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Uses

Tonic-Clonic Seizures

Mainly in the prophylactic management of tonic-clonic (grand mal) seizures with complex symptomatology (psychomotor seizures).

Partial Seizures

Mainly in the prophylactic management of partial seizures with complex symptomatology (psychomotor and temporal lobe seizures).

Effective in controlling partial seizures with autonomic symptoms†.

Absence (Petit Mal) Seizures

Not recommended for the treatment of pure absence (petit mal) seizures† since the drug may increase the frequency of these seizures; however, may be useful in conjunction with succinimide or oxazolidinedione anticonvulsants in the management of combined absence and tonic-clonic seizures.

Neurosurgical Seizures

Prevention and treatment of seizures occurring during and following neurosurgery.

Status Epilepticus

Diazepam generally considered the drug of choice for termination of status epilepticus.

Alternatively, concurrent IV administration of phenytoin (or fosphenytoin) and diazepam is a treatment of choice for termination of status epilepticus.

May be used parenterally, preferably by IV administration, in the treatment of status epilepticus; however, the usefulness of the drug in this condition is limited by the need for slow administration and its slow onset of action. Fosphenytoin is an alternative.

Cardiac Arrhythmias

Useful IV in the treatment of ventricular tachycardia† and paroxysmal atrial tachycardia†, particularly when conventional antiarrhythmic agents or cardioversion is ineffective.

Useful orally for maintenance therapy in the management of cardiac arrhythmias†.

Cardiac Glycoside Intoxication

Drug of choice IV for the treatment of arrhythmias caused by cardiac glycoside intoxication†.

Neuropathic Pain

May have beneficial effects in the symptomatic treatment of chronic pain arising from peripheral neuropathic syndromes† (e.g., trigeminal neuralgia†).

Dosage and Administration

General

Seizure Disorders

• Carefully and slowly adjust dosage according to individual requirements and response.
• When a patient is transferred from phenytoin to another anticonvulsant, gradually reduce the phenytoin dosage over a period of about 1 week while at the same time therapy is instituted with a low dose of the replacement drug.
• When phenytoin replaces phenobarbital or any other barbiturate anticonvulsant, reduce the dose of the barbiturate gradually over a period of 1 week to prevent withdrawal symptoms.
• Withdraw phenytoin slowly to avoid precipitating seizures or status epilepticus.

Oral Loading-Dose Regimens

• Therapeutic serum phenytoin concentrations can be achieved more rapidly (in 2–24 hours) by the use of an oral loading-dose regimen.
• Various regimens have been suggested, and clinicians should consult published protocols for information on specific regimens. (See Pediatric Patients and also Adults under Dosage for suggested regimen.)
• Reserve oral loading-dose regimens for patients in a clinic or hospital setting where serum phenytoin concentrations can be closely monitored.
• Patients with a history of renal or liver disease should not receive an oral loading-dose regimen.

Administration

Phenytoin and its sodium salt are administered orally.

Phenytoin sodium also may be administered by direct IV injection for the initial treatment of status epilepticus and for the prophylaxis of seizures during neurosurgery.

Phenytoin sodium also has been infused IV† cautiously. (See Dilution under IV Administration.)

Avoid sub-Q or perivascular injection because of risk of soft tissue irritation and inflammation. Administer IM only as a last resort. (See IM Administration.)

Oral Administration

Only extended phenytoin sodium capsules should be used for once-daily dosing regimens.

When refilling a prescription for a preparation previously labeled as phenytoin sodium capsules, the pharmacist should determine whether the brand has been reformulated, whether the brand is now extended phenytoin sodium capsules or prompt phenytoin sodium capsules, and which one the clinician intends that the patient continue to receive.

Monitor serum phenytoin concentrations when a patient is switched from extended phenytoin sodium capsules to prompt phenytoin sodium capsules.

Do not use oral formulations containing phenytoin as the base (e.g., suspensions, chewable tablets) for once-daily dosing regimens.

Minimize loss of phenytoin oral suspension during oral administration via a nasogastric tube (secondary to adherence to PVC tubing) by diluting (e.g., threefold) the suspension with a compatible diluent (e.g., sterile water, 5% dextrose, 0.9% sodium chloride) prior to administration, combined with flushing the tube with at least 20 mL of diluent after administration.

IV Administration

Inject IV preferably directly into a large vein through a large-gauge needle or IV catheter.

Following IV injection, inject 0.9% sodium chloride injection through the same needle or catheter to reduce local venous irritation from alkaline solution.

Generally not recommended for use in IV infusions† because of the possibility that precipitation may occur; however, can be infused IV safely provided adequate precautions are taken. (See Dilution.)

Dilution

IV infusion† is feasible provided appropriate precautions are taken, such as maintaining an optimal pH (e.g., ≥10 for 1 mg/mL dilutions), using a suitable infusion fluid (i.e., 0.9% sodium chloride injection or lactated Ringer's), using a sufficiently diluted solution (e.g., <6.7 mg/mL), starting the infusion immediately after preparation and completing administration within a relatively short period, using a 0.22-mcm inline filter, and carefully observing the admixture.

One suggested technique: Add 1 g to 1 L 0.9% sodium chloride or lactated Ringer's to provide a concentration of 1 mg/mL; these solutions generally have a pH ≥10 but final pH is not predictable. Infuse IV† with caution; start the infusion immediately after preparation, complete within a relatively short period, and watch closely for possible crystallization. Use a 0.22-mcm inline filter during infusion.

Crystallization generally occurs in more acidic solutions (e.g., dilutions in 5% dextrose), which should not be used. (See Solution Compatibility under Stability.)

Alternatively, fosphenytoin sodium (Cerebyx^®), a prodrug of phenytoin, can be used for IV infusion.

Rate of Administration

Adults: ≤50 mg/minute; preferably ≤25–50 mg/minute.

Pediatric patients: ≤1–3 mg/kg per minute; preferably, 0.5–1.5 mg/kg per minute.

Neonates: ≤1–3 mg/kg per minute; preferably ≤0.5 mg/kg per minute.

IM Administration

Administer IM only as a last resort because of erratic absorption from IM injection sites.

May be of some value for sustaining established therapeutic plasma concentrations when oral administration is not feasible.

Information regarding IM administration for >1 week is lacking; consider alternate routes for administering phenytoin (e.g., gastric intubation) when oral administration is not feasible for >1 week.

Fosphenytoin sodium can be administered IM for short-term replacement of oral phenytoin.

Dosage

Each 100 mg of phenytoin sodium contains approximately 92 mg of phenytoin; consider the difference when switching from the base to its sodium salt or vice versa.

Pediatric Patients

Seizure Disorders

Oral

Usual dosage: Initially, 5 mg/kg or 250 mg/m² daily in 2 or 3 equally divided doses; total dosage ≤300 mg daily.

Therapeutic serum concentrations achieved more rapidly with a 500- to 600-mg oral loading dose, in divided doses, followed by usual maintenance dosage 24 hours after initiating loading dose.

Adjust subsequent dosage carefully and slowly according to the patient’s requirements.

Neonates, maintenance dosage: Usually, 3–5 mg/kg daily.

Infants 1–12 months of age, maintenance dosage: Usually, 4–8 mg/kg daily.

Children 1–11 years of age, maintenance dosage: 4–10 mg/kg daily.

Adolescents, 12–17 years of age, maintenance dosage: 4–8 mg/kg daily.

Status Epilepticus

IV

15–20 mg/kg, at a rate ≤1–3 mg/kg per minute.

Preferably, 10–15 mg/kg, at a usual rate of 0.5–1.5 mg/kg per minute (maximum total dose of 20 mg/kg in 24 hours).

Replace parenteral administration with oral therapy as soon as possible.

Adults

Seizure Disorders

Prompt-Release preparations

Oral

Usual dosage: Initially, 100 mg 3 times daily.

A period of 5–10 days may be required to achieve anticonvulsant effects.

Increases to >300 mg daily may lead to markedly increased serum phenytoin concentrations; therefore, adjust dosage above this level carefully and slowly.

Therapeutic serum concentrations achieved more rapidly with a 1-g oral loading dose given as 400, 300, and 300 mg at 2-hour intervals, followed by usual maintenance dosage 24 hours after initiating loading dose.

Increase daily dosage gradually, if necessary, in increments of 100 mg every 2–4 weeks until desired response is achieved.

Dosing at 100 mg 4 times daily may benefit some patients, and others may require dosages up to 200 mg 3 times daily.

Optimum daily dose: Varies considerably but usually in the range of 4–7 mg/kg (300–600 mg daily for most adults).

IM

Increase the IM dosage by 50% over the previously established oral dosage.

First week back on oral therapy, reduce oral dosage to one-half the original oral dosage to avoid drug accumulation resulting from eventual absorption from the IM injection site; monitoring of serum concentrations recommended.

Limit IM therapy to 1 week. (See IM Administration under Administration.)

Extended-Release Preparations

Oral

For patients stabilized on a dosage of 100 mg 3 times daily, once-daily dosing with 300 mg as extended phenytoin sodium capsules may be considered.

Do not use prompt phenytoin sodium capsules nor oral phenytoin base suspensions or chewable tablets for once-daily dosing.

Status Epilepticus

IV

Initially, 10–15 mg/kg, by direct IV administration at a rate ≤50 mg/minute; the initial dose should be followed by IV or oral maintenance doses of 100 mg every 6–8 hours.

Preferably, 15–18 mg/kg, at a rate ≤25–50 mg/minute (maximum total dose of 1.5 g in 24 hours).

Oral therapy should replace parenteral administration as soon as possible.

Cardiac Arrhythmias

Ventricular Tachycardia

Oral

100 mg 2–4 times daily.

IV

100 mg by direct IV injection at 5-minute intervals until the arrhythmia is abolished or undesirable effects appear or until a total of 1 g is given.

Paroxysmal Atrial Tachycardia

Oral

100 mg 2–4 times daily.

IV

100 mg by direct IV injection at 5-minute intervals until the arrhythmia is abolished or undesirable effects appear or until a total of 1 g is given.

Cardiac Glycoside Intoxication

Oral

100 mg 2–4 times daily.

IV

100 mg by direct IV injection at 5-minute intervals until the arrhythmia is abolished or undesirable effects appear or until a total of 1 g is given.

Prescribing Limits

Pediatric Patients

Seizure Disorders

Oral

Total dosage should not exceed 300 mg daily.

Status Epilepticus

IV

Maximum total dose of 20 mg/kg in 24 hours.

Adults

Seizure Disorders

Prompt-Release Preparations

Oral

Increases in dosage to >300 mg daily may lead to markedly increased serum phenytoin concentrations; therefore, adjust dosage above this level carefully and slowly.

IM

Generally limit IM therapy to 1 week. (See IM Administration under Administration.)

The first week back on oral therapy, reduce the oral dosage to one-half the original oral dosage to avoid drug accumulation resulting from eventual absorption from the IM injection site; monitor serum concentrations.

Status Epilepticus

IV

Maximum total dose of 1.5 g in 24 hours.

Cardiac Arrhythmias

Ventricular Tachycardia

IV

Maximum total IV dose of 1 g.

Paroxysmal Atrial Tachycardia

IV

Maximum total IV dose of 1 g.

Cardiac Glycoside Intoxication

IV

Maximum IV dose of 1 g. Do not use oral loading-dose regimens.

Special Populations

Dosage in Hepatic Impairment

Consider reduced maintenance dosage in hepatic cirrhosis. Do not use oral loading-dose regimens.

Dosage in Renal Impairment

Do not use oral loading-dose regimens.

End-stage renal impairment generally can receive usual loading and maintenance dosages initially, adjusting as necessary.

Geriatric Patients

May show early signs of toxicity.

Geriatric patients with heart disease: It has been recommended that the drug be given at a rate of 50 mg over 2–3 minutes.

Obese Patients

Ideal or nonobese weight probably correlates best with maintenance dosages. Loading doses may require adjustment for increased volume of distribution.

Pregnancy

Monitor phenytoin therapy closely (phenytoin concentrations may decline) to ensure optimum seizure control.