Description

Simple

A medication used to prevent and control seizures.

Clinical

An anticonvulsant drug used in the prophylaxis and control of various types of seizures.

Overview

Phenytoin is classified as a hydantoin derivative and despite its narrow therapeutic index, it is one of the most commonly used anticonvulsants.[12,6,8] Since it's introduction about 80 years ago, phenytoin has not only been established as an effective anti-epileptic, but has also been investigated for several other indications such as bipolar disorder, retina protection, and wound healing.[7,Read more

Pharmacology

Indication

Phenytoin is indicated to treat grand mal seizures, complex partial seizures, and to prevent and treat seizures during or following neurosurgery.[14] Injectable phenytoin and [Fosphenytoin], which is the phosph... Read more

Pharmacodynamic

Phenytoin is an anticonvulsant with a narrow therapeutic index.[ Read more

Mechanism of action

Although phenytoin first appeared in the literature in 1946, it has taken decades for the mechanism of action to be more specifically elucidated.[ Read more

Absorption

Given its narrow therapeutic index, therapeutic drug monitoring is recommended to help guide dosing.[8, Read more

Protein binding

Phenytoin is roughly 90% protein bound.[4]

Volume of distribution

The volume of distribution of phenytoin is reported to be approximately 0.75 L/kg.[11]

Clearance

The clearance of phenytoin is non-linear.[10] At lower serum concentrations (less than 10 mg/L), eliminati... Read more

Half life

Oral administration: The half-life of phenytoin ranges from 7 to 42 hours, and is 22 hours on average.[ Read more

Route of elimination

The majority of phenytoin is excreted as inactive metabolites in the bile.[14,16] An estimated 1-5% of... Read more

Toxicity

The experience of phenytoin toxicity is not limited to situations of acute ingestion, but may also occur due to drug interactions or due to physiological circumstances that impact serum albumin (ie. kidney disease) or drug metabolism.[ Read more

Adverse Effects

Contraindications

  • Route:
    • Intramuscular
    • Intravenous
    • Oral
  • Dose Form:
    • Capsule, extended release
    • Injection
    • Suspension
  • Sex Group: all
  • Regions: US
  • With Drugs:
      • Name: Delavirdine
      • Drugbank Id: DB00705
  • Route:
    • Intramuscular
    • Intravenous
    • Oral
  • Dose Form:
    • Capsule, extended release
    • Injection
    • Suspension
  • Sex Group: all
  • Regions: US
  • Patient Conditions:
      • Name: History of prior acute hepatotoxicity attributable to phenytoin
      • Drugbank Id: DBCOND0124901
  • Route:
    • Intramuscular
    • Intravenous
    • Oral
  • Dose Form:
    • Capsule, extended release
    • Injection
    • Suspension
  • Sex Group: all
  • Regions: US
  • Patient Conditions:
      • Name: Hypersensitivity to phenytoin
      • Drugbank Id: DBCOND0124900
  • Route:
    • Intramuscular
    • Intravenous
  • Dose Form:
    • Injection
  • Sex Group: all
  • Regions: US
  • Patient Conditions Associated With:
      • Name: Adams-Stokes Syndrome
      • Drugbank Id: DBCOND0000492
  • Route:
    • Intramuscular
    • Intravenous
  • Dose Form:
    • Injection
  • Sex Group: all
  • Regions: US
  • Patient Conditions:
      • Name: Third degree AV block
      • Drugbank Id: DBCOND0107810
  • Route:
    • Intramuscular
    • Intravenous
  • Dose Form:
    • Injection
  • Sex Group: all
  • Regions: US
  • Patient Conditions:
      • Name: Atrioventricular block second degree
      • Drugbank Id: DBCOND0007764
  • Route:
    • Intramuscular
    • Intravenous
  • Dose Form:
    • Injection
  • Sex Group: all
  • Regions: US
  • Patient Conditions:
      • Name: Sinoatrial Block
      • Drugbank Id: DBCOND0000489
  • Route:
    • Intramuscular
    • Intravenous
  • Dose Form:
    • Injection
  • Sex Group: all
  • Regions: US
  • Patient Conditions:
      • Name: Sinus Bradycardia
      • Drugbank Id: DBCOND0042990

Food Interactions

  • Avoid alcohol.
  • Take at least 2 hours before or after antacids. Taking this medication with antacids can reduce absorption.
  • Take at least 2 hours before or after calcium supplements. Taking this medication with calcium supplements can reduce its absorption.
  • Take at least 2 hours before or after iron supplements. Taking this medication with iron supplements can reduce its absorption.
  • Take with food. Food reduces irritation and increases bioavailability.

Interactions

Type in a drug name to check for interaction with Phenytoin
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(6R)-Folinic acid
The serum concentration of Phenytoin can be decreased when it is combined with (6R)-Folinic acid.
(6S)-5,6,7,8-tetrahydrofolic acid
The serum concentration of Phenytoin can be decreased when it is combined with (6S)-5,6,7,8-tetrahydrofolic acid.
(R)-warfarin
The metabolism of (R)-warfarin can be increased when combined with Phenytoin.
(S)-Warfarin
The metabolism of (S)-Warfarin can be increased when combined with Phenytoin.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine
The metabolism of Phenytoin can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
1alpha-Hydroxyvitamin D5
The serum concentration of 1alpha-Hydroxyvitamin D5 can be decreased when it is combined with Phenytoin.
1alpha,24S-Dihydroxyvitamin D2
The serum concentration of 1alpha,24S-Dihydroxyvitamin D2 can be decreased when it is combined with Phenytoin.
2,5-Dimethoxy-4-ethylamphetamine
The therapeutic efficacy of Phenytoin can be decreased when used in combination with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine
The therapeutic efficacy of Phenytoin can be decreased when used in combination with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthine
The serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be decreased when it is combined with Phenytoin.
3,5-Dinitrocatechol
The metabolism of Phenytoin can be decreased when combined with 3,5-Dinitrocatechol.
4-Bromo-2,5-dimethoxyamphetamine
The therapeutic efficacy of Phenytoin can be decreased when used in combination with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarin
The metabolism of 4-hydroxycoumarin can be increased when combined with Phenytoin.
4-Methoxyamphetamine
The risk or severity of adverse effects can be increased when Phenytoin is combined with 4-Methoxyamphetamine.
5-fluorouridine
The serum concentration of Phenytoin can be increased when it is combined with 5-fluorouridine.
5-methoxy-N,N-dimethyltryptamine
The risk or severity of adverse effects can be increased when Phenytoin is combined with 5-methoxy-N,N-dimethyltryptamine.
5-methyltetrahydrofolic acid
The serum concentration of Phenytoin can be decreased when it is combined with 5-methyltetrahydrofolic acid.
6-O-benzylguanine
The serum concentration of 6-O-benzylguanine can be decreased when it is combined with Phenytoin.
7-Deazaguanine
The serum concentration of 7-Deazaguanine can be decreased when it is combined with Phenytoin.
7-Nitroindazole
The risk or severity of adverse effects can be increased when Phenytoin is combined with 7-Nitroindazole.
17 References
  1. 1 . Mallet L, Spinewine A, Huang A: The challenge of managing drug interactions in elderly people. Lancet. 2007 Jul 14;370(9582):185-191. doi: 10.1016/S0140-6736(07)61092-7.PubMed: 17630042
  2. 2 . Fischer JH, Patel TV, Fischer PA: Fosphenytoin: clinical pharmacokinetics and comparative advantages in the acute treatment of seizures. Clin Pharmacokinet. 2003;42(1):33-58. doi: 10.2165/00003088-200342010-00002.PubMed: 12489978
  3. 3 . Iorga A, Horowitz BZ: Phenytoin Toxicity .PubMed: 29494051
  4. 4 . Richens A: Clinical pharmacokinetics of phenytoin. Clin Pharmacokinet. 1979 May-Jun;4(3):153-69. doi: 10.2165/00003088-197904030-00001.PubMed: 383353
  5. 5 . Dagenais R, Wilby KJ, Elewa H, Ensom MHH: Impact of Genetic Polymorphisms on Phenytoin Pharmacokinetics and Clinical Outcomes in the Middle East and North Africa Region. Drugs R D. 2017 Sep;17(3):341-361. doi: 10.1007/s40268-017-0195-7.PubMed: 28748348
  6. 6 . Silvado CE, Terra VC, Twardowschy CA: CYP2C9 polymorphisms in epilepsy: influence on phenytoin treatment. Pharmgenomics Pers Med. 2018 Mar 29;11:51-58. doi: 10.2147/PGPM.S108113. eCollection 2018.PubMed: 29636628
  7. 7 . Keppel Hesselink JM: Phenytoin: a step by step insight into its multiple mechanisms of action-80 years of mechanistic studies in neuropharmacology. J Neurol. 2017 Sep;264(9):2043-2047. doi: 10.1007/s00415-017-8465-4. Epub 2017 Mar 27.PubMed: 28349209
  8. 8 . Gupta M, Tripp J: Phenytoin .PubMed: 31855364
  9. 9 . Abdelsayed M, Sokolov S: Voltage-gated sodium channels: pharmaceutical targets via anticonvulsants to treat epileptic syndromes. Channels (Austin). 2013 May-Jun;7(3):146-52. doi: 10.4161/chan.24380. Epub 2013 Mar 26.PubMed: 23531742
  10. 10 . Nation RL, Evans AM, Milne RW: Pharmacokinetic drug interactions with phenytoin (Part I). Clin Pharmacokinet. 1990 Jan;18(1):37-60.PubMed: 2178849
  11. 11 . Bergen DC: Pharmacokinetics of phenytoin: reminders and discoveries. Epilepsy Curr. 2009 Jul-Aug;9(4):102-4. doi: 10.1111/j.1535-7511.2009.01307.x.PubMed: 19693326
  12. 12 . Thorn CF, Whirl-Carrillo M, Leeder JS, Klein TE, Altman RB: PharmGKB summary: phenytoin pathway. Pharmacogenet Genomics. 2012 Jun;22(6):466-70. doi: 10.1097/FPC.0b013e32834aeedb.PubMed: 22569204
  13. 13 . Kinobe RT, Parkinson OT, Mitchell DJ, Gillam EM: P450 2C18 catalyzes the metabolic bioactivation of phenytoin. Chem Res Toxicol. 2005 Dec;18(12):1868-75. doi: 10.1021/tx050181o.PubMed: 16359177
  14. 14 . FDA Approved Drugs: Dilantin Link
  15. 15 . CEREBYX® FDA Label Link
  16. 16 . Dilantin® FDA Label (injectable formulation) Link
  17. 17 . Phenytoin: A Guide to Therapeutic Drug Monitoring Link