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General: Phenytoin capsules and solution for injection are formulated with the sodium salt of phenytoin. The free acid form of phenytoin is used in the phenytoin suspension (30 mg/5 mL [pediatric] and 125 mg/5 mL) and in the phenytoin tablets. 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.
Phenytoin serum level determinations may be necessary to achieve optimal dosage adjustments.
Optimum control without clinical signs of toxicity occurs most often with serum levels between 10 mcg/mL and 20 mcg/mL.
Parenteral phenytoin may be administered as a slow intravenous (IV) bolus or it may be administered via an IV infusion. Rapid infusion may be associated with adverse cardiovascular events (see General under Precautions).
Because of the risks of cardiac and local toxicity associated with intravenous phenytoin, oral phenytoin should be used whenever possible.
If administered in diluted form, parenteral phenytoin should be diluted with normal saline. Parenteral phenytoin should not be added to dextrose or dextrose-containing solutions due to the potential for precipitation.
Because of the risk of local toxicity, IV phenytoin should be administered directly into a large peripheral or central vein through a large-gauge catheter. Prior to the administration, the patency of the IV catheter should be tested with a flush of sterile saline. Each injection of parenteral phenytoin should then be followed by a flush of sterile saline through the same catheter to avoid local venous irritation due to the alkalinity of the solution (see Local Toxicity (Including Purple Glove Syndrome) under Precautions).
Bolus Administration: A bolus of parenteral phenytoin should be injected slowly, not exceeding 50 mg/min in adults, into a large vein through a large-gauge needle or IV catheter. Each injection of IV phenytoin should be preceded by a saline flush and followed by an injection of sterile saline through the same needle or catheter to avoid local venous irritation due to the alkalinity of the solution.
Infusion Administration: For administration by infusion, parenteral phenytoin should be diluted in 50 mL to 100 mL of normal saline with the final concentration of phenytoin in the solution not exceeding 10 mg/mL. Administration should commence immediately after the mixture has been prepared and must be completed within 1 hour (the infusion mixture should not be refrigerated). An in-line filter (0.22-0.50 microns) should be used. Each injection of IV phenytoin should be preceded by a saline flush and followed by an injection of sterile saline through the same needle or IV catheter to help reduce local venous irritation due to the alkalinity of the solution.
Dosage is not to exceed 50 mg/minute, intravenously in adults, and not to exceed 1 - 3 mg/kg/minute in neonates and children or 50 mg/minute, whichever is slower. There is a relatively small margin between full therapeutic effect and minimally toxic doses of this drug (see General under Precautions).
On occasions when intramuscular (IM) administration may be required (i.e., post-operatively in comatose patients), a sufficient dose must be administered intramuscularly to maintain the serum level within the therapeutic range. Where oral dosage is resumed following IM usage, the oral dosage should be adjusted to compensate for the slow, continuing IM absorption to avoid toxic symptoms. To avoid drug accumulation due to absorption from the muscle depots, it is recommended that for the first week back on oral phenytoin, the oral dose be reduced to one-half of the original dose (one-third of the IM dose).
Status Epilepticus: In adults, a loading dose of 10 mg/kg to 15 mg/kg should be administered slowly intravenously, at a rate not exceeding 50 mg/minute (this will require approximately 20 minutes in a 70 kg patient). The loading dose should be followed by a maintenance dose of 100 mg orally or intravenously every 6 to 8 hours.
Absorption of phenytoin in neonates and children may be unreliable after oral administration. A loading dose of 15 mg/kg to 20 mg/kg of phenytoin intravenously will usually produce serum concentrations of phenytoin within the generally accepted therapeutic range (10-20 mcg/mL). The drug should be injected slowly intravenously at a rate not exceeding 1 to 3 mg/kg/minute or 50 mg/minute, whichever is slower.
Continuous monitoring of the electrocardiogram and blood pressure is essential. The patient should be observed for signs of respiratory depression. Determination of phenytoin serum levels is advised when using phenytoin in the management of status epilepticus and in the subsequent establishment of maintenance dosage.
Other measures including concomitant administration of an IV benzodiazepine such as diazepam, or IV short-acting barbiturate, will usually be necessary for rapid control of seizures because of the required slow rate of administration of phenytoin.
If administration of parenteral phenytoin does not terminate seizures, the use of other anticonvulsants, IV barbiturates, general anesthesia, or other appropriate measures should be considered.
Intramuscular administration should not be used in the treatment of status epilepticus because the attainment of peak serum levels may require up to 24 hours (see General under Precautions).
Neurosurgery: Prophylactic dosage - 100 mg to 200 mg (2 mL to 4 mL) administered intramuscularly at approximately 4-hour intervals during surgery and continued during the post-operative period. When IM administration is required for a patient previously stabilized orally, compensating dosage adjustments are necessary to maintain therapeutic serum levels. When IM administration is used, the drug should be given by deep IM injection. An IM dose 50% greater than the oral dose is necessary to maintain these levels. When the patient is returned to oral administration, the dose should be reduced by 50% of the original oral dose for 1 week to prevent excessive serum levels due to sustained release form IM tissue sites.
If the patient requires more than a week of IM phenytoin, alternative routes should be explored, such as gastric intubation. For time periods less than 1 week, the patient shifted back from IM administration should receive one-half the original oral dose for the same period of time the patient received IM phenytoin. Monitoring serum levels would help prevent a fall into the subtherapeutic range. Serum drug level determinations are especially helpful when possible drug interactions are suspected.
Dosing in Special Populations: Patients with Renal or Hepatic Disease: see Precautions.
Elderly Patients: Phenytoin clearance is decreased slightly in elderly patients and lower or less frequent dosing may be required (see Pharmacology: Pharmacokinetics: Special Populations: Age under Actions).
