2 DOSAGE AND ADMINISTRATION
2.1 Adult Dosage
Divided daily dosage:
The recommended starting dose for adult patients who have received no previous treatment is one 100-mg DILANTIN (extended phenytoin sodium capsule, USP) by mouth three times daily. Adjust the dosage to suit individual requirements up to a maximum of two capsules three times a day. For most adults, the satisfactory maintenance dosage will be one capsule three to four times a day.
In adults, if seizure control is established with divided doses of three 100-mg DILANTIN (extended phenytoin sodium capsules, USP) daily, once-a-day dosage with 300 mg of DILANTIN (extended phenytoin sodium capsules, USP) may be considered. Studies comparing divided doses of 300 mg with a single daily dose of this quantity indicated absorption, peak serum levels, biologic half-life, difference between peak and minimum values, and urinary recovery were equivalent. Once-a-day dosage offers a convenience to the individual patient or to nursing personnel for institutionalized patients and is intended to be used only for patients requiring this amount of drug daily. A major problem in motivating noncompliant patients may also be lessened when the patient can take this drug once a day. However, patients should be cautioned not to miss a dose, inadvertently.
Only DILANTIN (extended phenytoin sodium capsules, USP) are recommended for once-a-day dosing. Inherent differences in dissolution characteristics and resultant absorption rates of phenytoin due to different manufacturing procedures and/or dosage forms preclude such recommendation for other phenytoin products. When a change in the dosage form or brand is prescribed, careful monitoring of phenytoin serum levels should be carried out.
Some authorities have advocated use of an oral loading dose of phenytoin in adults who require rapid steady-state serum levels and where intravenous administration is not desirable. This dosing 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.
Initially, one gram of DILANTIN (extended phenytoin sodium capsules, USP) is divided into three doses (400 mg, 300 mg, 300 mg) and administered at two-hour intervals. Normal maintenance dosage is then instituted 24 hours after the loading dose, with frequent serum level determinations.
2.2 Pediatric Dosage
The recommended starting dosage for pediatric patients is 5 mg/kg/day by mouth in two or three equally divided doses, with subsequent dosage individualized to a maximum of 300 mg daily in divided doses. A recommended daily maintenance dosage is usually 4 to 8 mg/kg/day in equally divided doses. Children over 6 years and adolescents may require the minimum adult dosage (300 mg/day).
2.3 Dosage Adjustments
Dosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations may be necessary for optimal dosage adjustments. Trough levels provide information about clinically effective serum level range and confirm patient compliance, and are obtained just prior to the patient's next scheduled dose. Peak levels indicate an individual's threshold for emergence of dose-related side effects and are obtained at the time of expected peak concentration. Therapeutic effect without clinical signs of toxicity occurs more often with serum total concentrations between 10 and 20 mcg/mL (unbound phenytoin concentrations between 1 and 2 mcg/mL), although some mild cases of tonic-clonic (grand mal) epilepsy may be controlled with lower serum levels of phenytoin. In patients with renal or hepatic disease, or in those with hypoalbuminemia, the monitoring of unbound phenytoin concentrations may be more relevant [see Dosage and Administration (2.5)].
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.
2.4 Switching Between Phenytoin Formulations
The free acid form of phenytoin is used in DILANTIN-125 Suspension and DILANTIN Infatabs. DILANTIN extended capsules and parenteral DILANTIN are formulated with the sodium salt of phenytoin. 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.
2.5 Dosing in Patients with Renal or Hepatic Impairment or Hypoalbuminemia
Because the fraction of unbound phenytoin is increased in patients with renal or hepatic disease, or in those with hypoalbuminemia, the monitoring of phenytoin serum levels should be based on the unbound fraction in those patients [see Warnings and Precautions (5.11) and Use in Specific Populations (8.6)].
2.6 Geriatric Dosage
Phenytoin clearance is decreased slightly in elderly patients and lower or less frequent dosing may be required [see Clinical Pharmacology (12.3)].
2.7 Dosing during Pregnancy
Decreased serum concentrations of phenytoin may occur during pregnancy because of altered phenytoin pharmacokinetics. Periodic measurement of serum phenytoin concentrations should be performed during pregnancy, and the DILANTIN dosage should be adjusted as necessary. Postpartum restoration of the original dosage will probably be indicated [see Use in Specific Populations (8.1)]. Because of potential changes in protein binding during pregnancy, the monitoring of phenytoin serum levels should be based on the unbound fraction.