Phenytoindosage

NOT FOR ONCE-A-DAY DOSING

Adult starting dose in patients who have received no previous treatment is two Infatabs three times a day, with dose adjustments as necessary. For most adults, the satisfactory maintenance dose will be six to eight Infatabs daily; an increase to twelve Infatabs daily may be made, if necessary.

Pediatric starting dose is 5 mg/kg/day in two to three equally divided doses, with dosage adjustments as necessary, up to a maximum of 300 mg daily. Maintenance dosage is 4 to 8 mg/kg/day.

Serum blood level determinations may be necessary for optimal dosage adjustments—the clinically effective serum total concentration is 10 to 20 mcg/mL (unbound phenytoin concentration is 1 to 2 mcg/mL).

2.1 Important

Administration Instructions NOT FOR ONCE-A-DAY DOSING. DILANTIN INFATABS can be either chewed thoroughly before being swallowed or swallowed whole.

2.2 Adult Dosage

The recommended starting dosage for adult patients who have received no previous treatment is two 50 mg Infatabs by mouth three times daily. Adjust the dosage to suit individual requirements up to a maximum of twelve Infatabs daily. For most adults, the satisfactory maintenance dosage will be six to eight Infatabs daily.

2.3 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). If the daily dosage cannot be divided equally, the larger dose should be given before retiring.

2.4 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 of 1 to 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. 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.

2.5 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.

2.6 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.

2.7 Geriatric

Dosage Phenytoin clearance is decreased slightly in elderly patients and lower or less frequent dosing may be required.

2.8 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. Because of potential changes in protein binding during pregnancy, the monitoring of phenytoin serum levels should be based on the unbound fraction.