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Prodilantin: Full Drug Profile

Medically reviewed by Min Clinic Staff | Updated: January 2026

Prodilantin - General Information

Prodilantin 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 Prodilantin

Prodilantin 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.

 

Prodilantin for patients

 

Prodilantin 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.

 

Prodilantin 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 Prodilantin

Prodilantin 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: Prodilantin 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 benzodiazepineChlordiazepoxide Possible increased levels of the hydantoin, decrease of benzodiazepineClorazepate Possible increased levels of the hydantoin, decrease of benzodiazepineDiazepam Possible increased levels of the hydantoin, decrease of benzodiazepineEstazolam Possible increased levels of the hydantoin, decrease of benzodiazepineFlurazepam Possible increased levels of the hydantoin, decrease of benzodiazepineLorazepam Possible increased levels of the hydantoin, decrease of benzodiazepineMidazolam Possible increased levels of the hydantoin, decrease of benzodiazepineOxazepam Possible increased levels of the hydantoin, decrease of benzodiazepineQuazepam Possible increased levels of the hydantoin, decrease of benzodiazepineTemazepam Possible increased levels of the hydantoin, decrease of benzodiazepineTriazolam Possible increased levels of the hydantoin, decrease of benzodiazepineCisplatin The antineoplasic agent decreases the effect of hydantoinMethotrexate The antineoplasic agent decreases the effect of hydantoinBleomycin The antineoplasic agent decreases the effect of hydantoinCarboplatin The antineoplasic agent decreases the effect of hydantoinCarmustine The antineoplasic agent decreases the effect of hydantoinVinblastine The antineoplasic agent decreases the effect of hydantoinAminophylline Decreased effect of both productsDyphylline Decreased effect of both productsTheophylline Decreased effect of both productsOxtriphylline Decreased effect of both productsWarfarin Increased hydantoin levels and risk of bleedingAcenocoumarol Increased hydantoin levels and risk of bleedingDicumarol Increased hydantoin levels and risk of bleedingAnisindione Increased hydantoin levels and risk of bleedingVoriconazole The hydantoin decreases the effect of voriconazoleVigabatrin Vigabatrin decreases the effect of hydantoinVecuronium Phenytoin decreases the effect of muscle relaxantTubocurarine Phenytoin decreases the effect of muscle relaxantTacrolimus The hydantoin decreases the effect of tacrolimusTelithromycin Telithromycin may possibly increase this agent's effect/toxicityPancuronium Phenytoin decreases the effect of muscle relaxantAtracurium Phenytoin decreases the effect of muscle relaxantDoxacurium Phenytoin decreases the effect of muscle relaxantGallamine Triethiodide Phenytoin decreases the effect of muscle relaxantMetocurine Phenytoin decreases the effect of muscle relaxantMivacurium Phenytoin decreases the effect of muscle relaxantAmiodarone Amiodarone increases the effect of hydantoinAprepitant This CYP3A4 inducer decreases the effect of aprepitantBetamethasone The enzyme inducer decreases the effect of the corticosteroidCapecitabine Capecitabine increases the effect of hydantoinChloramphenicol Increases phenytoin, modifies chloramphenicolCimetidine Cimetidine increases the effect of hydantoinCiprofloxacin Ciprofloxacin decreases the hydantoin effectClarithromycin Clarithromycin increases the effect and toxicity of phenytoinCortisone acetate The enzyme inducer decreases the effect of the corticosteroidDexamethasone The enzyme inducer decreases the effect of the corticosteroidFludrocortisone The enzyme inducer decreases the effect of the corticosteroidHydrocortisone The enzyme inducer decreases the effect of the corticosteroidMethylprednisolone The enzyme inducer decreases the effect of the corticosteroidParamethasone The enzyme inducer decreases the effect of the corticosteroidPrednisolone The enzyme inducer decreases the effect of the corticosteroidPrednisone The enzyme inducer decreases the effect of the corticosteroidTriamcinolone The enzyme inducer decreases the effect of the corticosteroidTrimethoprim Trimethoprim increases the effect of hydantoinTrioxsalen The hydantoin decreases the effect of psoraleneThiotepa Possible increase in thiotepa levelsTiclopidine Ticlopidine increases the effect of hydantoinTopiramate Increased phenytoin/decreased topiramateChlorotrianisene The enzyme inducer decreases the effect of hormonesDiethylstilbestrol The enzyme inducer decreases the effect of hormonesClomifene The enzyme inducer decreases the effect of hormonesEstradiol The enzyme inducer decreases the effect of hormonesConjugated Estrogens The enzyme inducer decreases the effect of hormonesEstriol The enzyme inducer decreases the effect of hormonesEstrone The enzyme inducer decreases the effect of hormonesEstropipate The enzyme inducer decreases the effect of hormonesMedroxyprogesterone The enzyme inducer decreases the effect of hormonesMegestrol The enzyme inducer decreases the effect of hormonesSertraline Sertraline increases the effect of hydantoinQuinestrol The enzyme inducer decreases the effect of hormonesChlorpheniramine The antihistamine increases the effect of hydantoinChlorpheniramine The antihistamine increases the effect of hydantoinClozapine Hydantoin decreases the effect of clozapineCyclosporine The hydantoin decreases the effect of cyclosporineDelavirdine The anticonvulsant decreases the effect of delavirdineDiazoxide Diazoxide decreases the hydantoin effectDisopyramide The hydantoin decreases the effect of disopyramideDisulfiram Disulfiram increases the effect of phenytoinDivalproex sodium Valproate increases the effect of hydantoinDopamine Risk of severe hypotensionDoxycycline The anticonvulsant decreases the effect of doxycyclineIrinotecan The hydantoin decreases the effect of irinotecanImatinib The hydantoin decreases the levels of imatinibGefitinib This CYP3A4 inducer may reduce gefitinib plasma concentrations and pharmacological effectsFluvoxamine Fluvoxamine increases the effect of hydantoinFolic Acid Folic acid decreases the levels of hydantoinFurosemide The hydantoin decreases the effect of furosemideGabapentin Gabapentin increases the effect of hydantoinFluorouracil Fluorouracil increases the effect of hydantoinFluoxetine Fluoxetine increases the effect of phenytoinFluconazole Fluconazole increases the effect of hydantoinFelodipine The hydantoin decreases the effect of felodipineFelbamate Increased phenytoin levels and decreased felbamate levelsEthinyl Estradiol This product may cause a slight decrease of contraceptive effectNisoldipine Phenytoin decreases the efficiency of nisoldipineMetyrapone The combination renders the test invalidMexiletine The hydantoin decreases the effect of mexiletineIsoniazid Isoniazid increases the effect of phenytoinItraconazole Phenytoin decreases the effect of itraconazoleLamotrigine Phenytoin may reduce levels of lamotrigineLevodopa The hydantoin decreases the effect of levodopaLevonorgestrel Phenytoin decreases the contraceptive effectLopinavir Levels of both drugs are affectedMebendazole The hydantoin decreases the efficiency of mebendazoleMestranol This product may cause a slight decrease of contraceptive effectMethadone The hydantoin decreases the effect of methadoneMethoxsalen The hydantoin decreases the effect of psoraleneMirtazapine The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effectsNorethindrone This product may cause a slight decrease of contraceptive effectSulfamethizole The sulfonamide increases the effect of hydantoinSulfadiazine The sulfonamide increases the effect of hydantoinSucralfate Sucralfate decreases the effect of hydantoinSirolimus The hydantoin decreases sirolimus levelsQuinidine The anticonvulsant decreases the effect of quinidineQuinupristin This combination presents an increased risk of toxicityRifampin Rifampin decreases the effect of hydantoinOmeprazole Omeprazole increases the effect of hydantoinOxcarbazepine Oxcarbazepine increases the effect of hydantoinOxyphenbutazone The NSAID increases the hydantoin effectPhenylbutazone The NSAID increases the hydantoin effectPosaconazole Modifications of drug levels for both agentsQuetiapine 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 Prodilantin: Liquid IntravenousLiquid 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