Phenytoin Oral Suspension

Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as Phenytoin Oral Suspension, during pregnancy. Physicians are advised to recommend that pregnant patients taking Phenytoin Oral Suspension enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/

Risk Summary

In humans, prenatal exposure to phenytoin may increase the risks for congenital malformations and other adverse developmental outcomes. An increased incidence of major malformations (such as orofacial clefts and cardiac defects) and abnormalities characteristic of fetal hydantoin syndrome (dysmorphic skull and facial features, nail and digit hypoplasia, growth abnormalities [including microcephaly], and cognitive deficits) has been reported among children born to epileptic women who took phenytoin alone or in combination with other antiepileptic drugs during pregnancy. There have been several reported cases of malignancies, including neuroblastoma, in children whose mothers received phenytoin during pregnancy.

Administration of phenytoin to pregnant animals resulted in an increased incidence of fetal malformations and other manifestations of developmental toxicity (including embryofetal death, growth impairment, and behavioral abnormalities) in multiple species at clinically relevant doses [see Data].

In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The overall incidence of malformations for children of epileptic women treated with antiepileptic drugs (including phenytoin) during pregnancy is about 10%, or two-to three-fold that in the general population. 

Clinical Considerations

Disease-associated maternal risk

An increase in seizure frequency may occur during pregnancy because of altered phenytoin pharmacokinetics. Periodic measurement of serum phenytoin concentrations may be valuable in the management of pregnant women as a guide to appropriate adjustment of dosage [see Dosage and Administration (2.4, 2.8)]. However, postpartum restoration of the original dosage will probably be indicated [see Clinical Pharmacology (12.3)].

Fetal/Neonatal Adverse Reactions

A potentially life-threatening bleeding disorder related to decreased levels of vitamin K-dependent clotting factors may occur in newborns exposed to phenytoin in utero. This drug-induced condition can be prevented with vitamin K administration to the mother before delivery and to the neonate after birth.

Data

Animal data

Administration of phenytoin to pregnant rats, rabbits, and mice during organogenesis resulted in embryofetal death, fetal malformations, and decreased fetal growth. Malformations (including craniofacial, cardiovascular, neural, limb, and digit abnormalities) were observed in rats, rabbits, and mice at doses as low as 100, 75, and 12.5 mg/kg, respectively.

Labor and Delivery

Risk Summary

Phenytoin is secreted in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Phenytoin Oral Suspension and any potential adverse effects on the breastfed infant from Phenytoin Oral Suspension or from the underlying maternal condition.

Pediatric Use

Initially, 5 mg/kg/day in two or three equally divided doses, with subsequent dosage individualized to a maximum of 300 mg daily. A recommended daily maintenance dosage is usually 4 to 8 mg/kg. Children over 6 years and adolescents may require the minimum adult dosage (300 mg/day) [see Dosage and Administration (2.3)].

Geriatric Use

Phenytoin clearance tends to decrease with increasing age [see Clinical Pharmacology (12.3)]. Lower or less frequent dosing may be required [see Dosage and Administration (2.7)].

Renal and/or Hepatic Impairment or Hypoalbuminemia

The liver is the chief site of biotransformation of phenytoin; patients with impaired liver function, elderly patients, or those who are gravely ill may show early signs of toxicity.

Because the fraction of unbound phenytoin is increased in patients with renal or hepatic disease, or in those with hypoalbuminemia, the monitoring of phenytoin serum levels should be based on the unbound fraction in those patients.

Do not take this medicine with any of the following medications:

• certain medicines used to treat HIV infection or AIDS that are given in combination with cobicistat

delavirdine

ibrutinib

ranolazine

This medicine may also interact with the following medications:

albendazole

alcohol

aspirin and aspirin-like medicines

certain medicines for blood pressure like nifedipine, nimodipine, and verapamil

certain medicines for cancer

certain medicines for cholesterol like atorvastatin, simvastatin, and fluvastatin

certain medicines for depression, anxiety, or psychotic disturbances

certain medicines for fungal infections like ketoconazole and itraconazole

certain medicines for irregular heart beat like amiodarone and quinidine

certain medicines for seizures like carbamazepine, phenobarbital, and topiramate

certain medicines for stomach problems like cimetidine and omeprazole

chloramphenicol

cyclosporine

diazoxide

digoxin

disulfiram

doxycycline

female hormones, like estrogens and birth control pills

furosemide

halothane

isoniazid

medicines that relax muscles for surgery

• medicines used to treat HIV infection or AIDS

methylphenidate

narcotic medicines for pain

phenothiazines like chlorpromazine, mesoridazine, prochlorperazine, thioridazine

praziquantel

reserpine

rifampin

St. John's Wort

steroid medicines like prednisone or cortisone

sulfonamides like sulfamethoxazole or sulfasalazine

supplements like folic acid or vitamin D

theophylline

ticlopidine

tolbutamide

warfarin

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.

Take this medicine by mouth. Follow the directions on the prescription label. Shake the bottle well before each dose. Use a specially marked spoon or dropper to measure your medicine. Ask your pharmacist if you do not have one. Household spoons are not accurate. Take this medicine with food if it upsets your stomach. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking this medicine suddenly. This increases the risk of seizures. Your doctor will tell you how much medicine to take. If your doctor wants you to stop the medicine, the dose will be slowly lowered over time to avoid any side effects.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:

• an alcohol abuse problem
• Asian ancestry
• blood disorders or disease
• diabetes
• heart problems
• kidney disease
• liver disease
• porphyria
• receiving radiation therapy
• suicidal thoughts, plans, or attempt; a previous suicide attempt by you or a family member
• thyroid disease
• an unusual or allergic reaction to phenytoin, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

What if I miss a dose?

If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What should I watch for while using this medicine?

Visit your doctor or health care professional for regular checks on your progress. This medicine needs careful monitoring. Your doctor or health care professional may schedule regular blood tests.

Wear a medical ID bracelet or chain, and carry a card that describes your disease and details of your medicine and dosage times.

Do not change brands or dosage forms of this medicine without discussing the change with your doctor or health care professional.

You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how this medicine affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells. Alcohol may interfere with the effect of this medicine. Avoid alcoholic drinks.

Birth control pills may not work properly while you are taking this medicine. Talk to your doctor about using an extra method of birth control.

This medicine can cause unusual growth of gum tissues. Visit your dentist regularly. Problems can arise if you need dental work, and in the day to day care of your teeth. Try to avoid damage to your teeth and gums when you brush or floss your teeth.

Do not take antacids at the same time as this medicine. If you get an upset stomach and want to take an antacid or medicine for diarrhea, make sure there is an interval of 2 to 3 hours before or after you took your phenytoin.

The use of this medicine may increase the chance of suicidal thoughts or actions. Pay special attention to how you are responding while on this medicine. Any worsening of mood, or thoughts of suicide or dying should be reported to your health care professional right away.

Women who become pregnant while using this medicine may enroll in the North American Antiepileptic Drug Pregnancy Registry by calling 1-888-233-2334. This registry collects information about the safety of antiepileptic drug use during pregnancy.

Where should I keep my medicine?

Keep out of the reach of children.

Store at room temperature between 20 and 25 degrees C (68 and 77 degrees F). Do not freeze. Protect from light. Throw away any unused medicine after the expiration date.