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)