Drug Facts
Composition & Profile
Identifiers & Packaging
HOW SUPPLIED Clorazepate Dipotassium Tablets, USP are available containing 3.75 mg, 7.5 mg or 15 mg of clorazepate dipotassium, USP. The 3.75 mg tablets are mottled blue colored, round, flat face tablets, debossed with "CL" and "11" separated by score-line on one side and plain on other side. They are available as follows: Bottles of 100 NDC 13107-282-01 Bottles of 500 NDC 13107-282-05 The 7.5 mg tablets are mottled peach colored, round, flat face tablets, debossed with "CL" and "14" separated by score-line on one side and plain on other side.They are available as follows: Bottles of 100 NDC 13107-283-01 Bottles of 500 NDC 13107-283-05 The 15 mg tablets are mottled white to off white colored, round, flat face tablets, debossed with "CL" and "17" separated by score-line on one side and plain on other side. They are available as follows: Bottles of 100 NDC 13107-284-01 Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from light and moisture. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. PHARMACIST: Dispense a Medication Guide with each prescription. Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 032, India Revised: 09/2023 Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides; PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 3.75 mg (100 Tablets Bottle) NDC 13107-282-01 Rx only Clorazepate Dipotassium Tablets, USP 3.75 mg CIV PHARMACIST: Dispense the Medication Guide provided separately to each patient. AUROBINDO 100 Tablets PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 3.75 mg 100 Tablets Container Label; PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 7.5mg (100 Tablets Bottle) NDC 13107-283-01 Rx only Clorazepate Dipotassium Tablets, USP 7.5 mg CIV PHARMACIST: Dispense the Medication Guide provided separately to each patient. AUROBINDO 100 Tablets PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 15 mg (100 Tablets Bottle); PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 7.5 mg (100 Tablets Bottle) NDC 13107-284-01 Rx only Clorazepate Dipotassium Tablets, USP 15 mg CIV PHARMACIST: Dispense the Medication Guide provided separately to each patient. AUROBINDO 100 Tablets PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 7.5 mg (100 Tablets Bottle)
- HOW SUPPLIED Clorazepate Dipotassium Tablets, USP are available containing 3.75 mg, 7.5 mg or 15 mg of clorazepate dipotassium, USP. The 3.75 mg tablets are mottled blue colored, round, flat face tablets, debossed with "CL" and "11" separated by score-line on one side and plain on other side. They are available as follows: Bottles of 100 NDC 13107-282-01 Bottles of 500 NDC 13107-282-05 The 7.5 mg tablets are mottled peach colored, round, flat face tablets, debossed with "CL" and "14" separated by score-line on one side and plain on other side.They are available as follows: Bottles of 100 NDC 13107-283-01 Bottles of 500 NDC 13107-283-05 The 15 mg tablets are mottled white to off white colored, round, flat face tablets, debossed with "CL" and "17" separated by score-line on one side and plain on other side. They are available as follows: Bottles of 100 NDC 13107-284-01 Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from light and moisture. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. PHARMACIST: Dispense a Medication Guide with each prescription. Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 032, India Revised: 09/2023 Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides
- PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 3.75 mg (100 Tablets Bottle) NDC 13107-282-01 Rx only Clorazepate Dipotassium Tablets, USP 3.75 mg CIV PHARMACIST: Dispense the Medication Guide provided separately to each patient. AUROBINDO 100 Tablets PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 3.75 mg 100 Tablets Container Label
- PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 7.5mg (100 Tablets Bottle) NDC 13107-283-01 Rx only Clorazepate Dipotassium Tablets, USP 7.5 mg CIV PHARMACIST: Dispense the Medication Guide provided separately to each patient. AUROBINDO 100 Tablets PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 15 mg (100 Tablets Bottle)
- PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 7.5 mg (100 Tablets Bottle) NDC 13107-284-01 Rx only Clorazepate Dipotassium Tablets, USP 15 mg CIV PHARMACIST: Dispense the Medication Guide provided separately to each patient. AUROBINDO 100 Tablets PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 7.5 mg (100 Tablets Bottle)
Overview
Chemically, clorazepate dipotassium is a benzodiazepine. The empirical formula is C 16 H 11 ClK 2 N 2 O 4 ; the molecular weight is 408.92; 1 H -1, 4 Benzodiazepine-3-carboxylic acid, 7-chloro-2,3-dihydro-2-oxo-5-phenyl-, potassium salt compound with potassium hydroxide (1:1) and the structural formula may be represented as follows: The compound occurs as a fine, white or light yellow crystalline powder. It is insoluble in the common organic solvents, but very soluble in water. Aqueous solutions are unstable, clear, light yellow, and alkaline. Clorazepate dipotassium tablets, USP contain 3.75 mg, 7.5 mg or 15 mg of clorazepate dipotassium, USP for oral administration. Inactive ingredients for clorazepate dipotassium tablets: croscarmellose sodium, magnesium oxide, magnesium stearate, microcrystalline cellulose, potassium carbonate, sodium chloride and sodium lauryl sulfate. The 3.75 mg tablets also contain FD&C Blue No. 2 Aluminum Lake and the 7.5 mg tablets also contain FD&C Yellow No. 6 Aluminum Lake. CHemical Structure
Indications & Usage
Clorazepate dipotassium tablets are indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. Clorazepate dipotassium tablets are indicated as adjunctive therapy in the management of partial seizures. The effectiveness of clorazepate dipotassium tablets in long-term management of anxiety, that is, more than 4 months, has not been assessed by systematic clinical studies. Long-term studies in epileptic patients, however, have shown continued therapeutic activity. The physician should reassess periodically the usefulness of the drug for the individual patient. Clorazepate dipotassium tablets are indicated for the symptomatic relief of acute alcohol withdrawal.
Dosage & Administration
For the Symptomatic Relief of Anxiety: Clorazepate dipotassium tablets are administered orally in divided doses. The usual daily dose is 30 mg. The dose should be adjusted gradually within the range of 15 to 60 mg daily in accordance with the response of the patient. In elderly or debilitated patients it is advisable to initiate treatment at a daily dose of 7.5 to 15 mg. Clorazepate dipotassium tablets may also be administered in a single dose daily at bedtime; the recommended initial dose is 15 mg. After the initial dose, the response of the patient may require adjustment of subsequent dosage. Lower doses may be indicated in the elderly patient. Drowsiness may occur at the initiation of treatment and with dosage increment. For the Symptomatic Relief of Acute Alcohol Withdrawal: The following dosage schedule is recommended: 1st 24 hours (Day 1) 30 mg initially; followed by 30 to 60 mg in divided doses 2nd 24 hours (Day 2) 45 to 90 mg in divided doses 3rd 24 hours (Day 3) 22.5 to 45 mg in divided doses Day 4 15 to 30 mg in divided doses Thereafter, gradually reduce the daily dose to 7.5 to 15 mg. Discontinue drug therapy as soon as patient’s condition is stable. The maximum recommended total daily dose is 90 mg. Avoid excessive reductions in the total amount of drug administered on successive days. As an Adjunct to Antiepileptic Drugs: In order to minimize drowsiness, the recommended initial dosages and dosage increments should not be exceeded. Adults: The maximum recommended initial dose in patients over 12 years old is 7.5 mg three times a day. Dosage should be increased by no more than 7.5 mg every week and should not exceed 90 mg/day. Children (9 to 12 years): The maximum recommended initial dose is 7.5 mg two times a day. Dosage should be increased by no more than 7.5 mg every week and should not exceed 60 mg/day. Discontinuation or Dosage Reduction of Clorazepate Dipotassium Tablets: To reduce the risk of withdrawal reactions, use a gradual taper to discontinue clorazepate dipotassium tablets or reduce the dosage. If a patient develops withdrawal reactions, consider pausing the taper or increasing the dosage to the previous tapered dosage level. Subsequently decrease the dosage more slowly (see WARNINGS and DRUG ABUSE AND DEPENDENCE ).
Warnings & Precautions
WARNINGS Risks from Concomitant Use with Opioids: Concomitant use of benzodiazepines, including clorazepate dipotassium, and opioids may result in profound sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of these drugs 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 clorazepate dipotassium 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 clorazepate dipotassium than indicated in the absence of an opioid and titrate based on clinical response. If an opioid is initiated in a patient already taking clorazepate dipotassium, 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 clorazepate dipotassium 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 PRECAUTIONS: Drug Interactions ). Abuse, Misuse, and Addiction: The use of benzodiazepines, including clorazepate dipotassium, exposes users to the risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death (see DRUG ABUSE AND DEPENDENCE: Abuse ). Before prescribing clorazepate dipotassium and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool). Use of clorazepate dipotassium, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of clorazepate dipotassium along with monitoring for signs and symptoms of abuse, misuse, and addiction. Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. If a substance use disorder is suspected, evaluate the patient and institute (or refer them for) early treatment, as appropriate. Dependence and Withdrawal Reactions: To reduce the risk of withdrawal reactions, use a gradual taper to discontinue clorazepate dipotassium or reduce the dosage (a patient-specific plan should be used to taper the dose) (see DOSAGE AND ADMINISTRATION: Discontinuation of Dosage Reduction of Clorazepate Dipotassium ). Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use. Acute Withdrawal Reactions The continued use of benzodiazepines, including clorazepate dipotassium, may lead to clinically significant physical dependence. Abrupt discontinuation or rapid dosage reduction of clorazepate dipotassium after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures) (see DRUG ABUSE AND DEPENDENCE: Dependence ). Protracted Withdrawal Syndrome In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months (see DRUG ABUSE AND DEPENDENCE ). Use in Depressive Neuroses or Psychotic Reactions: Clorazepate dipotassium tablets are not recommended for use in depressive neuroses or in psychotic reactions. Use in Children: Because of the lack of sufficient clinical experience, clorazepate dipotassium tablets are not recommended for use in patients less than 9 years of age. Interference with Psychomotor Performance: Patients taking clorazepate dipotassium 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 clorazepate dipotassium 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. Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including clorazepate dipotassium, 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 to 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 clorazepate dipotassium 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. Neonatal Sedation and Withdrawal Syndrome: Use of clorazepate dipotassium late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate (see PRECAUTIONS: Pregnancy ). Monitor neonates exposed to clorazepate dipotassium during pregnancy or labor for signs of sedation and monitor neonates exposed to clorazepate dipotassium during pregnancy for signs of withdrawal; manage these neonates accordingly.
Boxed Warning
RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation (See WARNINGS and PRECAUTIONS ). The use of benzodiazepines, including clorazepate dipotassium, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes. Before prescribing clorazepate dipotassium and throughout out treatment, assess each patient’s risk for abuse, misuse, and addiction (See WARNINGS ). The continued use of benzodiazepines, including clorazepate dipotassium, may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. Abrupt discontinuation or rapid dosage reduction of clorazepate dipotassium after continued use may precipitate acute withdrawal reactions, which can be life-threatening. To reduce the risk of withdrawal reactions, use a gradual taper to discontinue clorazepate dipotassium or reduce the dosage (See DOSAGE AND ADMINISTRATION and WARNINGS ).
Contraindications
Clorazepate dipotassium tablets are contraindicated in patients with a known hypersensitivity to the drug and in those with acute narrow angle glaucoma.
Adverse Reactions
The side effect most frequently reported was drowsiness. Less commonly reported (in descending order of occurrence) were: dizziness, various gastrointestinal complaints, nervousness, blurred vision, dry mouth, headache, and mental confusion. Other side effects included insomnia, transient skin rashes, fatigue, ataxia, genitourinary complaints, irritability, diplopia, depression, tremor, and slurred speech. There have been reports of abnormal liver and kidney function tests and of decrease in hematocrit. Decrease in systolic blood pressure has been observed. To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
Drug Interactions
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 clorazepate dipotassium 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 clorazepate dipotassium 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 clorazepate dipotassium tablets.
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