Does Dilantin (phenytoin) cause side effects?

Dilantin (phenytoin) is an anti-seizure medication (anticonvulsant) used to prevent or treat generalized tonic-clonic (grand mal) seizures, complex partial seizures (psychomotor seizures), and seizures occurring during or after neurosurgery. It may be used alone or with phenobarbital or other anticonvulsants. 

Common side effects of Dilantin include

Less common side effects of Dilantin include

  • overgrowth of the gums (in children and young adults during long-term therapy),
  • sexual dysfunction (such as decreased libido, impotence, and painful, prolonged erections),
  • darkened skin coloration (more commonly in women), and
  • unusual hair growth that may be irreversible.

Serious side effects of Dilantin include

  • severe rashes,
  • lymph node reactions,
  • increased blood sugar levels,
  • liver injury,
  • decreased platelet or white blood cell counts,
  • anemia,
  • weakening of the bones (osteomalacia), and
  • an increased risk of suicidal thinking and behavior. 

Drug interactions of Dilantin, because Dilantin may reduce the concentration of these drugs in the body, include

Drugs that increase Dilantin blood levels and toxicity include

Drugs that may decrease Dilantin levels and reduce effectiveness include

The oral absorption of Dilantin can be reduced by antacids containing magnesium, calcium carbonate, or aluminum; calcium salts; or enteral feeding products (tube feedings).

There is an increased risk of malformations and birth defects in women taking Dilantin. Dilantin should be used in pregnancy only if the physician feels that the potential benefit outweighs the risk. Dilantin is secreted into breast milk. Breastfeeding is not recommended while taking Dilantin.

What are the important side effects of Dilantin (phenytoin)?

Many adverse effects can occur during phenytoin therapy including:

Children and young adults can develop overgrowth of the gums during long-term therapy which requires regular treatment by a dentist. Good oral hygiene and gum massage may reduce the risk.

Rashes can occur in between 1 in 20 and 1 in 10 persons; some may be severe. Additionally, darkening coloration of the skin may develop (more commonly in women). Phenytoin can produce unusual growth of hair in some patients. This reaction most commonly affects the arms and legs but can also affect the trunk and face; it may be irreversible.

Various lymph node reactions have been reported with phenytoin therapy. Lymph nodes may swell, sometimes painfully.

Phenytoin causes serum glucose (sugar) to rise. Thus, blood sugar should be monitored closely when phenytoin is administered to patients with diabetes.

Phenytoin can potentially injure the liver although this is an uncommon occurrence.

Phenytoin can cause the platelet or white blood cell counts to drop, increasing the risk of bleeding or infection, respectively. Phenytoin also can cause anemia.

Because it interferes with vitamin D metabolism, phenytoin can cause weakening of the bones (osteomalacia).

Other important side effects caused by phenytoin include sexual dysfunction, such as:

Antiepileptic medications have been associated with an increased risk of suicidal thinking and behavior. Anyone considering the use of antiepileptic drugs must balance this risk of suicide with the clinical need for the antiepileptic drug.

Patients who begin antiepileptic therapy should be closely observed for clinical worsening, suicidal thoughts or unusual changes in behavior.

Dilantin (phenytoin) side effects list for healthcare professionals

The following serious adverse reactions are described elsewhere in the labeling:

  • Cardiovascular Risk Associated with Rapid Infusion
  • Withdrawal Precipitated Seizure, Status Epilepticus
  • Serious Dermatologic Reactions
  • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity
  • Hypersensitivity
  • Hepatic Injury
  • Hematopoietic Complications
  • Local toxicity (Including Purple Glove Syndrome)
  • Exacerbation of Porphyria
  • Teratogenicity and Other Harm to the Newborn
  • Hyperglycemia

The following adverse reactions associated with the use of Dilantin 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. The rate of administration is very important; it 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.

Body As A Whole

Allergic reactions in the form of rash and rarely more serious forms (see Skin and Appendages paragraph below) and DRESS have been observed. Anaphylaxis has also been reported.

There have also been reports of coarsening of facial features, systemic lupus erythematosus, periarteritis nodosa, and immunoglobulin abnormalities.

Cardiovascular

Severe cardiovascular events and fatalities have been reported with atrial and ventricular conduction depression and ventricular fibrillation. Severe complications are most commonly encountered in elderly or critically ill patients.

Digestive System

Acute hepatic failure, toxic hepatitis, liver damage, nausea, vomiting, constipation, enlargement of the lips, and gingival hyperplasia.

Hematologic And Lymphatic 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. While macrocytosis and megaloblastic anemia have occurred, these conditions usually respond to folic acid therapy. Lymphadenopathy, including benign lymph node hyperplasia, pseudolymphoma, lymphoma, and Hodgkin's Disease have been reported.

Laboratory Test Abnormality

Phenytoin may decrease serum concentrations of thyroid hormone (T4 and T3), sometimes with an accompanying increase in thyroid-stimulating hormone (TSH), but usually in the absence of clinical hypothyroidism. Phenytoin may also produce lower than normal values for dexamethasone or metyrapone tests. Phenytoin may also cause increased serum levels of glucose, alkaline phosphatase, and gamma glutamyl transpeptidase (GGT).

Nervous System

The most common adverse reactions encountered with phenytoin therapy are nervous system reactions and are usually dose-related. Reactions include nystagmus, ataxia, slurred speech, decreased coordination, somnolence, and mental confusion. Dizziness, vertigo, insomnia, transient nervousness, motor twitchings, paresthesia, and headaches have also been observed. There have also been rare reports of phenytoin induced dyskinesias, including chorea, dystonia, tremor and asterixis, similar to those induced by phenothiazine and other neuroleptic drugs. Cerebellar atrophy has been reported, and appears more likely in settings of elevated phenytoin levels and/or long-term phenytoin use.

A predominantly sensory peripheral polyneuropathy has been observed in patients receiving long-term phenytoin therapy.

Skin And Appendages

Dermatological manifestations sometimes accompanied by fever have included scarlatiniform or morbilliform rashes. A morbilliform rash (measles-like) is the most common; other types of dermatitis are seen more rarely. Other more serious forms which may be fatal have included bullous, exfoliative or purpuric dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. There have also been reports of hypertrichosis.

Local irritation, inflammation, tenderness, necrosis, and sloughing have been reported with or without extravasation of intravenous phenytoin.

Special Senses

Altered taste sensation including metallic taste.

Urogenital

Peyronie's disease

What drugs interact with Dilantin (phenytoin)?

Phenytoin is extensively bound to plasma proteins and is prone to competitive displacement. Phenytoin is metabolized by hepatic cytochrome P450 enzymes CYP2C9 and CYP2C19 and is particularly susceptible to inhibitory drug interactions because it is subject to saturable metabolism. Inhibition of metabolism may produce significant increases in circulating phenytoin concentrations and enhance the risk of drug toxicity. Monitoring of phenytoin serum levels is recommended when a drug interaction is suspected.

Phenytoin is a potent inducer of hepatic drug-metabolizing enzymes.

Drugs That Affect Phenytoin Concentrations

Table 1 includes commonly occurring drug interactions that affect phenytoin concentrations. However, this list is not intended to be inclusive or comprehensive. Individual prescribing information from relevant drugs should be consulted.

The addition or withdrawal of these agents in patients on phenytoin therapy may require an adjustment of the phenytoin dose to achieve optimal clinical outcome.

Table 1: Drugs That Affect Phenytoin Concentrations

Interacting Agent Examples
Drugs that may increase phenytoin serum levels
Antiepileptic drugs Ethosuximide, felbamate, oxcarbazepine, methsuximide, topiramate
Azoles Fluconazole, ketoconazole, itraconazole, miconazole, voriconazole
Antineoplastic agents Capecitabine, fluorouracil
Antidepressants Fluoxetine, fluvoxamine, sertraline
Gastric acid reducing agents H2 antagonists (cimetidine), omeprazole
Sulfonamides Sulfamethizole, sulfaphenazole, sulfadiazine, sulfamethoxazole-trimethoprim
Other Acute alcohol intake, amiodarone, chloramphenicol, chlordiazepoxide, disulfiram, estrogen, fluvastatin, isoniazid, methylphenidate, phenothiazines, salicylates, ticlopidine, tolbutamide, trazodone, warfarin
Drugs that may decrease phenytoin serum levels
Antineoplastic agents usually in combination Bleomycin, carboplatin, cisplatin, doxorubicin, methotrexate
Antiviral agents Fosamprenavir, nelfinavir, ritonavir
Antiepileptic drugs Carbamazepine, vigabatrin
Other Chronic alcohol abuse, diazepam, diazoxide, folic acid, reserpine, rifampin, St. John’s wortb, theophylline
Drugs that may either increase or decrease phenytoin serum levels
Antiepileptic drugs Phenobarbital, valproate sodium, valproic acid
b The induction potency of St. John's wort may vary widely based on preparation.

Drugs Affected By Phenytoin

Table 2 includes commonly occurring drug interactions affected by phenytoin. However, this list is not intended to be inclusive or comprehensive. Individual drug package inserts should be consulted. The addition or withdrawal of phenytoin during concomitant therapy with these agents may require adjustment of the dose of these agents to achieve optimal clinical outcome.

Table 2: Drugs Affected by Phenytoin

Interacting Agent Examples
Drugs whose efficacy is impaired by phenytoin
Azoles Fluconazole, ketoconazole, itraconazole, posaconazole, voriconazole
Antineoplastic agents Irinotecan, paclitaxel, teniposide
Delavirdine Phenytoin can substantially reduce the concentrations of delavirdine. This can lead to loss of virologic response and possible resistance.
Neuromuscular blocking agents Cisatracurium, pancuronium, rocuronium and vecuronium: resistance to the neuromuscular blocking action of the nondepolarizing neuromuscular blocking agents has occurred in patients chronically administered phenytoin. Whether or not phenytoin has the same effect on other non-depolarizing agents is unknown.
Prevention or Management:
Patients should be monitored closely for more rapid recovery from neuromuscular blockade than expected, and infusion rate requirements may be higher.
Warfarin Increased and decreased PT/INR responses have been reported when phenytoin is coadministered with warfarin
Other Corticosteroids, doxycycline, estrogens, furosemide, oral contraceptives, paroxetine, quinidine, rifampin, sertraline, theophylline, and vitamin D
Drugs whose level is decreased by phenytoin
Antiepileptic drugsa Carbamazepine, felbamate, lamotrigine, topiramate, oxcarbazepine,
Antilipidemic agents Atorvastatin, fluvastatin, simvastatin
Antiviral agents Efavirenz, lopinavir/ritonavir, indinavir, nelfinavir, ritonavir, saquinavir Fosamprenavir: phenytoin when given with fosamprenavir alone may decrease the concentration of amprenavir, the active metabolite. Phenytoin when given with the combination of fosamprenavir and ritonavir may increase the concentration of amprenavir
Calcium channel blockers Nifedipine, nimodipine, nisoldipine, verapamil
Other Albendazole (decreases active metabolite), chlorpropamide, clozapine, cyclosporine, digoxin, disopyramide, folic acid, methadone, mexiletine, praziquantel, quetiapine
a The effect of phenytoin on phenobarbital, valproic acid and sodium valproate serum levels is unpredictable

Drug/Laboratory Test Interactions

Care should be taken when using immunoanalytical methods to measure serum phenytoin concentrations following fosphenytoin administration.

Summary

Dilantin (phenytoin) is an anti-seizure medication (anticonvulsant) used to prevent or treat generalized tonic-clonic (grand mal) seizures, complex partial seizures (psychomotor seizures), and seizures occurring during or after neurosurgery. It may be used alone or with phenobarbital or other anticonvulsants. Common side effects of Dilantin include dizziness, drowsiness, difficulty focusing (vision), unsteady gate, tiredness, abnormal involuntary movements, nausea, vomiting, constipation, abdominal pain, and loss of appetite. There is an increased risk of malformations and birth defects in women taking Dilantin. Breastfeeding is not recommended while taking Dilantin.

Treatment & Diagnosis

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Medically Reviewed on 7/17/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.
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