Fosphenytoin sodium injection is a prodrug intended for parenteral administration; its active metabolite is phenytoin. 1.5 mg of fosphenytoin sodium is equivalent to 1 mg phenytoin sodium, and is referred to as 1 mg phenytoin sodium equivalents (PE). The amount and concentration of fosphenytoin is always expressed in terms of mg PE.
One mL of Pro-Epanutin contains 75 mg of fosphenytoin sodium (equivalent to 50 mg of phenytoin sodium) (see Section 4.2).
Pro-Epanutin is available in 10 mL and 2 mL vials.
Each 10 mL vial contains 500 mg PE.
Each 2 mL vial contains 100 mg PE.
For a full list of excipients, see Section 6.1
IMPORTANT NOTE: Throughout all Pro-Epanutin product labelling, the amount and concentration of fosphenytoin is always expressed in terms of phenytoin sodium equivalents (PE) to avoid the need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses. Pro-Epanutin should always be prescribed and dispensed in phenytoin sodium equivalent units (PE). Note, however, that fosphenytoin has important differences in administration from parenteral phenytoin sodium (see Section 4.4 Special Warnings and Precautions for Use).
Phenytoin sodium equivalents (PE):
1.5 mg of fosphenytoin is equivalent to 1 mg phenytoin sodium, and is referred to as 1 mg phenytoin sodium equivalents (PE) (see Section 4.4 Special Warnings and Precautions for Use).
Each 10 mL vial of Pro-Epanutin contains 500 mg PE.
Each 2 mL vial of Pro-Epanutin contains 100 mg PE.
Administration:
Pro-Epanutin may be administered by intravenous (IV) infusion or by intramuscular (IM) injection. The IM route should be considered for adult patients when there is not an urgent need to control seizures. If rapid phenytoin loading is a primary goal, IV administration of Pro-Epanutin is preferred because the time to achieve therapeutic plasma phenytoin concentrations following IV administration is faster as compared to IM administration.
Pro-Epanutin should not be administered by IM route in emergency situations such as status epilepticus.
Intramuscular (IM) injection is not recommended for children.
Products with particulate matter or discoloration should not be used.
Pro-Epanutin is intended for short-term parenteral administration, and has not been eva luated for periods of more than 5 days.
Intravenous (IV) infusion:
For IV infusion, Pro-Epanutin should be diluted in 5% glucose or 0.9% sodium chloride solution. The concentration should range from 1.5 to 25 mg PE/mL.
Because of the risk of hypotension, the recommended rate of administration by IV infusion in routine clinical settings is 50-100 mg PE/minute. Even in an emergency, it should not exceed 150 mg PE/minute. The use of a device controlling the rate of infusion is recommended.
Please refer to tables 1 to 10 for examples of dosing, dilution and infusion time calculations.
Continuous monitoring of electrocardiogram, blood pressure and respiratory function for the duration of the infusion is essential. The patient should also be observed throughout the period where maximal plasma phenytoin concentrations occur. This is approximately 30 minutes after the end of the Pro-Epanutin infusions.
Cardiac resuscitative equipment should be available (see Section 4.4 Special Warnings and Precautions for Use).
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Please refer to Tables 1-10 for examples of dosing, dilution, and infusion time calculations
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Population
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Indication
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Dosing Table
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Adults
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Status epilepticus
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Loading dose
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Table 1
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Status epilepticus
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Maintenance dose
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Table 2
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Seizure treatment or prophylaxis
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Loading dose
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Table 3
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Seizure treatment or prophylaxis
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Maintenance dose
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Table 4
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Temporary substitution for oral phenytoin
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Table 5
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Children (aged 5 years and older)
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Status epilepticus
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Loading dose
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Table 6
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Status epilepticus
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Maintenance dose
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Table 7
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Seizure treatment or prophylaxis
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Loading dose
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Table 8
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Seizure treatment or prophylaxis
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Maintenance dose
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Table 9
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Temporary substitution for oral phenytoin
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Table 10
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DOSAGE IN ADULTS
(For Dose reduction in the Elderly or patients with Renal or Hepatic impairment, please see guidance towards the end of this section.)
Status Epilepticus
Intramuscular (IM) administration of Pro-Epanutin is not recommended in the treatment of status epilepticus.
Loading dose:
In order to obtain rapid seizure control in patients with continuous seizure activity, IV diazepam or lorazepam should be administered prior to administration of Pro-Epanutin.
The loading dose of Pro-Epanutin is 15 mg PE/kg administered as a single dose by IV infusion.
Recommended IV infusion rate (for loading dose in adults): 100 to 150 mg PE/min (should not exceed 150 mg PE/minute even for emergency use). See Table 1 for infusion times.
If administration of Pro-Epanutin does not terminate seizures, the use of alternative anticonvulsants should be considered.
Table 1 displays dosing information for status epilepticus loading dose in adults.
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TABLE 1 STATUS EPILEPTICUS LOADING DOSE (ADULTS)
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Examples of IV loading doses of 15 mg PE†/kg, and recommendations for dilution (to 25 mg PE/mL) and IV infusion times (at maximum rate of 150 mg PE/min) by body weight
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Weight
(Kg)
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Dose
(mg PE)
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Volume of Pro-Epanutin
(50 mg PE/mL)
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Volume (mL) of diluent
(5% glucose or 0.9% sodium chloride)
for final concentration of 25 mg PE/mL
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Minimum Infusion Time
(minutes)
to achieve the maximum recommended infusion rate of 150 mg PE/minute
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No. of 10 mL vials to open
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Volume (mL) to draw up
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100
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1500
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3
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30
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30
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10
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95
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1425
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3
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28.5
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28.5
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9.5
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90
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1350
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3
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27
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27
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9
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85
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1275
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3
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