When prescribing Phenytek, question patients or family members extensively about the use of prescription and OTC medications, herbal products, vitamins, alcohol, and other substances. Interactions with phenytoin are common. Usually all necessary medications can be used, but the dosages may need to be adjusted to achieve therapeutic levels.

Effects of Phenytek (extended-release phenytoin) on other drugs
If combination therapy using phenytoin and another antiepileptic drug (AED) is begun, the dosage of the initial AED may need to be adjusted. Similarly, if a medication previously used in combination therapy is to be stopped, the dosage of the remaining AED may need to be changed.

Phenytoin will lower the blood levels of other AEDs:

• carbamazepine
• clonazepam
• lamotrigine
• oxcarbazepine
• tiagabine
• topiramate
• valproate
• zonisamide

Phenytoin also will lower the blood levels of other types of medication:

• acetaminophen
• amiodarone
• aminophylline
• chloramphenicol
• cholecalciferol
• cyclosporine
• dicoumarol
• digoxin
• disopyramide
• doxycycline
• estrogens
• felodipine
• folic acid
• furosemide
• itraconazole (large effect)
• levodopa
• meperidine
• methadone
• metronidazole
• mexiletine
• misonidazole
• nisoldipine
• oral contraceptives
• paroxetine
• phenobarbital (varies by individual)
• praziquantel
• prednisone/prednisolone
• psoralens
• quetiapine
• quinidine
• rifampin
• theophylline
• topotecan
• tirilazad
• tricyclic antidepressants
• vitamin D
• warfarin (variable effect)

Phenytoin may increase the blood levels of a few other drugs:

• phenobarbital (changes insignificant in most patients)
• warfarin (variable effect)

Effects of other drugs on Phenytek (extended-release phenytoin)
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. On the other hand, a person who chronically abuses alcohol may experience decreased levels of phenytoin and be more susceptible to seizures.

Aspirin and other salicylates are generally safe to take with phenytoin at the usual doses. If more than 1500 mg per day is taken, however, the total level of phenytoin in the blood may be decreased but the free level may increase. Effects may vary.

Medications that contain calcium, including some antacids, should not be taken at the same time as phenytoin, to prevent absorption problems. They can be used, but the times should be staggered.

A few other AEDs may decrease the blood level of phenytoin:

• carbamazepine (varies by individual)
• phenobarbital (varies by individual)
• valproate (variable)
• vigabatrin

Other medications that decrease the blood level of phenytoin include:

• alcohol (chronic abuse)
• aminophylline
• antacids containing calcium (if taken together)
• ciprofloxacin
• folic acid
• methotrexate
• reserpine
• rifampin
• sucralfate
• vinblastine

Other AEDs that increase the blood level of phenytoin include:

• carbamazepine (varies by individual)
• clobazam (varies by individual)
• diazepam
• ethosuximide
• felbamate
• methsuximide
• oxcarbazepine
• phenobarbital (varies by individual)
• topiramate
• valproate (varies by individual)

Other medications that increase the blood level of phenytoin include:

• alcohol (occasional moderate or large intake)
• amiodarone
• aspirin (more than 1500 mg/d)
• chloramphenicol
• chlordiazepoxide
• cimetidine
• dicoumarol
• diltiazem
• disulfiram
• estrogens
• fluconazole
• fluoxetine
• halothane
• isoniazid
• itraconazole
• methylphenidate
• metronidazole
• miconazole & flucytosine
• omeprazole
• phenothiazines
• propoxyphene
• ranitidine
• sertraline
• sulfonamides
• ticlopidine
• tolbutamide
• trazodone
• trimethoprim
• warfarin

AED Interaction Sheets:
Seizure drugs are often affected by drug-drug interactions. Print these informative sheets for practical help.

• Interaction sheet for phenytoin (Dilantin, Phenytek)