Label: TRIDIONE- trimethadione tablet, chewable
- NDC Code(s): 0074-3753-01
- Packager: AbbVie Inc.
- Category: HUMAN PRESCRIPTION DRUG LABEL
- DEA Schedule: None
- Marketing Status: New Drug Application
Updated November 2, 2018
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- SPL UNCLASSIFIED SECTION
BECAUSE OF ITS POTENTIAL TO PRODUCE FETAL MALFORMATIONS AND SERIOUS SIDE EFFECTS, TRIDIONE (trimethadione) SHOULD ONLY BE UTILIZED WHEN OTHER LESS TOXIC DRUGS HAVE BEEN FOUND INEFFECTIVE IN CONTROLLING PETIT MAL SEIZURES.Close
- CLINICAL PHARMACOLOGY
TRIDIONE has been shown to prevent pentylenetetrazol-induced and thujone-induced seizures in experimental animals; the drug has a less marked effect on seizures induced by picrotoxin, procaine, cocaine, or strychnine. Unlike the hydantoins and antiepileptic barbiturates, TRIDIONE does not modify the maximal seizure pattern in patients undergoing electroconvulsive therapy.
TRIDIONE has a sedative effect that may increase to the point of ataxia when excessive doses are used. A toxic dose of the drug in animals (approximately 2 g/kg) produced sleep, unconsciousness, and respiratory depression.Close
TRIDIONE (trimethadione) should be withdrawn promptly if skin rash appears, because of the grave possibility of the occurrence of exfoliative dermatitis or severe forms of erythema multiforme.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 Therapy need not be withdrawn unless the neutrophil count is 2500 or less; more frequent blood examinations should be done when the count is less than 3,000.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.
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.
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.
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 Epilepsy 1.0 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1.0 1.8 1.9 0.9 Total 2.4 4.3 1.8 1.9
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.
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).
- ADVERSE REACTIONS
Bleeding gums, epistaxis, retinal and petechial hemorrhages, vaginal bleeding, neutropenia, leukopenia, eosinophilia, thrombocytopenia, pancytopenia, agranulocytosis, hypoplastic anemia, and fatal aplastic anemia.
Gastric evacuation, either by induced emesis, or by lavage, or both, should be done immediately. General supportive care, including frequent monitoring of the vital signs and close observations of the patient, are required.Close
- DOSAGE AND ADMINISTRATION
Usual Adult Dosage
- HOW SUPPLIED
TRIDIONE Dulcet® Tablets (trimethadione tablets) are supplied as white, chewable tablets bearing the “a” logo and a two-letter code designation LE for the 150 mg tablet, in bottles of 100 (NDC 0074-3753-01).
- FDA-APPROVED MEDICATION GUIDE
Read this Medication Guide before you start taking TRIDIONE and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.
- Rash. This may need to be treated in a hospital and may be life-threatening.
Call your healthcare provider right away if you have any of these symptoms:
- skin rash
- sores in your mouth
- Blood problems that can be life-threatening. Call your healthcare provider right away if you have any of these symptoms:
- Fever, swollen glands, or sore throat that come and go or do not go away
- Frequent infections or an infection that does not go away
- Easy bruising
- Red or purple spots on your body
- Bleeding gums or nose bleeds
- Severe fatigue or weakness
- Liver problems. Call your healthcare provider right away if you have any of these symptoms:
- yellowing of your skin or the whites of your eyes (jaundice)
- dark urine
- nausea or vomiting
- loss of appetite
- pain on the right side of your stomach (abdomen)
- Kidney problems that may be life-threatening.
- Eye problems. Call your healthcare provider right away if you have any new changes in your vision such as:
- problems seeing in bright light
- blurred vision
- Birth defects in your unborn baby.
- Women who can become pregnant should talk to their healthcare provider about using other possible treatments instead of TRIDIONE. If the decision is made to use TRIDIONE, women should use effective birth control (contraception). Talk with your healthcare provider if you are pregnant or plan to become pregnant. Birth defects may occur even in children born to women who are not taking any medicines and do not have other risk factors.
- Tell your healthcare provider right away if you become pregnant while taking TRIDIONE. You and your healthcare provider should decide if you will continue to take TRIDIONE while you are pregnant.
- If you become pregnant while taking TRIDIONE, talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of antiepileptic drugs during pregnancy.
- Tell your healthcare provider right away if you are breastfeeding or plan to breastfeed. It is unknown if TRIDIONE passes into breast milk. Talk to your healthcare provider about the best way to feed your baby if you take TRIDIONE.
- Like other antiepileptic drugs, TRIDIONE may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.
Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:
- thoughts about suicide or dying
- attempts to commit suicide
- new or worse depression
- new or worse anxiety
- feeling agitated or restless
- panic attacks
- trouble sleeping (insomnia)
- new or worse irritability
- acting aggressive, being angry, or violent
- acting on dangerous impulses
- an extreme increase in activity and talking (mania)
- other unusual changes in behavior or mood
- Pay attention to any changes, especially sudden changes in mood, behaviors, thoughts, or feelings.
- Keep all follow-up visits with your healthcare provider as scheduled.
- Call your healthcare provider between visits as needed, especially if you are worried about symptoms.
Do not stop TRIDIONE without first talking to a healthcare provider. Stopping TRIDIONE suddenly can cause serious problems. Stopping a seizure medicine suddenly in a patient who has epilepsy can cause seizures that will not stop (status epilepticus).
- blood problems
- kidney problems
- liver problems
- eye problems
- depression, mood problems or suicidal thoughts or behavior
- any other medical conditions
Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist each time you get a new medicine.
- Take TRIDIONE exactly as your healthcare provider tells you.
- TRIDIONE can be chewed or swallowed whole.
- Your healthcare provider may change your dose of TRIDIONE. Do not change your dose of TRIDIONE without talking to your healthcare provider.
- If you take too much TRIDIONE, call your healthcare provider or local Poison Control Center right away.
- Do not stop taking TRIDIONE without talking to your healthcare provider. Stopping TRIDIONE suddenly can cause serious problems, including seizures that will not stop (status epilepticus).
- Do not drink alcohol or take other drugs that make you sleepy or dizzy while taking TRIDIONE until you talk to your healthcare provider. TRIDIONE taken with alcohol or drugs that cause sleepiness or dizziness may make your sleepiness or dizziness worse.
- Do not drive, operate heavy machinery, or do other dangerous activities until you know how TRIDIONE affects you. TRIDIONE can slow your thinking and motor skills.
- Symptoms that are like the symptoms of lupus or myasthenia gravis. Call your healthcare provider right away if you have any of these symptoms:
- droopy eyelids
- a rash on your cheeks or other parts of your body
- sensitivity to the sun
- new joint or muscle pains
- chest pain or shortness of breath
- swelling of your feet, ankles, and legs
- weakness of your arms or legs
- problems swallowing
- speech problems
- swollen glands (enlarged lymph nodes)
- increase in seizures
- feelings of anger and frustration
- changes in behavior
- Store TRIDIONE in the refrigerator at 36 to 460F (2 to 80C).
- Keep TRIDIONE in a tightly closed container.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use TRIDIONE for a condition for which it was not prescribed. Do not give TRIDIONE to other people, even if they have the same symptoms that you have. It may harm them.
This Medication Guide summarizes the most important information about TRIDIONE. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about TRIDIONE that is written for health professionals. For more information, go to www.rxabbvie.com or call 1-800-633-9110.Close
- Rash. This may need to be treated in a hospital and may be life-threatening.
- PRINCIPAL DISPLAY PANEL
- INGREDIENTS AND APPEARANCE
trimethadione tablet, chewable
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0074-3753 Route of Administration ORAL Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength TRIMETHADIONE (UNII: R7GV3H6FQ4) (TRIMETHADIONE - UNII:R7GV3H6FQ4) TRIMETHADIONE 150 mg Inactive Ingredients Ingredient Name Strength STARCH, CORN (UNII: O8232NY3SJ) LACTOSE (UNII: J2B2A4N98G) MAGNESIUM STEARATE (UNII: 70097M6I30) MAGNESIUM TRISILICATE (UNII: C2E1CI501T) SUCROSE (UNII: C151H8M554) Product Characteristics Color WHITE Score no score Shape SQUARE Size 10mm Flavor Imprint Code LE Contains Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0074-3753-01 100 in 1 BOTTLE; Type 0: Not a Combination Product 03/26/2014 04/12/2020 Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA005856 01/25/1946 04/12/2020 Labeler - AbbVie Inc. (078458370)