Phenytoin

Medically Reviewed by Dr. Harshi Dhingra, M.D.

Last Reviewed: Sep 01, 2023

Warnings

Phenytoin Risks, Warnings, and Complications

Phenytoin can cause or worsen health problems in some people. Talk to your doctor or pharmacist about other treatments for epilepsy if you are at an increased risk of adverse reactions or complications from this medication. Some of the risks of taking phenytoin include:

WITHDRAWAL SEIZURES: Stopping phenytoin therapy abruptly can result in an increased frequency and severity of seizures or status epilepticus (prolonged seizure). Tell your doctor if you want to stop taking phenytoin. They will tell you how to reduce your phenytoin dose slowly and switch you to other antiepileptic drugs if needed.
SUICIDAL THOUGHTS OR BEHAVIOR: Phenytoin and other antiepileptic drugs have been linked to an increased risk of suicidal thoughts or behavior. This can occur within a week of starting phenytoin therapy. The risk is highest when you first start phenytoin and after dose adjustments. People with a history of depression and patients treated concomitantly with other antiepileptic drugs are at an increased risk of this complication. Tell your doctor immediately if you notice any unusual moods, feelings of sadness, or suicidal thoughts or behavior. Your family and friends should know how to contact your healthcare provider if they notice any worsening depression or any changes in mood or behavior. If you have thoughts or plans of harming yourself, call 911 and seek emergency medical help.
LYMPHADENOPATHY: There may be a link between phenytoin and local or generalized lymphadenopathy (swollen lymph nodes). This could be a benign condition or something more serious, such as lymphoma or Hodgkin's disease. It is not clear if phenytoin is directly responsible for these changes. However, you should tell your doctor if you notice swollen glands with or without other symptoms such as fever, rash, nausea, vomiting, stomach pain, and/or yellowing of the skin or eyes. You may need to undergo further testing, or your doctor may recommend watchful waiting and monitoring. They may recommend trying to achieve seizure control with an alternative anticonvulsant medication.
ALCOHOL USE: Drinking alcohol can affect phenytoin concentrations. Acute alcohol use can increase serum phenytoin concentrations. Chronic alcohol use can decrease serum concentrations of this medication. Altered phenytoin pharmacokinetics and variations in the expected phenytoin serum levels can affect seizure control. Therefore, it is best to avoid alcohol while on phenytoin.
USE DURING PREGNANCY: During pregnancy, decreased serum concentrations of phenytoin can lead to an increase in seizure frequency. Your healthcare provider may recommend regular serum blood level determinations of phenytoin levels. This is to make sure you continue to have therapeutic range serum levels of phenytoin during pregnancy. Most pregnant patients are able to return to their original phenytoin dose after delivery.
HARM TO AN UNBORN BABY: Prenatal phenytoin exposure can increase the risk of congenital malformations and other adverse effects in an unborn baby. Talk to your doctor about the pros and cons of taking phenytoin if you are pregnant or planning a pregnancy in the near future.
SEVERE CUTANEOUS ADVERSE REACTIONS: Very rarely, phenytoin can cause a severe cutaneous adverse reaction that can be life-threatening, for example, Stevens-Johnson syndrome (SJS), exfoliative dermatitis, and toxic epidermal necrolysis (TEN). Seek immediate medical care if you develop signs and symptoms of allergic reactions, such as skin rash, hives, itching, blisters, or fever. The risk of these complications is higher in people of Asian ancestry who carry the HLA-B*1502 gene.
ANTICONVULSANT HYPERSENSITIVITY SYNDROME: This is a rare and potentially fatal allergic or hypersensitivity reaction in patients taking antiepileptic drugs. It affects multiple organs in the body. Signs and symptoms include fever, rash, swollen glands, and renal or hepatic impairment. The syndrome usually occurs 2-4 weeks after you first take an antiepileptic drug but can occur 3 or more months later. The risk of developing anticonvulsant hypersensitivity syndrome is higher in Black patients, those with a family history of this syndrome, and patients with a weakened immune system. A history of AHS in the past can result in a more severe drug reaction. If you develop AHS, your healthcare provider will discontinue phenytoin and treat you with supportive measures.
DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS): This is a rare complication of phenytoin therapy. Signs and symptoms include skin rash (small purple or red spots in the skin), fever, sore throat, swollen glands, and renal or hepatic impairment. It typically occurs within 8 weeks of starting treatment and can be life-threatening due to acute hepatic failure. Seek immediate medical care if you develop any of the above listed symptoms of a drug reaction with eosinophilia and systemic symptoms (DRESS).

Precautions Before Starting Phenytoin

Tell your doctor if you have ever had an allergic reaction to phenytoin, any of the active or inactive ingredients in phenytoin formulations, other medications such as fosphenytoin (Cerebyx) or ethotoin (Peganone), other antiepileptic drugs, or any other medications. Your pharmacy can give you a list of ingredients.

Give your doctor and pharmacist a complete list of your medications, including prescription medications, over-the-counter medicines, vitamins, supplements, and herbal products. This can help avoid potentially dangerous drug interactions between phenytoin and your other medications.

Give your doctor a complete medical history. Phenytoin may not be right for people with certain medical conditions, such as renal or hepatic disease (kidney or liver disease), heart disease, alcohol abuse, diabetes, porphyria, decreased bone mineral density, or low albumin levels.

Also, tell your doctor if you are of Asian descent (Chinese, Korean, Thai, Malaysian, Filipino, or Indian). People of Asian descent may have a genetic susceptibility to develop severe cutaneous adverse reactions with phenytoin use. Your provider will carefully weigh the risks versus benefits of prescribing this anti-seizure medicine to you.

Tell your health care professional if you are expecting a baby or you could be pregnant or plan to get pregnant shortly. Also, tell your doctor if you are nursing an infant with breast milk.

Precautions During Use of Phenytoin

Keep all your healthcare appointments during treatment. Your doctor will likely start you on a low dose of phenytoin and gradually increase the dose. They will measure serum phenytoin concentrations periodically and adjust your dose to achieve seizure control. Low circulating phenytoin concentrations may result in inadequate seizure control. Increased phenytoin serum concentrations can put you at risk of toxicity. Tell your doctor if your seizures are not well controlled. Do not change the phenytoin dose yourself without your doctor’s approval.

Phenytoin can make you drowsy and dizzy. Do not drive or do any hazardous activity that requires your full alertness until you know how this medicine affects you. Alcohol can make these side effects worse and affect phenytoin serum levels, thereby affecting seizure control. Therefore, it is not advisable to drink alcohol while on phenytoin.

If you are taking antacids such as Maalox, Tums, Mylanta, or others that contain magnesium, aluminum, or calcium, make sure you take them away from your phenytoin dose, as they can interfere with how the medicine works.

Call your doctor right away if you develop any changes in mood or behavior, worsening depression, or suicidal thoughts or behavior while on phenytoin.

Tell your doctor right away if you become pregnant while on this medication.

Phenytoin can increase the risk of damage to your gums. Take good care of your teeth and gums, and visit your dentist regularly during phenytoin therapy.

Tell all your healthcare providers you are on phenytoin, especially before any procedure, including dental procedures.

Phenytoin Drug Interactions

Other drugs can affect how phenytoin works. Possible interactions with other medications can increase the risk of severe adverse effects. Some of the medications that can have interactions with phenytoin include:

Delavirdine (Rescriptor), an antiviral drug prescribed to HIV patients
Other antiviral drugs such as efavirenz (Sustiva, in Atripla), lopinavir (in Kaletra), indinavir (Crixivan), saquinavir (Invirase), fosamprenavir (Lexiva), nelfinavir (Viracept), and ritonavir
Antiepileptic drugs carbamazepine (Tegretol, Carbatrol, Equetro, others), oxcarbazepine (Trilepta, Oxtellar XR), lamotrigine (Lamictal), topiramate (Topamax), vigabatrin (Sabril), ethosuximide (Zarontin), methsuximide (Celontin), felbamate (Felbatol), phenobarbital, and valproic acid (Depakene)
Medications used to treat worm infections, such as albendazole (Albenza) and praziquantel (Biltricide)
Anticoagulants or blood thinners such as warfarin (Coumadin, Jantoven)
Antiplatelet drugs such as ticlopidine
Medications used to treat heart rhythm abnormalities, such as amiodarone (Nexterone, Pacerone), disopyramide (Norpace), quinidine (in Nuedexta), and mexiletine
Antifungal medications such as ketoconazole (Nizoral), miconazole (Oravig), voriconazole (Vfend), fluconazole (Diflucan), itraconazole (Sporanox, Onmel, Tolsura), posaconazole (Noxafil)
Certain antibiotics such as bleomycin, chloramphenicol, doxycycline (Vibramycin, Acticlate, Monodox, Doryx, Oracea), and sulfa antibiotics
Cancer drugs such as capecitabine (Xeloda), cisplatin, carboplatin, doxorubicin (Doxil), irinotecan (Camptosar), methotrexate (Otrexup, Trexall, Rasuvo, Xatmep), teniposide, paclitaxel (Abraxane, Taxol), and fluorouracil
Antidepressants fluoxetine (Prozac, others), sertraline (Zoloft), paroxetine (Paxil, Pexeva), trazodone, and fluvoxamine (Luvox)
Anti-anxiety medications such as chlordiazepoxide (Librium, in Librax) and diazepam (Valium)
Cholesterol-lowering drugs such as atorvastatin (Lipitor, in Caduet), simvastatin (Zocor, in Vytorin), and fluvastatin (Lescol)
Antipsychotics such as clozapine (Fazaclo, Versacloz) and quetiapine (Seroquel)
Immunosuppressants like cyclosporine (Neoral, Gengraf, Sandimmune)
Medications used to manage low blood sugar, such as diazoxide (Proglycem)
Heart medications such as digoxin (Lanoxin)
Medications used to treat alcohol abuse such as disulfiram (Antabuse)
H2 antagonists such as famotidine (Pepcid), cimetidine (Tagamet), and nizatidine (Axid)
Proton pump inhibitors such as omeprazole (Prilosec)
Anti-ulcer medications like sucralfate (Carafate)
Diuretics or water pills such as furosemide (Lasix)
Hormone replacement therapy (HRT)
Hormonal contraceptives (birth control pills, rings, patches, or injections)
Antitubercular agents such as isoniazid (Laniazid, others) and rifampin (Rimactane, Rifadin, in Rifater, in Rifamate)
Medications used to treat mental illnesses
Anti-nausea drugs
Opioid pain medications such as methadone (Dolophine, Methadose)
Medications prescribed for ADHD such as methylphenidate (Concerta, Daytrana, Metadate, Ritalin)
Blood pressure medications such as nifedipine (Adalat, Procardia), nisoldipine (Sular), verapamil (Verelan, Calan, in Tarka), and nimodipine (Nymalize)
Antihypertensives such as reserpine
Oral corticosteroids such as prednisone (Rayos), prednisolone, dexamethasone, and methylprednisolone (Medrol)
Salicylate pain relievers such as aspirin
Nonsteroidal anti-inflammatory drugs such as magnesium salicylate (Doan's, others), diflunisal, choline salicylate, choline magnesium trisalicylate, and salsalate
Bronchodilators such as theophylline (Elixophyllin, Theochron, Theo-24)
Antidiabetic agents like tolbutamide
Folic acid therapy
Vitamin D
St. John’s Wort

Give your doctor or pharmacist a complete list of your medications, including prescription drugs, nonprescription drugs, dietary supplements, and herbal remedies. Also, tell your healthcare professional if you smoke, drink alcohol, or use recreational drugs because some of these substances can cause serious health complications when used with prescription medications.

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