CONTRAINDICATIONS SECTION.


CONTRAINDICATIONS. Chlordiazepoxide HCl capsules are contraindicated in patients with known hypersensitivity to the drug.

WARNINGS SECTION.


WARNINGS. Risks from Concomitant Use with Opioids. Concomitant use of benzodiazepines, including chlordiazepoxide, 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 decision is made to prescribe chlordiazepoxide 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 lower initial dose of chlordiazepoxide than indicated in the absence of an opioid and titrate based on clinical response. If an opioid is initiated in patient already taking chlordiazepoxide, prescribe 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 chlordiazepoxide 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). Abuse, Misuse, and Addiction. The use of benzodiazepines, including chlordiazepoxide, 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 chlordiazepoxide and throughout treatment, assess each patients risk for abuse, misuse, and addiction (e.g., using standardized screening tool). Use of chlordiazepoxide, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of chlordiazepoxide 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 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 gradual taper to discontinue chlordiazepoxide or reduce the dosage (a patient-specific plan should be used to taper the dose) (see DOSAGE AND ADMINISTRATION: Discontinuation or Dosage Reduction of chlordiazepoxide).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 ReactionsThe continued use of benzodiazepines, including chlordiazepoxide, may lead to clinically significant physical dependence. Abrupt discontinuation or rapid dosage reduction of chlordiazepoxide 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 protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months (see DRUG ABUSE AND DEPENDENCE: Dependence).Chlordiazepoxide HCl may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving vehicle or operating machinery. Similarly, it may impair mental alertness in children. The concomitant use of alcohol or other central nervous system depressants may have an additive effect. PATIENTS SHOULD BE WARNED ACCORDINGLY.. 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. Because use of these drugs is rarely matter of urgency, their use during this period should almost always be avoided. The possibility that 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 physicians about the desirability of discontinuing the drug.

ADVERSE REACTIONS SECTION.


ADVERSE REACTIONS. The necessity of discontinuing therapy because of undesirable effects has been rare. Drowsiness, ataxia and confusion have been reported in some patients -- particularly the elderly and debilitated. While these effects can be avoided in almost all instances by proper dosage adjustment, they have occasionally been observed at the lower dosage ranges. In few instances syncope has been reported.Other adverse reactions reported during therapy include isolated instances of skin eruptions, edema, minor menstrual irregularities, nausea and constipation, extrapyramidal symptoms, as well as increased and decreased libido. Such side effects have been infrequent, and are generally controlled with reduction of dosage. Changes in EEG patterns (low-voltage fast activity) have been observed in patients during and after chlordiazepoxide HCl treatment.Blood dyscrasias (including agranulocytosis), jaundice and hepatic dysfunction have occasionally been reported during therapy. When chlordiazepoxide HCl treatment is protracted, periodic blood counts and liver function tests are advisable.To report SUSPECTED ADVERSE EVENTS, contact Teva Pharmaceuticals USA, Inc., at 1-888-838-2872 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch for voluntary reporting of adverse reactions.

ANIMAL PHARMACOLOGY & OR TOXICOLOGY SECTION.


Animal Pharmacology. The drug has been studied extensively in many species of animals and these studies are suggestive of action on the limbic system of the brain, which recent evidence indicates is involved in emotional responses.Hostile monkeys were made tame by oral drug doses which did not cause sedation. Chlordiazepoxide HCl revealed taming action with the elimination of fear and aggression. The taming effect of chlordiazepoxide HCl was further demonstrated in rats made vicious by lesions in the septal area of the brain. The drug dosage which effectively blocked the vicious reaction was well below the dose which caused sedation in these animals.The LD50 of parenterally administered chlordiazepoxide HCl was determined in mice (72 hours) and rats (5 days), and calculated according to the method of Miller and Tainter, with the following results: mice, IV, 123 +- 12 mg/kg; mice, IM, 366 +- mg/kg; rats, IV, 120 +- mg/kg; rats, IM, 160 mg/kg.

BOXED WARNING SECTION.


WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS;ABUSE, MISUSE, ANDADDICTION; andDEPENDENCE 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 for 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 chlordiazepoxide hydrochloride capsules, 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 chlordiazepoxide hydrochloride capsules and throughout treatment, assess each patients risk for abuse, misuse, and addiction (see WARNINGS).The continued use of benzodiazepines, including chlordiazepoxide hydrochloride capsules, 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 chlordiazepoxide hydrochloride capsules after continued use may precipitate acute withdrawal reactions, which can be life-threatening. To reduce the risk of withdrawal reactions, use gradual taper to discontinue chlordiazepoxide hydrochloride capsules or reduce the dosage (see DOSAGE AND ADMINISTRATION and WARNINGS). Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for 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 chlordiazepoxide hydrochloride capsules, 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 chlordiazepoxide hydrochloride capsules and throughout treatment, assess each patients risk for abuse, misuse, and addiction (see WARNINGS).. The continued use of benzodiazepines, including chlordiazepoxide hydrochloride capsules, 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 chlordiazepoxide hydrochloride capsules after continued use may precipitate acute withdrawal reactions, which can be life-threatening. To reduce the risk of withdrawal reactions, use gradual taper to discontinue chlordiazepoxide hydrochloride capsules or reduce the dosage (see DOSAGE AND ADMINISTRATION and WARNINGS).

CLINICAL PHARMACOLOGY SECTION.


CLINICAL PHARMACOLOGY. Chlordiazepoxide HCl has antianxiety, sedative, appetite-stimulating and weak analgesic actions. The precise mechanism of action is not known. The drug blocks EEG arousal from stimulation of the brain stem reticular formation. It takes several hours for peak blood levels to be reached and the half-life of the drug is between 24 and 48 hours. After the drug is discontinued plasma levels decline slowly over period of several days. Chlordiazepoxide is excreted in the urine, with 1% to 2% unchanged and 3% to 6% as conjugate.. Animal Pharmacology. The drug has been studied extensively in many species of animals and these studies are suggestive of action on the limbic system of the brain, which recent evidence indicates is involved in emotional responses.Hostile monkeys were made tame by oral drug doses which did not cause sedation. Chlordiazepoxide HCl revealed taming action with the elimination of fear and aggression. The taming effect of chlordiazepoxide HCl was further demonstrated in rats made vicious by lesions in the septal area of the brain. The drug dosage which effectively blocked the vicious reaction was well below the dose which caused sedation in these animals.The LD50 of parenterally administered chlordiazepoxide HCl was determined in mice (72 hours) and rats (5 days), and calculated according to the method of Miller and Tainter, with the following results: mice, IV, 123 +- 12 mg/kg; mice, IM, 366 +- mg/kg; rats, IV, 120 +- mg/kg; rats, IM, 160 mg/kg.. Effects on Reproduction. Reproduction studies in rats fed 10, 20 and 80 mg/kg daily and bred through one or two matings showed no congenital anomalies, nor were there adverse effects on lactation of the dams or growth of the newborn. However, in another study at 100 mg/kg daily there was noted significant decrease in the fertilization rate and marked decrease in the viability and body weight of offspring which may be attributable to sedative activity, thus resulting in lack of interest in mating and lessened maternal nursing and care of the young. One neonate in each of the first and second matings in the rat reproduction study at the 100 mg/kg dose exhibited major skeletal defects. Further studies are in progress to determine the significance of these findings.

DESCRIPTION SECTION.


DESCRIPTION. Chlordiazepoxide hydrochloride, USP is the prototype for the benzodiazepine compounds. It is versatile therapeutic agent of proven value for the relief of anxiety. Chlordiazepoxide hydrochloride, USP is among the safer of the effective psychopharmacologic compounds available, as demonstrated by extensive clinical evidence.Chlordiazepoxide hydrochloride, USP is 7-chloro-2- (methylamino)-5-phenyl-3H-1,4-benzodiazepine 4-oxide hydrochloride. white to practically white crystalline substance, it is soluble in water. It is unstable in solution and the powder must be protected from light. The structural formula is: C16H14ClN3O HCl M.W. 336.22Each capsule, for oral administration, contains either mg, 10 mg or 25 mg of chlordiazepoxide hydrochloride, USP and has the following inactive ingredients: anhydrous lactose, D&C yellow no. 10, FD&C blue no. 1, FD&C blue no. aluminum lake, gelatin, hydrogenated vegetable oil, microcrystalline cellulose, pharmaceutical glaze, and titanium dioxide. The mg and 25 mg also contain D&C yellow no. 10 aluminum lake, FD&C blue no. aluminum lake, FD&C red no. 40 aluminum lake, propylene glycol, and synthetic black iron oxide. In addition, the mg contains D&C red no. 33 and the 10 mg also contains butyl paraben, edetate calcium disodium, dimethyl polysiloxane, ethylene glycol monoethyl ether, FD&C red no. 40, methyl paraben, propyl paraben, sodium, sodium lauryl sulfate, sodium propionate, and soya lecithin.. Chlordiazepoxide hydrochloride structural formula.

DOSAGE & ADMINISTRATION SECTION.


DOSAGE AND ADMINISTRATION. Because of the wide range of clinical indications for chlordiazepoxide HCl, the optimum dosage varies with the diagnosis and response of the individual patient. The dosage, therefore, should be individualized for maximum beneficial effects.ADULTSUSUAL DAILY DOSERelief of Mild and Moderate Anxiety Disorders and Symptoms of Anxiety5 mg or 10 mg, or times dailyRelief of Severe Anxiety Disorders and Symptoms of Anxiety 20 mg or 25 mg, or times dailyGeriatric Patients, or in the presence of debilitating disease.5 mg, to times daily. Preoperative Apprehension and Anxiety. On days preceding surgery, to 10 mg orally, or times daily. If used as preoperative medication, 50 to 100 mg IM hour prior to surgery.PEDIATRIC PATIENTSUSUAL DAILY DOSEBecause of the varied response of pediatric patients to CNS-acting drugs, therapy should be initiated with the lowest dose and increased as required. Since clinical experience in pediatric patients under years of age is limited, the use of the drug in this age group is not recommended.5 mg, to times daily (may be increased in some pediatric patients to 10 mg, to times daily) For the relief of withdrawal symptoms of acute alcoholism, the parenteral form is usually used initially. If the drug is administered orally, the suggested initial dose is 50 to 100 mg, to be followed by repeated doses as needed until agitation is controlled -- up to 300 mg per day. Dosage should then be reduced to maintenance levels.See package insert for Sterile Chlordiazepoxide Hydrochloride.Management of Overdosage: Manifestations of chlordiazepoxide overdosage includes somnolence, confusion, coma and diminished reflexes. Respiration, pulse and blood pressure should be monitored, as in all cases of drug overdosage, although, in general, these effects have been minimal following chlordiazepoxide overdosage. General supportive measures should be employed, along with immediate gastric lavage. Intravenous fluids should be administered and an adequate airway maintained. Hypotension may be combated by the use of norepinephrine or metaraminol. Dialysis is of limited value. There have been occasional reports of excitation in patients following chlordiazepoxide overdosage; if this occurs barbiturates should not be used. As with the management of intentional overdosage with any drug, it should be borne in mind that multiple agents may have been ingested.Flumazenil, specific benzodiazepine receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when an overdose with benzodiazepine is known or suspected. Prior to the administration of flumazenil, necessary measures should be instituted to secure airway, ventilation, and intravenous access. Flumazenil is intended as an adjunct to, not as substitute for, proper management of benzodiazepine overdose. Patients treated with flumazenil should be monitored for re-sedation, respiratory depression, and other residual benzodiazepine effects for an appropriate period after treatment. The prescriber should be aware of risk of seizure in association with flumazenil treatment, particularly in long-term benzodiazepine users and in cyclic antidepressant overdose. The complete flumazenil package insert including CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS should be consulted prior to use. Discontinuation or Dosage Reduction of Chlordiazepoxide. To reduce the risk of withdrawal reactions, use gradual taper to discontinue chlordiazepoxide or reduce the dosage. If 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: Dependence and Withdrawal Reactions and DRUG ABUSE AND DEPENDENCE: Dependence).

DRUG ABUSE AND DEPENDENCE SECTION.


DRUG ABUSE AND DEPENDENCE. Controlled Substance. Chlordiazepoxide is Schedule IV controlled substance.. Abuse. Chlordiazepoxide is benzodiazepine and CNS depressant with potential for abuse and addiction. Abuse is the intentional, non-therapeutic use of drug, even once, for its desirable psychological or physiological effects. Misuse is the intentional use, for therapeutic purposes, of drug by an individual in way other than prescribed by health care provider or for whom it was not prescribed. Drug addiction is cluster of behavioral, cognitive, and physiological phenomena that may include strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. Abuse and misuse may lead to addiction. 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. Benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders (see WARNINGS: Abuse, Misuse, and Addiction).The following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo.The following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. Death is more often associated with polysubstance use (especially benzodiazepines with other CNS depressants such as opioids and alcohol).. Dependence. Physical DependenceChlordiazepoxide may produce physical dependence from continued therapy. Physical dependence is state that develops as result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or significant dose reduction of drug. Abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening. Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses) and those who have had longer durations of use (see WARNINGS: Dependence and Withdrawal Reactions). To reduce the risk of withdrawal reactions, use gradual taper to discontinue chlordiazepoxide or reduce the dosage (see DOSAGE AND ADMINISTRATION: Discontinuation or Dosage Reduction of Chlordiazepoxide and WARNINGS: Dependence and Withdrawal Reactions).Acute Withdrawal Signs and Symptoms Acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g., nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis, hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. More severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures, and suicidality.Protracted Withdrawal Syndrome Protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond to weeks after initial benzodiazepine withdrawal. Protracted withdrawal symptoms may last weeks to more than 12 months. As result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used.Tolerance Tolerance to Chlordiazepoxide may develop from continued therapy. Tolerance is physiological state characterized by reduced response to drug after repeated administration (i.e., higher dose of drug is required to produce the same effect that was once obtained at lower dose). Tolerance to the therapeutic effect of chlordiazepoxide may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.

HOW SUPPLIED SECTION.


HOW SUPPLIED. Chlordiazepoxide Hydrochloride Capsules USP, mg are available as two-piece hard gelatin capsule with an aqua green opaque cap and yellow opaque body filled with white powder, imprinted in black ink stylized barr 158, packaged in bottles of 100 (NDC 0555-0158-02) and 500 (NDC 0555-0158-04) capsules.Chlordiazepoxide Hydrochloride Capsules USP, 10 mg are available as two-piece hard gelatin capsule with black opaque cap and green opaque body filled with white powder, imprinted in white ink stylized barr 033, packaged in bottles of 100 (NDC 0555-0033-02) and 1000 (NDC 0555-0033-05) capsules.Chlordiazepoxide Hydrochloride Capsules USP, 25 mg are available as two-piece hard gelatin capsule with an aqua green opaque cap and white opaque body filled with white powder, imprinted in black ink stylized barr 159, available in bottles of 100 (NDC 0555-0159-02) and 500 (NDC 0555-0159-04) capsules.Dispense in tight, light-resistant container as defined in the USP, with child-resistant closure (as required).Store at 20 to 25C (68 to 77F) [See USP Controlled Room Temperature] in dry place.KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.Manufactured For:Teva Pharmaceuticals USA, Inc. North Wales, PA 19454Rev. 2/2021.

INDICATIONS & USAGE SECTION.


INDICATIONS AND USAGE. Chlordiazepoxide HCl capsules are indicated for the management of anxiety disorders or for the short term relief of symptoms of anxiety, withdrawal symptoms of acute alcoholism, and preoperative apprehension and anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.The effectiveness of chlordiazepoxide HCl capsules in long term use, that is, more than months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient.

INFORMATION FOR PATIENTS SECTION.


Information for Patients. Advise the patient to read the FDA-approved patient labeling (Medication Guide).

OVERDOSAGE SECTION.


OVERDOSAGE. Manifestations of chlordiazepoxide overdosage includes somnolence, confusion, coma and diminished reflexes. Respiration, pulse and blood pressure should be monitored, as in all cases of drug overdosage, although, in general, these effects have been minimal following chlordiazepoxide HCl overdosage. General supportive measures should be employed, along with immediate gastric lavage. Intravenous fluids should be administered and an adequate airway maintained. Hypotension may be combated by the use of norepinephrine or metaraminol. Dialysis is of limited value. There have been occasional reports of excitation in patients following chlordiazepoxide HCl overdosage; if this occurs barbiturates should not be used. As with the management of intentional overdosage with any drug, it should be borne in mind that multiple agents may have been ingested. Flumazenil, specific benzodiazepine-receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when an overdose with benzodiazepine is known or suspected. Prior to the administration of flumazenil, necessary measures should be instituted to secure airway, ventilation and intravenous access. Flumazenil is intended as an adjunct to, not as substitute for, proper management of benzodiazepine overdose. Patients treated with flumazenil should be monitored for re-sedation, respiratory depression and other residual benzodiazepine effects for an appropriate period after treatment. The prescriber should be aware of risk of seizure in association with flumazenil treatment, particularly in long term benzodiazepine users and in cyclic antidepressant overdose. The complete flumazenil package insert, including CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS, should be consulted prior to use.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.


Package/Label Display Panel. NDC 0555-0158-02CIVChlordiazepoxide Hydrochloride Capsules USP5 mgPHARMACIST: Dispense the accompanying Medication Guide to each patient.Rx only100 CAPSULES. 1.

PEDIATRIC USE SECTION.


Pediatric Use. Because of the varied response of pediatric patients to CNS-acting drugs, therapy should be initiated with the lowest dose and increased as required (see DOSAGE AND ADMINISTRATION). Since clinical experience with chlordiazepoxide HCl in pediatric patients under years of age is limited, use in this age group is not recommended. Hyperactive aggressive pediatric patients should be monitored for paradoxical reactions to chlordiazepoxide HCl (see PRECAUTIONS).

PRECAUTIONS SECTION.


PRECAUTIONS. In elderly and debilitated patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia or oversedation (10 mg or less per day initially, to be increased gradually as needed and tolerated). In general, the concomitant administration of chlordiazepoxide HCl and other psychotropic agents is not recommended. If such combination therapy seems indicated, careful consideration should be given to the pharmacology of the agents to be employed -- particularly when the known potentiating compounds such as MAO inhibitors and phenothiazines are to be used. The usual precautions in treating patients with impaired renal or hepatic function should be observed.Paradoxical reactions, e.g., exctextent, stimulation and acute rage, have been reported in psychiatric patients and in hyperactive aggressive pediatric patients, and should be watched for during chlordiazepoxide HCl therapy. The usual precautions are indicated when chlordiazepoxide HCl is used in the treatment of anxiety states where there is any evidence of impending depression; it should be borne in mind that suicidal tendencies may be present and protective measures may be necessary. Although clinical studies have not established cause and effect relationship, physicians should be aware that variable effects on blood coagulation have been reported very rarely in patients receiving oral anticoagulants and chlordiazepoxide HCl. In view of isolated reports associating chlordiazepoxide with exacerbation of porphyria, caution should be exercised in prescribing chlordiazepoxide to patients suffering from this disease.. Pediatric Use. Because of the varied response of pediatric patients to CNS-acting drugs, therapy should be initiated with the lowest dose and increased as required (see DOSAGE AND ADMINISTRATION). Since clinical experience with chlordiazepoxide HCl in pediatric patients under years of age is limited, use in this age group is not recommended. Hyperactive aggressive pediatric patients should be monitored for paradoxical reactions to chlordiazepoxide HCl (see PRECAUTIONS).. Information for Patients. Advise the patient to read the FDA-approved patient labeling (Medication Guide).. Risks from Concomitant Use with Opioids. Advise both patients and caregivers about the risks of potentially fatal respiratory depression and sedation when chlordiazepoxide is used with opioids and not to use such drugs concomitantly unless supervised by health care provider. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined (see WARNINGS: Risks from Concomitant Use with Opioids and PRECAUTIONS: Drug Interactions).. Abuse, Misuse, and Addiction. Inform patients that the use of chlordiazepoxide, even at recommended dosages, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose and death, especially when used in combination with other medications (e.g., opioid analgesics), alcohol, and/or illicit substances. Inform patients about the signs and symptoms of benzodiazepine abuse, misuse, and addiction; to seek medical help if they develop these signs and/or symptoms; and on the proper disposal of unused drug (see WARNINGS: Abuse, Misuse, and Addiction and DRUG ABUSE AND DEPENDENCE). Withdrawal Reactions. Inform patients that the continued use of chlordiazepoxide may lead to clinically significant physical dependence and that abrupt discontinuation or rapid dosage reduction of chlordiazepoxide may precipitate acute withdrawal reactions, which can be life-threatening. Inform patients that in some cases, patients taking benzodiazepines have developed protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months. Instruct patients that discontinuation or dosage reduction of chlordiazepoxide may require slow taper (see WARNINGS: Dependence and Withdrawal Reactions and DRUG ABUSE AND DEPENDENCE). 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.

SPL MEDGUIDE SECTION.


MEDICATION GUIDE. MEDICATION GUIDEChlordiazepoxide Hydrochloride (klor dye az pox ide hye droe klor ide) Capsules, C-IVWhat is the most important information should know about Chlordiazepoxide HClChlordiazepoxide HCl is benzodiazepine medicine. Taking benzodiazepines with opioid medicines, alcohol, or other central nervous system depressants (CNS) (including street drugs) can cause severe drowsiness, breathing problems (respiratory depression), coma and death. Get emergency help right away if any of the following happens: shallow or slowed breathingbreathing stops (which may lead to the heart stopping)excessive sleepiness (sedation)Do not drive or operate heavy machinery until you know how taking Chlordiazepoxide HCl with opioids affects you.Risk of abuse, misuse, and addiction. There is risk of abuse, misuse, and addiction with benzodiazepines, including Chlordiazepoxide HCl, which can lead to overdose and serious side effects including coma and death.Serious side effects including coma and death have happened in people who have abused or misused benzodiazepines, including Chlordiazepoxide HCl. These serious side effects may also include delirium, paranoia, suicidal thoughts or actions, seizures, and difficulty breathing. Call your healthcare provider or go to the nearest hospital emergency room right away if you get any of these serious side effects. You can develop an addiction even if you take Chlordiazepoxide HCl exactly as prescribed by your healthcare provider.Take Chlordiazepoxide HCl exactly as your healthcare provider prescribed. Do not share your Chlordiazepoxide HCl with other people.Keep Chlordiazepoxide HCl in safe place and away from children.Physical dependence and withdrawal reactions. Chlordiazepoxide HCl can cause physical dependence and withdrawal reactions, especially if you continue to take Chlordiazepoxide HCl for several days to several weeks.Do not suddenly stop taking Chlordiazepoxide HCl Stopping Chlordiazepoxide HCl suddenly can cause serious and life-threatening side effects, including unusual movements, responses, or expressions, seizures, sudden and severe mental or nervous system changes, depression, seeing or hearing things that others do not see or hear, an extreme increase in activity or talking, losing touch with reality, and suicidal thoughts or actions. Call your healthcare provider or go to the nearest hospital emergency room right away if you get any of these symptoms. Some people who suddenly stop benzodiazepines have symptoms that can last for several weeks to more than 12 months, including, anxiety, trouble remembering, learning, or concentrating, depression, problems sleeping feeling like insects are crawling under your skin, weakness, shaking, muscle twitching, burning or prickling feeling in your hands, arms, legs or feet, and ringing in your ears.Physical dependence is not the same as drug addiction. Your healthcare provider can tell you more about the differences between physical dependence and drug addiction.Do not take more Chlordiazepoxide HCl than prescribed or take Chlordiazepoxide HCl for longer than prescribed.What is Chlordiazepoxide HClChlordiazepoxide HCl is prescription medicine used:to treat anxiety disordersfor the short-term relief of the symptoms of anxietyto treat withdrawal symptoms of acute alcoholismpreoperatively to treat apprehension and anxiety Chlordiazepoxide HCl is federal controlled substance (C-IV) because it contains chlordiazepoxide that can be abused or lead to dependence. Keep Chlordiazepoxide HCl in safe place to prevent misuse and abuse. Selling or giving away Chlordiazepoxide HCl may harm others, and is against the law. Tell your healthcare provider if you have abused or been dependent on alcohol, prescription medicines or street drugs.It is not known if Chlordiazepoxide HCl is safe and effective in children under years of age.It is not known if Chlordiazepoxide HCl is safe and effective for use for longer than months.Do not take Chlordiazepoxide HCl if you are allergic to chlordiazepoxide or to any of the ingredients in Chlordiazepoxide HCl capsules. See the end of this Medication Guide for complete list of ingredients in Chlordiazepoxide HCl capsules.Before you take Chlordiazepoxide HCl, tell your healthcare provider about all of your medical conditions, including if you:have or have had depression, mood problems, or suicidal thoughts or behaviorhave history of drug or alcohol abuse or addictionhave liver or kidney problemsare pregnant or plan to become pregnant. Chlordiazepoxide HCl may harm your unborn baby. You and your healthcare provider should decide if you should take Chlordiazepoxide HCl while you are pregnant.are breastfeeding or plan to breastfeed. Chlordiazepoxide HCl may pass into your breast milk and may harm your baby. Talk to your healthcare provider about the best way to feed your baby if you take Chlordiazepoxide HCl.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.Taking Chlordiazepoxide HCl with certain other medicines can cause side effects or affect how well Chlordiazepoxide HCl or the other medicines work.Ask your healthcare provider if you are not sure if you are taking any of these medicines. Your healthcare provider can tell you if it is safe to take Chlordiazepoxide HCl with your other medicines.Do not start or stop any other medicines during treatment with Chlordiazepoxide HCl without talking to your healthcare provider first. Stopping Chlordiazepoxide HCl suddenly may cause you to have serious side effects. See, What are the possible side effects of Chlordiazepoxide HCl Know the medicines you take. Keep list of them to show to your healthcare provider and pharmacist when you get new medicine.How should take Chlordiazepoxide HClTake Chlordiazepoxide HCl exactly as your healthcare provider tells you to take it. If you take too much Chlordiazepoxide HCl, call your healthcare provider or go to the nearest hospital emergency room right away.What are the possible side effects of Chlordiazepoxide HClChlordiazepoxide HCl may cause serious side effects, including:See What is the most important information should know about Chlordiazepoxide HClChlordiazepoxide HCl can make you sleepy or dizzy and can slow your thinking and motor skills.Do not drive, operate heavy machinery, or do other dangerous activities until you know how Chlordiazepoxide HCl affects you.Do not drink alcohol or take other drugs that may make you sleepy or dizzy while taking Chlordiazepoxide HCl without first talking to your healthcare provider. When taken with alcohol or drugs that cause sleepiness or dizziness, Chlordiazepoxide HCl may make your sleepiness or dizziness much worse.The most common side effects of Chlordiazepoxide HCl include:drowsinessloss of control of body movements (ataxia)confusionThese are not all the possible side effects of chlordiazepoxide. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should store Chlordiazepoxide HClStore Chlordiazepoxide HCl at room temperature between 68F to 77F (20C to 25C).Keep Chlordiazepoxide HCl capsules in tightly closed container and out of the light.Keep Chlordiazepoxide HCl and all medicines out of the reach of children.General information about the safe and effective use of Chlordiazepoxide HCl.Medicines are sometimes prescribed for purposes other than those listed in Medication Guide. Do not use Chlordiazepoxide HCl for condition for which it was not prescribed. Do not give Chlordiazepoxide HCl to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Chlordiazepoxide HCl that is written for health professionals.What are the ingredients in Chlordiazepoxide HClActive ingredient: chlordiazepoxide hydrochlorideInactive ingredients: anhydrous lactose, D&C yellow no. 10, FD&C blue no. 1, FD&C blue no. aluminum lake, gelatin, hydrogenated vegetable oil, microcrystalline cellulose, pharmaceutical glaze, and titanium dioxide. The mg and 25 mg also contain D&C yellow no. 10 aluminum lake, FD&C blue no. aluminum lake, FD&C red no. 40 aluminum lake, propylene glycol, and synthetic black iron oxide. In addition, the mg contains D&C red no. 33 and the 10 mg also contains butyl paraben, edetate calcium disodium, dimethyl polysiloxane, ethylene glycol monoethyl ether, FD&C red no. 40, methyl paraben, propyl paraben, sodium, sodium lauryl sulfate, sodium propionate, and soya lecithin.Manufactured For:Teva Pharmaceuticals USA, Inc. North Wales, PA 19454For more information, go to www.tevagenerics.com or call 1-888-838-2872.This Medication Guide has been approved by the U.S. Food and Drug Administration Rev. 1/2021. Chlordiazepoxide HCl is benzodiazepine medicine. Taking benzodiazepines with opioid medicines, alcohol, or other central nervous system depressants (CNS) (including street drugs) can cause severe drowsiness, breathing problems (respiratory depression), coma and death. Get emergency help right away if any of the following happens: shallow or slowed breathing. breathing stops (which may lead to the heart stopping). excessive sleepiness (sedation). Risk of abuse, misuse, and addiction. There is risk of abuse, misuse, and addiction with benzodiazepines, including Chlordiazepoxide HCl, which can lead to overdose and serious side effects including coma and death.Serious side effects including coma and death have happened in people who have abused or misused benzodiazepines, including Chlordiazepoxide HCl. These serious side effects may also include delirium, paranoia, suicidal thoughts or actions, seizures, and difficulty breathing. Call your healthcare provider or go to the nearest hospital emergency room right away if you get any of these serious side effects. You can develop an addiction even if you take Chlordiazepoxide HCl exactly as prescribed by your healthcare provider.Take Chlordiazepoxide HCl exactly as your healthcare provider prescribed. Do not share your Chlordiazepoxide HCl with other people.Keep Chlordiazepoxide HCl in safe place and away from children.. Serious side effects including coma and death have happened in people who have abused or misused benzodiazepines, including Chlordiazepoxide HCl. These serious side effects may also include delirium, paranoia, suicidal thoughts or actions, seizures, and difficulty breathing. Call your healthcare provider or go to the nearest hospital emergency room right away if you get any of these serious side effects. You can develop an addiction even if you take Chlordiazepoxide HCl exactly as prescribed by your healthcare provider.. Take Chlordiazepoxide HCl exactly as your healthcare provider prescribed. Do not share your Chlordiazepoxide HCl with other people.. Keep Chlordiazepoxide HCl in safe place and away from children.. Physical dependence and withdrawal reactions. Chlordiazepoxide HCl can cause physical dependence and withdrawal reactions, especially if you continue to take Chlordiazepoxide HCl for several days to several weeks.. Do not suddenly stop taking Chlordiazepoxide HCl Stopping Chlordiazepoxide HCl suddenly can cause serious and life-threatening side effects, including unusual movements, responses, or expressions, seizures, sudden and severe mental or nervous system changes, depression, seeing or hearing things that others do not see or hear, an extreme increase in activity or talking, losing touch with reality, and suicidal thoughts or actions. Call your healthcare provider or go to the nearest hospital emergency room right away if you get any of these symptoms. Some people who suddenly stop benzodiazepines have symptoms that can last for several weeks to more than 12 months, including, anxiety, trouble remembering, learning, or concentrating, depression, problems sleeping feeling like insects are crawling under your skin, weakness, shaking, muscle twitching, burning or prickling feeling in your hands, arms, legs or feet, and ringing in your ears.. Physical dependence is not the same as drug addiction. Your healthcare provider can tell you more about the differences between physical dependence and drug addiction.. Do not take more Chlordiazepoxide HCl than prescribed or take Chlordiazepoxide HCl for longer than prescribed.. Chlordiazepoxide HCl is prescription medicine used:to treat anxiety disordersfor the short-term relief of the symptoms of anxietyto treat withdrawal symptoms of acute alcoholismpreoperatively to treat apprehension and anxiety to treat anxiety disorders. for the short-term relief of the symptoms of anxiety. to treat withdrawal symptoms of acute alcoholism. preoperatively to treat apprehension and anxiety. Chlordiazepoxide HCl is federal controlled substance (C-IV) because it contains chlordiazepoxide that can be abused or lead to dependence. Keep Chlordiazepoxide HCl in safe place to prevent misuse and abuse. Selling or giving away Chlordiazepoxide HCl may harm others, and is against the law. Tell your healthcare provider if you have abused or been dependent on alcohol, prescription medicines or street drugs.. It is not known if Chlordiazepoxide HCl is safe and effective in children under years of age.. It is not known if Chlordiazepoxide HCl is safe and effective for use for longer than months.. have or have had depression, mood problems, or suicidal thoughts or behavior. have history of drug or alcohol abuse or addiction. have liver or kidney problems. are pregnant or plan to become pregnant. Chlordiazepoxide HCl may harm your unborn baby. You and your healthcare provider should decide if you should take Chlordiazepoxide HCl while you are pregnant.. are breastfeeding or plan to breastfeed. Chlordiazepoxide HCl may pass into your breast milk and may harm your baby. Talk to your healthcare provider about the best way to feed your baby if you take Chlordiazepoxide HCl.. Take Chlordiazepoxide HCl exactly as your healthcare provider tells you to take it. If you take too much Chlordiazepoxide HCl, call your healthcare provider or go to the nearest hospital emergency room right away.. See What is the most important information should know about Chlordiazepoxide HCl. Chlordiazepoxide HCl can make you sleepy or dizzy and can slow your thinking and motor skills.. Do not drive, operate heavy machinery, or do other dangerous activities until you know how Chlordiazepoxide HCl affects you.. Do not drink alcohol or take other drugs that may make you sleepy or dizzy while taking Chlordiazepoxide HCl without first talking to your healthcare provider. When taken with alcohol or drugs that cause sleepiness or dizziness, Chlordiazepoxide HCl may make your sleepiness or dizziness much worse.. drowsiness. loss of control of body movements (ataxia). confusion. Store Chlordiazepoxide HCl at room temperature between 68F to 77F (20C to 25C).. Keep Chlordiazepoxide HCl capsules in tightly closed container and out of the light.. Keep Chlordiazepoxide HCl and all medicines out of the reach of children.

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Effects on Reproduction. Reproduction studies in rats fed 10, 20 and 80 mg/kg daily and bred through one or two matings showed no congenital anomalies, nor were there adverse effects on lactation of the dams or growth of the newborn. However, in another study at 100 mg/kg daily there was noted significant decrease in the fertilization rate and marked decrease in the viability and body weight of offspring which may be attributable to sedative activity, thus resulting in lack of interest in mating and lessened maternal nursing and care of the young. One neonate in each of the first and second matings in the rat reproduction study at the 100 mg/kg dose exhibited major skeletal defects. Further studies are in progress to determine the significance of these findings.