Phenytoin

Follow the doctor's directions. Call if you have any questions. Ask the doctor what to do if you forget a dose. The way the medicine is taken depends, of course, on what form the doctor has prescribed.

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.

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!

Brain cells need to work (fire) at a certain rate to function normally. During a seizure, brain cells are forced to work much more rapidly than normal. Phenytoin helps prevent brain cells from working as fast as a seizure requires them to. The cells are prevented from all firing together in an uncontrolled surge, so seizures can be stopped when they are just beginning.

Usually there is little or no change in the normal functions of brain cells when standard amounts of phenytoin are taken.

After medicine is swallowed, it must be absorbed into the blood so it can move throughout the body. The process of absorbing, digesting, and excreting a medicine or food is called metabolism. The way the body metabolizes a particular medicine affects how often it must be taken. It also determines whether it will interact with other medicines or be affected by conditions such as liver disease.

Like many other medicines, phenytoin is broken down (digested) in the liver. If the person also takes other medicines that are digested in the liver, things can get complicated. How well each medicine works and how quickly it leaves the body may be changed.

This is why the doctor needs to know about everything that a person takes—not just prescription medicines but even things like vitamins, herbs, alcohol, and aspirin. These things can affect how much phenytoin is prescribed.

Phenytoin is highly effective for seizures and is one of the most commonly used seizure medicines in North America. It is best used for partial-onset seizures, which begin in one area of the brain. Its effectiveness in controlling seizures has been extensively studied in careful scientific trials in great numbers of patients.

Many studies have compared phenytoin with other seizure medicines, to see which medicine is best for people who have just begun treatment for epilepsy. On average, the results were about the same for phenytoin as for several other seizure medicines that are often used.

Differences in side effects may be important in deciding which medicine is best for each person. Because some people do better with phenytoin and others do better with something else, it's difficult to forecast the results in any given person.

If seizures continue, or if bothersome side effects occur, the doctor probably will change the amount of phenytoin prescribed. 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. Many are available. No single combination is best for everyone

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:

• 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. Most people get over these side effects without a change in the amount of phenytoin they're taking. But if the side effects persist, it is usually a sign that the level of phenytoin in the body is too high. A change in the dose or type of phenytoin may help. No one should stop taking phenytoin or change the amount they take without their doctor's guidance, however.

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 if a drug rash occurs with phenytoin.

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, but not always, 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.

Long-term use of phenytoin also 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.

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. 

 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, but it is important to remember that most people who take phenytoin 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. The doctor should be informed about fever, rash, and swollen, tender lymph glands. These usually are found in the neck, armpits, or groin.

Phenytoin (like other seizure medicines) should never be stopped without instructions from the doctor. Abruptly stopping phenytoin can lead to nonstop seizures (called status epilepticus), a life-threatening condition. The levels of other medicines in the body might go up or down too. Then their side effects may increase or they will be less effective. The doctor may be able to prescribe a different medicine if phenytoin is causing unpleasant side effects.

On July 10, 2008, an advisory panel was convened by the Food and Drug Administration (FDA) to review data that the FDA had previously collected from drug studies showing an association between many of the antiepileptic drugs (AEDs) and suicidal ideation and behavior, which together are called suicidality. According to the FDA’s Alert, among the patients with epilepsy in these drug studies, 1 out of 1000 people taking the placebo (inactive substance) showed suicidality compared to approximately 3.5 out of 1000 people who took an AED. The FDA advisory panel voted to accept the FDA's data at its meeting on July 10.

• 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 purposes other than the ones approved by the Food and Drug Administration (FDA). It is legal to prescribe medicines for these "off-label uses."

Phenytoin has two common off-label uses:

• It may be helpful in treating a kind of face pain called trigeminal neuralgia. The seizure medicine carbamazepine (Tegretol or Carbatrol) is usually more effective, however.
• Doctors sometimes use phenytoin to treat patients with 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.

People with liver disease and those who must take certain other types of medicines may need to be extra cautious about taking phenytoin. That is why it is so important to make sure the doctor knows about any liver disease and about every kind of medicine that is being taken. Most of the time, phenytoin can be taken successfully if the patient works with the doctor to determine the correct amount to take.

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 want to 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, 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 drinks a moderate or large amount, 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.

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)
• zonisamide (Zonegran)

It also lowers the levels of many other types of medicine, reducing their effectiveness. Check with the doctor or pharmacist.

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, or may even vary from time to time for the same person. Make sure that the doctor is aware of all the medicines being used.  

Phenytoin has been used for many years to treat children with partial and generalized tonic-clonic seizures. It can cause side effects from high doses and allergic reactions at any dosage. Often it is not chosen as a first-choice medication for young children because it may have troublesome effects on appearance when used for a long time.

The first sign of an allergic reaction to phenytoin is a rash, so if you see any skin problems, call a doctor immediately. In rare cases, allergic reactions to phenytoin can result in damage to the liver or bone marrow.

The most common side effect related to phenytoin in children is jerky movements of the eyes called nystagmus. These movements often do not interfere with a child's vision.

Other side effects from high doses include unsteadiness in the feet and hands, sleepiness, and vomiting. These may be avoidable if the dosage is increased slowly. They should quickly disappear when the dosage is reduced.

In a few children, phenytoin causes problems with thinking or behavior, mood change, slow or clumsy movements, or a loss of energy.

One fairly common side effect in children is overgrowth of the gums. This occurs in almost one-half of children. Braces can make this problem even more severe. Thorough brushing, daily flossing, and regular visits to the dental hygienist will diminish the swelling. A few children need gum surgery.

Some young people who take fairly high doses of phenytoin also have increased growth and darkening of hair on the face and body, called hirsutism. These effects are especially troublesome for young women.

The doctor may prescribe the liquid form of phenytoin for young children who have trouble swallowing pills. Children usually start with a dose of 5 milligrams (mg) per kilogram (kg, about 2.2 pounds) of their body weight per day. This is usually given in two or three equally divided doses.

Most children do best at about 4 to 8 mg per kg per day. The highest dose recommended is 300 mg per day. Children older than 6 years and adolescents may require the minimum adult dosage of 300 mg per day.

In the United States, the Food and Drug Administration (FDA) assigns each medication to a <link:http://my.epilepsy.com/web/info/women_pregnancy_fda>Pregnancy Category</link> according to whether it has been proven to be harmful in pregnancy. Phenytoin is listed in Pregnancy Category D. This means that there is a risk to the baby, but the benefits may outweigh the risk for some women.

In fact, a large majority of women who use phenytoin during pregnancy have normal, healthy babies. Certain types of defects are increased when phenytoin is taken during the first 3 months of pregnancy, but they are still relatively uncommon. Some of these are growth delay, mental retardation, mild facial defects, and short fingers with small nails. The risk of defects is higher for women who take more than one seizure medicine. Women with a family history of birth defects also have a higher risk.

All women who are capable of becoming pregnant should take 0.4 mg (400 mcg) of the vitamin called folic acid every day because it helps to prevent one type of birth defect. (The most well-known of these is spina bifida, in which the spinal cord is not completely enclosed.) These defects are more common in the babies of women who take phenytoin during the first 4 to 6 weeks of pregnancy. If the doctor thinks a woman is at especially high risk, a much larger dose of folic acid—4 mg (4000 mcg) per day—may be recommended.

Women with epilepsy who are pregnant or thinking about becoming pregnant should talk to their doctor about their seizure medicines. Taking more than one seizure medicine may increase the risk of birth defects, so doctors sometimes gradually reduce the number or amount of seizure medicines taken by women planning for pregnancy. This is not done routinely, however, because it increases the risk of seizures. Some kinds of seizures can injure the baby, so women should not stop using seizure medicines or reduce the amount without the doctor’s OK.

About 20% to 35% of women have seizures more often during pregnancy because of changes in hormones or changes in how their seizure medicine is handled by the body. It is helpful for the doctor to check the levels of medicine in the blood regularly during pregnancy so that the dosage can be adjusted if necessary.

Some babies born to mothers taking phenytoin have had inadequate blood clotting within the first 24 hours after birth. It is recommended that the mother be given about 10 mg of vitamin K per day during the last month of pregnancy to prevent this problem.

If you are taking phenytoin, breast-feeding is generally safe, although a small amount of the medication will appear in your milk. The level in breast milk is about 10% of the level in the mother's blood.

Doctors have prescribed phenytoin to people over 65 for many years with good results. These seniors do have a few special problems, however.

Most seniors take more medicines than younger people, so there’s a greater risk that the medicines may affect each other. Phenytoin interacts with a number of medicines often used by seniors, such as warfarin (Coumadin) and aspirin.

Seniors also tend to be more sensitive than younger adults to medicines and their side effects. For instance, many seniors have a problem with unsteadiness even before they start taking phenytoin. Since it also can be a side effect of this medicine, the problem may become worse and cause real trouble, especially since seniors are more likely to be seriously hurt if they fall.

To reduce side effects, the doctor probably will prescribe a low dose of phenytoin to start and then be very cautious about any increases. It’s especially important for seniors keep the doctor informed about any changes that they notice.

The bodies of older people do not always digest phenytoin completely, and it is more slowly eliminated. This means that it may be difficult to achieve a constant, appropriate level. As a rule, older people require smaller doses than younger adults and most of them need to take the pills only once a day.

The best amount is the amount that completely controls seizures without causing troublesome side effects. It depends on many factors, which are different for every individual. Follow the doctor's directions. Call if you have any questions.

To avoid unwanted side effects, the doctor will prescribe a low dose to start and increase it gradually until seizures are controlled. Most adults do well with 300 to 500 milligrams per day, to be taken in one or two doses. Seniors often need less. Cigarette smokers often need more. Children (until they reach their teens) require a higher dose relative to their weight. They usually need to take phenytoin two or three times a day.

No one should stop taking phenytoin or change the amount they take without talking to the doctor first. Stopping any seizure medicine all at once can cause a problem that may be life-threatening.

Don’t use more phenytoin than the doctor prescribes. Talk to the doctor about what to do if one or two extra capsules are taken by accident. For a larger overdose, call a poison control center or emergency room right away.

In the United States, companies that manufacture medicines are required to publish certain kinds of information about each product. This document is commonly known as a "package insert" because it is usually included with each package of the medicine.

You can also read these documents (also called "prescribing information") online. The package insert for Dilantin (phenytoin) is available at:

• http://labeling.pfizer.com/ShowLabeling.aspx?id=546

Some of the information may differ in other countries.

To learn how to read and understand a package insert, see How to read a package insert.