"The U.S. Food and Drug Administration today approved Aptiom (eslicarbazepine acetate) as an add-on medication to treat seizures associated with epilepsy.
Epilepsy is a brain disorder caused by abnormal or excessive activity in the brain"...
TRIDIONE may cause serious side effects. Strict medical supervision of the patient is mandatory, especially during the initial year of therapy.
TRIDIONE (trimethadione) should be withdrawn promptly if skin rash appears, because of the grave possibility of the occurrence of exfoliative dermatitis or severe forms of erythema multiforme. Even a minor acneiform or morbilliform rash should be allowed to clear completely before treatment with TRIDIONE is resumed; reinstitute therapy cautiously.
A complete blood count should be done prior to initiating therapy with TRIDIONE, and at monthly intervals thereafter. A marked depression of the blood count is an indication for withdrawal of the drug. If no abnormality appears within 12 months, the interval between blood counts may be extended. A moderate degree of neutropenia with or without a corresponding drop in the leukocyte count is not uncommon. Therapy need not be withdrawn unless the neutrophil count is 2500 or less; more frequent blood examinations should be done when the count is less than 3,000. Other blood dyscrasias, including leukopenia, eosinophilia, thrombocytopenia, pancytopenia, agranulocytosis, hypoplastic anemia, and fatal aplastic anemia, have occurred. Patients should be advised to report immediately such signs and symptoms as sore throat, fever, malaise, easy bruising, petechiae, or epistaxis, or others that may be indicative of an infection or bleeding tendency. TRIDIONE should ordinarily not be used in patients with severe blood dyscrasias.
Liver function tests should be done prior to initiating therapy with TRIDIONE, and at monthly intervals thereafter. Hepatitis has been reported rarely. Jaundice or other signs of liver dysfunction are an indication for withdrawal of the drug. TRIDIONE should ordinarily not be used in patients with severe hepatic impairment.
A urinalysis should be done prior to initiating therapy with TRIDIONE and at monthly intervals thereafter. Fatal nephrosis has been reported. Persistent or increasing albuminuria, or the development of any other significant renal abnormality, is an indication for withdrawal of the drug. TRIDIONE should ordinarily not be used in patients with severe renal dysfunction.
Hemeralopia has occurred; this appears to be an effect of TRIDIONE on the neural layers of the retina, and usually can be reversed by a reduction in dosage. Scotomata are an indication for withdrawal of the drug. Caution should be observed when treating patients who have diseases of the retina or optic nerve.
Lupus- And Myasthenia-like Syndromes
Manifestations of systemic lupus erythematosus have been associated with the use of TRIDIONE, as they have with the use of certain other anticonvulsants. Lymphadenopathies simulating malignant lymphoma have occurred. Lupus-like manifestations or lymph node enlargement are indications for withdrawal of the drug. Signs and symptoms may disappear after discontinuation of therapy, and specific treatment may be unnecessary.
A myasthenia gravis-like syndrome has been associated with the chronic use of trimethadione. Symptoms suggestive of this condition are indications for withdrawal of the drug.
Drugs known to cause toxic effects similar to those of TRIDIONE should be avoided or used only with extreme caution during therapy with TRIDIONE.
Usage During Pregnancy And Lactation
THERE ARE MULTIPLE REPORTS IN THE CLINICAL LITERATURE WHICH INDICATE THAT THE USE OF ANTICONVULSANT DRUGS DURING PREGNANCY RESULTS IN AN INCREASED INCIDENCE OF BIRTH DEFECTS IN THE OFFSPRING. DATA ARE MORE EXTENSIVE WITH RESPECT TO TRIMETHADIONE, PARAMETHADIONE, PHENYTOIN AND PHENOBARBITAL THAN WITH OTHER ANTICONVULSANT DRUGS.
THEREFORE, ANTICONVULSANT DRUGS SUCH AS TRIDIONE (TRIMETHADIONE) SHOULD BE ADMINISTERED TO WOMEN OF CHILDBEARING POTENTIAL ONLY IF THEY ARE CLEARLY SHOWN TO BE ESSENTIAL IN THE MANAGEMENT OF THEIR SEIZURES. EFFECTIVE MEANS OF CONTRACEPTION SHOULD ACCOMPANY THE USE OF TRIDIONE IN SUCH PATIENTS. IF A PATIENT BECOMES PREGNANT WHILE TAKING TRIDIONE, TERMINATION OF THE PREGNANCY SHOULD BE CONSIDERED. A PATIENT WHO REQUIRES THERAPY WITH TRIDIONE AND WHO WISHES TO BECOME PREGNANT SHOULD BE ADVISED OF THE RISKS.
REPORTS HAVE SUGGESTED THAT THE MATERNAL INGESTION OF ANTICONVULSANT 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 TRIDIONE 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 PROPHYLACTIC VITAMIN K BE GIVEN TO THE MOTHER ONE MONTH PRIOR TO, AND DURING DELIVERY, AND TO THE INFANT, INTRAVENOUSLY, IMMEDIATELY AFTER BIRTH. THE SAFETY OF TRIDIONE FOR USE DURING LACTATION HAS NOT BEEN ESTABLISHED.
To provide information regarding the effects of in utero exposure to Tridione, physicians are advised to recommend that pregnant patients taking Tridione 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/.
Suicidal Behavior And Ideation
Antiepileptic drugs (AEDs), including Tridione, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed.
Table 1 shows absolute and relative risk by indication for all evaluated AEDs.
Table 1: Risk by indication for antiepileptic drugs in
the pooled analysis
|Indication||Placebo Patients with Events Per 1000 Patients||Drug Patients with Events Per 1000 Patients||Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients||Risk Difference :Additional Drug Patients with Events Per 1000 Patients|
The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
Anyone considering prescribing Tridione or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
Abrupt discontinuation of TRIDIONE may precipitate petit mal status. TRIDIONE should always be withdrawn gradually unless serious adverse effects dictate otherwise. In the latter case, another anticonvulsant may be substituted to protect the patient.
Usage During Pregnancy And Lactation
Information For Patients
Physicians should inform patients and their caregivers of the availability of a Medication Guide, and they should be instructed to read the Medication Guide prior to taking Tridione. Patients should be instructed to take Tridione only as prescribed.
Suicidal Thinking and Behavior
Patients, their caregivers, and families should be counseled that AEDs, including Tridione, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to the healthcare providers.
Patients should be encouraged to enroll in the NAAED Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 (see WARNINGS).This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 2/8/2016
Additional Tridione Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
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