Which Condition is a Contraindication of Phenytoin? Understanding the Risks

October 13, 2025 •

4 min read

Epilepsy affects approximately 50 million people worldwide, making effective and safe treatment essential [1.7.1, 1.7.3]. This article explores a critical safety question: which condition is a contraindication of phenytoin, a widely used anticonvulsant medication?

Quick Summary

Key contraindications for phenytoin include a history of hypersensitivity to the drug or other hydantoins, certain cardiac conditions like sinus bradycardia, and prior acute hepatotoxicity from the medication [1.2.2, 1.3.3].

Key Points

Hypersensitivity: A history of allergic reaction to phenytoin or other hydantoins is an absolute contraindication [1.3.3].
Cardiac Conditions: Phenytoin is contraindicated in patients with sinus bradycardia, sino-atrial block, and 2nd/3rd degree A-V block [1.2.2].
Liver Damage: Previous acute liver toxicity caused by phenytoin prohibits its reuse [1.3.3].
Drug Interactions: Co-administration with the HIV drug delavirdine is contraindicated due to loss of virologic response [1.2.3].
Pregnancy Risk: Phenytoin can cause fetal harm and is associated with congenital malformations, requiring careful risk-benefit analysis [1.3.3].
IV Risk: A black box warning exists for cardiovascular risk, including hypotension and arrhythmias, with rapid intravenous infusion [1.3.1, 1.3.3].
Monitoring: Patients with renal or hepatic disease require close monitoring of unbound phenytoin levels due to increased toxicity risk [1.2.2].

Understanding Phenytoin and Its Role

Phenytoin, also known by brand names like Dilantin and Phenytek, is a long-standing anticonvulsant medication used to control certain types of seizures [1.5.5, 1.4.4]. It works by slowing down impulses in the brain that cause seizures, specifically by blocking voltage-gated sodium channels [1.4.4, 1.4.2]. Its primary applications include treating generalized tonic-clonic status epilepticus and preventing seizures that may occur during or after neurosurgery [1.3.3]. While effective, phenytoin has a narrow therapeutic range and a significant list of potential side effects and interactions, making it crucial for healthcare providers and patients to understand its contraindications thoroughly.

Absolute Contraindications: When Phenytoin Must Be Avoided

An absolute contraindication is a condition that makes a particular treatment or procedure absolutely inadvisable. For phenytoin, several such conditions exist.

History of Hypersensitivity: The most definitive contraindication is a history of hypersensitivity to phenytoin, its ingredients, or other hydantoins (a class of drugs including fosphenytoin and ethotoin) [1.2.2, 1.3.3]. Allergic reactions can be severe and include life-threatening skin conditions like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) [1.5.2, 1.3.3].

Specific Cardiac Conditions: Because of its effect on ventricular automaticity, intravenous phenytoin is contraindicated in patients with sinus bradycardia, sino-atrial block, and second- and third-degree atrioventricular (AV) block [1.2.2, 1.4.6]. It is also contraindicated for individuals with Adams-Stokes syndrome, a condition characterized by sudden fainting due to heart rhythm problems [1.2.2, 1.3.3]. The rapid intravenous administration of phenytoin carries a black box warning for the risk of severe hypotension and cardiac arrhythmias [1.3.1, 1.3.3].

Previous Liver Injury: If a patient has a history of acute hepatotoxicity (liver damage) that was attributable to phenytoin, the drug should be immediately discontinued and not used again [1.2.2, 1.3.3].

Coadministration with Delavirdine: Phenytoin is contraindicated for use with delavirdine, a non-nucleoside reverse transcriptase inhibitor used to treat HIV. Phenytoin can significantly reduce the concentration of delavirdine, leading to a loss of virologic response and potential drug resistance [1.2.2, 1.2.3].

Relative Contraindications and Conditions Requiring Caution

Beyond absolute contraindications, many conditions require caution and careful monitoring. These are often called relative contraindications, where the benefits of the drug must be weighed carefully against the potential risks.

Pregnancy: Prenatal exposure to phenytoin is associated with an increased risk of congenital malformations, known as fetal hydantoin syndrome, which can include facial defects, growth abnormalities, and cognitive deficits [1.3.3, 1.2.2]. While seizure control is vital during pregnancy, the risks must be carefully managed [1.2.6].
Hepatic or Renal Impairment: Patients with liver or kidney disease may have an increased fraction of unbound (active) phenytoin in their blood, heightening the risk of toxicity. Close monitoring of unbound phenytoin concentrations is recommended for these individuals [1.2.2, 1.3.3].
Alcohol Use: Acute alcohol intake can increase phenytoin serum levels, while chronic alcohol use can decrease them, affecting both toxicity risk and seizure control [1.2.2, 1.6.2].
Diabetes: Phenytoin can inhibit insulin release and raise blood sugar levels, requiring careful monitoring in diabetic patients [1.3.3, 1.6.3].
Porphyria: There are reports linking phenytoin to the exacerbation of porphyria, a genetic enzyme disorder [1.2.4, 1.6.3].
Suicidal Thoughts or Depression: Like many antiepileptic drugs, phenytoin carries a warning for an increased risk of suicidal thoughts and behaviors. Patients should be monitored for mood changes [1.5.3, 1.5.2].

Drug Interactions

Phenytoin is a potent inducer of hepatic enzymes and is highly protein-bound, leading to numerous drug interactions [1.3.3]. It can decrease the effectiveness of many medications, including oral contraceptives, some anticoagulants (like warfarin), corticosteroids, and certain antiviral agents [1.2.3, 1.6.1]. Conversely, other drugs, such as amiodarone, fluconazole, and cimetidine, can increase phenytoin levels, raising the risk of toxicity [1.2.2].

Phenytoin vs. Other Anticonvulsants

Choosing an antiepileptic drug involves balancing efficacy, side effect profile, and patient-specific factors. Carbamazepine is another common first-line treatment for certain seizures and is often compared to phenytoin [1.2.8].


Feature	Phenytoin	Carbamazepine
Mechanism	Blocks voltage-gated sodium channels [1.4.2].	Also blocks voltage-gated sodium channels.
Black Box Warning	Cardiovascular risk with rapid IV infusion [1.3.3].	Serious dermatologic reactions (SJS/TEN), particularly in patients with the HLA-B*1502 allele, and risk of aplastic anemia and agranulocytosis.
Common Side Effects	Gingival hyperplasia, nystagmus, ataxia, hirsutism [1.2.1, 1.2.5].	Dizziness, drowsiness, ataxia, nausea, vomiting.
Key Contraindications	History of hypersensitivity, specific heart blocks, prior phenytoin-induced liver injury [1.2.2, 1.3.3].	Hypersensitivity to carbamazepine or tricyclic antidepressants, bone marrow depression, co-administration with MAOIs.
Monitoring	Therapeutic drug monitoring is crucial due to non-linear pharmacokinetics [1.4.2].	Therapeutic drug monitoring and CBC are recommended.

Conclusion

While phenytoin is an effective medication for controlling seizures, it is contraindicated in several specific situations, most notably in patients with a history of hypersensitivity, certain serious cardiac rhythm disorders, and prior phenytoin-induced liver damage [1.2.2, 1.3.3]. Numerous other conditions, including pregnancy, liver or kidney disease, and co-administration with a wide array of other drugs, require significant caution and diligent medical supervision. Understanding these contraindications and risks is paramount for ensuring patient safety and achieving optimal therapeutic outcomes in the management of epilepsy.

Authoritative Link: For more detailed information, consult the FDA's prescribing information for Phenytoin.

Frequently Asked Questions

A history of a hypersensitivity reaction to phenytoin or other hydantoins is a major contraindication, as it can lead to severe and potentially fatal skin reactions like Stevens-Johnson syndrome [1.3.3].

Phenytoin is contraindicated in specific heart conditions, such as sinus bradycardia, sino-atrial block, and second and third-degree A-V block, due to its effects on cardiac rhythm [1.2.2].

Pregnancy is considered an absolute contraindication by some sources because phenytoin can harm the developing fetus, causing birth defects known as fetal hydantoin syndrome. However, the decision must balance this risk against the danger of uncontrolled seizures during pregnancy [1.2.1, 1.3.3].

Acute alcohol use can increase your phenytoin blood levels, raising the risk of side effects, while chronic alcohol use can lower them, increasing your risk of seizures [1.6.2].

The black box warning for intravenous (IV) phenytoin highlights the risk of severe cardiovascular reactions, such as severe low blood pressure and dangerous heart arrhythmias, if the medication is infused too quickly [1.3.1, 1.3.3].

Yes, cases of acute liver toxicity and failure have been reported with phenytoin. A history of liver damage caused by phenytoin is a contraindication for taking the drug again [1.3.3].

Yes, phenytoin can induce the metabolism of oral contraceptives, decreasing their effectiveness and potentially leading to contraceptive failure. Alternative or additional birth control methods are recommended [1.2.3, 1.2.6].