ADMINISTRATION ROUTES:
IV, PO
ALTERNATIVE NAMES:
Dilantin, Phenytoin
ICU INDICATIONS:
- Seizures and seizure prophylaxis
PRESENTATION AND ADMINISTRATION:
IV:
100 mg / 2 mL and 250 mg / 5 mL
IV injection:
Inject undiluted into a large vein. Do not exceed the following administration rates:
- Adults: max rate 50 mg/min
- Elderly or cardiovascular disease: max rate 25 mg/min
- Children/ neonates: max rate 1 mg/kg/min
If administerd by a peripheral vein, follow bolus dose with 20 mL of 0.9% saline to reduce the irritation caused by the alkalinity of the solution.
Intermittent infusion:
Dilute phenytoin in 50 - 100 mL of 0.9% saline immediately before use. Final concentration must not exceed 6.7 mg/mL. Infuse within 1 hour via an in-line filter (0.22 - 0.5 micron).
Do not infuse at a rate exceeding 50 mg/min (adults) or 3 mg/kg/min (children/ neonates). Inspect closely for appearance of precipitate during infusion.
Intermittent infusion, although widely used, is not recommended by the manufacturer due to the risk of precipitation.
Compatible with 0.9% saline only
PO:
Dilantin infatabs 50 mg tablets (yellow)
Dilantin 30 mg capsules (white), 100 mg capsules (white/orange) Dilantin paediatric suspension 30 mg/5 mL
DOSAGE:
IV:
Loading dose:
15 - 20 mg/kg (max 1500 mg) IV over 1 hour
Maintenance dose:
100 mg TDS IV or PO
300 mg OD can also be used
Start maintenance dose 12 hours after loading dose
PO/NG:
For NG use, stop feed for 2 hours before and 2 hours after administration of phenytoin. For ease of use, administration as 300 mg OD is preferrable.
Note: Oral Capsules, IV medication & liquid are not bioequivalent; dose adjustment is needed. Please consult with the ICU pharmacist.
DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:
Dose as in normal renal function
DOSAGE IN PAEDIATRICS:
Loading dose:
20 mg/kg (max 1.5 g) IV over 1 hour
Maintenance dose (IV or PO):
2 - 5 mg/kg/dose BD
Start maintenance dose 12 hours after loading dose
CLINICAL PHARMACOLOGY:
Phenytoin sodium is an antiepileptic drug, related to the barbiturates in chemical structure. It binds to sodium channels in depolarising neurones, blocking sodium influx. This reduces neuronal excitability and thus the spread of electrical activity. Other anti-epileptic mechanisms may come from GABA enhancement, glutamate receptor blockade, and inhibiting neuronal calcium influx.
Intravenous administration has an onset of action within 30 - 60 minutes with an effect persisting up to 24 hours. Phenytoin is highly protein bound (around 90%). The plasma halif-life is between 10 - 15 hours. Phenytoin exhibits dose-dependent pharmacokinetics so the apparent half-life changes with dose & serum concentration. There may be considerable patient varation in phenytoin pharmacokinetics.
Phenytoin is hepatically metabolised. Metabolism is increased in children, pregnant or menstruating women, or during acute trauma. Some patients may metabolise phenytoin more slowly due to genetic polymorphism.
CONTRAINDICATIONS:
- Hypersensitivity to phenytoin
- Sinus bradycardia, sino-atrial block, second and third degree AV block
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.
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, phenytoin must be stopped and alternative therapy considered.
Patients with impaired liver function, elderly patients, or those who are gravely ill may show early signs of toxicity.
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 IN ICU:
Drugs which may increase phenytoin serum levels include:
- Acute alcohol intake
- Amiodarone
- Diazepam
- Warfarin
- H2-antagonists
- Isoniazid
- Sulfonamides.
Drugs which may decrease phenytoin serum levels include:
- Carbamazepine
- Chronic alcohol abuse,
Drugs which may either increase or decrease phenytoin serum levels include:
- Phenobarbitone
- Sodium valproate
- Valproic acid.
Drugs whose efficacy is impaired by phenytoin include:
- Corticosteroids
- Warfarin
- Furosemide
- Oral contraceptives
- Rifampicin
- Theophylline.
Although not a true drug interaction, tricyclic antidepressants may precipitate seizures in susceptible patients and phenytoin dosage may need to be adjusted.
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
Thrombocytopaenia, leukopaenia, granulocytopaenia, agranulocytosis, and pancytopaenia with or without bone marrow suppression. While macrocytosis and megaloblastic anaemia 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