CLINICAL PHARMACOLOGY:

  • Phenytoin sodium is an antiepileptic drug. Phenytoin sodium is related to the barbiturates in chemical structure.

CONTRAINDICATIONS:

  1. hypersensitivity to phenytoin

WARNINGS

  • Withdrawal:
    Abrupt withdrawal of phenytoin in epileptic patients may precipitate status epilepticus. When, in the judgment of the clinician, the need for dosage reduction, discontinuation, or substitution of alternative antiepileptic medication arises, this should be done gradually. However, in the event of an allergic or hypersensitivity reaction, rapid substitution of alternative therapy may be necessary.
  • Effect of alcohol:
    Acute alcoholic intake may increase phenytoin serum levels, while chronic alcohol use may decrease serum levels. Use in pregnancy A number of reports suggest an association between the use of antiepileptic drugs, including phenytoin, by women with epilepsy and a higher incidence of birth defects in children born to these women.

PRECAUTIONS

  • General:
    Phenytoin is NOT indicated for toxicological seizures or seizures due to hypoglycaemia. Phenytoin should be discontinued if a skin rash appears. If the rash is exfoliative, purpuric, or bullous or if lupus erythematosus, Stevens-Johnson syndrome, or toxic epidermal necrolysis is suspected, use of this drug should not be resumed and alternative therapy should be considered.
    The liver is the chief site of biotransformation of phenytoin; patients with impaired liver function, elderly patients, or those who are gravely ill may show early signs of toxicity. A small percentage of individuals who have been treated with phenytoin have been shown to metabolize the drug slowly. Slow metabolism may be due to limited enzyme availability and lack of induction; it appears to be genetically determined.
    Phenytoin is not effective for absence (petit mal) seizures. If tonic-clonic (grand mal) and absence (petit mal) seizures are present, combined drug therapy is needed.
  • Laboratory Tests:
    Phenytoin levels should only be measured if there is a specific clinical indication (i.e. if there is concern about toxicity or ongoing seizures despite phenytoin administration) Specimens should be collected in SST (Yellow) or Plain (Red). Sampling time is not critical. Routine specimens are for total phenytoin. It is possible to measure free phenytoin (green tube); however, this is a send away test and is not routinely indicated. For patients with low albumin total phenytoin levels will not represent active phenytoin levels in the blood.
  • Drug/Laboratory Test Interactions: None known.

IMPORTANT DRUG INTERACTIONS FOR THE ICU

  • Drugs which may increase phenytoin serum levels include:
    acute alcohol intake, amiodarone, diazepam, warfarin, H2-antagonists, isoniazid, and ulfonamides.
  • Drugs which may decrease phenytoin levels include:
    carbamazepine, chronic alcohol abuse, Drugs which may either increase or decrease phenytoin serum levels include: phenobarbital, sodium valproate, and valproic acid.
  • Although not a true drug interaction, tricyclic antidepressants may precipitate seizures in susceptible patients and phenytoin dosage may need to be adjusted.
  • Drugs whose efficacy is impaired by phenytoin include:
    corticosteroids, warfarin, frusemide, oral contraceptives, rifampin, and theophylline.

ADVERSE REACTIONS

  • Central Nervous System:
    Nystagmus, ataxia, slurred speech, decreased coordination and mental confusion.
  • Gastrointestinal System:
    Nausea, vomiting, constipation, toxic hepatitis and liver damage.
  • Skin:
    Dermatological manifestations sometimes accompanied by fever have included scarlatiniform or morbilliform rashes. A morbilliform rash (measles-like) is the most common; other types of dermatitis are seen more rarely. Other more serious forms which may be fatal have included bullous, exfoliative or purpuric dermatitis, lupus erythematosus, Stevens-Johnson syndrome, and toxic epidermal necrolysis.
  • Haemopoietic System:
    Thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, and pancytopenia with or without bone marrow suppression. While macrocytosis and megaloblastic anemia have occurred, these conditions usually respond to folic acid therapy. Lymphadenopathy including benign lymph node hyperplasia, pseudolymphoma, lymphoma, and Hodgkin’s disease have been reported.
  • Cardiovascular:
    Bradycardia, heart block, periarteritis nodosa.
  • Immunologic:
    Hypersensitivity syndrome (which may include, but is not limited to, symptoms such as arthralgias, eosinophilia, fever, liver dysfunction, lymphadenopathy or rash), systemic lupus erythematosus, and immunoglobulin abnormalities.

Critical Care Drug Manual

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