II. Classification: Hydantoin
- Phenytoin (Dilantin)
- Fosphenytoin (Cerebyx)
- Phenytoin congeners (limited use)
- Mephenytoin
- Ethotoin
- Phenacemide
III. History
- Phenytoin Oldest non-sedative antiepileptic drug (1938)
- Based on research into phenobarbital antiseizure effect
IV. Indications
- Partial Seizures
- Generalized tonic-clonic Seizures
V. Contraindications
- Pregnancy (See Fetal Hydantoin Syndrome)
VI. Pharmacokinetics: Phenytoin
- Fosphenytoin (Cerebyx) has similar pharmacokinetics to Phenytoin
- Hepatic metabolism
- Highly protein bound
- Onset: 10-30 minutes
- Half-life: 12 to 24-36 hours
- Average half life for moderate dosages: 24 hours
- Very long half-life at toxic concentrations
- Therapeutic level: 10-20 mcg/ml
VII. Dosing: Phenytoin or Dilantin (Adults)
-
Status Epilepticus
- Dose: 20 mg/kg IV (at 1 mg/kg/min up to 50 mg/min) up to to 1000 mg maximum
- May repeat once with Phenytoin 5-10 mg/kg IV
- Maintenance with Phenytoin 50 mg/min
- Loading dose
- Oral loading regimen
- Dose 1: 400 mg orally
- Dose 2: 300-400 mg orally at 2 hours after dose 1
- Dose 3: 300-400 mg orally at 4 hours after dose 1
- Parenteral loading regimen
- Dose: 10-20 mg/kg (average 1 gram) IV
- Do not administer faster than 50 mg/min
- Oral loading regimen
- Maintenance dose
- Initial: 5 mg/kg to 300 mg/day divided qd to tid
- Titrating dose
- Avoid increasing dose by >25-30 mg per trial
- Wait for steady state (7 days) before level recheck
VIII. Dosing: Fosphenytoin or Cerebyx
-
Status Epilepticus
- Dose: 20 mg/kg IV or IM (at 3 mg/kg/min up to 150 mg/min) up to 1000 mg maximum
- Preferred over Phenytoin for Status Epilepticus
- Fosphenytoin can be infused with dextrose
- Fosphenytoin has lower risk of arrhythmia (due to no Ethylene Glycol in base)
- Fosphenytoin may be given IM or delivered a faster IV rate (not tissue toxic)
- However onset of activity is similar to that with Phenytoin (as Fosphenytoin is converted to active Phenytoin form)
IX. Drug Interactions
- Drugs that increase plasma Phenytoin levels
- Amiodarone
- Clobazam
- Fluconazole
- Ranitidine
- Phenylbutazone
- Sulfonamides
- Benzodiazepines
- Anticoagulants
- Isoniazid
- Drugs that decrease Phenytoin level or free fraction
- Influenza Vaccine
- Tolbutamide
- Carboplatin
- Rifampicin
- Theophylline
- Phenobarbital
- Carbamazepine
- Phenytoin decreases plasma level of other drug
- Doxorubicin
X. Adverse Effects
- See Dilantin Toxicity
- Fetal Hydantoin Syndrome
- Drug hypersensitivity
- Common chronic changes associated with Phenytoin
- Gingival Hyperplasia
- Hirsutism
- Coarse facial features
- Peripheral Neuropathy (decreased Deep Tendon Reflex)
- Other effects
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| phenytoin (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| PHENYTOIN 125 MG/5 ML SUSP | Generic | $0.08 per ml |
| PHENYTOIN 50 MG INFATAB | Generic | $0.32 each |
| PHENYTOIN 50 MG TABLET CHEW | Generic | $0.32 each |
| PHENYTOIN SOD EXT 100 MG CAP | Generic | $0.27 each |
| PHENYTOIN SOD EXT 300 MG CAP | Generic | $1.73 each |
| dilantin (on 6/1/2017 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| DILANTIN 100 MG CAPSULE | Generic | $0.27 each |
| DILANTIN 125 MG/5 ML SUSP | Generic | $0.08 per ml |
| DILANTIN 30 MG CAPSULE | $0.94 each | |
| DILANTIN 50 MG INFATAB | Generic | $0.32 each |
Ontology: Ethotoin (C0015046)
| Definition (NCI) | A hydantoin anticonvulsant with anti-epileptic activity. The mechanism of action is not completely known, but is thought to be fairly similar to phenytoin. Ethotoin influences synaptic transmission by altering sodium and calcium ion influx across neuronal membranes in the repolarization, depolarization, and membrane stability phase and interferes with the calcium uptake in presynaptic terminals. This inhibits neuronal firing and results in the stabilization of neuronal membranes, thereby preventing the spread of seizure activity at the motor cortex. |
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| MSH | C084606 |
| SnomedCT | 64463006, 371384002 |
| LNC | LP16138-7, MTHU016713 |
| English | ethotoin, 2,4-Imidazolidinedione, 3-ethyl-5-phenyl-, 3-ethyl-5-phenyl-2,4-imidazolidinedione, Hydantoin, 3-ethyl-5-phenyl-, ethotoin (medication), ETHOTOIN, ethotoin [Chemical/Ingredient], Ethylphenylhydantoin, Ethotoin (substance), Ethotoin product (product), Ethotoin product, Ethotoin |
| Spanish | etotoína (producto), etotoína, producto (producto), etotoína, producto, etilfenilhidantoína, etotoína (sustancia), etotoína |
Ontology: Hydantoins (C0020209)
| Definition (MSH) | Compounds based on imidazolidine dione. Some derivatives are ANTICONVULSANTS. |
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| MSH | D006827 |
| English | Hydantoins, Imidazolidine 2,4 Diones, Imidazolidine-2,4-Diones, Hydantoins [Chemical/Ingredient], hydantoin, hydantoins |
| Swedish | Hydantoiner |
| Czech | hydantoiny |
| Finnish | Hydantoiinit |
| Russian | GIDANTOINY, ETOTOIN, ГИДАНТОИНЫ, ЭТОТОИН |
| Croatian | Not Translated[Hydantoins] |
| Spanish | Hidantoínas |
| Polish | Hydantoiny pochodne |
| Japanese | グリコリル尿素, ヒダントイン |
| French | Hydantoïnes |
| German | Hydantoine |
| Italian | Idantoine |
| Portuguese | Hidantoínas |
Ontology: Mephenytoin (C0025381)
| Definition (NCI) | A heterocyclic organic compound with anticonvulsant property. Although the mechanism of action is not well established, mephenytoin potentially promotes sodium efflux from neurons in motor cortex, and stabilizes the threshold against hyperexcitability caused by excessive stimulation. Thus this agent reduces the membrane sodium gradient and prevents cortical seizure signal spreading. It may cause blood dyscrasias, therefore, this agent was only used after other less toxic anticonvulsants had failed. |
| Definition (MSH) | An anticonvulsant effective in tonic-clonic epilepsy (EPILEPSY, TONIC-CLONIC). It may cause blood dyscrasias. |
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| MSH | D008617 |
| SnomedCT | 28344001, 417526007 |
| LNC | LP16185-8, MTHU011049 |
| English | Mefenetoin, Mephenytoin, Methoin, Methyl Phenetoin, Phenetoin, Methyl, 2,4-Imidazolidinedione, 5-ethyl-3-methyl-5-phenyl-, 5 Ethyl 3 Methyl 5 Phenylhydantoin, 5-Ethyl-3-Methyl-5-Phenylhydantoin, mephenytoin, mephenytoin (discontinued) (medication), mephenytoin (discontinued), Mephenytoin [Chemical/Ingredient], 3-Methyl-5,5-phenylethylhydantoin, 3-Ethylnirvanol, Methylphenylethylhydantoin, Mephenytoin (substance), Mephenytoin (product), MEPHENYTOIN |
| Czech | mefenytoin |
| Finnish | Mefenytoiini |
| Russian | METILFENETOIN, MEFENITOIN, METOIN, МЕТИЛФЕНЕТОИН, МЕТОИН, МЕФЕНИТОИН |
| Japanese | メチルフェネトイン, メトイン, フェナントイン, メフェニトイン |
| Swedish | Mefenytoin |
| Spanish | Mefenitoína, Metoína, Metil Fenetoína, mefenitoína (sustancia), mefenitoína, metilfeniletilhidantoína, metoína, mefenitoína (producto) |
| Polish | Mefenytoina, Mezantoina |
| Portuguese | Metilfenitoína, Mefenitoína, Metoína |
| French | Méphénytoïne |
| German | Mephenytoin, Methoin, Methylphenetoin |
| Italian | Mefenitoina |
Ontology: Phenytoin (C0031507)
| Definition (NCI) | A hydantoin derivative and a non-sedative antiepileptic agent with anticonvulsant activity. Phenytoin potentially acts by promoting sodium efflux from neurons located in the motor cortex reducing post-tetanic potentiation at synapses. The reduction of potentiation prevents cortical seizure foci spreading to adjacent areas, stabilizing the threshold against hyperexcitability. In addition, this agent appears to reduce sensitivity of muscle spindles to stretch causing muscle relaxation. |
| Definition (MSH) | An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. |
| Definition (CSP) | anticonvulsant used in a wide variety of seizures; also an anti-arrhythmic and a muscle relaxant. |
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| MSH | D010672 |
| SnomedCT | 255672002, 387220006, 40556005 |
| CPT | 1011174 |
| LNC | LP14732-9, MTHU002993 |
| English | Phenytoin, 5,5-Diphenylhydantoin, Diphenylhydantoin, Fenitoin, 2,4-Imidazolidinedione, 5,5-diphenyl-, 5,5-Diphenyl-2,4-imidazolidinedione, diphenylhydantoin, Phenytoin - chemical, Phenytoin [Chemical/Ingredient], dph, fenitoin, phenytoin, PHENYTOIN, Phenytoin - chemical (substance), DPH, Phenylhydantoin, Phenytoin product, Phenytoin (product), Phenytoin (substance) |
| Swedish | Fenytoin |
| Czech | fenytoin, difenylthiohydantoin, difenylhydantoin |
| Finnish | Fenytoiini |
| Russian | DIFENIN, FENITOIN, FENANTOIN, DIFENILTIOGIDANTOIN, DIFENILGIDANTOIN, ДИФЕНИЛГИДАНТОИН, ДИФЕНИЛТИОГИДАНТОИН, ДИФЕНИН, ФЕНАНТОИН, ФЕНИТОИН |
| Japanese | ヒダントール, ジランチン, フェニトイン, アレビアチン, ジフェニルヒダントイン, ジフェニルヒダントインナトリウム, フェニトインナトリウム |
| Italian | Difenilidantoina, 5,5-Difenilidantoina, Fenitoina |
| Croatian | FENITOIN |
| Spanish | Fenitoína, Difenilhidantoína, fenitoína - químico (sustancia), fenitoína - químico, difenilhidantoína, fenitoína (producto), fenitoína (sustancia), fenitoína |
| Polish | Fenytoina, Dilantin, Epanutin |
| French | Phénytoïne |
| German | Diphenylhydantoin, Fenitoin, Phenytoin |
| Portuguese | Difenilidantoína, Fenitoína |
Ontology: phenacemide (C0070525)
| Concepts | Organic Chemical (T109) , Pharmacologic Substance (T121) |
| MSH | C005396 |
| SnomedCT | 18712002, 400358006 |
| LNC | LP15178-4, MTHU002567 |
| English | (phenylacetyl)urea, benzeneacetamide, N-(aminocarbonyl)-, phenacemide, phenuron, phenacemide [Chemical/Ingredient], phenylacetylurea, Phenacemide, Phenylacetylcarbamide, Phenylacetylurea, Phenacemide (product), Phenacemide (substance), PHENACEMIDE |
| Spanish | fenacemida (producto), fenacemida (sustancia), fenacemida, fenilacetilcarbamida, fenilacetilurea |
Ontology: fosphenytoin (C0244656)
| Definition (NCI) | A water-soluble phosphate ester prodrug of phenytoin, a hydantoin derivative with anticonvulsant activity. Fosphenytoin is hydrolyzed to phenytoin by phosphatases. Phenytoin exerts its effect mainly by promoting sodium efflux and stabilizes neuronal membranes in the motor cortex. This leads to a suppression of excessive neuronal firing and limits the spread of seizure activity. |
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| MSH | C043114 |
| SnomedCT | 108397000, 372484000 |
| LNC | LP61620-8, MTHU021879 |
| English | 2,4-Imidazolidinedione, 5,5-diphenyl-3-((phosphonooxy)methyl)-, (SP-4-2)-, 3-(hydroxymethyl)phenytoin phosphate ester, fosphenytoin, FOSPHENYTOIN, fosphenytoin (as phenytoin equivalent), fosphenytoin [Chemical/Ingredient], Fosphenytoin (product), Fosphenytoin (substance), Fosphenytoin |
| Spanish | fosfenitoína (sustancia), fosfenitoína, fosfofenitoína (producto), fosfofenitoína (sustancia), fosfofenitoína |
Ontology: Cerebyx (C0525944)
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| MSH | C043114 |
| English | Cerebyx |
Ontology: Dilantin (C0699512)
| Definition (CHV) | a kind of epilepsy treatment drug |
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| MSH | D010672 |
| English | dilantin, Park Davis brand of Phenytoin, Dilantin |
