Phenytoin (Dilantin ®)

Usual Diluents

Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate]

[Package insert: Revised June 2016.]

Loading Dose: A loading dose of parenteral Phenytoin Sodium Injection should be injected slowly, not exceeding 50 mg per minute in adults and 1-3 mg/kg/min (or 50 mg per minute, whichever is slower) in pediatric patients.

Infusion: For infusion administration, parenteral Phenytoin Sodium Injection should be diluted in normal saline with the final concentration of phenytoin sodium in the solution no less than 5 mg/mL. Administration should commence immediately after the mixture has been prepared and must be completed within 1 to 4 hours (the infusion mixture should not be refrigerated). An in-line filter (0.22-0.55 microns) should be used.

Sample dilution:
[1000 mg] [180 mL ] [ 20 - 30 minutes]
Total volume: Drug plus solution - 200 ml. Conc: 5 mg/mL.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

The diluted infusion mixture (Phenytoin Sodium Injection plus normal saline) should not be refrigerated. If the undiluted parenteral Phenytoin Sodium Injection is refrigerated or frozen, a precipitate might form: this will dissolve again after the solution is allowed to stand at room temperature. The product is still suitable for use. A faint yellow coloration may develop, however this has no effect on the potency of the solution.

Stability / Miscellaneous

Usual IV loading dose: 15 mg/kg TBW

Maintenance dose (started 18-24h after load): 6 mg/kg ibw IV/PO in divided doses q8 to 12h. (The IV maintenance dose should never be given qd in a single dose).

Sampling: 18 to 24h after loading dose, then q5 to 7 days to assess trend. Average time to steady state: 10 to 14days.
Half-life: 7-42hrs (average=24h).

Capsules/injection= 92% phenytoin. Elixir/tabs=100% phenytoin.

Equation used to estimate the dose req'd to increase current level to normal range if subtherapeutic: = [0.7 x IBW x (15 - current level) ] / 0.92* * (if capsules/injection used)

Adjusted phenytoin concentration if low serum albumin= measured total concentration / [ (0.2 x albumin) + 0.1]

DOSAGE AND ADMINISTRATION
Because of the increased risk of adverse cardiovascular reactions associated with rapid administration, intravenous administration should not exceed 50 mg per minute in adults. In pediatric patients, the drug should be administered at a rate not exceeding 1-3 mg/kg/min or 50 mg per minute, whichever is slower.

As non-emergency therapy, Phenytoin Sodium Injection should be administered more slowly as either a loading dose or by intermittent infusion. Because of the risks of cardiac and local toxicity associated with intravenous phenytoin, oral phenytoin should be used whenever possible.

Because adverse cardiovascular reactions have occurred during and after infusions, careful cardiac monitoring is needed during and after the administration of intravenous Phenytoin Sodium Injection. Reduction in rate of administration or discontinuation of dosing may be needed.

Because of the risk of local toxicity, intravenous Phenytoin Sodium Injection 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 Sodium Injection 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.

Phenytoin Sodium Injection can be given diluted with normal saline. The addition of parenteral Phenytoin Sodium Injection to dextrose and dextrose-containing solutions should be avoided due to lack of solubility and resultant precipitation.

Treatment with Phenytoin Sodium Injection can be initiated either with a loading dose or an infusion:

Loading Dose: A loading dose of parenteral Phenytoin Sodium Injection should be injected slowly, not exceeding 50 mg per minute in adults and 1-3 mg/kg/min (or 50 mg per minute, whichever is slower) in pediatric patients.

Infusion: For infusion administration, parenteral Phenytoin Sodium Injection should be diluted in normal saline with the final concentration of phenytoin sodium in the solution no less than 5 mg/mL. Administration should commence immediately after the mixture has been prepared and must be completed within 1 to 4 hours (the infusion mixture should not be refrigerated). An in-line filter (0.22-0.55 microns) should be used.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

The diluted infusion mixture (Phenytoin Sodium Injection plus normal saline) should not be refrigerated. If the undiluted parenteral Phenytoin Sodium Injection is refrigerated or frozen, a precipitate might form: this will dissolve again after the solution is allowed to stand at room temperature. The product is still suitable for use. A faint yellow coloration may develop, however this has no effect on the potency of the solution.

Status Epilepticus
In adults, a loading dose of 10 to 15 mg/kg should be administered slowly intravenously, at a rate not exceeding 50 mg per minute (this will require approximately 20 minutes in a 70-kg patient).

The loading dose should be followed by maintenance doses of 100 mg orally or intravenously every 6-8 hours.

In the pediatric population, a loading dose of 15-20 mg/kg of phenytoin sodium intravenously will usually produce plasma 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 1-3 mg/kg/min or 50 mg per 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 plasma 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 intravenous benzodiazepine such as diazepam, or an intravenous 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 Sodium Injection does not terminate seizures, the use of other anticonvulsants, intravenous barbiturates, general anesthesia and other appropriate measures should be considered.

Intramuscular administration should not be used in the treatment of status epilepticus because the attainment of peak plasma levels may require up to 24 hours.

Nonemergent Loading and Maintenance Dosing
Because of the risks of cardiac and local toxicity associated with intravenous phenytoin, oral phenytoin should be used whenever possible. In adults, a loading dose of 10 to 15 mg/kg should be administered slowly. The rate of intravenous administration should not exceed 50 mg per minute in adults and 1-3 mg/kg/min (or 50 mg per minute, whichever is slower) in pediatric patients. Slower administration rates are recommended to minimize the cardiovascular adverse reactions. Continuous monitoring of the electrocardiogram, blood pressure, and respiratory function is essential.

The loading dose should be followed by maintenance doses of oral or intravenous phenytoin every 6-8 hours.

Ordinarily, Phenytoin Sodium Injection should not be given intramuscularly because of the risk of necrosis, abscess formation, and erratic absorption. If intramuscular administration is required, compensating dosage adjustments are necessary to maintain therapeutic plasma levels. An intramuscular dose 50% greater than the oral dose is necessary to maintain these levels. When returned to oral administration, the dose should be reduced by 50% of the original oral dose for one week to prevent excessive plasma levels due to sustained release from intramuscular tissue sites.

Monitoring plasma levels would help prevent a fall into the subtherapeutic range. Serum blood level determinations are especially helpful when possible drug interactions are suspected.

IV Substitution For Oral Phenytoin Therapy

When treatment with oral phenytoin is not possible, IV phenytoin can be substituted for oral phenytoin at the same total daily dose. Phenytoin capsules are approximately 90% bioavailable by the oral route. Phenytoin is 100% bioavailable by the IV route. For this reason, plasma phenytoin concentrations may increase modestly when IV phenytoin is substituted for oral phenytoin sodium therapy. The rate of administration for IV phenytoin should be no greater than 50 mg per minute in adults and 1-3 mg/kg/min (or 50 mg per minute, whichever is slower) in pediatric patients.

Serum concentrations should be monitored and care should be taken when switching a patient from the sodium salt to the free acid form. Phenytoin Sodium Injection is 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.

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: A loading dose of 15-20 mg/kg of Phenytoin Sodium Injection intravenously will usually produce plasma 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 1-3 mg/kg/min or 50 mg per minute, whichever is slower.

HOW SUPPLIED
Phenytoin Sodium Injection, USP is supplied in the following:
NDC Container Concentration Fill Quantity

0409-1844-32 Carpuject® with Luer Lock 50 mg/mL-2 mL; Box of 10
Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]

Do not freeze.

To prevent needle-stick injuries, needles should not be recapped, purposely bent, or broken by hand.

Revised: July, 2007
Printed in USA EN-1562
Hospira, Inc., Lake Forest, IL 60045 USA
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Phenytoin Sodium Injection, USP-50 mg/mL
2 mL (100 mg) DOSETTE vials packaged in 25s (NDC0641-0493-25)
5 mL (250 mg) Single Use vials packaged in 25s (NDC0641-2555-45)

Manufactured by
Baxter Healthcare Corporation
Deerfield, IL 60015 USA
For Product Inquiry 1 800 ANA DRUG (1-800-262-3784)
MLT-15/1.0

Source: [package insert]