Last reviewed 2026-04-20 · How we verify

Cerebyx (FOSPHENYTOIN)

Cerebyx works by stabilizing the inactivated state of sodium channels, preventing the rapid firing of neurons that can lead to seizures.

Fosphenytoin (Cerebyx), marketed by Pfizer, is a sodium channel stabilizer primarily indicated for the treatment of Generalized Tonic-Clonic Status Epilepticus. Its key strength lies in its mechanism of action, which effectively prevents rapid neuronal firing, offering a robust therapeutic option in critical seizure management. The primary risk is the competition from off-patent drugs such as phenytoin, which has seven generics available, potentially eroding market share.

At a glance

Mechanism of action

Fosphenytoin is prodrug of phenytoin and accordingly, its anticonvulsant effects are attributable to phenytoin. The precise mechanism by which phenytoin exerts its therapeutic effect has not been established but is thought to involve the voltage-dependent blockade of membrane sodium channels resulting in reduction in sustained high-frequency neuronal discharges.

Approved indications

• Generalized Tonic-Clonic Status Epilepticus
• Seizures During Neurosurgery
• Substitute for Oral Phenytoin

Boxed warnings

• WARNING: CARDIOVASCULAR RISK ASSOCIATED WITH RAPID INFUSION RATES The rate of intravenous fosphenytoin sodium injection 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 administering intravenous fosphenytoin sodium injection. 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 [see Dosage and Administration ( 2.3 , 2.4 ) and Warnings and Precautions ( 5.2 )]. WARNING: CARDIOVASCULAR RISK ASSOCIATED WITH RAPID INFUSION RATES See full prescribing information for complete boxed warning. The rate of intravenous fosphenytoin sodium 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 administering intravenous fosphenytoin sodium. Reduction in rate of administration or discontinuation of dosing may be needed ( 2.3 , 2.4 , 5.2 ) .

Common side effects

• Nystagmus
• Dizziness
• Somnolence
• Ataxia
• Pruritus
• Hypotension
• Tachycardia
• Paresthesia
• Pelvic Pain
• Asthenia
• Back Pain
• Headache

Drug interactions

• Drugs highly bound to albumin
• Phenytoin
• Antiepileptic drugs (Ethosuximide, felbamate, oxcarbazepine, methsuximide, topiramate)
• Azoles (Fluconazole, ketoconazole, itraconazole, miconazole, voriconazole)
• Antineoplastic agents (Capecitabine, fluorouracil)
• Antidepressants (Fluoxetine, fluvoxamine, sertraline)
• Gastric acid reducing agents (H2 antagonists like cimetidine, omeprazole)
• Sulfonamides (Sulfamethizole, sulfaphenazole, sulfadiazine, sulfamethoxazole-trimethoprim)
• Other (Acute alcohol intake, amiodarone, chloramphenicol, chlordiazepoxide, disulfiram, estrogen, fluvastatin, isoniazid, methylphenidate, phenothiazines, salicylates, ticlopidine, tolbutamide, trazodone, warfarin)
• Antineoplastic agents (Bleomycin, carboplatin, cisplatin, doxorubicin, methotrexate)
• Antiviral agents (Fosamprenavir, nelfinavir, ritonavir)
• Antiepileptic drugs (Carbamazepine, vigabatrin)

Key clinical trials

• A Platform Protocol to Investigate Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis in Patients With Hematologic Malignancies Undergoing Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation (PHASE2)
• Antiseizure Medication in Seizure Networks at Early Acute Brain Injury (PHASE4)
• The Efficacy and Safety of Levetiracetam Versus Fosphenytoin in Convulsive Status Epilepticus (PHASE4)
• NPC-06 to Pain Associated With Acute Herpes Zoster (PHASE3)
• Phenytoin as Treatment for Acute Exacerbations of Trigeminal Neuralgia - a Prospective Systematic Study of 20 Patients
• Established Status Epilepticus Treatment Trial (PHASE3)
• Double Cord Blood Transplant for Patients With Malignant and Non-malignant Disorders (PHASE1,PHASE2)
• Comparison Between Lorazepam, Clonazepam and Clonazepam + Fosphenytoin for the Treatment of Out-of-hospital Generalized Status Epilepticus (PHASE3)

Primary sources

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