pharmacopeia
GET
/api/v1/drug/phenytoin

Boxed warning

CARDIOVASCULAR RISK ASSOCIATED WITH RAPID INFUSION The rate of intravenous Phenytoin Sodium Injection administration should not exceed 50 mg per minute in adults and 1 to 3 mg/kg/min (or 50 mg per minute, whichever is slower) in pediatric patients because of the risk of severe hypotension and cardiac arrhythmias. Careful cardiac monitoring is needed during and after administering intravenous Phenytoin Sodium Injection. Although the risk of cardiovascular toxicity increases with infusion rates above the recommended infusion rate, these events have also been reported at or below the recommended infusion rate. Reduction in rate of administration or discontinuation of dosing may be needed [see Dosage and Administration (2.1) and Warnings and Precautions (5.1) ] . W ARN ING: CARDIOVASCULAR RISK ASSOCIATED WITH RAPID INFUSION S ee full prescribing information for complete boxed warning . The rate of intravenous Phenytoin Sodium Injection administration should not exceed 50 mg per minute in adults and 1 to 3 mg/kg/min (or 50 mg per minute, whichever is slower) in pediatric patients because of the risk of severe hypotension and cardiac arrhythmias. Careful cardiac monitoring is needed during and after administering intravenous Phenytoin Sodium Injection. Reduction in rate of administration or discontinuation of dosing may be needed ( 2.1 , 5.1 ).

2D structure
5,5-diphenylimidazolidine-2,4-dione
SMILES C1=CC=C(C=C1)C2(C(=O)NC(=O)N2)C3=CC=CC=C3
InChIKey CXOFVDLJLONNDW-UHFFFAOYSA-N

Mechanism of action

Sourced from openFDA

The precise mechanism by which phenytoin exerts its therapeutic effect has not been established but is thought to involve the voltage-dependent blockade of membrane sodium channels resulting in a reduction in sustained high-frequency neuronal discharges.

Indications

Sourced from openFDA
  • Parenteral Phenytoin Sodium Injection is indicated for the treatment of generalized tonic-clonic status epilepticus, and prevention and treatment of seizures occurring during neurosurgery. Intravenous phenytoin can also be substituted, as short-term use, for oral phenytoin.ICD-10: G40.909

Contraindications

Sourced from openFDA
  • Phenytoin Sodium Injection is contraindicated in patients with: A history of hypersensitivity to phenytoin, its inactive ingredients, or other hydantoins [see Warnings and Precautions (5.5) ] . Sinus bradycardia, sino-atrial block, second and third degree A-V block, and Adams-Stokes syndrome because of the effect of parenteral phenytoin on ventricular automaticity.contraindicated

Dosage & administration

Sourced from openFDA

For Status Epilepticus and Non-emergent Loading Dose: Adult loading dose is 10 to 15 mg/kg at a rate not exceeding 50 mg/min. ( 2.2 ) Pediatric loading dose is 15 to 20 mg/kg at a rate not exceeding 1 to 3 mg/kg/min or 50 mg/min, whichever is slower. ( 2.8 ) Continuous monitoring of the electrocardiogram, blood pressure, and respiratory function is essential. ( 2.2 ) Maintenance Dosing: Initial loading dose should be followed by maintenance doses of oral or intravenous Phenytoin Sodium Injection every 6 to 8 hours. ( 2.2 , 2.3 ) Intramuscular Administration: Because of erratic absorption and local toxicity, Phenytoin Sodium Injection should ordinarily not be given intramuscularly. ( 2.2 , 2.3 ) 2.1 General Dosing Information Because of the increased risk of adverse cardiovascular reactions associated with rapid administration, intravenous administration should not exceed 50 mg per minute in adults. In pediatric patients, the drug should be administered at a rate not exceeding 1 to 3 mg/kg/min or 50 mg per minute, whichever is slower. As non-emergency therapy, Phenytoin Sodium Injection should be administered more slowly as either a loading dose or by intermittent infusion. Because of the risks of cardiac and local toxicity associated with intravenous phenytoin, oral phenytoin should be used whenever possible. Because adverse cardiovascular reactions have occurred during and after infusions, careful cardiac monitoring is needed during and after the administration of intravenous Phenytoin Sodium Injection.

Warnings & precautions

Sourced from openFDA

Withdrawal Precipitated Seizure : May precipitate status epilepticus. Dose reductions or discontinuation should be done gradually. ( 5.2 ) Serious Dermatologic Reactions : Discontinue phenytoin at the first sign of a rash, unless the rash is clearly not drug-related. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered. ( 5.3 ) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan hypersensitivity : If signs or symptoms of hypersensitivity are present, evaluate the patient immediately. Discontinue if an alternative etiology cannot be established. ( 5.4 ) Hematopoietic Complications: If occurs, follow-up observation is indicated and an alternative antiepileptic treatment should be used. ( 5.7 ) 5.1 Cardiovascular Risk Associated with Rapid Infusion Rapid intravenous administration of Phenytoin Sodium Injection increases the risk of adverse cardiovascular reactions, including severe hypotension and cardiac arrhythmias. Cardiac arrhythmias have included bradycardia, heart block, ventricular tachycardia, and ventricular fibrillation which have resulted in asystole, cardiac arrest, and death. Severe complications are most commonly encountered in critically ill patients, elderly patients, and patients with hypotension and severe myocardial insufficiency. However, cardiac events have also been reported in adults and children without underlying cardiac disease or comorbidities and at recommended doses and infusion rates. Intravenous administration should not exceed 50 mg per minute in adults.

Adverse reactions

Sourced from openFDA

The following serious adverse reactions are described elsewhere in the labeling: Cardiovascular Risk Associated with Rapid Infusion [see Warnings and Precautions (5.1) ] Withdrawal Precipitated Seizure, Status Epilepticus [see Warnings and Precautions (5.2) ] Serious Dermatologic Reactions [see Warnings and Precautions (5.3) ] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see W arnings and Precautions (5.4) ] Hypersensitivity [see Warnings and Precautions (5.5) ] Hepatic Injury [see Warnings and Precautions (5.6) ] Hematopoietic Complications [see Warnings and Precautions (5.7) ] Local toxicity (Including Purple Glove Syndrome) [see Warnings and Precautions (5.8) ] Exacerbation of Porphyria [see Warnings and Precautions (5.10) ] Teratogenicity and Other Harm to the Newborn [see Warnings and Precautions (5.11) ] Hyperglycemia [see Warnings and Precautions (5.12) ] The following adverse reactions associated with the use of Phenytoin Sodium Injection were identified in clinical studies or postmarketing reports. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The most notable signs of toxicity associated with the intravenous use of this drug are cardiovascular collapse and/or CNS depression. Hypotension does occur when the drug is administered rapidly by the intravenous route.

Use in specific populations

Sourced from openFDA

Pregnancy: Prenatal exposure to phenytoin may increase the risks for congenital malformations and other adverse developmental outcomes. ( 5.11 , 8.1 ) Renal and/or Hepatic Impairment or Hypoalbuminemia: Monitor unbound phenytoin concentrations in these patients. ( 8.6 ) 8.1 Pregnancy P regnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as Phenytoin Sodium Injection, during pregnancy. Physicians are advised to recommend that pregnant patients taking phenytoin enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/ . Risk Summary In humans, prenatal exposure to phenytoin may increase the risks for congenital malformations and other adverse developmental outcomes. Prenatal phenytoin exposure is associated with an increased incidence of major malformations (including orofacial clefts and cardiac defects).

Pharmacokinetics

Sourced from openFDA
Metabolism
Absorption A fall in serum levels may occur when patients are changed from oral to intramuscular administration. The drop is caused by slower absorption, as compared to oral administration, because of the poor water solubility of phenytoin.

Overdosage

Sourced from openFDA

The lethal dose in pediatric patients is not known. The lethal dose in adults is estimated to be 2 to 5 grams. The initial symptoms are nystagmus, ataxia, and dysarthria. Other signs are tremor, hyperreflexia, lethargy, slurred speech, blurred vision, nausea, and vomiting. The patient may become comatose and hypotensive. Death is caused by respiratory and circulatory depression. There are marked variations among individuals with respect to phenytoin serum levels where toxicity may occur. Nystagmus, on lateral gaze, usually appears at 20 mcg/mL, ataxia at 30 mcg/mL, dysarthria and lethargy appear when the serum concentration is over 40 mcg/mL, but as high a concentration as 50 mcg/mL has been reported without evidence of toxicity. As much as 25 times the therapeutic dose has been taken to result in a serum concentration over 100 mcg/mL with complete recovery. Irreversible cerebellar dysfunction and atrophy have been reported. Treatment: Treatment is nonspecific since there is no known antidote. The adequacy of the respiratory and circulatory systems should be carefully observed and appropriate supportive measures employed.

Approval history

Sourced from openFDA
  • Jan 6, 1953NDANDA008762Viatris
  • Jul 16, 1975ANDAANDA084307Hikma
  • Aug 27, 1976ANDAANDA084349Viatris
  • Feb 26, 1979ANDAANDA084427Pharmacia
  • Dec 28, 1998ANDAANDA040298Mylan
  • Mar 8, 2004ANDAANDA040521Taro
  • Sep 5, 2006ANDAANDA040684Taro
  • Sep 13, 2006ANDAANDA040573Acella

FAERS reports

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Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
40,103 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Drug Ineffective4,47111%
  2. 2Convulsion3,5228.8%
  3. 3Seizure3,0717.7%
  4. 4Drug Interaction2,2525.6%
  5. 5Toxicity To Various Agents1,8764.7%
  6. 6Off Label Use1,6674.2%
  7. 7Fall1,5944.0%
  8. 8Dizziness1,5333.8%
  9. 9Drug Hypersensitivity1,3543.4%
  10. 10Headache1,2973.2%
  11. 11Fatigue1,2833.2%
  12. 12Nausea1,2753.2%
  13. 13Stevens-johnson Syndrome1,2253.1%
  14. 14Pyrexia1,1542.9%
  15. 15Rash1,1202.8%

Literature

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Recent PubMed references pinned to Phenytoin as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

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The 10 most recently updated of 125 ClinicalTrials.gov registrations naming Phenytoin as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Pharmacogenomics

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CPIC-curated drug–gene pairs for Phenytoin. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

Frequently asked questions

How does Phenytoin work?
The precise mechanism by which phenytoin exerts its therapeutic effect has not been established but is thought to involve the voltage-dependent blockade of membrane sodium channels resulting in a reduction in sustained high-frequency neuronal discharges.
What is Phenytoin used for?
According to FDA labeling, Phenytoin carries indications including: Parenteral Phenytoin Sodium Injection is indicated for the treatment of generalized tonic-clonic status epilepticus, and prevention and treatment of seizures occurring during neurosurgery. Intravenous phenytoin can also be substituted, as short-term use, for oral phenytoin.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Phenytoin?
Phenytoin is classified as Hydantoin derivatives, Anti-epileptic Agent, Cytochrome P450 1A2 Inducers, Cytochrome P450 2B6 Inducers, Cytochrome P450 2C19 Inducers, Cytochrome P450 2C8 Inducers, Cytochrome P450 2C9 Inducers, Cytochrome P450 2D6 Inducers, Cytochrome P450 3A Inducers, Sodium Channel Interactions, Decreased Central Nervous System Disorganized Electrical Activity, Decreased Disorganized Electrical Activity, Decreased Organized Electrical Activity.
What are the brand names for Phenytoin?
Phenytoin is marketed under brand names including Dilantin, Euthaphen, Euthasol, Phenytek.
What are the contraindications for Phenytoin?
Phenytoin labeling lists contraindications including: Phenytoin Sodium Injection is contraindicated in patients with: A history of hypersensitivity to phenytoin, its inactive ingredients, or other hydantoins [see Warnings and Precautions (5.5) ] . Sinus bradycardia, sino-atrial block, second and third degree A-V block, and Adams-Stokes syndrome because of the effect of parenteral phenytoin on ventricular automaticity.. Always consult the full prescribing information and a clinician.
Note. Data for phenytoin is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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