What are the adverse drug effects of Phenytoin (Dilantin)?

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From the Guidelines

Phenytoin can cause several adverse effects, including ataxia, nystagmus, tremor, and somnolence, which are dose-related and can be mitigated with proper dosing and monitoring 1. When considering the administration of phenytoin, it is essential to weigh the benefits and risks of different routes of administration.

  • Intravenous administration of phenytoin can cause serious adverse effects, including hypotension, bradyarrhythmias, cardiac arrest, and extravasation injuries 1.
  • Fosphenytoin, a pro-drug of phenytoin, has a better safety profile than intravenous phenytoin, with fewer adverse events, including phlebitis, purple glove syndrome, tissue necrosis, and cardiac effects 1.
  • Oral loading of phenytoin can take longer to reach therapeutic levels, but it is generally cheaper and may have fewer serious adverse effects compared to intravenous administration 1. Some key points to consider when administering phenytoin include:
  • Monitoring serum phenytoin levels to balance seizure control with toxicity risk, as phenytoin has a narrow therapeutic index (10-20 mcg/mL) 1.
  • Being aware of the potential for dose-dependent neurological effects, such as ataxia, slurred speech, and nystagmus, which can signal toxicity 1.
  • Considering the risk of blood dyscrasias, such as agranulocytosis and thrombocytopenia, and the need for periodic blood monitoring 1. Overall, the choice of administration route and dosing strategy should be individualized based on the patient's specific needs and medical history, with a focus on minimizing adverse effects and optimizing seizure control 1.

From the FDA Drug Label

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 serum sickness, e.g., fever, rash, and liver involvement. Skin reactions Dilantin can cause rare, serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal Anticonvulsant Hypersensitivity Syndrome Anticonvulsant Hypersensitivity Syndrome (AHS) is a rare drug induced, multiorgan syndrome which is potentially fatal and occurs in some patients taking anticonvulsant medication. The most common side effects of DILANTIN include: problems with walking and coordination slurred speech confusion dizziness trouble sleeping nervousness tremor headache nausea vomiting constipation rash

Adverse Drug Effects of Phenytoin:

  • Serious Skin Reactions: Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and exfoliative dermatitis
  • Anticonvulsant Hypersensitivity Syndrome (AHS): a rare, potentially fatal, multiorgan syndrome
  • Lymphadenopathy: may occur with or without symptoms and signs resembling serum sickness
  • Common Side Effects:
    • problems with walking and coordination
    • slurred speech
    • confusion
    • dizziness
    • trouble sleeping
    • nervousness
    • tremor
    • headache
    • nausea
    • vomiting
    • constipation
    • rash 2 2

From the Research

Phenytoin Adverse Drug Effects

  • Cardiovascular adverse effects:
    • Rapid infusion rate (>50 mg/min) of phenytoin can cause increased mortality 3
    • No serious cardiovascular adverse effects leading to death were met in clinical trials with recommended infusion rates and dosages 3
    • Slower infusion rate recommended for old patients and patients with cardiovascular co-morbidity 3
  • Neurological adverse effects:
    • Unsteady gait, dizziness/vertigo, nausea/vomiting, general weakness, and drowsiness are common presenting symptoms of acute phenytoin intoxication 4
    • Phenytoin can cause behavioral disorders, neurologic disorders, and gingival hyperplasia and hirsutism 5
    • Reversible polyneuropathy after oral use of phenytoin, with no evidence for clear neurotoxicity on the level of peripheral nerves 6
  • Other adverse effects:
    • DRESS syndrome and cerebellar atrophy are associated with phenytoin use 7
    • Digestive tract disorders, particularly at high plasma levels 5
    • Phenytoin has a narrow therapeutic index and poses a high risk of poisoning 7

Management of Adverse Effects

  • Temporary withdrawal of phenytoin and supportive care for acute phenytoin intoxication 4
  • Careful follow-up of heart rhythm and blood pressure for patients with cardiovascular co-morbidity 3
  • Monitoring of plasma levels to minimize the risk of adverse effects 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Cardiovascular adverse effects of phenytoin.

Journal of neurology, 2016

Research

Acute phenytoin intoxication: causes, symptoms, misdiagnoses, and outcomes.

The Kaohsiung journal of medical sciences, 2004

Research

Phenytoin: neuroprotection or neurotoxicity?

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2017

Research

Phenytoin - An anti-seizure drug: Overview of its chemistry, pharmacology and toxicology.

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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