Chlordiazepoxide Hcl And Clidinium Bromide Prescribing Information
- 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 (seeand
WARNINGS:Risks From Concomitant Use with OpioidsConcomitant use of benzodiazepines, including chlordiazepoxide hydrochloride and clidinium bromide capsules, 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 chlordiazepoxide hydrochloride and clidinium bromide capsules 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. Advise both patients and caregivers about the risks of respiratory depression and sedation when chlordiazepoxide hydrochloride and clidinium bromide capsule is used with opioids (see
PRECAUTIONS).Abuse, Misuse, and AddictionThe use of benzodiazepines, including chlordiazepoxide hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules, 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).Before prescribing chlordiazepoxide hydrochloride and clidinium bromide capsules and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool). Use of chlordiazepoxide hydrochloride and clidinium bromide capsules, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of chlordiazepoxide hydrochloride and clidinium bromide capsules 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 ReactionsTo reduce the risk of withdrawal reactions, use a gradual taper to discontinue chlordiazepoxide hydrochloride and clidinium bromide capsules or reduce the dosage (a patient-specific plan should be used to taper the dosage) (see
DOSAGE AND ADMINISTRATION).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 hydrochloride and clidinium bromide capsules, may lead to clinically significant physical dependence. Abrupt discontinuation or rapid dosage reduction of chlordiazepoxide hydrochloride and clidinium bromide capsules 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).Protracted Withdrawal SyndromeIn 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).Effects on the Ability to Drive or Operate MachineryAs in the case of other preparations containing CNS-acting drugs, patients receiving chlordiazepoxide hydrochloride and clidinium bromide capsules should be cautioned about possible combined effects with opioids, alcohol and other CNS depressants. For the same reason, they should be cautioned against hazardous occupations requiring complete mental alertness, such as operating machinery or driving a motor vehicle.
Neonatal Sedation and Withdrawal SyndromeUse of benzodiazepines 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
). Monitor neonates exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules, which contains a benzodiazepine (chlordiazepoxide hydrochloride), during pregnancy and labor for signs of sedation and monitor neonates exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules during pregnancy for signs of withdrawal; manage these neonates accordingly.PRECAUTIONS, PregnancyandPRECAUTIONS:CNS Adverse ReactionsIn geriatric or debilitated patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia, oversedation or confusion (not more than 2 chlordiazepoxide hydrochloride and clidinium bromide capsules per day initially, to be increased gradually as needed and tolerated). In general, the concomitant administration of chlordiazepoxide hydrochloride and clidinium bromide capsules 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 the 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 to chlordiazepoxide hydrochloride, e.g., excitement, stimulation and acute rage, have been reported in psychiatric patients and should be watched for during chlordiazepoxide hydrochloride and clidinium bromide capsules therapy. The usual precautions are indicated when chlordiazepoxide hydrochloride 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.
Information for PatientsAbuse, Misuse, and AddictionInform patients that the use of chlordiazepoxide hydrochloride and clidinium bromide capsules, 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 (seeWARNINGS).Withdrawal ReactionsInform patients that the continued use of chlordiazepoxide hydrochloride and clidinium bromide capsules may lead to clinically significant physical dependence and that abrupt discontinuation or rapid dosage reduction of chlordiazepoxide hydrochloride and clidinium bromide capsules may precipitate acute withdrawal reactions, which can be life-threatening. Inform patients that in some cases, patients taking benzodiazepines have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months. Instruct patients that discontinuation or dosage reduction of chlordiazepoxide hydrochloride and clidinium bromide capsules may require a slow taper (see
WARNINGSandDRUG ABUSE AND DEPENDENCE).Concomitant Use with Opioids and Other CNS DepressantsInform patients and caregivers that potentially fatal additive effects may occur if chlordiazepoxide hydrochloride and clidinium bromide capsules are used with opioids or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a health care provider (see
WARNINGSandPRECAUTIONS, Drug Interactions).PregnancyAdvise pregnant females that use of chlordiazepoxide hydrochloride and clidinium bromide capsules 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 newborns (see
WARNINGS, Neonatal Sedation and Withdrawal Syndrome and PRECAUTIONS, Pregnancy). Instruct patients to inform their healthcare provider if they are pregnant.NursingInstruct patients to notify their healthcare provider if they are breastfeeding or intend to breastfeed (see
PRECAUTIONS, Nursing Mothers).Drug InteractionsOpioidsThe concomitant use of benzodiazepines, including chlordiazepoxide hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules, and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration.
Benzodiazepines interact at GABAAsites 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 chlordiazepoxide hydrochloride and clidinium bromide capsules and opioids, and follow patients closely for respiratory depression and sedation.
Oral AnticoagulantsAlthough clinical studies have not established a 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 hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules.
PregnancyRisk SummaryChlordiazepoxide HydrochlorideNeonates born to mothers using benzodiazepines during the later stages of pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal (see
WARNINGS, Neonatal Sedation and Withdrawal SyndromeandPRECAUTIONS,Clinical Considerations). Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects(see Data).Clidinium BromideOver decades of use, there is an absence of published data on orally administered clidinium bromide in pregnant women, including an absence of any reports of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical ConsiderationsFetal/Neonatal Adverse ReactionsBenzodiazepines cross the placenta and may produce respiratory depression, hypotonia and sedation in neonates. Monitor neonates exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules, which contains a benzodiazepine (chlordiazepoxide hydrochloride), during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules during pregnancy for signs of withdrawal. Manage these neonates accordingly (
see WARNINGS, Neonatal Sedation and Withdrawal Syndrome).DataHuman DataPublished data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. Although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted. In addition, the majority of more recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol. Tobacco and other medications, have not confirmed these findings.
Animal DataOral daily doses of 2.5 mg/kg chlordiazepoxide hydrochloride with 1.25 mg/kg clidinium bromide or 25 mg/kg chlordiazepoxide hydrochloride with 12.5 mg/kg clidinium bromide (0.6 and 6.1 times, respectively, the maximum recommended clinical dose for both drugs, based on body surface area) were administered to rats in a reproduction study through two successive matings. In the first mating, no significant differences were noted between the control or the treated groups, with the exception of a slight decrease in the number of animals surviving during lactation among those receiving the highest dosage. In the second mating, similar results were obtained except for a slight decrease in the number of pregnant females and in the percentage of offspring surviving until weaning. No congenital anomalies were observed in both matings in either the control or treated groups.
Nursing MothersChlordiazepoxide HydrochlorideThere are no data on the presence of chlordiazepoxide in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. However, there are reports of sedation, poor feeding and poor weight gain in infants exposed to other benzodiazepines through breast milk.
Reproduction studies in rats fed chlordiazepoxide hydrochloride, 10, 20 and 80 mg/kg daily (2.4, 4.8 and 19.4 times respectively, the maximum recommended clinical dose of 40 mg/day, based on body surface area), and bred through one or two matings showed no adverse effects on lactation of the dams.
Clidinium BromideThere are no data on the presence of clidinium in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. As with other anticholinergic drugs, clidinium may cause suppression of lactation.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for chlordiazepoxide hydrochloride and clidinium bromide capsules and any potential adverse effects on the breastfed infant from chlordiazepoxide hydrochloride and clidinium bromide capsules. Infants exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules through breast milk should be monitored for sedation, poor feeding and poor weight gain.
Pediatric UseSafety and effectiveness in pediatric patients have not been established.
Geriatric UseGeriatric subjects may be particularly prone to experiencing drowsiness, ataxia and confusion while receiving chlordiazepoxide hydrochloride and clidinium bromide capsules. These effects can usually be avoided with proper dosage adjustment, although they have occasionally been observed even at the lower dosage ranges. Dosing in geriatric subjects should be initiated cautiously (no more than 2 capsules per day) and increased gradually if needed and tolerated (see
DOSAGE AND ADMINISTRATION). Chlordiazepoxide hydrochloride and clidinium bromide capsules is contraindicated in the presence of glaucoma, prostatic hypertrophy and benign bladder neck obstruction (seeCONTRAINDICATIONS).,PRECAUTIONS:CNS Adverse ReactionsIn geriatric or debilitated patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia, oversedation or confusion (not more than 2 chlordiazepoxide hydrochloride and clidinium bromide capsules per day initially, to be increased gradually as needed and tolerated). In general, the concomitant administration of chlordiazepoxide hydrochloride and clidinium bromide capsules 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 the 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 to chlordiazepoxide hydrochloride, e.g., excitement, stimulation and acute rage, have been reported in psychiatric patients and should be watched for during chlordiazepoxide hydrochloride and clidinium bromide capsules therapy. The usual precautions are indicated when chlordiazepoxide hydrochloride 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.
Information for PatientsAbuse, Misuse, and AddictionInform patients that the use of chlordiazepoxide hydrochloride and clidinium bromide capsules, 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 (seeWARNINGS).Withdrawal ReactionsInform patients that the continued use of chlordiazepoxide hydrochloride and clidinium bromide capsules may lead to clinically significant physical dependence and that abrupt discontinuation or rapid dosage reduction of chlordiazepoxide hydrochloride and clidinium bromide capsules may precipitate acute withdrawal reactions, which can be life-threatening. Inform patients that in some cases, patients taking benzodiazepines have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months. Instruct patients that discontinuation or dosage reduction of chlordiazepoxide hydrochloride and clidinium bromide capsules may require a slow taper (see
WARNINGSandDRUG ABUSE AND DEPENDENCE).Concomitant Use with Opioids and Other CNS DepressantsInform patients and caregivers that potentially fatal additive effects may occur if chlordiazepoxide hydrochloride and clidinium bromide capsules are used with opioids or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a health care provider (see
WARNINGSandPRECAUTIONS, Drug Interactions).PregnancyAdvise pregnant females that use of chlordiazepoxide hydrochloride and clidinium bromide capsules 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 newborns (see
WARNINGS, Neonatal Sedation and Withdrawal Syndrome and PRECAUTIONS, Pregnancy). Instruct patients to inform their healthcare provider if they are pregnant.NursingInstruct patients to notify their healthcare provider if they are breastfeeding or intend to breastfeed (see
PRECAUTIONS, Nursing Mothers).Drug InteractionsOpioidsThe concomitant use of benzodiazepines, including chlordiazepoxide hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules, and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration.
Benzodiazepines interact at GABAAsites 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 chlordiazepoxide hydrochloride and clidinium bromide capsules and opioids, and follow patients closely for respiratory depression and sedation.
Oral AnticoagulantsAlthough clinical studies have not established a 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 hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules.
PregnancyRisk SummaryChlordiazepoxide HydrochlorideNeonates born to mothers using benzodiazepines during the later stages of pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal (see
WARNINGS, Neonatal Sedation and Withdrawal SyndromeandPRECAUTIONS,Clinical Considerations). Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects(see Data).Clidinium BromideOver decades of use, there is an absence of published data on orally administered clidinium bromide in pregnant women, including an absence of any reports of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical ConsiderationsFetal/Neonatal Adverse ReactionsBenzodiazepines cross the placenta and may produce respiratory depression, hypotonia and sedation in neonates. Monitor neonates exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules, which contains a benzodiazepine (chlordiazepoxide hydrochloride), during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules during pregnancy for signs of withdrawal. Manage these neonates accordingly (
see WARNINGS, Neonatal Sedation and Withdrawal Syndrome).DataHuman DataPublished data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. Although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted. In addition, the majority of more recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol. Tobacco and other medications, have not confirmed these findings.
Animal DataOral daily doses of 2.5 mg/kg chlordiazepoxide hydrochloride with 1.25 mg/kg clidinium bromide or 25 mg/kg chlordiazepoxide hydrochloride with 12.5 mg/kg clidinium bromide (0.6 and 6.1 times, respectively, the maximum recommended clinical dose for both drugs, based on body surface area) were administered to rats in a reproduction study through two successive matings. In the first mating, no significant differences were noted between the control or the treated groups, with the exception of a slight decrease in the number of animals surviving during lactation among those receiving the highest dosage. In the second mating, similar results were obtained except for a slight decrease in the number of pregnant females and in the percentage of offspring surviving until weaning. No congenital anomalies were observed in both matings in either the control or treated groups.
Nursing MothersChlordiazepoxide HydrochlorideThere are no data on the presence of chlordiazepoxide in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. However, there are reports of sedation, poor feeding and poor weight gain in infants exposed to other benzodiazepines through breast milk.
Reproduction studies in rats fed chlordiazepoxide hydrochloride, 10, 20 and 80 mg/kg daily (2.4, 4.8 and 19.4 times respectively, the maximum recommended clinical dose of 40 mg/day, based on body surface area), and bred through one or two matings showed no adverse effects on lactation of the dams.
Clidinium BromideThere are no data on the presence of clidinium in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. As with other anticholinergic drugs, clidinium may cause suppression of lactation.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for chlordiazepoxide hydrochloride and clidinium bromide capsules and any potential adverse effects on the breastfed infant from chlordiazepoxide hydrochloride and clidinium bromide capsules. Infants exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules through breast milk should be monitored for sedation, poor feeding and poor weight gain.
Pediatric UseSafety and effectiveness in pediatric patients have not been established.
Geriatric UseGeriatric subjects may be particularly prone to experiencing drowsiness, ataxia and confusion while receiving chlordiazepoxide hydrochloride and clidinium bromide capsules. These effects can usually be avoided with proper dosage adjustment, although they have occasionally been observed even at the lower dosage ranges. Dosing in geriatric subjects should be initiated cautiously (no more than 2 capsules per day) and increased gradually if needed and tolerated (see
DOSAGE AND ADMINISTRATION). Chlordiazepoxide hydrochloride and clidinium bromide capsules is contraindicated in the presence of glaucoma, prostatic hypertrophy and benign bladder neck obstruction (seeCONTRAINDICATIONS).).Drug InteractionsOpioidsThe concomitant use of benzodiazepines, including chlordiazepoxide hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules, and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration.
Benzodiazepines interact at GABAAsites 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 chlordiazepoxide hydrochloride and clidinium bromide capsules and opioids, and follow patients closely for respiratory depression and sedation.
Oral AnticoagulantsAlthough clinical studies have not established a 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 hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules.
PregnancyRisk SummaryChlordiazepoxide HydrochlorideNeonates born to mothers using benzodiazepines during the later stages of pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal (see
WARNINGS, Neonatal Sedation and Withdrawal SyndromeandPRECAUTIONS,Clinical Considerations). Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects(see Data).Clidinium BromideOver decades of use, there is an absence of published data on orally administered clidinium bromide in pregnant women, including an absence of any reports of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical ConsiderationsFetal/Neonatal Adverse ReactionsBenzodiazepines cross the placenta and may produce respiratory depression, hypotonia and sedation in neonates. Monitor neonates exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules, which contains a benzodiazepine (chlordiazepoxide hydrochloride), during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules during pregnancy for signs of withdrawal. Manage these neonates accordingly (
see WARNINGS, Neonatal Sedation and Withdrawal Syndrome).DataHuman DataPublished data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. Although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted. In addition, the majority of more recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol. Tobacco and other medications, have not confirmed these findings.
Animal DataOral daily doses of 2.5 mg/kg chlordiazepoxide hydrochloride with 1.25 mg/kg clidinium bromide or 25 mg/kg chlordiazepoxide hydrochloride with 12.5 mg/kg clidinium bromide (0.6 and 6.1 times, respectively, the maximum recommended clinical dose for both drugs, based on body surface area) were administered to rats in a reproduction study through two successive matings. In the first mating, no significant differences were noted between the control or the treated groups, with the exception of a slight decrease in the number of animals surviving during lactation among those receiving the highest dosage. In the second mating, similar results were obtained except for a slight decrease in the number of pregnant females and in the percentage of offspring surviving until weaning. No congenital anomalies were observed in both matings in either the control or treated groups.
Nursing MothersChlordiazepoxide HydrochlorideThere are no data on the presence of chlordiazepoxide in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. However, there are reports of sedation, poor feeding and poor weight gain in infants exposed to other benzodiazepines through breast milk.
Reproduction studies in rats fed chlordiazepoxide hydrochloride, 10, 20 and 80 mg/kg daily (2.4, 4.8 and 19.4 times respectively, the maximum recommended clinical dose of 40 mg/day, based on body surface area), and bred through one or two matings showed no adverse effects on lactation of the dams.
Clidinium BromideThere are no data on the presence of clidinium in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. As with other anticholinergic drugs, clidinium may cause suppression of lactation.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for chlordiazepoxide hydrochloride and clidinium bromide capsules and any potential adverse effects on the breastfed infant from chlordiazepoxide hydrochloride and clidinium bromide capsules. Infants exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules through breast milk should be monitored for sedation, poor feeding and poor weight gain.
- The use of benzodiazepines, including chlordiazepoxide hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide 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 and clidinium bromide capsules and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (see).
WARNINGS:Risks From Concomitant Use with OpioidsConcomitant use of benzodiazepines, including chlordiazepoxide hydrochloride and clidinium bromide capsules, 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 chlordiazepoxide hydrochloride and clidinium bromide capsules 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. Advise both patients and caregivers about the risks of respiratory depression and sedation when chlordiazepoxide hydrochloride and clidinium bromide capsule is used with opioids (see
PRECAUTIONS).Abuse, Misuse, and AddictionThe use of benzodiazepines, including chlordiazepoxide hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules, 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).Before prescribing chlordiazepoxide hydrochloride and clidinium bromide capsules and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool). Use of chlordiazepoxide hydrochloride and clidinium bromide capsules, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of chlordiazepoxide hydrochloride and clidinium bromide capsules 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 ReactionsTo reduce the risk of withdrawal reactions, use a gradual taper to discontinue chlordiazepoxide hydrochloride and clidinium bromide capsules or reduce the dosage (a patient-specific plan should be used to taper the dosage) (see
DOSAGE AND ADMINISTRATION).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 hydrochloride and clidinium bromide capsules, may lead to clinically significant physical dependence. Abrupt discontinuation or rapid dosage reduction of chlordiazepoxide hydrochloride and clidinium bromide capsules 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).Protracted Withdrawal SyndromeIn 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).Effects on the Ability to Drive or Operate MachineryAs in the case of other preparations containing CNS-acting drugs, patients receiving chlordiazepoxide hydrochloride and clidinium bromide capsules should be cautioned about possible combined effects with opioids, alcohol and other CNS depressants. For the same reason, they should be cautioned against hazardous occupations requiring complete mental alertness, such as operating machinery or driving a motor vehicle.
Neonatal Sedation and Withdrawal SyndromeUse of benzodiazepines 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
). Monitor neonates exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules, which contains a benzodiazepine (chlordiazepoxide hydrochloride), during pregnancy and labor for signs of sedation and monitor neonates exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules during pregnancy for signs of withdrawal; manage these neonates accordingly.PRECAUTIONS, Pregnancy - The continued use of benzodiazepines, including chlordiazepoxide hydrochloride and clidinium bromide 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 and clidinium bromide capsules 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 chlordiazepoxide hydrochloride and clidinium bromide capsules or reduce the dosage (seeand
WARNINGS:Risks From Concomitant Use with OpioidsConcomitant use of benzodiazepines, including chlordiazepoxide hydrochloride and clidinium bromide capsules, 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 chlordiazepoxide hydrochloride and clidinium bromide capsules 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. Advise both patients and caregivers about the risks of respiratory depression and sedation when chlordiazepoxide hydrochloride and clidinium bromide capsule is used with opioids (see
PRECAUTIONS).Abuse, Misuse, and AddictionThe use of benzodiazepines, including chlordiazepoxide hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules, 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).Before prescribing chlordiazepoxide hydrochloride and clidinium bromide capsules and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool). Use of chlordiazepoxide hydrochloride and clidinium bromide capsules, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of chlordiazepoxide hydrochloride and clidinium bromide capsules 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 ReactionsTo reduce the risk of withdrawal reactions, use a gradual taper to discontinue chlordiazepoxide hydrochloride and clidinium bromide capsules or reduce the dosage (a patient-specific plan should be used to taper the dosage) (see
DOSAGE AND ADMINISTRATION).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 hydrochloride and clidinium bromide capsules, may lead to clinically significant physical dependence. Abrupt discontinuation or rapid dosage reduction of chlordiazepoxide hydrochloride and clidinium bromide capsules 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).Protracted Withdrawal SyndromeIn 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).Effects on the Ability to Drive or Operate MachineryAs in the case of other preparations containing CNS-acting drugs, patients receiving chlordiazepoxide hydrochloride and clidinium bromide capsules should be cautioned about possible combined effects with opioids, alcohol and other CNS depressants. For the same reason, they should be cautioned against hazardous occupations requiring complete mental alertness, such as operating machinery or driving a motor vehicle.
Neonatal Sedation and Withdrawal SyndromeUse of benzodiazepines 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
). Monitor neonates exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules, which contains a benzodiazepine (chlordiazepoxide hydrochloride), during pregnancy and labor for signs of sedation and monitor neonates exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules during pregnancy for signs of withdrawal; manage these neonates accordingly.PRECAUTIONS, Pregnancy).DOSAGE AND ADMINISTRATION:Recommended DosageBecause of the varied individual responses to tranquilizers and anticholinergics, the optimum dosage of chlordiazepoxide hydrochloride and clidinium bromide capsules varies with the diagnosis and response of the individual patient. The dosage, therefore, should be individualized for maximum beneficial effects. The usual maintenance dose is 1 or 2 capsules, 3 or 4 times a day administered before meals and at bedtime.
Recommended Geriatric DosageDosage should be limited to the smallest effective amount to preclude the development of ataxia, oversedation or confusion. The initial dose should not exceed 2 chlordiazepoxide hydrochloride and clidinium bromide capsules per day, to be increased gradually as needed and tolerated. Elderly patients have an increased risk of dose-related adverse reactions (see
PRECAUTIONS).Discontinuationor Dosage Reduction ofChlordiazepoxide Hydrochloride and Clidinium Bromide CapsulesTo reduce the risk of withdrawal reactions, use a gradual taper to discontinue chlordiazepoxide hydrochloride and clidinium bromide capsules 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
WARNINGSandDRUG ABUSE AND DEPENDENCE).
Chlordiazepoxide hydrochloride and clidinium bromide capsule is indicated to control emotional and somatic factors in gastrointestinal disorders. Chlordiazepoxide hydrochloride and clidinium bromide capsules may also be used as adjunctive therapy in the treatment of peptic ulcer and in the treatment of the irritable bowel syndrome (irritable colon, spastic colon, mucous colitis) and acute enterocolitis.
Because of the varied individual responses to tranquilizers and anticholinergics, the optimum dosage of chlordiazepoxide hydrochloride and clidinium bromide capsules varies with the diagnosis and response of the individual patient. The dosage, therefore, should be individualized for maximum beneficial effects. The usual maintenance dose is 1 or 2 capsules, 3 or 4 times a day administered before meals and at bedtime.
Dosage should be limited to the smallest effective amount to preclude the development of ataxia, oversedation or confusion. The initial dose should not exceed 2 chlordiazepoxide hydrochloride and clidinium bromide capsules per day, to be increased gradually as needed and tolerated. Elderly patients have an increased risk of dose-related adverse reactions (see
In geriatric or debilitated patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia, oversedation or confusion (not more than 2 chlordiazepoxide hydrochloride and clidinium bromide capsules per day initially, to be increased gradually as needed and tolerated). In general, the concomitant administration of chlordiazepoxide hydrochloride and clidinium bromide capsules 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 the 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 to chlordiazepoxide hydrochloride, e.g., excitement, stimulation and acute rage, have been reported in psychiatric patients and should be watched for during chlordiazepoxide hydrochloride and clidinium bromide capsules therapy. The usual precautions are indicated when chlordiazepoxide hydrochloride 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.
Inform patients that the use of chlordiazepoxide hydrochloride and clidinium bromide capsules, 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 that the continued use of chlordiazepoxide hydrochloride and clidinium bromide capsules may lead to clinically significant physical dependence and that abrupt discontinuation or rapid dosage reduction of chlordiazepoxide hydrochloride and clidinium bromide capsules may precipitate acute withdrawal reactions, which can be life-threatening. Inform patients that in some cases, patients taking benzodiazepines have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months. Instruct patients that discontinuation or dosage reduction of chlordiazepoxide hydrochloride and clidinium bromide capsules may require a slow taper (see
Inform patients and caregivers that potentially fatal additive effects may occur if chlordiazepoxide hydrochloride and clidinium bromide capsules are used with opioids or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a health care provider (see
Advise pregnant females that use of chlordiazepoxide hydrochloride and clidinium bromide capsules 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 newborns (see
Instruct patients to notify their healthcare provider if they are breastfeeding or intend to breastfeed (see
The concomitant use of benzodiazepines, including chlordiazepoxide hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules, and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration.
Benzodiazepines interact at GABAAsites 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 chlordiazepoxide hydrochloride and clidinium bromide capsules and opioids, and follow patients closely for respiratory depression and sedation.
Although clinical studies have not established a 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 hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules.
Neonates born to mothers using benzodiazepines during the later stages of pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal (see
Over decades of use, there is an absence of published data on orally administered clidinium bromide in pregnant women, including an absence of any reports of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia and sedation in neonates. Monitor neonates exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules, which contains a benzodiazepine (chlordiazepoxide hydrochloride), during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules during pregnancy for signs of withdrawal. Manage these neonates accordingly (
Published data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. Although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted. In addition, the majority of more recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol. Tobacco and other medications, have not confirmed these findings.
Oral daily doses of 2.5 mg/kg chlordiazepoxide hydrochloride with 1.25 mg/kg clidinium bromide or 25 mg/kg chlordiazepoxide hydrochloride with 12.5 mg/kg clidinium bromide (0.6 and 6.1 times, respectively, the maximum recommended clinical dose for both drugs, based on body surface area) were administered to rats in a reproduction study through two successive matings. In the first mating, no significant differences were noted between the control or the treated groups, with the exception of a slight decrease in the number of animals surviving during lactation among those receiving the highest dosage. In the second mating, similar results were obtained except for a slight decrease in the number of pregnant females and in the percentage of offspring surviving until weaning. No congenital anomalies were observed in both matings in either the control or treated groups.
There are no data on the presence of chlordiazepoxide in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. However, there are reports of sedation, poor feeding and poor weight gain in infants exposed to other benzodiazepines through breast milk.
Reproduction studies in rats fed chlordiazepoxide hydrochloride, 10, 20 and 80 mg/kg daily (2.4, 4.8 and 19.4 times respectively, the maximum recommended clinical dose of 40 mg/day, based on body surface area), and bred through one or two matings showed no adverse effects on lactation of the dams.
There are no data on the presence of clidinium in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. As with other anticholinergic drugs, clidinium may cause suppression of lactation.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for chlordiazepoxide hydrochloride and clidinium bromide capsules and any potential adverse effects on the breastfed infant from chlordiazepoxide hydrochloride and clidinium bromide capsules. Infants exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules through breast milk should be monitored for sedation, poor feeding and poor weight gain.
Safety and effectiveness in pediatric patients have not been established.
Geriatric subjects may be particularly prone to experiencing drowsiness, ataxia and confusion while receiving chlordiazepoxide hydrochloride and clidinium bromide capsules. These effects can usually be avoided with proper dosage adjustment, although they have occasionally been observed even at the lower dosage ranges. Dosing in geriatric subjects should be initiated cautiously (no more than 2 capsules per day) and increased gradually if needed and tolerated (see
To reduce the risk of withdrawal reactions, use a gradual taper to discontinue chlordiazepoxide hydrochloride and clidinium bromide capsules 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
Concomitant use of benzodiazepines, including chlordiazepoxide hydrochloride and clidinium bromide capsules, 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 chlordiazepoxide hydrochloride and clidinium bromide capsules 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. Advise both patients and caregivers about the risks of respiratory depression and sedation when chlordiazepoxide hydrochloride and clidinium bromide capsule is used with opioids (see
The use of benzodiazepines, including chlordiazepoxide hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules, 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
Before prescribing chlordiazepoxide hydrochloride and clidinium bromide capsules and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool). Use of chlordiazepoxide hydrochloride and clidinium bromide capsules, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of chlordiazepoxide hydrochloride and clidinium bromide capsules 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.
To reduce the risk of withdrawal reactions, use a gradual taper to discontinue chlordiazepoxide hydrochloride and clidinium bromide capsules or reduce the dosage (a patient-specific plan should be used to taper the dosage) (see
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.
The continued use of benzodiazepines, including chlordiazepoxide hydrochloride and clidinium bromide capsules, may lead to clinically significant physical dependence. Abrupt discontinuation or rapid dosage reduction of chlordiazepoxide hydrochloride and clidinium bromide capsules after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures) (see
In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months (see
As in the case of other preparations containing CNS-acting drugs, patients receiving chlordiazepoxide hydrochloride and clidinium bromide capsules should be cautioned about possible combined effects with opioids, alcohol and other CNS depressants. For the same reason, they should be cautioned against hazardous occupations requiring complete mental alertness, such as operating machinery or driving a motor vehicle.
Use of benzodiazepines 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
Chlordiazepoxide hydrochloride and clidinium bromide capsule contains chlordiazepoxide hydrochloride, a Schedule IV controlled substance and clidinium bromide, which is not a controlled substance. Chlordiazepoxide hydrochloride and clidinium bromide capsule is exempted from Schedule IV and is not controlled under the Controlled Substances Act.
Chlordiazepoxide hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules, is a CNS depressant with a potential for abuse and addiction. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a 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 of benzodiazepines 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
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).
Chlordiazepoxide hydrochloride and clidinium bromide capsules may produce physical dependence from continued therapy. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, a 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
To reduce the risk of withdrawal reactions, use a gradual taper to discontinue chlordiazepoxide hydrochloride and clidinium bromide capsules or reduce the dosage (see
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 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 4 to 6 weeks after initial benzodiazepine withdrawal. Protracted withdrawal symptoms may last weeks to more than 12 months. As a 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 to chlordiazepoxide hydrochloride and clidinium bromide capsules may develop from continued therapy. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). Tolerance to the therapeutic effects of chlordiazepoxide hydrochloride and clidinium bromide capsules may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.
Chlordiazepoxide hydrochloride and clidinium bromide capsule is contraindicated in the presence of glaucoma (since the anticholinergic component may produce some degree of mydriasis) and in patients with prostatic hypertrophy and benign bladder neck obstruction. It is contraindicated in patients with known hypersensitivity to chlordiazepoxide hydrochloride and/or clidinium bromide.
No side effects or manifestations not seen with either compound alone have been reported with the administration of chlordiazepoxide hydrochloride and clidinium bromide capsules. However, since chlordiazepoxide hydrochloride and clidinium bromide capsules contains chlordiazepoxide hydrochloride and clidinium bromide, the possibility of untoward effects which may be seen with either of these two compounds cannot be excluded.
When chlordiazepoxide hydrochloride has been used alone 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 a few instances syncope has been reported.
Other adverse reactions reported during therapy with chlordiazepoxide hydrochloride 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 hydrochloride treatment.
Blood dyscrasias, including agranulocytosis, jaundice and hepatic dysfunction have occasionally been reported during therapy with chlordiazepoxide hydrochloride. When chlordiazepoxide hydrochloride treatment is protracted, periodic blood counts and liver function tests are advisable.
Adverse effects reported with use of chlordiazepoxide hydrochloride and clidinium bromide capsules are those typical of anticholinergic agents, i.e., dryness of the mouth, blurring of vision, urinary hesitancy and constipation. Constipation has occurred most often when chlordiazepoxide hydrochloride and clidinium bromide capsules therapy has been combined with other spasmolytic agents and/or a low residue diet.
The concomitant use of benzodiazepines, including chlordiazepoxide hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules, and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration.
Benzodiazepines interact at GABA
A 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 chlordiazepoxide hydrochloride and clidinium bromide capsules and opioids, and follow patients closely for respiratory depression and sedation.
Although clinical studies have not established a 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 hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules.
Neonates born to mothers using benzodiazepines during the later stages of pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal (see
Concomitant use of benzodiazepines, including chlordiazepoxide hydrochloride and clidinium bromide capsules, 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 chlordiazepoxide hydrochloride and clidinium bromide capsules 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. Advise both patients and caregivers about the risks of respiratory depression and sedation when chlordiazepoxide hydrochloride and clidinium bromide capsule is used with opioids (see
The use of benzodiazepines, including chlordiazepoxide hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules, 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
Before prescribing chlordiazepoxide hydrochloride and clidinium bromide capsules and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool). Use of chlordiazepoxide hydrochloride and clidinium bromide capsules, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of chlordiazepoxide hydrochloride and clidinium bromide capsules 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.
To reduce the risk of withdrawal reactions, use a gradual taper to discontinue chlordiazepoxide hydrochloride and clidinium bromide capsules or reduce the dosage (a patient-specific plan should be used to taper the dosage) (see
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.
The continued use of benzodiazepines, including chlordiazepoxide hydrochloride and clidinium bromide capsules, may lead to clinically significant physical dependence. Abrupt discontinuation or rapid dosage reduction of chlordiazepoxide hydrochloride and clidinium bromide capsules after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures) (see
In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months (see
As in the case of other preparations containing CNS-acting drugs, patients receiving chlordiazepoxide hydrochloride and clidinium bromide capsules should be cautioned about possible combined effects with opioids, alcohol and other CNS depressants. For the same reason, they should be cautioned against hazardous occupations requiring complete mental alertness, such as operating machinery or driving a motor vehicle.
Use of benzodiazepines 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
In geriatric or debilitated patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia, oversedation or confusion (not more than 2 chlordiazepoxide hydrochloride and clidinium bromide capsules per day initially, to be increased gradually as needed and tolerated). In general, the concomitant administration of chlordiazepoxide hydrochloride and clidinium bromide capsules 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 the 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 to chlordiazepoxide hydrochloride, e.g., excitement, stimulation and acute rage, have been reported in psychiatric patients and should be watched for during chlordiazepoxide hydrochloride and clidinium bromide capsules therapy. The usual precautions are indicated when chlordiazepoxide hydrochloride 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.
Inform patients that the use of chlordiazepoxide hydrochloride and clidinium bromide capsules, 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 that the continued use of chlordiazepoxide hydrochloride and clidinium bromide capsules may lead to clinically significant physical dependence and that abrupt discontinuation or rapid dosage reduction of chlordiazepoxide hydrochloride and clidinium bromide capsules may precipitate acute withdrawal reactions, which can be life-threatening. Inform patients that in some cases, patients taking benzodiazepines have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months. Instruct patients that discontinuation or dosage reduction of chlordiazepoxide hydrochloride and clidinium bromide capsules may require a slow taper (see
Inform patients and caregivers that potentially fatal additive effects may occur if chlordiazepoxide hydrochloride and clidinium bromide capsules are used with opioids or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a health care provider (see
Advise pregnant females that use of chlordiazepoxide hydrochloride and clidinium bromide capsules 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 newborns (see
Instruct patients to notify their healthcare provider if they are breastfeeding or intend to breastfeed (see
The concomitant use of benzodiazepines, including chlordiazepoxide hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules, and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration.
Benzodiazepines interact at GABAAsites 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 chlordiazepoxide hydrochloride and clidinium bromide capsules and opioids, and follow patients closely for respiratory depression and sedation.
Although clinical studies have not established a 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 hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules.
Neonates born to mothers using benzodiazepines during the later stages of pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal (see
Over decades of use, there is an absence of published data on orally administered clidinium bromide in pregnant women, including an absence of any reports of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia and sedation in neonates. Monitor neonates exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules, which contains a benzodiazepine (chlordiazepoxide hydrochloride), during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules during pregnancy for signs of withdrawal. Manage these neonates accordingly (
Published data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. Although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted. In addition, the majority of more recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol. Tobacco and other medications, have not confirmed these findings.
Oral daily doses of 2.5 mg/kg chlordiazepoxide hydrochloride with 1.25 mg/kg clidinium bromide or 25 mg/kg chlordiazepoxide hydrochloride with 12.5 mg/kg clidinium bromide (0.6 and 6.1 times, respectively, the maximum recommended clinical dose for both drugs, based on body surface area) were administered to rats in a reproduction study through two successive matings. In the first mating, no significant differences were noted between the control or the treated groups, with the exception of a slight decrease in the number of animals surviving during lactation among those receiving the highest dosage. In the second mating, similar results were obtained except for a slight decrease in the number of pregnant females and in the percentage of offspring surviving until weaning. No congenital anomalies were observed in both matings in either the control or treated groups.
There are no data on the presence of chlordiazepoxide in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. However, there are reports of sedation, poor feeding and poor weight gain in infants exposed to other benzodiazepines through breast milk.
Reproduction studies in rats fed chlordiazepoxide hydrochloride, 10, 20 and 80 mg/kg daily (2.4, 4.8 and 19.4 times respectively, the maximum recommended clinical dose of 40 mg/day, based on body surface area), and bred through one or two matings showed no adverse effects on lactation of the dams.
There are no data on the presence of clidinium in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. As with other anticholinergic drugs, clidinium may cause suppression of lactation.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for chlordiazepoxide hydrochloride and clidinium bromide capsules and any potential adverse effects on the breastfed infant from chlordiazepoxide hydrochloride and clidinium bromide capsules. Infants exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules through breast milk should be monitored for sedation, poor feeding and poor weight gain.
Safety and effectiveness in pediatric patients have not been established.
Geriatric subjects may be particularly prone to experiencing drowsiness, ataxia and confusion while receiving chlordiazepoxide hydrochloride and clidinium bromide capsules. These effects can usually be avoided with proper dosage adjustment, although they have occasionally been observed even at the lower dosage ranges. Dosing in geriatric subjects should be initiated cautiously (no more than 2 capsules per day) and increased gradually if needed and tolerated (see
Over decades of use, there is an absence of published data on orally administered clidinium bromide in pregnant women, including an absence of any reports of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia and sedation in neonates. Monitor neonates exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules, which contains a benzodiazepine (chlordiazepoxide hydrochloride), during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules during pregnancy for signs of withdrawal. Manage these neonates accordingly (
Concomitant use of benzodiazepines, including chlordiazepoxide hydrochloride and clidinium bromide capsules, 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 chlordiazepoxide hydrochloride and clidinium bromide capsules 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. Advise both patients and caregivers about the risks of respiratory depression and sedation when chlordiazepoxide hydrochloride and clidinium bromide capsule is used with opioids (see
The use of benzodiazepines, including chlordiazepoxide hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules, 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
Before prescribing chlordiazepoxide hydrochloride and clidinium bromide capsules and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool). Use of chlordiazepoxide hydrochloride and clidinium bromide capsules, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of chlordiazepoxide hydrochloride and clidinium bromide capsules 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.
To reduce the risk of withdrawal reactions, use a gradual taper to discontinue chlordiazepoxide hydrochloride and clidinium bromide capsules or reduce the dosage (a patient-specific plan should be used to taper the dosage) (see
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.
The continued use of benzodiazepines, including chlordiazepoxide hydrochloride and clidinium bromide capsules, may lead to clinically significant physical dependence. Abrupt discontinuation or rapid dosage reduction of chlordiazepoxide hydrochloride and clidinium bromide capsules after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures) (see
In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months (see
As in the case of other preparations containing CNS-acting drugs, patients receiving chlordiazepoxide hydrochloride and clidinium bromide capsules should be cautioned about possible combined effects with opioids, alcohol and other CNS depressants. For the same reason, they should be cautioned against hazardous occupations requiring complete mental alertness, such as operating machinery or driving a motor vehicle.
Use of benzodiazepines 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
Published data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. Although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted. In addition, the majority of more recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol. Tobacco and other medications, have not confirmed these findings.
Oral daily doses of 2.5 mg/kg chlordiazepoxide hydrochloride with 1.25 mg/kg clidinium bromide or 25 mg/kg chlordiazepoxide hydrochloride with 12.5 mg/kg clidinium bromide (0.6 and 6.1 times, respectively, the maximum recommended clinical dose for both drugs, based on body surface area) were administered to rats in a reproduction study through two successive matings. In the first mating, no significant differences were noted between the control or the treated groups, with the exception of a slight decrease in the number of animals surviving during lactation among those receiving the highest dosage. In the second mating, similar results were obtained except for a slight decrease in the number of pregnant females and in the percentage of offspring surviving until weaning. No congenital anomalies were observed in both matings in either the control or treated groups.
There are no data on the presence of chlordiazepoxide in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. However, there are reports of sedation, poor feeding and poor weight gain in infants exposed to other benzodiazepines through breast milk.
Reproduction studies in rats fed chlordiazepoxide hydrochloride, 10, 20 and 80 mg/kg daily (2.4, 4.8 and 19.4 times respectively, the maximum recommended clinical dose of 40 mg/day, based on body surface area), and bred through one or two matings showed no adverse effects on lactation of the dams.
There are no data on the presence of clidinium in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. As with other anticholinergic drugs, clidinium may cause suppression of lactation.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for chlordiazepoxide hydrochloride and clidinium bromide capsules and any potential adverse effects on the breastfed infant from chlordiazepoxide hydrochloride and clidinium bromide capsules. Infants exposed to chlordiazepoxide hydrochloride and clidinium bromide capsules through breast milk should be monitored for sedation, poor feeding and poor weight gain.