Cerebyx

Cerebyx - General Information

Cerebyx is a water-soluble phenytoin prodrug used only in hospitals for the treatment of epileptic seizures. It works by slowing down impulses in the brain that cause seizures. Its main mechanism is to block frequency-dependent, use-dependent and voltage-dependent neuronal sodium channels, and therefore limit repetitive firing of action potentials.

Pharmacology of Cerebyx

Cerebyx is a water-soluble phenytoin prodrug used only in hospitals for the treatment of epileptic seizures. Following parenteral administration of fosphenytoin, fosphenytoin is converted to the anticonvulsant phenytoin. For every mmol of fosphenytoin administered, one mmol of phenytoin is produced. The pharmacological and toxicological effects of fosphenytoin include those of phenytoin.

Cerebyx for patients

Cerebyx Interactions

No drugs are known to interfere with the conversion of fosphenytoin to phenytoin. Conversion could be affected by alterations in the level of phosphatase activity, but given the abundance and wide distribution of phosphatases in the body it is unlikely that drugs would affect this activity enough to affect conversion of fosphenytoin to phenytoin. Drugs highly bound to albumin could increase the unbound fraction of fosphenytoin. Although, it is unknown whether this could result in clinically significant effects, caution is advised when administering Cerebyx with other drugs that significantly bind to serum albumin.

The pharmacokinetics and protein binding of fosphenytoin, phenytoin, and diazepam were not altered when diazepam and Cerebyx were concurrently administered in single submaximal doses.

The most significant drug interactions following administration of Cerebyx are expected to occur with drugs that interact with phenytoin. Phenytoin is extensively bound to serum plasma proteins and is prone to competitive displacement. Phenytoin is metabolized by hepatic cytochrome P450 enzymes and is particularly susceptible to inhibitory drug interactions because it is subject to saturable metabolism. Inhibition of metabolism may produce significant increases in circulating phenytoin concentrations and enhance the risk of drug toxicity. Phenytoin is a potent inducer of hepatic drug-metabolizing enzymes.

The most commonly occurring drug interactions are listed below:

• Drugs that may increase plasma phenytoin concentrations include: acute alcohol intake, amiodarone, chboramphenicol, chlordiazepoxide, cimetidine, diazepam, dicumarol, disulfiram, estrogens, ethosuximide, fluoxetine, H2-antagonists, halothane, isoniazid, methylphenidate, phenothiazines, phenylbutazone, salicylates, succinimides, sulfonamides, tolbutamide, trazodone.
• Drugs that may decrease plasma phenytoin concentrations include: carbamazepine, chronic alcohol abuse, reserpine.
• Drugs that may either increase or decrease plasma phenytoin concentrations include: phenobarbital, vaiproic acid, and sodium valproate. Similarly, the effects of phenytoin on phenobarbital, valproic acid and sodium plasma valproate concentrations are unpredictable.
• Although not a true drug interaction, tricyclic antidepressants may precipitate seizures in susceptible patients and Cerebyx dosage may need to be adjusted.
• Drugs whose efficacy is impaired by phenytoin include: anticoagulants, corticosteroids, coumarin, digitoxin, doxycycline, estrogens, furosemide, oral contraceptives, rifampin, quinidine, theophylline, vitamin D.

Monitoring of plasma phenytoin concentrations may be helpful when possible drug interactions are suspected.

Drug/Laboratory Test Interactions

Phenytoin may decrease serum concentrations of 14. It may also produce artifactually low results in dexamethasone or metyrapone tests. Phenytoin may also cause increased serum concentrations of glucose, alkaline phosphatase, and gamma glutamyl transpeptidase (GGT).

Care should be taken when using immunoanalytical methods to measure plasma phenytoin concentrations following Cerebyx administration.

Cerebyx Contraindications

Cerebyx is contraindicated in patients who have demonstrated hypersensitivity to Cerebyx or its ingredients, or to phenytoin or other hydantoins.

Because of the effect of parenteral phenytoin on ventricular automaticity, Cerebyx is contraindicated in patients with sinus bradycardia, sino-atrial block, second and third degree A-V block, and Adams-Stokes syndrome.

Additional information about Cerebyx

Cerebyx Indication: For the control of generalized convulsive status epilepticus and prevention and treatment of seizures occurring during neurosurgery. It can also be substituted, short-term, for oral phenytoin.
Mechanism Of Action: Cerebyx is a prodrug of phenytoin and accordingly, its anticonvulsant effects are attributable to phenytoin. Phenytoin acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. By promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of post-tetanic potentiation at synapses. Loss of post-tetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas.
Drug Interactions: Alprazolam Possible increased levels of the hydantoin, decrease of benzodiazepine
Chlordiazepoxide Possible increased levels of the hydantoin, decrease of benzodiazepine
Clorazepate Possible increased levels of the hydantoin, decrease of benzodiazepine
Diazepam Possible increased levels of the hydantoin, decrease of benzodiazepine
Estazolam Possible increased levels of the hydantoin, decrease of benzodiazepine
Flurazepam Possible increased levels of the hydantoin, decrease of benzodiazepine
Lorazepam Possible increased levels of the hydantoin, decrease of benzodiazepine
Midazolam Possible increased levels of the hydantoin, decrease of benzodiazepine
Oxazepam Possible increased levels of the hydantoin, decrease of benzodiazepine
Quazepam Possible increased levels of the hydantoin, decrease of benzodiazepine
Temazepam Possible increased levels of the hydantoin, decrease of benzodiazepine
Triazolam Possible increased levels of the hydantoin, decrease of benzodiazepine
Cisplatin The antineoplasic agent decreases the effect of hydantoin
Methotrexate The antineoplasic agent decreases the effect of hydantoin
Bleomycin The antineoplasic agent decreases the effect of hydantoin
Carboplatin The antineoplasic agent decreases the effect of hydantoin
Carmustine The antineoplasic agent decreases the effect of hydantoin
Vinblastine The antineoplasic agent decreases the effect of hydantoin
Aminophylline Decreased effect of both products
Dyphylline Decreased effect of both products
Theophylline Decreased effect of both products
Oxtriphylline Decreased effect of both products
Warfarin Increased hydantoin levels and risk of bleeding
Acenocoumarol Increased hydantoin levels and risk of bleeding
Dicumarol Increased hydantoin levels and risk of bleeding
Anisindione Increased hydantoin levels and risk of bleeding
Voriconazole The hydantoin decreases the effect of voriconazole
Vigabatrin Vigabatrin decreases the effect of hydantoin
Vecuronium Phenytoin decreases the effect of muscle relaxant
Tubocurarine Phenytoin decreases the effect of muscle relaxant
Tacrolimus The hydantoin decreases the effect of tacrolimus
Telithromycin Telithromycin may possibly increase this agent's effect/toxicity
Pancuronium Phenytoin decreases the effect of muscle relaxant
Atracurium Phenytoin decreases the effect of muscle relaxant
Doxacurium Phenytoin decreases the effect of muscle relaxant
Gallamine Triethiodide Phenytoin decreases the effect of muscle relaxant
Metocurine Phenytoin decreases the effect of muscle relaxant
Mivacurium Phenytoin decreases the effect of muscle relaxant
Amiodarone Amiodarone increases the effect of hydantoin
Aprepitant This CYP3A4 inducer decreases the effect of aprepitant
Betamethasone The enzyme inducer decreases the effect of the corticosteroid
Capecitabine Capecitabine increases the effect of hydantoin
Chloramphenicol Increases phenytoin, modifies chloramphenicol
Cimetidine Cimetidine increases the effect of hydantoin
Ciprofloxacin Ciprofloxacin decreases the hydantoin effect
Clarithromycin Clarithromycin increases the effect and toxicity of phenytoin
Cortisone acetate The enzyme inducer decreases the effect of the corticosteroid
Dexamethasone The enzyme inducer decreases the effect of the corticosteroid
Fludrocortisone The enzyme inducer decreases the effect of the corticosteroid
Hydrocortisone The enzyme inducer decreases the effect of the corticosteroid
Methylprednisolone The enzyme inducer decreases the effect of the corticosteroid
Paramethasone The enzyme inducer decreases the effect of the corticosteroid
Prednisolone The enzyme inducer decreases the effect of the corticosteroid
Prednisone The enzyme inducer decreases the effect of the corticosteroid
Triamcinolone The enzyme inducer decreases the effect of the corticosteroid
Trimethoprim Trimethoprim increases the effect of hydantoin
Trioxsalen The hydantoin decreases the effect of psoralene
Thiotepa Possible increase in thiotepa levels
Ticlopidine Ticlopidine increases the effect of hydantoin
Topiramate Increased phenytoin/decreased topiramate
Chlorotrianisene The enzyme inducer decreases the effect of hormones
Diethylstilbestrol The enzyme inducer decreases the effect of hormones
Clomifene The enzyme inducer decreases the effect of hormones
Estradiol The enzyme inducer decreases the effect of hormones
Conjugated Estrogens The enzyme inducer decreases the effect of hormones
Estriol The enzyme inducer decreases the effect of hormones
Estrone The enzyme inducer decreases the effect of hormones
Estropipate The enzyme inducer decreases the effect of hormones
Medroxyprogesterone The enzyme inducer decreases the effect of hormones
Megestrol The enzyme inducer decreases the effect of hormones
Sertraline Sertraline increases the effect of hydantoin
Quinestrol The enzyme inducer decreases the effect of hormones
Chlorpheniramine The antihistamine increases the effect of hydantoin
Chlorpheniramine The antihistamine increases the effect of hydantoin
Clozapine Hydantoin decreases the effect of clozapine
Cyclosporine The hydantoin decreases the effect of cyclosporine
Delavirdine The anticonvulsant decreases the effect of delavirdine
Diazoxide Diazoxide decreases the hydantoin effect
Disopyramide The hydantoin decreases the effect of disopyramide
Disulfiram Disulfiram increases the effect of phenytoin
Divalproex sodium Valproate increases the effect of hydantoin
Dopamine Risk of severe hypotension
Doxycycline The anticonvulsant decreases the effect of doxycycline
Irinotecan The hydantoin decreases the effect of irinotecan
Imatinib The hydantoin decreases the levels of imatinib
Gefitinib This CYP3A4 inducer may reduce gefitinib plasma concentrations and pharmacological effects
Fluvoxamine Fluvoxamine increases the effect of hydantoin
Folic Acid Folic acid decreases the levels of hydantoin
Furosemide The hydantoin decreases the effect of furosemide
Gabapentin Gabapentin increases the effect of hydantoin
Fluorouracil Fluorouracil increases the effect of hydantoin
Fluoxetine Fluoxetine increases the effect of phenytoin
Fluconazole Fluconazole increases the effect of hydantoin
Felodipine The hydantoin decreases the effect of felodipine
Felbamate Increased phenytoin levels and decreased felbamate levels
Ethinyl Estradiol This product may cause a slight decrease of contraceptive effect
Nisoldipine Phenytoin decreases the efficiency of nisoldipine
Metyrapone The combination renders the test invalid
Mexiletine The hydantoin decreases the effect of mexiletine
Isoniazid Isoniazid increases the effect of phenytoin
Itraconazole Phenytoin decreases the effect of itraconazole
Lamotrigine Phenytoin may reduce levels of lamotrigine
Levodopa The hydantoin decreases the effect of levodopa
Levonorgestrel Phenytoin decreases the contraceptive effect
Lopinavir Levels of both drugs are affected
Mebendazole The hydantoin decreases the efficiency of mebendazole
Mestranol This product may cause a slight decrease of contraceptive effect
Methadone The hydantoin decreases the effect of methadone
Methoxsalen The hydantoin decreases the effect of psoralene
Mirtazapine The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects
Norethindrone This product may cause a slight decrease of contraceptive effect
Sulfamethizole The sulfonamide increases the effect of hydantoin
Sulfadiazine The sulfonamide increases the effect of hydantoin
Sucralfate Sucralfate decreases the effect of hydantoin
Sirolimus The hydantoin decreases sirolimus levels
Quinidine The anticonvulsant decreases the effect of quinidine
Quinupristin This combination presents an increased risk of toxicity
Rifampin Rifampin decreases the effect of hydantoin
Omeprazole Omeprazole increases the effect of hydantoin
Oxcarbazepine Oxcarbazepine increases the effect of hydantoin
Oxyphenbutazone The NSAID increases the hydantoin effect
Phenylbutazone The NSAID increases the hydantoin effect
Posaconazole Modifications of drug levels for both agents
Quetiapine Phenytoin decreases the effect of quetiapine
Food Interactions: Avoid alcohol.
Take with food.
Do not take calcium, aluminum, magnesium or Iron supplements within 2 hours of taking this medication.
Generic Name: Fosphenytoin
Synonyms: Fosphenytoin sodium; (3-Phosphoryloxymethyl)phenytoin; Fosfenitoina [inn-spanish]; Fosphenytoine [inn-french]; Fosphenytoinum [inn-latin]
Drug Category: Anticonvulsants
Drug Type: Small Molecule; Approved

Other Brand Names containing Fosphenytoin: Prodilantin; Cerebyx;
Absorption: Fosphenytoin is completely bioavailable following lM administration.
Toxicity (Overdose): Nausea, vomiting, lethargy, tachycardia, bradycardia, asystole, cardiac arrest, hypotension, syncope, hypocalcemia, metabolic acidosis, and death have been reported in cases of overdosage with fosphenytoin. The median lethal dose of fosphenytoin given intravenously in mice and rats was 156 mg PE/kg and approximately 250 mg PE/kg, or about 0.6 and 2 times, respectively, the maximum human loading dose on a mg/m2 basis. Signs of acute toxicity in animals included ataxia, labored breathing, ptosis, and hypoactivity.
Protein Binding: Extensively bound (95% to 99%) to human plasma proteins, primarily albumin.
Biotransformation: Hepatic.
Half Life: Fosphenytoin has a half-life of approximately 15 minutes.
Dosage Forms of Cerebyx: Liquid Intravenous
Liquid Intravenous
Chemical IUPAC Name: [2,5-dioxo-4,4-di(phenyl)imidazolidin-1-yl]methyl dihydrogen phosphate
Chemical Formula: C16H15N2O6P
Fosphenytoin on Wikipedia: https://en.wikipedia.org/wiki/Fosphenytoin
Organisms Affected: Humans and other mammals