Phenytoin (FEN-ih-toe-in) is the generic name (non–brand name) of a widely used seizure medicine. Common brand names for this type of medicine include Dilantin, Phenytek, and Epanutin (in the UK), but it is also sold using the name phenytoin or phenytoin sodium.
People who switch from brand-name Dilantin to generic phenytoin possibly risk having more seizures or side effects during the changeover, because the body does not absorb the different types in the same way. Switching from one company's generic phenytoin to another company's may have similar risks. So can switching from generic phenytoin to Dilantin.
All these risks are not fully known. For some people the effects of changing from one type to another are very small. Some use generic phenytoin successfully by always using the same company's product. Then the dosage can be adjusted to achieve the best results.
What's important is that you and the doctor should know what you're getting from the pharmacy and be able to control what type of seizure medicine you get.
Forms of phenytoin
The same medicine is available in several forms because people's needs vary. The name or appearance may differ from country to country, or even from manufacturer to manufacturer, but usually the dose (measured in milligrams, abbreviated "mg") will be the same. In the United States, several companies sell generic phenytoin, in these forms:
Capsules
Two kinds of capsules of generic phenytoin are available in the United States:
100-milligram (mg) extended phenytoin sodium
100-milligram (mg) prompt phenytoin sodium
The "extended" capsules are similar to brand-name Dilantin Kapseals. This medicine is absorbed more slowly than the medicine in the "prompt" capsules. Most people use the extended capsules.
Liquid
Suspension, 125 mg per 5 milliliters (mL)
Products from different companies all contain the same kind of medicine, but check with the pharmacist or your doctor if you get pills that look different from the ones you have been taking. You need to be careful because pills from a different company may not work the same way in your body.
Swallow each capsule whole. Don't bite it or break it open. The capsules should be stored at a temperature below 86°F (30°C). Protect them from light and moisture—don't keep them in a damp bathroom, for instance.
To use the liquid suspension, shake the bottle thoroughly just before measuring. Use the same standard-size medicine spoon or dropper each time to get an accurate dose. Do not mix liquid phenytoin with any other liquid. Store the bottle at room temperature, between 68º and 77ºF (20°-25°C). Protect it from light and from freezing.
It's OK to take any form of phenytoin either with food or without food, but be consistent day in and day out. A person who usually takes it with meals should do that all the time.
Don't use more than the doctor prescribes. If one or two extra capsules are taken, call the doctor for advice. For a larger overdose, call your local poison control center or emergency room right away unless you have other specific directions from your doctor.
Don't stop using phenytoin or change the amount taken without talking to the doctor first. Stopping any seizure medicine all at once can affect other medicines in the body. It may even cause nonstop seizures that can be life-threatening.
What if I forget?
A forgotten dose should be taken right away. If it is almost time for the next dose, just use one dose—not a double dose—and call the doctor's office for more advice.
Do your best to follow the doctor's directions. If you forget doses often, it may be a good idea to get a special pillbox or watch with an alarm to remind you. You also may want to ask the doctor whether you can use Phenytek,a type of phenytoin that is taken only once a day.
Taking the amount of seizure medicine the doctor prescribes and taking it at the right time every single day are the most important steps in preventing seizures!
Phenytoin is a widely used and effective treatment for epilepsy in people of all ages. It can be used alone or with other seizure medicines to control:
Partial seizures
Primary generalized tonic-clonic seizures (grand mal)
Phenytoin is best used for partial-onset seizures—that is, seizures that begin in a limited area of the brain. Sometimes these seizures spread throughout the brain (generalize). Phenytoin generally is not effective against absence seizures and infantile spasms.
Phenytoin may be somewhat helpful in treating clonic, myoclonic, and atonic seizures. It also may help with some types of seizures that occur as part of epilepsy syndromes like the Lennox-Gastaut syndrome.
Many studies have compared phenytoin with other seizure medicines for the treatment of newly diagnosed epilepsy. For instance, one study of 622 adults compared phenytoin with carbamazepine (Tegretol, Carbatrol), primidone (Mysoline), and phenobarbital. All four medications were about equally effective in controlling tonic-clonic seizures. Overall, phenytoin and carbamazepine were the most successful of these four medications, largely because they caused fewer intolerable side effects than primidone or phenobarbital. The choice between phenytoin and carbamazepine will be influenced by individual needs and responses.
A similar British study of newly diagnosed epilepsy included valproate (Depakote, Depakene) instead of primidone. Again, the four medicines were about equally successful in stopping seizures. (Overall, 27% of patients had no seizures and 75% had had none for at least 1 year by the end of a 3-year follow-up.) The medications differed in the number of patients who needed to stop taking them because of intolerable side effects, however. Phenytoin had the lowest rate, only 3%.
Another study compared phenytoin with valproate in treating a group of patients with newly diagnosed generalized tonic-clonic, clonic, or tonic seizures. Of the patients treated with phenytoin, 76% had no seizures during the study period after the level of medicine in the blood reached a high enough level. The comparable figure for the patients who took valproate was 82%.
The results in everyday life are not always as good as in these studies. Sometimes patients don't take all their medicine on time, or the individual's seizures cannot be controlled at a dosage that can be taken without side effects. Because of individual differences, adjustments in the amount taken are often needed to reduce seizures or side effects.
If seizures continue to occur, the doctor first may suggest a change in the dosage of phenytoin by itself (called monotherapy). If that doesn’t work, the next step may be either to prescribe a different seizure medicine by itself or to prescribe a combination of phenytoin and another seizure medicine. (The use of more than one medicine at the same time is called combination therapy or polytherapy.) Carbamazepine is often used in combination with phenytoin, but many other medicines are also available. No single combination is best for everyone.
Phenytoin also has often been prescribed to prevent seizures in people who have suffered a serious brain injury. However, studies generally find only a short-term reduction in seizures, not long-term prevention of epilepsy.
Most people who take phenytoin don't have too much trouble with side effects. That's one of the reasons it’s used so much. The most common complaints (usually not too severe) are:
sleepiness
jerking movements of the eyes
decreased coordination
shaking of the hands
slowed thinking and movement
memory problems
slurred speech
poor concentration
If these problems do not go away within several days, or are really bothersome, call the doctor. Sometimes the doctor can help with these side effects by changing the prescription:
reducing the overall amount of phenytoin
changing the amount taken at certain times, such as taking a greater proportion of the phenytoin at bedtime to reduce daytime sleepiness
prescribing smaller doses, to be taken more often
changing the prescription from regular phenytoin to Phenytek, a form of phenytoin that is released into the body more slowly and evenly
No one should stop taking phenytoin or change the amount they take or when they take it without their doctor's guidance.
People who have just started taking phenytoin (or who have just started taking a larger amount) should be careful during activities that might be dangerous, until they know whether they are having any side effects.
Allergic reactions
Approximately 1 in 10 people who take phenytoin have a red rash within the first few weeks of taking it. If this happens, tell the doctor or nurse right away, to be sure that it's not the beginning of a serious problem. It's rare for the rash to be serious, but don't ignore it. It's often necessary to switch to a different seizure medicine.
Long-term side effects
Some other side effects only appear after a person has been using phenytoin for a number of months or years. They are usually related to taking high doses. The most common ones affect appearance:
overgrowth of the gums
excessive hair on the face or body
acne
coarseness of facial features
Overgrowth of the gums (gingival hyperplasia) is more common in children than in adults. It can be reduced by vigorous brushing, daily flossing, and regular visits to the dentist, who may recommend additional treatments. If phenytoin is stopped, the gum problems won’t get worse, and in some cases will go away within a few months.
Some people who take phenytoin for several years may have damage to the nerves in their legs. Faulty reflexes can be seen in a minority of this group.
Damage to the part of the brain called the cerebellum may affect others who take phenytoin for a long time, especially if they take high doses. Damage severe enough to produce significant problems is uncommon, however.
Long-term use of phenytoin has been found to cause weakening of the bones. Bone disease is even more likely if a combination of seizure medicines is used. People taking phenytoin should exercise, take vitamin D supplements, and eat foods rich in calcium. Some non-food sources of calcium, such as Tums and Os-Cal, reduce absorption of phenytoin. They can be used but should not be taken within about 2 hours after taking the phenytoin. (This restriction does not apply to food sources of calcium such as dairy products.) Many doctors now recommend bone-density studies for anyone taking phenytoin.
Other serious reactions to phenytoin are very rare but everyone who takes this medicine should at least be aware of them because a very small number of people have died because of them. A complete list of all reactions to phenytoin can be found in the package insert for brand-name Dilantin, but it is important to remember that most people who take it have none of these serious problems.
As with many other seizure medicines, there is a very small chance of developing a rash so serious that hospitalization may be required. (It has been estimated that this happens to 2 to 5 people out of each 10,000 who take phenytoin). Though the risk is small, call the doctor promptly if you notice a rash, since in a few cases these rashes are fatal.
In rare cases, allergic reactions to phenytoin can result in damage to the liver or bone marrow. The doctor may perform blood tests from time to time to look for early stages of this kind of damage.
Another rare reaction to phenytoin is disease of the lymph nodes. Tell the doctor about any fever, rash, or swollen, tender lymph glands. These usually are found in the neck, armpits, or groin.
Taking antiepileptic medicines may increase the risk of having suicidal thoughts or actions;
Do not make any changes to the medication regimen without first talking with the responsible healthcare professional;
Pay close attention to any day-to-day changes in mood, behavior and actions. These changes can happen very quickly so it is important to be mindful of any sudden differences.
Be aware of common warning signs that might be a signal for risk of suicide. Some of these are:
Talking or thinking about wanting to hurt yourself or end your life
Withdrawing from friends and family
Becoming depressed or having your depression get worse
Becoming preoccupied with death and dying
Giving away prized possessions
We again urge patients and families to contact their doctor before stopping an epilepsy medication because this may possibly lead to seizures and worsening of mood.
Often doctors find that medicines are useful for more than one purpose. It is legal to prescribe medicines for "off-label uses" even though the FDA has not formally approved such use. Common off-label uses of phenytoin include:
Treating a type of facial pain called trigeminal neuralgia. Phenytoin's effectiveness for this purpose has not been proven, however, and carbamazepine (Tegretol, Carbatrol) should be considered the first choice. Phenytoin may be added if carbamazepine is not effective.
Treating nerve disorders like diabetic neuropathy and Fabry's disease. Phenytoin seems to be only slightly effective but it may help other pain-relieving medications.
Treating certain psychiatric disorders, such as the mania of bipolar disorder. Few studies have shown a definite benefit, however. Another reason for caution in this kind of use is that phenytoin interacts with many of the medicines generally used to treat psychiatric disorders.
Any time a doctor suggests a new prescription, be sure to talk about what other medicines, supplements, herbs, and vitamins are already being taken. Sometimes one kind of medicine changes the way another kind of medicine works in the body. If two kinds of medicine affect each other, the doctor may prescribe something else or change the amount to be taken.
This is true not only for prescription medicines, but also for medicines you just pick up off the shelf at the store. For instance, aspirin (ASA) is generally safe to take with phenytoin at the usual doses, but if more than 1500 mg per day is taken, the level of phenytoin in the blood will be increased.
Interactions like this can also occur with herbal products (St. John's wort, for example), vitamins, a few kinds of food (like grapefruit juice), and even cigarettes!
Some substances that are safe to use in small amounts with phenytoin can be a problem if larger amounts are used. For instance, one or two drinks of alcohol will seldom affect the level of phenytoin in any important way, but if a person who does not often consume alcohol has several drinks within a short time, the level of phenytoin in the blood may be significantly increased, causing problems with side effects. On the other hand, a person who chronically abuses alcohol may have lower levels of phenytoin and be more likely to have seizures.
Medicines that contain calcium, including some antacids, can prevent the body from absorbing phenytoin. They can be used, but not near the time of a dose of phenytoin. They should not be taken for a couple of hours after the phenytoin. This limitation does not apply to foods such as dairy products, which also contain calcium.
How does phenytoin affect other medicines?
Phenytoin makes birth control pills less effective, so the chances of becoming pregnant are greater. Women who use pills for birth control should talk to the doctor who prescribed them right away if they start taking phenytoin. The same is true for some other forms of birth control such as Depo-Provera or implants. Phenytoin does not affect barrier types of birth control, like condoms, IUDs, and diaphragms.
Phenytoin also affects the way the body handles many other medicines. For instance, it reduces the levels of other seizure medicines:
carbamazepine (Tegretol, Carbatrol)
felbamate (Felbatol)
lamotrigine (Lamictal)
tiagabine (Gabitril)
topiramate (Topamax)
valproate (Depakote, Depakene)
zonisamide (Zonegran)
If combination therapy using phenytoin and another seizure medicine is begun, the dosage of the first medicine may need to be adjusted. Similarly, if a seizure medicine previously used in combination therapy is to be stopped, the dosage of the remaining medicine may need to be changed.
Phenytoin also reduces the levels of many other types of medicine, making them less effective. Check with the doctor or pharmacist. Here are some common ones:
acetaminophen (Tylenol)
amiodarone (Cordarone)
aminophylline
cyclosporine
digoxin
estrogens
folic acid
furosemide (Lasix)
itraconazole (Sporanox) (large effect)
levodopa (Sinemet)
meperidine (Demerol)
methadone
metronidazole (Flagyl)
oral contraceptives
paroxetine (Paxil)
phenobarbital (possible)
prednisone/prednisolone (steroids)
theophylline (Slo-Bid, Theo-Dur)
tricyclic antidepressants (Elavil, Sinequan, and others)
vitamin D
warfarin (Coumadin) (effect varies from person to person)
Phenytoin may increase the blood level of a few other medicines, possibly including warfarin (Coumadin)—the effect on warfarin varies from person to person.
How do other medicines affect phenytoin?
Some other medicines do affect the level of phenytoin in the body, either raising it or lowering it. Many of these interactions vary from person to person, however. Some may even vary from time to time for the same person. Make sure that your doctor is aware of all the medicines being used.
A few other seizure medicines may reduce the level of phenytoin in the blood:
carbamazepine (Tegretol, Carbatrol) (varies by individual)
phenobarbital (varies by individual)
valproate (Depakote, Depakene) (variable)
vigabatrin (Sabril)
Other substances that reduce the level of phenytoin include:
alcohol (chronic abuse)
aminophylline
antacids containing calcium (if taken together)
ciprofloxacin (Cipro)
folic acid
methotrexate
sucralfate (Carafate)
vinblastine
Other AEDs that increase the blood level of phenytoin include:
carbamazepine (Tegretol, Carbatrol) (varies by individual)
clobazam (Frisium) (possible)
diazepam (Valium, Diastat)
ethosuximide (Zarontin)
felbamate (Felbatol)
methsuximide (Celontin)
oxcarbazepine (Trileptal)
phenobarbital (varies by individual)
topiramate (Topamax)
valproate (Depakote, Depakene) (possible)
Other medications that increase the blood level of phenytoin include:
alcohol (occasional moderate or large intake)
amiodarone
aspirin (more than 1500 mg/d)
chlordiazepoxide (Librium)
chlorpromazine (Thorazine)
cimetidine (Tagamet)
diltiazem (Cardizem)
disulfiram (Antabuse)
esomeprazole (Nexium) (small effect)
estrogens
fluconazole (Diflucan)
fluoxetine (Prozac)
itraconazole (Sporanox)
methylphenidate (Ritalin)
metronidazole (Flagyl)
omeprazole (Prilosec)
propoxyphene (Darvon, Darvocet)
ranitidine (Zantac)
sulfonamides (sulfa drugs)
tolbutamide
trimethoprim (Bactrim)
The U.S. Food and Drug Administration (FDA) lists phenytoin in Pregnancy Category D. This indicates that there is clear evidence of risk to the human fetus, but the benefits may outweigh the risk for pregnant women who have a serious condition that cannot be treated effectively with a safer drug.
The babies of women taking phenytoin have a greater than usual number of major birth defects like cleft lip, cleft palate, and heart malformations. Defects like these occur in 2-3% of all pregnancies but affect 4-7% of the babies of women taking only phenytoin. (This rate is similar to that for women taking other seizure medicines.) There is also an increased chance of minor birth defects such as short fingers and widely spaced eyes. When these babies are re-examined after several years, however, these minor defects are often undetectable or very subtle.
Women taking phenytoin used to be warned about a disorder called "fetal hydantoin syndrome," but this concept is no longer accepted. Phenytoin does not clearly differ from other seizure medicines in the type of defects that may occur.
The risk of defects is higher for women who take more than one AED and for women with a family history of birth defects.
Women who are capable of becoming pregnant should take 400 mcg (0.4 mg) of folic acid (folate) daily to help prevent a type of birth defect called a neural tube defect. (The best-known of these is spina bifida, in which the spinal cord is not completely enclosed.) Women at high risk, such as those with a history of this kind of defect in a previous pregnancy, should take 4000 mcg (4 mg) daily, beginning before they become pregnant.
About 20% to 35% of women have seizures more often during pregnancy because of changes in hormones or changes in how phenytoin is handled by the body. The doctor may recommend checking the level of medication in the blood regularly during pregnancy so that the dosage can be adjusted as needed.
No studies have been performed to demonstrate the effect of specific seizure medicines during labor and delivery. Possible causes of seizures include:
failure or inability to take medication
sleep deprivation
hyperventilation
stress
pain
Some babies born to mothers taking phenytoin have had inadequate blood clotting within the first 24 hours after birth. Taking 10 mg of vitamin K per day during the last month of pregnancy may prevent this problem.
Breast-feeding by mothers taking phenytoin should be safe for healthy, full-term newborns, although a small amount of the medication will appear in the milk. The level in breast milk is about 10% of the level in the mother's blood.
People who switch from brand-name Dilantin to generic phenytoin possibly risk having more seizures or side effects during the changeover, because the body does not absorb the different types in the same way. Switching from one company's generic phenytoin to another company's may have similar risks. So can switching from generic phenytoin to Dilantin.
All these risks are not fully known. For some people the effects of changing from one type to another are very small. Some use generic phenytoin successfully by always using the same company's product. Then the dosage can be adjusted to achieve the best results.
What's important is that you and the doctor should know what you're getting from the pharmacy and be able to control what type of seizure medicine you get.
Forms of phenytoin
The same medicine is available in several forms because people's needs vary. The name or appearance may differ from country to country, or even from manufacturer to manufacturer, but usually the dose (measured in milligrams, abbreviated "mg") will be the same. In the United States, several companies sell generic phenytoin, in these forms:
Capsules
Two kinds of capsules of generic phenytoin are available in the United States:
100-milligram (mg) extended phenytoin sodium
100-milligram (mg) prompt phenytoin sodium
The "extended" capsules are similar to brand-name Dilantin Kapseals. This medicine is absorbed more slowly than the medicine in the "prompt" capsules. Most people use the extended capsules.
Liquid
Suspension, 125 mg per 5 milliliters (mL)
Products from different companies all contain the same kind of medicine, but check with the pharmacist or your doctor if you get pills that look different from the ones you have been taking. You need to be careful because pills from a different company may not work the same way in your body.
Swallow each capsule whole. Don't bite it or break it open. The capsules should be stored at a temperature below 86°F (30°C). Protect them from light and moisture—don't keep them in a damp bathroom, for instance.
To use the liquid suspension, shake the bottle thoroughly just before measuring. Use the same standard-size medicine spoon or dropper each time to get an accurate dose. Do not mix liquid phenytoin with any other liquid. Store the bottle at room temperature, between 68º and 77ºF (20°-25°C). Protect it from light and from freezing.
It's OK to take any form of phenytoin either with food or without food, but be consistent day in and day out. A person who usually takes it with meals should do that all the time.
Don't use more than the doctor prescribes. If one or two extra capsules are taken, call the doctor for advice. For a larger overdose, call your local poison control center or emergency room right away unless you have other specific directions from your doctor.
Don't stop using phenytoin or change the amount taken without talking to the doctor first. Stopping any seizure medicine all at once can affect other medicines in the body. It may even cause nonstop seizures that can be life-threatening.
What if I forget?
A forgotten dose should be taken right away. If it is almost time for the next dose, just use one dose—not a double dose—and call the doctor's office for more advice.
Do your best to follow the doctor's directions. If you forget doses often, it may be a good idea to get a special pillbox or watch with an alarm to remind you. You also may want to ask the doctor whether you can use Phenytek,a type of phenytoin that is taken only once a day.
Taking the amount of seizure medicine the doctor prescribes and taking it at the right time every single day are the most important steps in preventing seizures!
Phenytoin is a widely used and effective treatment for epilepsy in people of all ages. It can be used alone or with other seizure medicines to control:
Partial seizures
Primary generalized tonic-clonic seizures (grand mal)
Phenytoin is best used for partial-onset seizures—that is, seizures that begin in a limited area of the brain. Sometimes these seizures spread throughout the brain (generalize). Phenytoin generally is not effective against absence seizures and infantile spasms.
Phenytoin may be somewhat helpful in treating clonic, myoclonic, and atonic seizures. It also may help with some types of seizures that occur as part of epilepsy syndromes like the Lennox-Gastaut syndrome.
Many studies have compared phenytoin with other seizure medicines for the treatment of newly diagnosed epilepsy. For instance, one study of 622 adults compared phenytoin with carbamazepine (Tegretol, Carbatrol), primidone (Mysoline), and phenobarbital. All four medications were about equally effective in controlling tonic-clonic seizures. Overall, phenytoin and carbamazepine were the most successful of these four medications, largely because they caused fewer intolerable side effects than primidone or phenobarbital. The choice between phenytoin and carbamazepine will be influenced by individual needs and responses.
A similar British study of newly diagnosed epilepsy included valproate (Depakote, Depakene) instead of primidone. Again, the four medicines were about equally successful in stopping seizures. (Overall, 27% of patients had no seizures and 75% had had none for at least 1 year by the end of a 3-year follow-up.) The medications differed in the number of patients who needed to stop taking them because of intolerable side effects, however. Phenytoin had the lowest rate, only 3%.
Another study compared phenytoin with valproate in treating a group of patients with newly diagnosed generalized tonic-clonic, clonic, or tonic seizures. Of the patients treated with phenytoin, 76% had no seizures during the study period after the level of medicine in the blood reached a high enough level. The comparable figure for the patients who took valproate was 82%.
The results in everyday life are not always as good as in these studies. Sometimes patients don't take all their medicine on time, or the individual's seizures cannot be controlled at a dosage that can be taken without side effects. Because of individual differences, adjustments in the amount taken are often needed to reduce seizures or side effects.
If seizures continue to occur, the doctor first may suggest a change in the dosage of phenytoin by itself (called monotherapy). If that doesn’t work, the next step may be either to prescribe a different seizure medicine by itself or to prescribe a combination of phenytoin and another seizure medicine. (The use of more than one medicine at the same time is called combination therapy or polytherapy.) Carbamazepine is often used in combination with phenytoin, but many other medicines are also available. No single combination is best for everyone.
Phenytoin also has often been prescribed to prevent seizures in people who have suffered a serious brain injury. However, studies generally find only a short-term reduction in seizures, not long-term prevention of epilepsy.
Most people who take phenytoin don't have too much trouble with side effects. That's one of the reasons it’s used so much. The most common complaints (usually not too severe) are:
sleepiness
jerking movements of the eyes
decreased coordination
shaking of the hands
slowed thinking and movement
memory problems
slurred speech
poor concentration
If these problems do not go away within several days, or are really bothersome, call the doctor. Sometimes the doctor can help with these side effects by changing the prescription:
reducing the overall amount of phenytoin
changing the amount taken at certain times, such as taking a greater proportion of the phenytoin at bedtime to reduce daytime sleepiness
prescribing smaller doses, to be taken more often
changing the prescription from regular phenytoin to Phenytek, a form of phenytoin that is released into the body more slowly and evenly
No one should stop taking phenytoin or change the amount they take or when they take it without their doctor's guidance.
People who have just started taking phenytoin (or who have just started taking a larger amount) should be careful during activities that might be dangerous, until they know whether they are having any side effects.
Allergic reactions
Approximately 1 in 10 people who take phenytoin have a red rash within the first few weeks of taking it. If this happens, tell the doctor or nurse right away, to be sure that it's not the beginning of a serious problem. It's rare for the rash to be serious, but don't ignore it. It's often necessary to switch to a different seizure medicine.
Long-term side effects
Some other side effects only appear after a person has been using phenytoin for a number of months or years. They are usually related to taking high doses. The most common ones affect appearance:
overgrowth of the gums
excessive hair on the face or body
acne
coarseness of facial features
Overgrowth of the gums (gingival hyperplasia) is more common in children than in adults. It can be reduced by vigorous brushing, daily flossing, and regular visits to the dentist, who may recommend additional treatments. If phenytoin is stopped, the gum problems won’t get worse, and in some cases will go away within a few months.
Some people who take phenytoin for several years may have damage to the nerves in their legs. Faulty reflexes can be seen in a minority of this group.
Damage to the part of the brain called the cerebellum may affect others who take phenytoin for a long time, especially if they take high doses. Damage severe enough to produce significant problems is uncommon, however.
Long-term use of phenytoin has been found to cause weakening of the bones. Bone disease is even more likely if a combination of seizure medicines is used. People taking phenytoin should exercise, take vitamin D supplements, and eat foods rich in calcium. Some non-food sources of calcium, such as Tums and Os-Cal, reduce absorption of phenytoin. They can be used but should not be taken within about 2 hours after taking the phenytoin. (This restriction does not apply to food sources of calcium such as dairy products.) Many doctors now recommend bone-density studies for anyone taking phenytoin.
Other serious reactions to phenytoin are very rare but everyone who takes this medicine should at least be aware of them because a very small number of people have died because of them. A complete list of all reactions to phenytoin can be found in the package insert for brand-name Dilantin, but it is important to remember that most people who take it have none of these serious problems.
As with many other seizure medicines, there is a very small chance of developing a rash so serious that hospitalization may be required. (It has been estimated that this happens to 2 to 5 people out of each 10,000 who take phenytoin). Though the risk is small, call the doctor promptly if you notice a rash, since in a few cases these rashes are fatal.
In rare cases, allergic reactions to phenytoin can result in damage to the liver or bone marrow. The doctor may perform blood tests from time to time to look for early stages of this kind of damage.
Another rare reaction to phenytoin is disease of the lymph nodes. Tell the doctor about any fever, rash, or swollen, tender lymph glands. These usually are found in the neck, armpits, or groin.
Taking antiepileptic medicines may increase the risk of having suicidal thoughts or actions;
Do not make any changes to the medication regimen without first talking with the responsible healthcare professional;
Pay close attention to any day-to-day changes in mood, behavior and actions. These changes can happen very quickly so it is important to be mindful of any sudden differences.
Be aware of common warning signs that might be a signal for risk of suicide. Some of these are:
Talking or thinking about wanting to hurt yourself or end your life
Withdrawing from friends and family
Becoming depressed or having your depression get worse
Becoming preoccupied with death and dying
Giving away prized possessions
We again urge patients and families to contact their doctor before stopping an epilepsy medication because this may possibly lead to seizures and worsening of mood.
Often doctors find that medicines are useful for more than one purpose. It is legal to prescribe medicines for "off-label uses" even though the FDA has not formally approved such use. Common off-label uses of phenytoin include:
Treating a type of facial pain called trigeminal neuralgia. Phenytoin's effectiveness for this purpose has not been proven, however, and carbamazepine (Tegretol, Carbatrol) should be considered the first choice. Phenytoin may be added if carbamazepine is not effective.
Treating nerve disorders like diabetic neuropathy and Fabry's disease. Phenytoin seems to be only slightly effective but it may help other pain-relieving medications.
Treating certain psychiatric disorders, such as the mania of bipolar disorder. Few studies have shown a definite benefit, however. Another reason for caution in this kind of use is that phenytoin interacts with many of the medicines generally used to treat psychiatric disorders.
Any time a doctor suggests a new prescription, be sure to talk about what other medicines, supplements, herbs, and vitamins are already being taken. Sometimes one kind of medicine changes the way another kind of medicine works in the body. If two kinds of medicine affect each other, the doctor may prescribe something else or change the amount to be taken.
This is true not only for prescription medicines, but also for medicines you just pick up off the shelf at the store. For instance, aspirin (ASA) is generally safe to take with phenytoin at the usual doses, but if more than 1500 mg per day is taken, the level of phenytoin in the blood will be increased.
Interactions like this can also occur with herbal products (St. John's wort, for example), vitamins, a few kinds of food (like grapefruit juice), and even cigarettes!
Some substances that are safe to use in small amounts with phenytoin can be a problem if larger amounts are used. For instance, one or two drinks of alcohol will seldom affect the level of phenytoin in any important way, but if a person who does not often consume alcohol has several drinks within a short time, the level of phenytoin in the blood may be significantly increased, causing problems with side effects. On the other hand, a person who chronically abuses alcohol may have lower levels of phenytoin and be more likely to have seizures.
Medicines that contain calcium, including some antacids, can prevent the body from absorbing phenytoin. They can be used, but not near the time of a dose of phenytoin. They should not be taken for a couple of hours after the phenytoin. This limitation does not apply to foods such as dairy products, which also contain calcium.
How does phenytoin affect other medicines?
Phenytoin makes birth control pills less effective, so the chances of becoming pregnant are greater. Women who use pills for birth control should talk to the doctor who prescribed them right away if they start taking phenytoin. The same is true for some other forms of birth control such as Depo-Provera or implants. Phenytoin does not affect barrier types of birth control, like condoms, IUDs, and diaphragms.
Phenytoin also affects the way the body handles many other medicines. For instance, it reduces the levels of other seizure medicines:
carbamazepine (Tegretol, Carbatrol)
felbamate (Felbatol)
lamotrigine (Lamictal)
tiagabine (Gabitril)
topiramate (Topamax)
valproate (Depakote, Depakene)
zonisamide (Zonegran)
If combination therapy using phenytoin and another seizure medicine is begun, the dosage of the first medicine may need to be adjusted. Similarly, if a seizure medicine previously used in combination therapy is to be stopped, the dosage of the remaining medicine may need to be changed.
Phenytoin also reduces the levels of many other types of medicine, making them less effective. Check with the doctor or pharmacist. Here are some common ones:
acetaminophen (Tylenol)
amiodarone (Cordarone)
aminophylline
cyclosporine
digoxin
estrogens
folic acid
furosemide (Lasix)
itraconazole (Sporanox) (large effect)
levodopa (Sinemet)
meperidine (Demerol)
methadone
metronidazole (Flagyl)
oral contraceptives
paroxetine (Paxil)
phenobarbital (possible)
prednisone/prednisolone (steroids)
theophylline (Slo-Bid, Theo-Dur)
tricyclic antidepressants (Elavil, Sinequan, and others)
vitamin D
warfarin (Coumadin) (effect varies from person to person)
Phenytoin may increase the blood level of a few other medicines, possibly including warfarin (Coumadin)—the effect on warfarin varies from person to person.
How do other medicines affect phenytoin?
Some other medicines do affect the level of phenytoin in the body, either raising it or lowering it. Many of these interactions vary from person to person, however. Some may even vary from time to time for the same person. Make sure that your doctor is aware of all the medicines being used.
A few other seizure medicines may reduce the level of phenytoin in the blood:
carbamazepine (Tegretol, Carbatrol) (varies by individual)
phenobarbital (varies by individual)
valproate (Depakote, Depakene) (variable)
vigabatrin (Sabril)
Other substances that reduce the level of phenytoin include:
alcohol (chronic abuse)
aminophylline
antacids containing calcium (if taken together)
ciprofloxacin (Cipro)
folic acid
methotrexate
sucralfate (Carafate)
vinblastine
Other AEDs that increase the blood level of phenytoin include:
carbamazepine (Tegretol, Carbatrol) (varies by individual)
clobazam (Frisium) (possible)
diazepam (Valium, Diastat)
ethosuximide (Zarontin)
felbamate (Felbatol)
methsuximide (Celontin)
oxcarbazepine (Trileptal)
phenobarbital (varies by individual)
topiramate (Topamax)
valproate (Depakote, Depakene) (possible)
Other medications that increase the blood level of phenytoin include:
alcohol (occasional moderate or large intake)
amiodarone
aspirin (more than 1500 mg/d)
chlordiazepoxide (Librium)
chlorpromazine (Thorazine)
cimetidine (Tagamet)
diltiazem (Cardizem)
disulfiram (Antabuse)
esomeprazole (Nexium) (small effect)
estrogens
fluconazole (Diflucan)
fluoxetine (Prozac)
itraconazole (Sporanox)
methylphenidate (Ritalin)
metronidazole (Flagyl)
omeprazole (Prilosec)
propoxyphene (Darvon, Darvocet)
ranitidine (Zantac)
sulfonamides (sulfa drugs)
tolbutamide
trimethoprim (Bactrim)
The U.S. Food and Drug Administration (FDA) lists phenytoin in Pregnancy Category D. This indicates that there is clear evidence of risk to the human fetus, but the benefits may outweigh the risk for pregnant women who have a serious condition that cannot be treated effectively with a safer drug.
The babies of women taking phenytoin have a greater than usual number of major birth defects like cleft lip, cleft palate, and heart malformations. Defects like these occur in 2-3% of all pregnancies but affect 4-7% of the babies of women taking only phenytoin. (This rate is similar to that for women taking other seizure medicines.) There is also an increased chance of minor birth defects such as short fingers and widely spaced eyes. When these babies are re-examined after several years, however, these minor defects are often undetectable or very subtle.
Women taking phenytoin used to be warned about a disorder called "fetal hydantoin syndrome," but this concept is no longer accepted. Phenytoin does not clearly differ from other seizure medicines in the type of defects that may occur.
The risk of defects is higher for women who take more than one AED and for women with a family history of birth defects.
Women who are capable of becoming pregnant should take 400 mcg (0.4 mg) of folic acid (folate) daily to help prevent a type of birth defect called a neural tube defect. (The best-known of these is spina bifida, in which the spinal cord is not completely enclosed.) Women at high risk, such as those with a history of this kind of defect in a previous pregnancy, should take 4000 mcg (4 mg) daily, beginning before they become pregnant.
About 20% to 35% of women have seizures more often during pregnancy because of changes in hormones or changes in how phenytoin is handled by the body. The doctor may recommend checking the level of medication in the blood regularly during pregnancy so that the dosage can be adjusted as needed.
No studies have been performed to demonstrate the effect of specific seizure medicines during labor and delivery. Possible causes of seizures include:
failure or inability to take medication
sleep deprivation
hyperventilation
stress
pain
Some babies born to mothers taking phenytoin have had inadequate blood clotting within the first 24 hours after birth. Taking 10 mg of vitamin K per day during the last month of pregnancy may prevent this problem.
Breast-feeding by mothers taking phenytoin should be safe for healthy, full-term newborns, although a small amount of the medication will appear in the milk. The level in breast milk is about 10% of the level in the mother's blood.