II. Classification: Hydantoin
- Phenytoin (Dilantin)
- Fosphenytoin (Cerebyx)
- Phenytoin congeners (limited use)
- Mephenytoin
- Ethotoin
- Phenacemide
III. Mechanism
IV. History
- Phenytoin is the oldest non-Sedative antiepileptic drug (1938)
- Developed based on research into Phenobarbital antiseizure effect
V. Indications
- Partial Seizures
- Generalized tonic-clonic Seizures
VI. Contraindications
- Pregnancy (See Fetal Hydantoin Syndrome)
VII. Pharmacokinetics: Phenytoin
- Fosphenytoin (Cerebyx) has similar Pharmacokinetics to Phenytoin and is preferred for IV use
- Hepatic metabolism
- Large volume of distribution (0.7 L/kg)
- Highly Protein bound (90%)
- Phenytoin levels must be interpreted in relation to the Serum Albumin level
- Onset: 10-30 minutes
- Therapeutic level: 10-20 mcg/ml
-
Half-Life: 12 to 24-36 hours
- Average half life for moderate dosages: 24 hours
- Very long Half-Life (zero order elimination) at toxic concentrations (>40 mcg/ml)
VIII. Dosing: Phenytoin or Dilantin (Adults)
-
Status Epilepticus
- Fosphenytoin is preferred for IV use
- Initial: 20 mg/kg IV (at 1 mg/kg/min up to 50 mg/min) up to to 1000 mg maximum
- May repeat once at 5-10 mg/kg IV
- Maintenance: 50 mg/min or 100 mg IV or orally every 6 to hours
-
Epilepsy
- Start Option 1: Oral dose start
- Start 100 mg orally three times daily
- Advance dosing based on serum concentrations
- Start Option 2: Oral loading regimen
- Dose 1: 400 mg orally
- Dose 2: 300 mg orally at 2 hours after dose 1
- Dose 3: 300 mg mg orally at 4 hours after dose 1
- Start subsequent maintenance dosing on next day
- Start Option 3: Parenteral loading regimen
- Dose: 10-20 mg/kg (average 1 gram) IV
- Do not administer faster than 50 mg/min
- Maintenance dose
- Initial: 5 mg/kg to 300 mg/day divided daily to three times daily
- Titrating dose
- Avoid increasing dose by >25-30 mg per trial
- Wait for steady state (7 days) before level recheck
- Start Option 1: Oral dose start
IX. Dosing: Phenytoin or Dilantin (Children)
-
Status Epilepticus
- Fosphenytoin is preferred for IV use
- Initial: 15 to 20 mg/kg IV (at 1 mg/kg/min up to 50 mg/min)
- May repeat once at 5-10 mg/kg IV
-
Epilepsy
- Start 5 mg/kg/day orally divided 2 to 3 times daily
- Titrate to therapeutic serum level
- Typical range: 4 to 8 mg/kg/day up to 300 mg/day
X. Drug Interactions
- Decreases Oral Contraceptive efficacy
- Drugs that increase plasma Phenytoin levels
- Drugs that decrease Phenytoin level or free fraction
- Phenytoin decreases plasma level of other drug
XI. Adverse Effects
- See Dilantin Toxicity
- Fetal Hydantoin Syndrome
- Neurologic effects
- Intravenous Effects
- CNS Depression
- Severe Hypotension
- Arrhythmias
-
Drug Hypersensitivity
- Fever
- Lymphadenopathy
- Drug-Induced Agranulocytosis or Bone Marrow suppression
- Common chronic changes associated with Phenytoin
- Gingival Hyperplasia
- Hirsutism
- Coarse facial features
- Peripheral Neuropathy (decreased Deep Tendon Reflex)
- Other effects
- Hepatotoxicity
- Drug-Induced Rash
- Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis
- More common in Asian heritage with HLA-B 1502 Mutation
- Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS Syndrome)
- Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis
- Pancreatitis
- Osteoporosis
- Folic Acid Deficiency
XII. Monitoring
- Monitor Phenytoin levels to ensure in therapeuti range
- Hypoalbuminemia may increase free fraction of Phenytoin
- Routine Labs every 6 to 12 months
- Complete Blood Count with Platelet Count (myelosuppression risk)
- Liver Function Tests (hepatotoxicity risk)
- May decrease circulating Thyroid Hormone
- May increase Thyroid Stimulating Hornone (TSH)
XIII. Safety
- Pregnancy: Category D
- Lactation: Contraindicated
XIV. Resources
- Phenytoin Injection (DailyMed)
- Phenytoin Extended Release Capsule (DailyMed)
- Phenytoin Capsule (DailyMed)
XV. References
- (2022) Presc Lett, Resource #361206, Antiseizure Medications
- Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 56-7
- Hamilton (2020) Tarascon Pocket Pharmacopoeia
Images: Related links to external sites (from Bing)
Related Studies
| phenytoin (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| PHENYTOIN 125 MG/5 ML SUSP | Generic | $0.08 per ml |
| PHENYTOIN 50 MG INFATAB CHEW | Generic | $0.23 each |
| PHENYTOIN 50 MG TABLET CHEW | Generic | $0.23 each |
| PHENYTOIN SOD EXT 100 MG CAP | Generic | $0.13 each |
| PHENYTOIN SOD EXT 200 MG CAP | Generic | $1.00 each |
| PHENYTOIN SOD EXT 300 MG CAP | Generic | $1.72 each |
| dilantin (on 3/23/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| DILANTIN 100 MG CAPSULE | Generic | $0.13 each |
| DILANTIN 30 MG CAPSULE | $1.23 each | |
| DILANTIN 50 MG INFATAB | Generic | $0.23 each |
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: 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 |
