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Black Box Warning
Title
See full prescribing information for complete Boxed Warning.
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Content
Overview
Phenytoin (oral) is an anticonvulsant that is FDA approved for the treatment of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery. There is a Black Box Warning for this drug as shown here. Common adverse reactions include morbilliform eruption, rash, constipation, gingival enlargement, nausea, vomiting, ataxia, coordination problem, nystagmus, slurred speech, confusion, feeling nervous.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Seizure, Generalized Tonic-Clonic and Complex Partial (psychomotor and temporal lobe) SeizuresView additional information
Dosing Information
In patients receiving no previous therapy, recommended initial doses are 100 milligrams orally 3 times daily; for most adults, satisfactory maintenance doses are 100 milligrams 3 times daily to 4 times daily, but doses of 200 milligrams 3 times daily may be required.
If seizure control is satisfactory on a divided dose regimen of three 100 milligrams Dilantin Kapseals(R) daily, once-a-day dosing with Dilantin Kapseals(R), 300 milligrams/day, may be considered. Close serum level monitoring is indicated when changing from prompt to extended, or vice versa.
Loading doses may be utilized to rapidly achieve therapeutic phenytoin levels. This regimen should be reserved for patients in a clinic or hospital setting where phenytoin serum levels can be closely monitored. Patients with a history of renal or liver disease should not receive the oral loading regimen. The manufacturer recommends 1 gram divided into 3 doses (400 milligrams, 300 milligrams, and 300 milligrams) administered at two-hourly intervals. Normal maintenance dosage is then instituted 24 hours after the loading dose, with frequent serum level determinations
Seizure, During and following neurosurgery
Dosing Information
For prophylaxis of seizures during neurosurgical procedures, 100 to 200 milligrams (2 to 4 milliliters) intramuscularly (IM) is indicated at approximately 4-hour intervals during surgery and continued during the postoperative period
Seizure, During neurosurgery; Treatment and Prophylaxis- IV route
Nonemergent loading and maintenance dose:
Patients who have not received treatment previously may receive injectable phenytoin sodium solution as a nonemergent loading dose of 10 to 15 mg/kg IV loading dose at a rate not exceeding 50 mg/min, although slower administration rates are recommended to minimize potential cardiovascular reactions. The loading dose should be followed by maintenance doses of oral or IV phenytoin every 6 to 8 hours.
Substitution for oral phenytoin:
When use of oral phenytoin is not possible, IV phenytoin sodium may be substituted at the same total daily dose, administered at a rate not to exceed 50 mg/min. Due to differences in bioavailability, plasma phenytoin concentrations may increase when IV phenytoin is substituted for oral phenytoin therapy
Seizure, During neurosurgery; Treatment and Prophylaxis- oral route:
Patients who have not received treatment previously may be started on the extended-release capsules at a dose of 100 milligrams (mg) orally 3 times daily with adjustments based on individual requirements. Most adults will be satisfactorily maintained on 100 mg 3 to 4 times daily. If necessary, the dose may be increased to 200 mg 3 times daily. For patients established on 100 mg 3 times a day, therapy may be switched to once daily dosing using one 300 mg extended-release capsule [28].
Some authorities recommended use of oral loading doses of phenytoin in patients who require rapid steady-state serum levels but intravenous administration is not desirable. In this case, oral loading doses should be reserved for patients in a clinic or hospital setting where serum levels can be closely monitored. Oral loading regimens should not be administered to patients with a history or renal or liver disease. The recommended loading dose regimen is 1 gram divided into 3 doses (400 milligram (mg), 300 mg, 300 mg) administered every 2 hours. Normal maintenance dose should then begin 24 hours after the loading dose with frequent serum level determinations
Status epilepticus
Dosing Information
For the treatment of status epilepticus, the manufacturer recommends a loading dose of 10 to 15 milligrams/kilogram (mg/kg) administered slowly intravenously at a rate not exceeding 50 mg/minute. The loading dose should be followed by maintenance doses of 100 mg orally or intravenously every 6 to 8 hours. Determination of phenytoin plasma levels is recommended in the subsequent establishment of maintenance dosing].
One author recommends a loading dose of phenytoin for the treatment of status epilepticus of 20 milligrams/kilogram (mg/kg), intravenously at a maximal rate of 50 mg/minute [96]. As much as 30 mg/kg may be required in some patients. Other sources have used an initial loading dose of 18 mg/kg.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Phenytoin in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Phenytoin in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Seizure, Durind and following neurosurgery
Dosing Information
Seizure, During neurosurgery; Treatment and Prophylaxis- IV route
Nonemergent loading and maintenance dose:
Patients who have not received treatment previously may receive injectable phenytoin sodium solution as a nonemergent loading dose of 15 to 20 mg/kg IV loading dose at a rate not exceeding 1 to 3 mg/kg/min or 50 mg/min (whichever is slower), although slower administration rates are recommended to minimize potential cardiovascular reactions.
Substitution for oral phenytoin:
When use of oral phenytoin is not possible, IV phenytoin sodium may be substituted at the same total daily dose, administered at a rate not to exceed 1 to 3 mg/kg/min or 50 mg per minute (whichever is slower). Due to differences in bioavailability, plasma phenytoin concentrations may increase when IV phenytoin is substituted for oral phenytoin therapy
Seizure, During neurosurgery; Treatment and Prophylaxis- oral route:
The initial dose is 5 milligrams/kilogram (mg/kg) orally per day divided equally into 2 or 3 doses to a subsequent maximum of 300 mg/day. The usual maintenance dose of 4 to 8 mg/kg/day is instituted 24 hours after the loading dose. Children over the age of 6 years may require the minimum adult dose of 300 mg/day
Seizure, Generalized Tonic-Clonic and Complex Partial (psychomotor and temporal lobe) Seizures
Dosing information
The initial recommended oral dosage of phenytoin suspension or chewable tablets or phenytoin sodium extended-release capsules is 5 milligrams/kilogram (mg/kg) per day (in 2 or 3 divided doses). Dosage should be individualized up to 300 mg daily. In infants and children, usual maintenance doses are 4 to 8 mg/kg/day, in 2 or 3 divided doses. Children over the age of 6 years may require the minimum adult dose of 300 mg/day.
In studies based on Michaelis-Menten pharmacokinetics, children in younger age groups require larger doses/kilogram/day than older children. The average milligram/kilogram/day (mg/kg) dose required to achieve a phenytoin level of 15 micrograms/milliliter was as follows: 0.5 to 3 years of age, 9.7 mg/kg/day; 4 to 6 years of age, 7.5 mg/kg/day; 7 to 9 years of age, 7 mg/kg/day; 10 to 16 years of age, 6 mg/kg/day.
Status epilepticus
Dosing information
For the treatment of status epilepticus, the manufacturer recommends a loading doses of 15 to 20 milligrams/kilogram (mg/kg) administered slowly intravenously at a rate not exceeding 1 to 3 mg/kg/minute or 50 mg/min (whichever is slower). Determination of phenytoin plasma levels is recommended in the subsequent establishment of maintenance dosing.
In neonates, a loading dose of 15 to 20 mg/kg IV, administered slowly (do not exceed 1 to 3 mg/kg/min) is recommended
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
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Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Phenytoin (oral) in pediatric patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Phenytoin (oral) in pediatric patients.
Contraindications
Condition1
Warnings
Title
See full prescribing information for complete Boxed Warning.
ConditionName:
Content
Description
Precautions
Description
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Phenytoin (oral) in the drug label.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Phenytoin (oral) in the drug label.
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Phenytoin (oral) in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Phenytoin (oral) during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Phenytoin (oral) with respect to nursing mothers.
Pediatric Use
There is no FDA guidance on the use of Phenytoin (oral) with respect to pediatric patients.
Geriatic Use
There is no FDA guidance on the use of Phenytoin (oral) with respect to geriatric patients.
Gender
There is no FDA guidance on the use of Phenytoin (oral) with respect to specific gender populations.
Race
There is no FDA guidance on the use of Phenytoin (oral) with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Phenytoin (oral) in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Phenytoin (oral) in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Phenytoin (oral) in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Phenytoin (oral) in patients who are immunocompromised.
Administration and Monitoring
Administration
When given in equal doses, Dilantin Infatabs yield higher plasma levels than Dilantin Kapseals®. For this reason serum concentrations should be monitored and care should be taken when switching a patient from the sodium salt to the free acid form.
Dilantin® Kapseals® is formulated with the sodium salt of phenytoin. The free acid form of phenytoin is used in Dilantin-125 Suspension and Dilantin Infatabs. Because there is approximately an 8% increase in drug content with the free acid form over that of the sodium salt, dosage adjustments and serum level monitoring may be necessary when switching from a product formulated with the free acid to a product formulated with the sodium salt and vice versa.
General
Not for once-a-day dosing.
Dosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations may be necessary for optimal dosage adjustments—the clinically effective serum level is usually 10–20 mcg/mL. With recommended dosage, a period of seven to ten days may be required to achieve steady-state blood levels with phenytoin and changes in dosage (increase or decrease) should not be carried out at intervals shorter than seven to ten days.
Dilantin Infatabs can be either chewed thoroughly before being swallowed or swallowed whole.
Adult Dosage
Patients who have received no previous treatment may be started on two Infatabs three times daily, and the dose is then adjusted to suit individual requirements. For most adults, the satisfactory maintenance dosage will be six to eight Infatabs daily; an increase to twelve Infatabs daily may be made, if necessary.
Dosing in Special Populations
Patients with Renal or Hepatic Disease
Due to an increased fraction of unbound phenytoin in patients with renal or hepatic disease, or in those with hypoalbuminemia, the interpretation of total phenytoin plasma concentrations should be made with caution. Unbound phenytoin concentrations may be more useful in these patient populations.
Elderly Patients
Phenytoin clearance is decreased slightly in elderly patients and lower or less frequent dosing may be required.
Pediatric
Initially, 5 mg/kg/day in two or three equally divided doses, with subsequent dosage individualized to a maximum 300 mg daily. A recommended daily maintenance dosage is usually 4 to 8 mg/kg. Children over 6 years old and adolescents may require the minimum adult dose (300 mg/day). If the daily dosage cannot be divided equally, the larger dose should be given before retiring.
Monitoring
There is limited information regarding Monitoring of Phenytoin (oral) in the drug label.
Description
IV Compatibility
There is limited information regarding IV Compatibility of Phenytoin (oral) in the drug label.
Overdosage
Acute Overdose
Signs and Symptoms
Description
Management
Description
Chronic Overdose
There is limited information regarding Chronic Overdose of Phenytoin (oral) in the drug label.
Pharmacology
There is limited information regarding Phenytoin (oral) Pharmacology in the drug label.
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