Tranxene T-Tab

Clorazepate is a benzodiazepine (ben-zoe-dye-AZE-eh-peen). Clorazepate affects chemicals in the brain that may be unbalanced and cause anxiety or seizures.

Clorazepate is used to treat anxiety disorders, partial seizures, or alcohol withdrawal symptoms.

Clorazepate may also be used for purposes not listed in this medication guide.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have:

• confusion, unusual thoughts or behavior;

• problems with urination; or

• a light-headed feeling, like you might pass out.

Common side effects may include:

• dizziness, drowsiness;

• confusion;

• blurred vision;

• upset stomach; or

• dry mouth.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In the U.S.

• Gen-Xene
• Tranxene
• Tranxene-SD
• Tranxene T-Tab

Available Dosage Forms:

• Tablet
• Tablet, Extended Release
• Capsule

Therapeutic Class: Antianxiety

Pharmacologic Class: Benzodiazepine, Long Acting

Clorazepate is used to relieve symptoms of anxiety and alcohol withdrawal. This medicine may also be used with other medicines to treat partial seizures.

Clorazepate is a benzodiazepine. Benzodiazepines belong to the group of medicines called central nervous system (CNS) depressants, which are medicines that slow down the nervous system.

This medicine is available only with your doctor's prescription.

Risks from Concomitant Use with Opioids:

Concomitant use of benzodiazepines, including TRANXENE, and opioids may result in profound sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. If a decision is made to prescribe TRANXENE concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation. In patients already receiving an opioid analgesic, prescribe a lower initial dose of TRANXENE than indicated in the absence of an opioid and titrate based on clinical response. If an opioid is initiated in a patient already taking TRANXENE, prescribe a lower initial dose of the opioid and titrate based upon clinical response.

Advise both patients and caregivers about the risks of respiratory depression and sedation when TRANXENE is used with opioids. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined (see DRUG INTERACTIONS).

Use in Depressive Neuroses or Psychotic Reactions:

TRANXENE tablets are not recommended for use in depressive neuroses or in psychotic reactions.

Use in Children:

Because of the lack of sufficient clinical experience, TRANXENE tablets are not recommended for use in patients less than 9 years of age.

Interference with Psychomotor Performance:

Patients taking TRANXENE tablets should be cautioned against engaging in hazardous occupations requiring mental alertness, such as operating dangerous machinery including motor vehicles.

Concomitant Use with CNS Depressants:

Since TRANXENE has a central nervous system depressant effect, patients should be advised against the simultaneous use of other CNS depressant drugs, and cautioned that the effects of alcohol may be increased.

Physical and Psychological Dependence:

Withdrawal symptoms (similar in character to those noted with barbiturates and alcohol) have occurred following abrupt discontinuance of clorazepate. Withdrawal symptoms associated with the abrupt discontinuation of benzodiazepines have included convulsions, delirium, tremor, abdominal and muscle cramps, vomiting, sweating, nervousness, insomnia, irritability, diarrhea, and memory impairment. The more severe withdrawal symptoms have usually been limited to those patients who had received excessive doses over an extended period of time. Generally milder withdrawal symptoms have been reported following abrupt discontinuance of benzodiazepines taken continuously at therapeutic levels for several months. Consequently, after extended therapy, abrupt discontinuation of clorazepate should generally be avoided and a gradual dosage tapering schedule followed.

Caution should be observed in patients who are considered to have a psychological potential for drug dependence.

Evidence of drug dependence has been observed in dogs and rabbits which was characterized by convulsive seizures when the drug was abruptly withdrawn or the dose was reduced; the syndrome in dogs could be abolished by administration of clorazepate.

Suicidal Behavior and Ideation:

Antiepileptic drugs (AEDs), including TRANXENE, 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.

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 TRANXENE 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.

Usage in Pregnancy:

An increased risk of congenital malformations associated with the use of minor tranquilizers (chlordiazepoxide, diazepam, and meprobamate) during the first trimester of pregnancy has been suggested in several studies. Clorazepate dipotassium, a benzodiazepine derivative, has not been studied adequately to determine whether it, too, may be associated with an increased risk of fetal abnormality. Because use of these drugs is rarely a matter of urgency, their use during this period should almost always be avoided. The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered. Patients should be advised that if they become pregnant during therapy or intend to become pregnant they should communicate with their physician about the desirability of discontinuing the drug.

To provide information regarding the effects of in utero exposure to TRANXENE, physicians are advised to recommend that pregnant patients taking TRANXENE 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/.

Usage during Lactation:

TRANXENE tablets should not be given to nursing mothers since it has been reported that nordiazepam is excreted in human breast milk.

In those patients in which a degree of depression accompanies the anxiety, suicidal tendencies may be present and protective measures may be required. The least amount of drug that is feasible should be available to the patient.

Patients taking TRANXENE tablets for prolonged periods should have blood counts and liver function tests periodically. The usual precautions in treating patients with impaired renal or hepatic function should also be observed.

In elderly or debilitated patients, the initial dose should be small, and increments should be made gradually, in accordance with the response of the patient, to preclude ataxia or excessive sedation.

Information for Patients:

To assure the safe and effective use of benzodiazepines, patients should be informed that, since benzodiazepines may produce psychological and physical dependence, it is essential that they consult with their physician before either increasing the dose or abruptly discontinuing this drug.

Patients, their caregivers, and families should be counseled that AEDs, including TRANXENE, 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 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 Usage in Pregnancy).

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with clorazepate dipotassium and should counsel them in its appropriate use. A patient Medication Guide is available for TRANXENE. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is available at www.recordatirarediseases.com.

Pediatric Use:

See WARNINGS.

Geriatric Use:

Clinical studies of TRANXENE were not adequate to determine whether subjects aged 65 and over respond differently than younger subjects. Elderly or debilitated patients may be especially sensitive to the effects of all benzodiazepines, including TRANXENE. In general, elderly or debilitated patients should be started on lower doses of TRANXENE and observed closely, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy. Dose adjustments should also be made slowly, and with more caution in this patient population (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).

The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABAA sites and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and monitor patients closely for respiratory depression and sedation.

If TRANXENE is to be combined with other drugs acting on the central nervous system, careful consideration should be given to the pharmacology of the agents to be employed. Animal experience indicates that clorazepate dipotassium prolongs the sleeping time after hexobarbital or after ethyl alcohol, increases the inhibitory effects of chlorpromazine, but does not exhibit monoamine oxidase inhibition. Clinical studies have shown increased sedation with concurrent hypnotic medications. The actions of the benzodiazepines may be potentiated by barbiturates, narcotics, phenothiazines, monoamine oxidase inhibitors or other antidepressants.

If TRANXENE tablets are used to treat anxiety associated with somatic disease states, careful attention must be paid to possible drug interaction with concomitant medication.

In bioavailability studies with normal subjects, the concurrent administration of antacids at therapeutic levels did not significantly influence the bioavailability of TRANXENE tablets.

NDC 55292-302-01

100 Tablets

Tranxene* T-Tab® Tablets
(clorazepate dipotassium tablets, USP)

7.5 mg CIV

DISPENSE THE ENCLOSED MEDICATION GUIDE TO EACH PATIENT. GO TO www.recordatirarediseases.com

Rx only 

RECORDATI RARE DISEASES GROUP

Each tablet contains 7.5 mg clorazepate dipotassium.

See package insert for full prescribing information.

Store at 20-25ºC (68-77ºF). See USP controlled room temperature.

Protect from moisture. Keep bottle tightly closed.

Dispense in a USP tight, light-resistant container.

Do not accept if seal over bottle opening is broken or missing.

Manufactured by:
AbbVie LTD
Barceloneta, PR 00617

For: Recordati Rare Diseases Inc.
Lebanon, NJ 08833, U.S.A.

Exp.

Lot

04-B186-R6 (4390)

Applies to clorazepate: oral tablet

General

The most commonly reported side effect was dizziness.

Psychiatric

Frequency not reported: Insomnia, suicidal ideation/behavior, irritability, depression

Nervous system

Frequency not reported: Dizziness, nervousness, headache, mental confusion, tremor, slurred speech, ataxia[Ref]

Hepatic

Frequency not reported: Abnormal liver function tests

Renal

Frequency not reported: Abnormal kidney function tests

Hematologic

Frequency not reported: Decreased hematocrit

Other

Frequency not reported: Fatigue[Ref]

Dermatologic

Frequency not reported: Transient skin rash

Cardiovascular

Frequency not reported: Decrease in systolic blood pressure

Gastrointestinal

Frequency not reported: Gastrointestinal complaints, dry mouth

Genitourinary

Frequency not reported: Genitourinary complaints

Ocular

Frequency not reported: Blurred vision, diplopia

Some side effects of Tranxene T-Tab may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.