Phenytoin (injection)
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];
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Overview
Phenytoin (injection) is an antiepileptic that is FDA approved for the treatment of generalized tonic-clonic status epilepticus and prevention and treatment of seizures occurring during neurosurgery. Parenteral phenytoin should be used only when oral phenytoin administration is not possible. Common adverse reactions include morbilliform eruption, rash, drug-induced gingival hyperplasia, ataxia, decreased coordination, nystagmus, Slurred speech and confusion.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indications
Parenteral Phenytoin Sodium Injection is indicated for the control of generalized tonic-clonic status epilepticus and prevention and treatment of seizures occurring during neurosurgery. Parenteral phenytoin should be used only when oral phenytoin administration is not possible.
Dosage
- Treatment with Phenytoin Sodium Injection can be initiated either with a loading dose or an infusion:
Loading Dose: A loading dose of parenteral Phenytoin Sodium Injection should be injected slowly, not exceeding 50 mg per minute in adults
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Phenytoin (injection) in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Phenytoin (injection) in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Phenytoin (injection) FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Phenytoin (injection) in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Phenytoin (injection) in pediatric patients.
Contraindications
Phenytoin is contraindicated in patients with a history of hypersensitivity to phenytoin, its inactive ingredients, or other hydantoins.
Because of its effect on ventricular automaticity, phenytoin is contraindicated in sinus bradycardia, sino-atrial block, second and third degree A-V block, and patients with Adams-Stokes syndrome.
Coadministration of phenytoin is contraindicated with delavirdine due to potential for loss of virologic response and possible resistance to delavirdine or to the class of non-nucleoside reverse transcriptase inhibitors.
Warnings
Cardiovascular Risk Associated with Rapid Infusion 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 1-3 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. Reduction in rate of administration or discontinuation of dosing may be needed.
Adverse cardiovascular reactions include 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.
Withdrawal Precipitated Seizure, Status Epilepticus Antiepileptic drugs should not be abruptly discontinued because of the possibility of increased seizure frequency, including status epilepticus. When, in the judgment of the clinician, the need for dosage reduction, discontinuation, or substitution of alternative antiepileptic medication arises, this should be done gradually. However, in the event of an allergic or hypersensitivity reaction, rapid substitution of alternative therapy may be necessary. In this case, alternative therapy should be an antiepileptic drug not belonging to the hydantoin chemical class.
Serious Dermatologic Reactions Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome (SJS), have been reported with phenytoin treatment. The onset of symptoms is usually within 28 days, but can occur later. Phenytoin should be discontinued 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. If a rash occurs, the patient should be evaluated for signs and symptoms of Drug Reaction with Eosinophilia and Systemic Symptoms (see DRESS/MULTIORGAN HYPERSENSITIVITY below).
Studies in patients of Chinese ancestry have found a strong association between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA-B gene, in patients using carbamazepine. Limited evidence suggests that HLA-B*1502 may be a risk factor for the development of SJS/TEN in patients of Asian ancestry taking other antiepileptic drugs associated with SJS/TEN, including phenytoin. Consideration should be given to avoiding phenytoin as an alternative for carbamazepine in patients positive for HLA-B*1502.
The use of HLA-B*1502 genotyping has important limitations and must never substitute for appropriate clinical vigilance and patient management. The role of other possible factors in the development of, and morbidity from, SJS/TEN, such as antiepileptic drug (AED) dose, compliance, concomitant medications, comorbidities, and the level of dermatologic monitoring have not been studied.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as Multiorgan Hypersensitivity, has been reported in patients taking antiepileptic drugs, including phenytoin. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash and/or lymphadenopathy, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its expression, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Phenytoin Sodium Injection should be discontinued if an alternative etiology for the signs or symptoms cannot be established.
Hypersensitivity Phenytoin and other hydantoins are contraindicated in patients who have experienced phenytoin hypersensitivity (see CONTRAINDICATIONS). Additionally, consider alternatives to structurally similar drugs such as carboxamides (e.g., carbamazepine), barbiturates, succinimides, and oxazolidinediones (e.g., trimethadione) in these same patients. Similarly, if there is a history of hypersensitivity reactions to these structurally similar drugs in the patient or immediate family members, consider alternatives to phenytoin.
Hepatic Injury Cases of acute hepatotoxicity, including infrequent cases of acute hepatic failure, have been reported with phenytoin. These events may be part of the spectrum of DRESS or may occur in isolation. Other common manifestations include jaundice, hepatomegaly, elevated serum transaminase levels, leukocytosis, and eosinophilia. The clinical course of acute phenytoin hepatotoxicity ranges from prompt recovery to fatal outcomes. In these patients with acute hepatotoxicity, phenytoin should be immediately discontinued and not re-administered.
Hematopoietic System Hematopoietic complications, some fatal, have occasionally been reported in association with administration of phenytoin. These have included thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, and pancytopenia with or without bone marrow suppression.
There have been a number of reports suggesting a relationship between phenytoin and the development of lymphadenopathy (local or generalized) including benign lymph node hyperplasia, pseudolymphoma, lymphoma, and Hodgkin’s Disease. Although a cause and effect relationship has not been established, the occurrence of lymphadenopathy indicates the need to differentiate such a condition from other types of lymph node pathology. Lymph node involvement may occur with or without symptoms and signs resembling DRESS. In all cases of lymphadenopathy, follow-up observation for an extended period is indicated and every effort should be made to achieve seizure control using alternative antiepileptic drugs.
Local Toxicity (including Purple Glove Syndrome) Soft tissue irritation and inflammation has occurred at the site of injection with and without extravasation of intravenous phenytoin.
Edema, discoloration and pain distal to the site of injection (described as “purple glove syndrome”) have also been reported following peripheral intravenous phenytoin injection. Soft tissue irritation may vary from slight tenderness to extensive necrosis, and sloughing. The syndrome may not develop for several days after injection. Although resolution of symptoms may be spontaneous, skin necrosis and limb ischemia have occurred and required such interventions as fasciotomies, skin grafting, and, in rare cases, amputation.
Because of the risk of local toxicity, intravenous Phenytoin Sodium Injection should be administered directly into a large peripheral or central vein through a large-gauge catheter. Prior to the administration, the patency of the IV catheter should be tested with a flush of sterile saline. Each injection of parenteral Phenytoin Sodium Injection should then be followed by a flush of sterile saline through the same catheter to avoid local venous irritation due to the alkalinity of the solution.
Intramuscular Phenytoin Sodium Injection administration may cause pain, necrosis, and abscess formation at the injection site (see DOSAGE AND ADMINISTRATION).
Exacerbation of Porphyria
In view of isolated reports associating phenytoin with exacerbation of porphyria, caution should be exercised in using this medication in patients suffering from this disease.
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Phenytoin (injection) Clinical Trials Experience in the drug label.
Postmarketing Experience
There is limited information regarding Phenytoin (injection) Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Phenytoin (injection) Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Phenytoin (injection) in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Phenytoin (injection) in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Phenytoin (injection) during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Phenytoin (injection) in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Phenytoin (injection) in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Phenytoin (injection) in geriatric settings.
Gender
There is no FDA guidance on the use of Phenytoin (injection) with respect to specific gender populations.
Race
There is no FDA guidance on the use of Phenytoin (injection) with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Phenytoin (injection) in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Phenytoin (injection) in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Phenytoin (injection) in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Phenytoin (injection) in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Phenytoin (injection) Administration in the drug label.
Monitoring
There is limited information regarding Phenytoin (injection) Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Phenytoin (injection) and IV administrations.
Overdosage
There is limited information regarding Phenytoin (injection) overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Phenytoin (injection) Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Phenytoin (injection) Mechanism of Action in the drug label.
Structure
There is limited information regarding Phenytoin (injection) Structure in the drug label.
Pharmacodynamics
There is limited information regarding Phenytoin (injection) Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Phenytoin (injection) Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Phenytoin (injection) Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Phenytoin (injection) Clinical Studies in the drug label.
How Supplied
There is limited information regarding Phenytoin (injection) How Supplied in the drug label.
Storage
There is limited information regarding Phenytoin (injection) Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Phenytoin (injection) Patient Counseling Information in the drug label.
Precautions with Alcohol
Acute alcoholic intake may increase phenytoin serum levels while chronic alcoholic use may decrease serum levels.
Brand Names
There is limited information regarding Phenytoin (injection) Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Phenytoin (injection) Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.