Usual Adult Dose for Status Epilepticus

Loading dose: 15 to 20 mg PE/kg IV; infuse at 100 to 150 mg PE/min

• Maximum infusion rate: 150 mg PE/min

Maintenance dose: 4 to 6 mg PE/kg/day in divided doses at a rate no greater than 150 mg PE/min

• After initial maintenance dose, subsequent doses should be individualized to achieve therapeutic phenytoin concentrations

Comments:

• The maximal rate of IV administration should not be exceeded due to cardiovascular risk associated with rapid infusion rates.
• Continuously monitor electrocardiogram, blood pressure, and respiratory function throughout the IV infusion and for approximately 10 to 20 minutes at the end of the infusion when maximal serum phenytoin concentrations are expected.
• Because the full antiepileptic effect of phenytoin is not immediate, other measures, including concomitant administration of an IV benzodiazepine may be necessary for control of status epilepticus.
• If this drug does not terminate seizures, the use of alternative anticonvulsants should be considered.

Use: For the treatment of generalized tonic-clonic status epilepticus

Usual Adult Dose for Epilepsy

Loading dose: 10 to 20 mg PE/kg IV; infuse at a rate no greater than 150 mg PE/min

• May be administered as a single IM dose when IV access is impossible

Maintenance dose: 4 to 6 mg PE/kg/day IV in divided doses at a rate no greater than 150 mg PE/min

• After initial maintenance dose, subsequent doses should be individualized to achieve therapeutic phenytoin concentrations

Comments:

• The maximal rate of IV administration should not be exceeded due to cardiovascular risk associated with rapid infusion rates.
• Continuously monitor electrocardiogram, blood pressure, and respiratory function throughout the IV infusion and for approximately 10 to 20 minutes at the end of the infusion when maximal serum phenytoin concentrations are expected.
• When treatment with oral phenytoin is not possible, this drug can be substituted for oral phenytoin at the same total daily phenytoin sodium equivalents (PE) dose.
• Because of the risks of cardiac and local toxicity associated with IV administration, oral phenytoin should be used whenever possible.

Uses:

• Prevention and treatment of seizures occurring during neurosurgery
• Short term substitute for oral phenytoin

Usual Pediatric Dose for Status Epilepticus

Cerebyx:
Less than 17 years:
Loading dose: 15 to 20 mg PE/kg IV; infuse at 2 mg PE/min (or 150 mg PE/min, whichever is slower)

Maintenance Dose:

• Initial Maintenance Dose: 2 to 4 mg PE/kg/day IV administered 12 hours after loading dose; infuse at 1 to 2 mg PE/kg/min or 100 mg PE/min, whichever is slower
• Maintenance dose after Initial Maintenance Dose: 4 to 8 mg PE/kg/day in 2 divided doses (every 12 hours); infuse at 1 to 2 mg PE/kg/min or 100 mg PE/min, whichever is slower

17 years or older: See Adult Dosing

Comments:

• The maximal rate of IV administration should not be exceeded due to cardiovascular risk associated with rapid infusion rates.
• Continuously monitor electrocardiogram, blood pressure, and respiratory function throughout the IV infusion and for approximately 10 to 20 minutes at the end of the infusion when maximal serum phenytoin concentrations are expected.
• Because the full antiepileptic effect of phenytoin is not immediate, other measures, including concomitant administration of an IV benzodiazepine may be necessary for control of status epilepticus.
• If this drug does not terminate seizures, the use of alternative anticonvulsants should be considered.
• Sesquient is not approved for status epilepticus in pediatric patients as the safety of rapid IV administration is unknown; this formulation contains betadex sulfobutyl ether sodium and the rate of administration for patients 2 to 17 years should not exceed 0.4 mg PE/kg/min.

Use: For the treatment of generalized tonic-clonic status epilepticus (Cerebyx only)

Usual Pediatric Dose for Epilepsy

Cerebyx:
Less than 17 years:
Loading Dose: 10 to 15 mg PE/kg IV; infuse at 1 to 2 mg PE/kg/min or 150 mg PE/min, whichever is slower

Maintenance Doses:

• Initial Maintenance Dose: 2 to 4 mg PE/kg/day IV administered 12 hours after loading dose; infuse at 1 to 2 mg PE/kg/min or 100 mg PE/min, whichever is slower
• Maintenance dose after Initial Maintenance Dose: 4 to 8 mg PE/kg/day in 2 divided doses (every 12 hours); infuse at 1 to 2 mg PE/kg/min or 100 mg PE/min, whichever is slower

17 years or older: See Adult Dosing

Comments:

• The maximal rate of IV administration should not be exceeded due to cardiovascular risk associated with rapid infusion rates.
• Continuously monitor electrocardiogram, blood pressure, and respiratory function throughout the IV infusion and for approximately 10 to 20 minutes at the end of the infusion when maximal serum phenytoin concentrations are expected.
• When treatment with oral phenytoin is not possible, this drug can be substituted for oral phenytoin at the same total daily phenytoin sodium equivalents (PE) dose.
• Because of the risks of cardiac and local toxicity associated with IV administration, oral phenytoin should be used whenever possible.
• IM administration should ordinarily not be used in pediatric patients
• Sesquient is not approved for prevention and treatment of seizures occurring during neurosurgery in pediatric patients as the safety of rapid IV administration is unknown; this formulation contains betadex sulfobutyl ether sodium and is approved as a short term substitute for oral phenytoin in patients 2 to 17 years old at a rate of administration not to exceed 0.4 mg PE/kg/min.

Use: Prevention and treatment of seizures occurring during neurosurgery (Cerebyx)

SUBSTITUTION FOR ORAL PHENYTOIN: When treatment with oral phenytoin is not possible, IV fosphenytoin can be substituted for oral phenytoin at the same total daily phenytoin sodium equivalents (PE) dose.

• Cerebyx: For use in all pediatric patients: Maximum infusion rate: 1 to 2 mg PE/kg/min or 100 mg PE/min, whichever is slower
• Sesquient: For use in all pediatric 2 years and older: Maximum infusion rate: 0.4 mg PE/kg/min

Renal Dose Adjustments

Use with caution; monitor unbound phenytoin concentrations

Severe Renal Impairment (eGFR 15 to 29 mL/min/1.73 m2):

• Sesquient: Closely monitor serum creatinine levels; if the serum creatinine level increases, consider changing to oral phenytoin (this is because sulfobutylether beta-cyclodextrin sodium salt is known to accumulate in patients with moderate to severe renal impairment)

Liver Dose Adjustments

Use with caution; monitor unbound phenytoin concentrations

Dose Adjustments

Elderly: A lower dose or less frequent dosing may be needed as the clearance of phenytoin is decreased slightly in elderly patients

Monitoring Phenytoin Levels:

• Fosphenytoin doses are selected to attain therapeutic serum total phenytoin concentrations of 10 to 20 mcg/mL (unbound phenytoin concentrations of 1 to 2 mcg/mL)
• Phenytoin concentrations should not be monitored until conversion to phenytoin is essentially complete; this occurs approximately 2 hours after the end of the IV infusion or 4 hours after IM injection

Monitoring Phenytoin Levels in Patients with Hypoalbuminemia (including patients with renal or hepatic impairment) and When Used During Pregnancy:

• Unbound phenytoin serum levels should be measured in patients with renal or hepatic disease, in those with hypoalbuminemia, and in patients during pregnancy due to an increase in unbound phenytoin

Precautions

US BOXED WARNINGS: Cardiovascular Risk Associated with Rapid Infusion Rates:

• The rate of IV administration should not exceed 150 mg phenytoin sodium equivalents (PE) per minute in adults and 2 mg PE/kg/min (or 150 mg/PE/min whichever is slower) in pediatric patients because of the risk of severe hypotension and cardiac arrhythmias.
• Careful cardiac monitoring is needed during and after IV administration of this drug. Although the risk of cardiovascular toxicity increases with infusion rates above the recommended infusion rate, these events have also been reported at or below the recommended infusion rate. Reduction in rate of administration or discontinuation of dosing may be needed.

Safety and efficacy of Sesquient have not been established in patients younger than 2 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:
For IV infusion; do not exceed IV infusion rates due to cardiovascular risks

• Cerebyx: May be administered IM in adult patients when IV access is impossible; should not be used for status epilepticus

DOSING ERRORS:

• Be aware that dosing errors have occurred due to confusion with the concentration of fosphenytoin and total amount of drug in the vial; the fosphenytoin concentration is 50 mg PE/mL in both the 2 mL and 10 mL vials; the 2 mL vial of Cerebyx (fosphenytoin) contains a total of 100 mg PE; the 10 mL vial of Cerebyx (fosphenytoin) contains a total of 500 mg PE
• Doses of fosphenytoin are always expressed in terms of milligrams of phenytoin sodium equivalents (mg PE): fosphenytoin 1 mg PE is equivalent to 1 mg phenytoin sodium and therefore no adjustment should be made when substituting fosphenytoin for phenytoin sodium or vice versa

Storage requirements:

• Cerebyx vials should be stored at 2C to 8C (36F to 46F); vials should not be stored at room temperature for more than 48 hours
• Sesquient vials: Store at room temperature; excursions permitted between 15C and 30C (59F to 86F)

Reconstitution/preparation techniques:

• Prior to IV infusion, dilute in D5W or NS to a concentration of 1.5 to 25 mg PE/mL
• Sesquient: Diluted Sesquient solution is stable for 4 hours at room temperature

General:

• Sesquient is a room temperature stable formulation of fosphenytoin has been approved by the FDA for status epilepticus and prevention and treatment of seizures occurring during neurosurgery in adults; the safety of rapid administration of betadex sulfobutyl ether sodium (excipient) in pediatric patients is unknown and therefore its rate of administration differs from other IV fosphenytoin products. For this reason, emergent use in pediatric patients is not approved.
• Both Cerebyx and Sesquient may be substituted, short-term, for oral phenytoin, but only when oral phenytoin administration is not possible.
• Cerebyx may be administered by IM injection; however, the IM route should not be used for the emergency control of seizures such as status epilepticus; IM administration should ordinarily not be used in pediatric patients.

Monitoring:

• Cardiac monitoring: Continuous ECG, blood pressure, and respiratory function monitoring during the IV infusion and for 10 to 20 minutes after the end of the infusion
• Phenytoin levels should be monitored to ensure therapeutic levels and minimize toxicity; must wait until conversion to phenytoin is complete before collecting samples
• Dermatologic monitoring: Monitor for rash and other signs and symptoms of severe cutaneous adverse reactions
• Psychiatric: Monitor for emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior

Patient advice:

• Patients should be advised of the risk of cardiovascular adverse reactions with IV administration and should be instructed to report any cardiac signs or symptoms they are experiencing.
• Patients should be aware of signs and symptoms of potential hematologic, dermatologic, hypersensitivity, or hepatic reactions. These symptoms may include, but are not limited to angioedema, fever, sore throat, rash, ulcers in the mouth, easy bruising, lymphadenopathy and petechial or purpuric hemorrhage, anorexia, nausea/vomiting, or jaundice. The patient should be advised to report any occurrence immediately to their healthcare provider.
• Patients should be cautioned about the use of other drugs or alcoholic beverages without first seeking physician advice.
• Patients, their caregivers, and families should be counseled that antiepileptic drugs (AEDs) may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior.
• Women of childbearing potential should speak to their healthcare provider if they become pregnant, intend to become pregnant, or if they are breastfeeding or intend to breastfeed.