Phenytoin (Na)

Phenytoin (Na) is oral and parenteral hydantoin anticonvulsant first synthesized in 1908. Although it has been used in many diverse conditions, its only approved use is as an anticonvulsant, specifically, for the prophylactic management of tonic-clonic seizures and partial seizures with complex symptomatology. Anticonvulsant drugs can elevate the seizure threshold and/or limit the spread of seizure discharge. Phenytoin exerts its anticonvulsant effect mainly by limiting the spread of seizure activity and reducing seizure propagation, unlike phenobarbital and carbamazepine, which elevate the seizure threshold. Phenytoin was originally approved by the FDA in 1939.

Brands
EPITOIN EPITOIN DILANTIN DILANTIN EPILANTIN EPILANTIN EPINAT EPINAT EPINAT PHENTON-S DI-HYDEN DI-HYDEN SHALENTIN FENTIN EPIGRAN
Adult Dose
Dose: 150 to 300 mg
Single Dose: 220 (225)
Frequency: 24 hourly
Route: PO
Instructions:
Neonatal
Dose: 4 to 5 mg/kg
Single Dose: 4.5 (4.5)
Frequency: 12 hourly
Route: Intravenous
Instructions: For 6 months and above children
Paedriatic
Dose: 3.75 to 4.5
Single Dose: 4.1 (4.125)
Frequency: 12 hourly
Route: Oral
Instructions: For Children 3-6 Yrs of Age
Characteristics
Phenytoin (Na) also known as Diphenyl hydantoin Na, Diphenyl hydantoin Na. . It is of Natural origin and belongs to Imidazolidinedione. It belongs to Na-Channel Antagonist pharmacological group on the basis of mechanism of action. The Molecular Weight of Phenytoin (Na) is 274.30. Its pKa is 8.3.
Contraindications
Phenytoin (Na) is contraindicated in conditions like Porphyrias.
Effects
The severe or irreversible adverse effects of Phenytoin (Na), which give rise to further complications include Ataxia, Nausea, Vomiting, Hypotension, Drowsiness, Nystagmus, Coma, Hyperglycemia, Stupor, Blurred vision.Phenytoin (Na) produces potentially life-threatening effects which include Hepatitis, Dermatitis. which are responsible for the discontinuation of Phenytoin (Na) therapy.The signs and symptoms that are produced after the acute overdosage of Phenytoin (Na) include Death.The symptomatic adverse reactions produced by Phenytoin (Na) are more or less tolerable and if they become severe, they can be treated symptomatically, these include Skin rashesX, Elevated alkaline phosphatase, Folate deficiency, Hypocalcemia.
Indications
Phenytoin (Na) is primarily indicated in conditions like Convulsions, Epilepsy, Migraine prophylaxis, Myotonia, Prophylaxis of epilepsy, Status epilepticus, Status epilepticus; seizures in neurosurgery, TIC douloureaux, Ventricular arrhythmias.
Interactions
Phenytoin (Na) is known to interact with other drugs, the details of drug interactions is as follows:DrugDetailsSeverityOnsetManagementAbacavirPhenytoin reduces plasma concentration of abacavir. Abiraterone acetatePhenytoin and other liver enzyme inducers (e.g carbamazepine, rifampicin, phenobarbital) accelerates the metabolism of abiraterone acetate by inducing CYP3A4 and thereby lowers the systemic exposure of abiraterone acetate.Combination should be avoided or used with caution.AceclofenacAceclofenac (and other NSAIDs) enhances the effect of phenytoin.Acepromazine (Maleate)Acetazolamide (Na)Acetazolamide potentiate effect of phenytoinAcyclovirAfatinibmay decreases the level of afatinibuse alternative or increase dose of afatinibAlbendazoleAlcoholAlcuronium (Cl)AlfacalcidolAllopurinolAlprazolamAmiodarone (HCl)Amiodarone inhibits the hepatic metabolism of Phenytoin resulting in an increased plasma concentration of phenytoin.MajorSerum phenytoin concentration should be monitored.Amitriptyline (HCl)Amlodipine (Besylate)Amlodipine may decrease the metabolism of Phenytoin. ModerateMonitor for Phenytoin toxicity when Amlodipine is initiated/dose increased, or decreased Phenytoin effects if Amlodipine is discontinued/dose decreased. Amoxapineplasma concentration of amoxapine possibly reduced by Phenytoin (Na).AmprenavirPlasma concentration of Amprenavir possibly reduced byv Phenytoin.ArtesunateConcurrent use may decrease artesunate serum concentrations. Avoid co-administration if possible. Monitor closely for therapeutic efficacy. Artesunate dose may need to be increased with co-administration.AspirinAspirin enhances effects of Phenytoin.AuranofinAzapropazoneBamifyllineBeclomethasone (Dipropionate)reduced efficasy of corticosteroids in asthmatic , arthritic, renal and other patients who recieve phenytoin or phenobarbital BenorylateBetamethasoneMetabolism of corticosteroids (e.g Betamethasone) possibly accelerated by Phenytoin (reduced effect).MajorBleomycinBleomycin reduces absorption of Phenytoin.BromazepamBupropion (HCl)Plasma concentration of Bupropion reduced by Phenytoin.BusulphanCytotoxics (e.g Busulphan) reduce absorption of Phenytoin.CaffeineCalcifediolCalciferolCanagliflozinco administration may decrease the efficacy of canagliflozinincrease the dose to 300mg once dailyCarbamazepinePhenytoin may decrease Carbamazepine levels, and Carbamazepine may have variable effects on Phenytoin levels. The mechanism may be related to induction of CYP450 hepatic metabolism of Carbamazepine and alteration of Phenytoin metabolism. ModerateClose observation for clinical and laboratory evidence of altered effects is recommended, perticularly when one drug is started or discontinued. Patients should be advised to notify their physician if they experience loss of seizure control or symptoms of Phenytoin toxicity (nausea, drowsiness, visual disturbances, change in mental status, ataxia).ChloramphenicolChloramphenicol increases he serum level of phenytin results in increased toxicity while phenytoin may increase or decrease the serum level of chlormphenicol.ModerateConcomitant use should be avoided. Closely monitor for serum concentration of phenytoin and observe for sign of toxicity.Chlordiazepoxide (HCl)Chlorpheniramine (Maleate)ChlorphenpyridaminChlorpromazine (HCl)ChlorpropamidePhenytoin cause hyperlycemia, hypoinsulinemia and glucose intolerance and thus diminishes the hypoglycemic effect of chlorpropamide.While chlorpropamide inhibits the metabolism of phenytoin thus increases its plasma concentration and pharmacological effects.ModerateClosely monitor the level of phenytoin and blood glucose. Patient should notify to physician if experience the symptoms of phenytoin toxiity.CholecalciferolCholine Magnesium TrisalicylateCimetidine (HCl)Cimetidine (HCl)CiprofloxacinCiprofloxacin may either increase or decrease the plasma concentration of phenytoin, thus increasing the risk of phenytoin toxicity or seizure.ModerateClosely monitor the plasma concentration of phenytoin whenever start or discontinue ciprofloxacin. Adjust the dose of phenytoin accordingly.ClarithromycinClarithromycin alters the clearence of phenytoin.MinorDuring coadministration caution is advised.ClobazamClofibrateClofibrateClomipramine (HCl)ClonazepamClonazepamClopidogrelClozapinePhenytoin reduces the plasma concentration of clozapine by inducing its hepatic metabolism.ModerateClosely monitor the altered effect of clozapine especially when start, change or discontinue hydantoin.conjugated Estrogens/BazedoxifeneThe metabolism of bazedoxifene may be increased by concomitant use of phenytoin. dose adjustment requiredCorticotropinCortisone (Acetate)Co-TrimoxazoleCyclosporin ADabrafenibStrong CYP3A4 inducers may decrease levels of dabrafenibConsider alternate therapyDeflazacortDesogestrelDesonideDexamethasoneDexamethasoneDexamphetamine (Sulphate)DextropropoxypheneDiazepamMetabolic elimination of phenytoin is altered by DiazepamDiazoxideDigitoxinDigoxinDiltiazem (HCl)Phenytoin markedly decreases serum levels of Diltiazem through inducing their first pass metabolism and systemic clearance while diltiazem increases phenytoin plasma levels by inhibiting CYP450 3A4 metabolism. Monitoring of the altered effects are required.DisopyramidePhenytoin decreases plasma level and therapeutic effects of disopyramide by induction of disopyramide metabolism.Disopyramide AUC decreases by 52% and half life upto 51%.ModerateClose observation of Disopyramide effectsi.e.dry mouth, blurry vision, urinary retention or worsening of irregular heart beat must be done.DisulfiramDisulfiram may inhibit hepatic microsomal metabolism of phenytoin and decreases its elimination rate thus increasing serum level upto 73% to 500%.Moderateclosely observed yhe serum level and toxicity of phenytoin.Dolutegravirdecreased level of dolutegravircoadministration should be avoidedDopamine (HCl)Coadministration results in severe hypotension by catecholamine depletion and hydantoin-induced myocardial depression.MajorThis combination should be avoided.DorzolamideDoxacuriumLong-term administration of phenytoin reduces the efficacy of doxacurium by inducing hepatic enzyme and thus enhances hepatic clearence.ModerateIncrease the dose of doxacurium and closely monitor for altered effect of doxacuriumDoxicycline HyclateDoxycyclineDoxycyclineDydrogesteroneEsomeprazoleEsomeprazole decrease clearance of phenytoin by inhibiting CYP450EstazolamEstradiol (Valerate)Estradiol.EthinyloestradiolEthosuximideEthynodiol (Diacetate)EtodolacEtretinateFelbamateFelodipineFenbufenFenoprofenFloctafenineFluconazoleFluconazole inhibit CYO450 2C9 and 2C19 hepatic metabolism thus increases phenytion serum levels result in phenytoin toxicity.ModerateMonitoring of serum phenytoin levels,patient response and tolerance.Adjust dose of phenytoin.Fludrocortisone (Acetate)Flunarizine (HCl)FlunisolideFluoxetine (HCl)toxcity of phenytoin is precipitated by fluoxetineFluprednisoloneFlurbiprofenFluticasone PropionateFluvoxamine (Maleate)FormestaneFrusemide or FurosemidePhenytoin may diminish the diuretic effect of Furosemide. ModerateMonitor for decreased therapeutic effects of Furosemide if phenytoin is initiated/dose increased, or increased effects if phenytoin is discontinued/dose decreased.GabapentinGemfibrozilGestodeneHalothaneHydrocortisoneIloprostIndinavir (Sulphate)Influenza VaccineInterferon AlphaIsoniazidIsoniazidIsosorbide (Dinitrate)Phenytoin may increase the metabolism of Isosorbide(Dinitrate). ModerateConsider an alternative drug in order to avoid therapeutic failure of Isosorbide(Dinitrate). Some combinations are specifically contraindicated by manufacturers. Suggested dosage adjustments are also offered by some manufacturers. Please review applicable package inserts. Monitor for decreased effects of Isosorbide(Dinitrate) if Phenytoin is initiated/dose increased, and increased effects if Phenytoin is discontinued/dose decreased.IsradipineItraconazoleKetoconazolePhenytoin reduces the serum levels of ketoconazole upto 90% by enhancing first-pass and hepatic metabolism of ketoconazole.ModerateThis combination should be avoided.LamotrigineLansoprazoleLercanidipine (HCl)LevodopaLevonorgestrelLiothyronine (Na)LynoestrenolMebendazoleMeclofenamic AcidMegestrol (Acetate)MeloxicamMeprobamateMestranolMethotrexateMethotrexate markedly decrease plasma phenytoin concentration, absorption and seizures but increases its metabolism.ModeratePhenytoin dosage must be increased during therapy and to decreased after therapy.Careful monitoring of seizures activity is recommended.MethoxsalenMethylamphetamineAmphetamines may delay the intestinal absorption of ethosuximide, phenobarbital, and phenytoin. The mechanism of interaction and clinical significance are unknown. MinorMethylphenidate (HCl)Methylphenidate (HCl)MethylprednisoloneMetronidazoleMetronidazole increases the serum concentration of phenytoin by inhibiting its metabolism. Also phentytoin increases elimination of metronidazole.ModerateSerum level of phenytoin should be closely monitor and dose of phenytoin should be adjusted accordingly.MetyraponeMexiletineMianserinMibefradil (Di HCl)Miconazole (Nitrate)MidazolamMultiple VitaminsConcurrent use should be avoided if multi vitamins contain folic acid.NaproxenNaproxen displaces Phenytoin from Protein binding sites NifedipineNimodipineNitrendipinePhenytoin (Na) may decrease the levels/effects of nitrendipine.NorethisteroneNorgestimateNortriptyline (HCl)Omeprazoleomeperzole decrease the clearance of phenytoinOndansetron (HCl)By concurrent use the clearance of ondansetron was significantly increased and ondansetron blood concentrations were decreased. However, on the basis of available data, no dosage adjustment for ondansetron is recommended for patients on these drugs.No dosage adjustment for ondansetron is recommended for patients on these drugs.OxaprozinParoxetinePerphenazinePethidine (HCl)Phenobarbital SodiumPhenytoin causes rise in plasma concentration of phenobarbital sodium.PhenobarbitonePhenobarbitonePhenylalaninePhenylalanine may enhance the tardive dyskinesia side effects of Phenytoin (Na).Phenylbutazone Phenylbutazone PioglitazonePraziquantel Prednisolone and PrednisonePrednisolone and Prednisonephenyton increase clearance of prednisolone and prednisone by enhancing metabolismPrednisolone TebutatePhenytoin Na decrease efficacy of Prednisolone tebutate.PrimidonePrimidoneProchlorperazineProgesteronePropoxyphenePropoxyphenePropranolol (HCl)PyridoxineQuinestrolPhenytoin diminishes the effect of conjugated estrogens in a menopausal women.QuinidineRiboflavin (Vitamin B2)Phenytoin may affect riboflavin levels in the body.RifabutinRitonavirSaquinavirSecnidazoleSodium ValproateSorafenibmay a increase metabolism of sorafenib and thus decrease sorafenib concentrations.StreptozotocinSucralfateSulfadimidine Sulfadimidine inhibits the metabolism of phenytoin and enhances their action.SulfadoxineSulfanilamideSulfisoxazoleSulphadiazineSulphafurazole DiethanolamineSulphafurazole diethanolamine increases effect of phenytoin.SulphamethizolePhenytoin (Na) may be displaced from protein binding sites or their metabolism may be inhibited by some sulfonamides, resulting in increased or prolonged effects or toxicity.Dosage adjustments may be necessary during and after sulfonamide therapySulphamethoxazoleSulphinpyrazoneSunitinibMay decrease sunitinib concentrations.TacrolimusTelithromycinPhenytoin (Na) is likely to result in subtherapeutic levels of telithromycin and loss of effect.TeniposidePhenytoin and phenobarbital increases the clearance of teniposide, the resultant decrease in systemic exposure might reduce its efficacy.The dose of teniposide need to be reduced.TenoxicamTheophyllineThiopentone (Na)Thyroxine (Na)Tiagabine (HCl)TiboloneTiclopidine (HCl)Tienilic AcidTocainide (HCl)TolbutamideTopiramateTrazodone (HCl)TrimethoprimVecuronium (Br)Phenytoin produce resistance to muscle-relaxant effects of vecuronium.ModerateClosely monitor the neuromuscular blockage.VemurafenibPhenytoin induces P-gp and CYP3A4.Vitamin KVORICONAZOLEVoriconazole may increase the serum concentration of phenytoin by decreasing its metabolism. Consider alternate antifungal therapy Vortioxetinelevel of vortioxetine increasesuse with caution, closely monitor and incease the dose of vortioxetineWarfarin (Na)Phenytoin may enhance the anticoagulant effect of Warfarin. Warfarin may increase the serum concentration of Phenytoin. MajorDelayedConsideration should be given to using Warfarin instead of Dicumarol in phenytoin-treated patients, as Warfarin appears to exhibit a safer interaction profile. Monitor for increased effects of Warfarin (possibly transient), and significantly decreased effects of Dicumarol, if Phenytoin is initiated/dose increased, and the opposite effects if Phenytoin is discontinued/dose decreased. Monitor for increased serum concentrations/toxic effects of Phenytoin if Warfarin is initiated/dose increased, or decreased serum concentrations/effects if Warfarin is discontinued/dose decreased. These effects would manifest during the first 1-2 months of therapy, if at all. Zolpidem (Tartrate)Zopiclone These interactions are sometimes beneficial and sometimes may pose threats to life. Always consult your physician for the change of dose regimen or an alternative drug of choice that may strictly be required.
Interfrence
Increased Alkaline Phosphatase LevelsIncreased blood glucose levelElevations of gamma glutamyl transpeptidase
Risks
Drug should not be given to Paediatrics, Pregnant Mothers, Geriatrics, and Neonates.If prescribing authority justifies the benefits of the drug against the possible damages he/she should reevaluate them and consult the reference material and previous studies.
Storage
Caps, Syrup Store in a well closed container, Below 40°C. Inj Store at room temperature. Do not Freeze.
Warnings
Phenytoin should be used with caution in patients with liver, lungs, heart diseases and blood disorders. Perform blood counts before initiating the therapy. Administer cautiously in the presence of advanced atrioventricular (AV) block. Do not exceed an I/V infusion rate of 50mg/min. Discontinue use if skin rashes appear.
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