DailyMed Label: CHLORDIAZEPOXIDE HCL AND CLIDINIUM BROMIDE

DailyMed Label: CHLORDIAZEPOXIDE HCL AND CLIDINIUM BROMIDE

2023

DailyMed Prescription

CHLORDIAZEPOXIDE HCL AND CLIDINIUM BROMIDE

CHLORDIAZEPOXIDE HCL AND CLIDINIUM BROMIDE

Micro Labs Limited

NDC: 42571-381

NDC: 42571-381

NDC: 42571-381

NDC: 42571-381

NDC: 42571-381

NDC: 42571-381

Chlordiazepoxide hydrochloride and clidinium bromide capsules, USP is a fixed-combination of chlordiazepoxide hydrochloride, a benzodiazepine, and clidinium bromide, an anticholinergic. Each chlordiazepoxide hydrochloride and clidinium bromide capsules USP, 5 mg/2.5 mg contains the active ingredients 5 mg chlordiazepoxide hydrochloride and 2.5 mg clidinium bromide. Each capsule also contains the inactive ingredients lactose monohydrate, magnesium stearate,  pregelatinised starch, talc, D&C Yellow No. 10, FD&C Blue No. 1, gelatin, and titanium dioxide. The imprinting ink contains black iron oxide, potassium hydroxide, and shellac. Chlordiazepoxide hydrochloride is 7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine 4-oxide hydrochloride. A colorless, crystalline substance, it is soluble in water. It is unstable in solution and the powder must be protected from light. The molecular weight is 336.22. The structural formula of chlordiazepoxide hydrochloride is as follows:   Clidinium bromide is a synthetic anticholinergic agent which has been shown in experimental and clinical studies to have antispasmodic and antisecretory effects on the gastrointestinal tract. Structurally clidinium bromide is: The drug product meets USP Dissolution Test 2. chlrodiazepoxideandclidinium-structure.jpg chlrodiazepoxideandclidinium-structure1.jpg

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.

Recommended Dosage   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.   Recommended Geriatric Dosage   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 PRECAUTIONS ). Discontinuation or Dosage Reduction of Chlordiazepoxide Hydrochloride and Clidinium Bromide Capsules    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 WARNINGS   and DRUG ABUSE AND DEPENDENCE ).

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.

CNS Adverse Reactions   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. Abuse, Misuse, and Addiction 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 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 ) . Withdrawal Reactions 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 WARNINGS   and DRUG ABUSE AND DEPENDENCE ) . Concomitant Use with Opioids and Other CNS Depressants  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 WARNINGS   and   PRECAUTIONS , Drug Interactions ). Pregnancy 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 WARNINGS , Neonatal Sedation and Withdrawal Syndrome and PRECAUTIONS , Pregnancy ). Instruct patients to inform their healthcare provider if they are pregnant. Nursing Instruct patients to notify their healthcare provider if they are breastfeeding or intend to breastfeed (see PRECAUTIONS , Nursing Mothers ). Opioids 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. Oral Anticoagulants  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. Pregnancy   Risk Summary Chlordiazepoxide Hydrochloride 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 WARNINGS , Neonatal Sedation and Withdrawal Syndrome and PRECAUTIONS ,   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 Bromide 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. Clinical Considerations Fetal/Neonatal Adverse Reactions 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 ( see WARNINGS , Neonatal Sedation and Withdrawal Syndrome ). Data Human Data 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. Animal Data 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. Nursing Mothers   Chlordiazepoxide Hydrochloride 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. Clidinium Bromide 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 DOSAGE AND ADMINISTRATION ). Chlordiazepoxide hydrochloride and clidinium bromide capsules is contraindicated in the presence of glaucoma, prostatic hypertrophy and benign bladder neck obstruction (see CONTRAINDICATIONS ).

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.

Opioids 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. Oral Anticoagulants  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. Pregnancy   Risk Summary Chlordiazepoxide Hydrochloride 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 WARNINGS , Neonatal Sedation and Withdrawal Syndrome and PRECAUTIONS ,   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 Bromide 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. Clinical Considerations Fetal/Neonatal Adverse Reactions 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 ( see WARNINGS , Neonatal Sedation and Withdrawal Syndrome ). Data Human Data 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. Animal Data 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. Nursing Mothers   Chlordiazepoxide Hydrochloride 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. Clidinium Bromide 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.

Chlordiazepoxide hydrochloride and clidinium bromide capsules, USP is available in green opaque cap, green opaque body, each containing 5 mg chlordiazepoxide hydrochloride and 2.5 mg clidinium bromide, size "4" hard gelatin capsules imprinted with "ML" on cap and "5/2.5" on body with black ink, filled with white to off-white powder. Bottles of 100                                   NDC 42571-381-01 Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Keep out of reach of children.   Dispense in tight, light-resistant container as defined in USP/NF. Manufactured by: Micro Labs Limited Goa-403 722, INDIA. Manufactured for: Micro Labs USA, Inc.                  Somerset, NJ 08873 Rev. 04/2023

NDC 42571-381-01 Rx Only Chlordiazepoxide HCl and Clindinium Bromide Capsules, USP 5 mg/2.5 mg 100 Capsules Micro Labs Limited chlrodiazepoxideandclidinium-label.jpg