Peganone Description

PEGANONE (ethotoin tablets, USP) is an oral antiepileptic of the hydantoin series and is chemically identified as 3-ethyl-5-phenyl-2,4-imidazolidinedione. It is represented by the following structural formula:

PEGANONE tablets are available in a dosage strength of 250 mg.

Inactive Ingredients

Acacia, lactose, sodium carboxymethylcellulose, stearic acid and talc.

Peganone Indications And Usage

PEGANONE (ethotoin tablets, USP) is indicated for the control of tonic-clonic (grand mal) and complex partial (psychomotor) seizures.

Peganone Contraindications

PEGANONE (ethotoin tablets, USP) is contraindicated in patients with hepatic abnormalities or hematologic disorders.

Peganone Side Effects

PEGANONE (ETHOTOIN TABLETS, USP) CAN CAUSE FETAL HARM WHEN ADMINISTERED TO A PREGNANT WOMAN.  THERE ARE MULTIPLE REPORTS IN THE CLINICAL LITERATURE WHICH INDICATE THAT THE USE OF ANTIEPILEPTIC DRUGS DURING PREGNANCY RESULTS IN AN INCREASED INCIDENCE OF BIRTH DEFECTS IN THE OFFSPRING. ALTHOUGH DATA ARE MORE EXTENSIVE WITH RESPECT TO PHENYTOIN AND PHENOBARBITAL, REPORTS INDICATE A POSSIBLE SIMILAR ASSOCIATION WITH THE USE OF OTHER ANTIEPILEPTIC DRUGS.  THEREFORE, ANTIEPILEPTIC DRUGS SHOULD BE ADMINISTERED TO WOMEN OF CHILD-BEARING POTENTIAL ONLY IF THEY ARE CLEARLY SHOWN TO BE ESSENTIAL IN THE MANAGEMENT OF THEIR SEIZURES.

ANTIEPILEPTIC DRUGS SHOULD NOT BE DISCONTINUED IN PATIENTS IN WHOM THE DRUG IS ADMINISTERED TO PREVENT MAJOR SEIZURES BECAUSE OF THE STRONG POSSIBILITY OF PRECIPITATING STATUS EPILEPTICUS WITH ATTENDANT HYPOXIA AND RISK TO BOTH MOTHER AND THE UNBORN CHILD. CONSIDERATION SHOULD, HOWEVER, BE GIVEN TO DISCONTINUATION OF ANTIEPILEPTICS PRIOR TO AND DURING PREGNANCY WHEN THE NATURE, FREQUENCY AND SEVERITY OF THE SEIZURES DO NOT POSE A SERIOUS THREAT TO THE PATIENT. IT IS NOT, HOWEVER, KNOWN WHETHER EVEN MINOR SEIZURES CONSTITUTE SOME RISK TO THE DEVELOPING EMBRYO OR FETUS.

REPORTS HAVE SUGGESTED THAT THE MATERNAL INGESTION OF ANTIEPILEPTIC DRUGS, PARTICULARLY BARBITURATES, IS ASSOCIATED WITH A NEONATAL COAGULATION DEFECT THAT MAY CAUSE BLEEDING DURING THE EARLY (USUALLY WITHIN 24 HOURS OF BIRTH) NEONATAL PERIOD. THE POSSIBILITY OF THE OCCURRENCE OF THIS DEFECT WITH THE USE OF PEGANONE SHOULD BE KEPT IN MIND. THE DEFECT IS CHARACTERIZED BY DECREASED LEVELS OF VITAMIN K-DEPENDENT CLOTTING FACTORS, AND PROLONGATION OF EITHER THE PROTHROMBIN TIME OR THE PARTIAL THROMBOPLASTIN TIME, OR BOTH. IT HAS BEEN SUGGESTED THAT VITAMIN K BE GIVEN PROPHYLACTICALLY TO THE MOTHER ONE MONTH PRIOR TO AND DURING DELIVERY, AND THE INFANT, INTRAVENOUSLY, IMMEDIATELY AFTER BIRTH.

IF PEGANONE IS USED DURING PREGNANCY, OR IF THE PATIENT BECOMES PREGNANT WHILE TAKING THIS DRUG, THE PATIENT SHOULD BE APPRISED OF THE POTENTIAL HAZARD TO THE FETUS.

Peganone Precautions

General

Blood dyscrasias have been reported in patients receiving PEGANONE. Although the etiologic role of PEGANONE has not been definitely established, physicians should be alert for general malaise, sore throat and other symptoms indicative of possible blood dyscrasia.

There is some evidence suggesting that hydantoin-like compounds may interfere with folic acid metabolism, precipitating a megaloblastic anemia. If this should occur during gestation, folic acid therapy should be considered.

Information For Patients

Patients should be advised to report immediately such signs and symptoms as sore throat, fever, malaise, easy bruising, petechiae, epistaxis, skin rash or others that may be indicative of an infection or bleeding tendency.

Laboratory Tests

Liver function tests should be performed if clinical evidence suggests the possibility of hepatic dysfunction. Signs of liver damage are indication for withdrawal of the drug.

It is recommended that blood counts and urinalyses be performed when therapy is begun and at monthly intervals for several months thereafter. As in patients receiving other hydantoin compounds and other antiepileptic drugs, blood dyscrasias have been reported in patients receiving PEGANONE (ethotoin tablets, USP).  Marked depression of the blood count is indication for withdrawal of the drug.

Drug Interactions

PEGANONE used in combination with other drugs known to adversely affect the hematopoietic system should be avoided if possible.

A two-way interaction between the hydantoin antiepileptic, phenytoin, and the coumarin anticoagulants has been suggested. Presumably, phenytoin acts as a stimulator of coumarin metabolism and has been reported to cause decreased serum levels of the coumarin anticoagulants and increased prothrombin-proconvertin concentrations. Conversely, the coumarin anticoagulants have been reported to increase the serum levels and prolong the serum half-life of phenytoin by inhibiting its metabolism. Although there is no documentation of such, a similar interaction between ethotoin and the coumarin anticoagulants may occur. Caution is therefore advised when administering PEGANONE to patients receiving coumarin anticoagulants.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

No data are available on long-term potential for carcinogenicity in animals or humans.

Pregnancy

Pregnancy Category D. See ? Warnings ? section.

Nonteratogenic Effects

Reports have suggested that the maternal ingestion of antiepileptic drugs, particularly barbiturates, is associated with a neonatal coagulation defect that may cause bleeding during the early (usually within 24 hours of birth) neonatal period. The possibility of the occurrence of this defect with the use of PEGANONE should be kept in mind. See ? WARNINGS ? section.

Nursing Mothers

Ethotoin is excreted in breast milk. Because of the potential for serious adverse reactions in nursing infants from ethotoin, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in the pediatric population were established on the basis of open-label, uncontrolled experience in patients down to the age of one with various types of seizures.

Geriatric Use

Clinical studies of Peganone did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.  In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Peganone Overdosage

Symptoms of acute overdosage include drowsiness, visual disturbance, nausea and ataxia. Coma is possible at very high dosage.

Treatment should be begun by inducing emesis; gastric lavage may be considered as an alternative. General supportive measures will be necessary. A careful evaluation of blood-forming organs should be made following recovery.

Peganone Information For Patients

Patients should be advised to report immediately such signs and symptoms as sore throat, fever, malaise, easy bruising, petechiae, epistaxis, skin rash or others that may be indicative of an infection or bleeding tendency.