and chlordiazepoxide hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules.

bromide capsules is used with opioids (see precautions ). abuse, misuse, and addiction 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 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 reactions 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 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 reactions 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 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 syndrome in some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months (see drug abuse and dependence ). effects on the ability to drive or operate machinery 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. usage in pregnancy an increased risk of congenital malformations associated with the use of minor tranquilizers (chlordiazepoxide, diazepam and meprobamate) during the first trimester of pregnancy has been suggested in several studies. because use of these drugs is rarely a matter of urgency, their use during this period should almost always be avoided. the possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered. patients should be advised that if they become pregnant during therapy or intend to become pregnant they should communicate with their physicians about the desirability of discontinuing the drug. as with all anticholinergic drugs, an inhibiting effect on lactation may occur (see animal pharmacology ).

k of withdrawal reactions, use a gradual taper to discontinue chlordiazepoxide hydrochloride and clidinium bromide 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 ).

lated 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. to report suspected adverse reactions, contact ascend laboratories, llc at 1-877-asc-rx01 (877-272-7901) or fda at 1-800-fda-1088 or www.fda.gov/medwatch.

and chlordiazepoxide hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules.

approximating that of atropine sulfate against acetylcholine-induced spasms in isolated intestinal strips. on oral administration in mice, it proved an effective antisialagogue in preventing pilocarpine-induced salivation. spontaneous intestinal motility in both rats and dogs is reduced following oral dosing with 0.1 to 0.25 mg/kg. potent cholinergic ganglionic blocking effects (vagal) were produced with intravenous usage in anesthetized dogs. oral doses of 2.5 mg/kg to dogs produced signs of nasal dryness and slight pupillary dilation. in two other species, monkeys and rabbits, doses of 5 mg/kg, po, given three times daily for 5 days did not produce apparent secretory or visual changes. the oral ld 50 of single doses of clidinium bromide is 860 ± 57 mg/kg as determined in mice observed over a period of 5 days following dosage; the calculations were made according to the method of miller and tainter. effects on reproduction: reproduction studies in rats fed chlordiazepoxide hydrochloride, 10, 20 and 80 mg/kg daily, and bred through one or two matings showed no congenital anomalies, nor were there adverse effects on lactation of the dams or growth of the newborn. however, in another study at 100 mg/kg daily there was noted a significant decrease in the fertilization rate and a marked decrease in the viability and body weight of offspring which may be attributable to sedative activity, thus resulting in lack of interest in mating and lessened maternal nursing and care of the young. one neonate in each of the first and second matings in the rat reproduction study at the 100 mg/kg dose exhibited major skeletal defects. further studies are in progress to determine the significance of these findings. two series of reproduction experiments with clidinium bromide were carried out in rats, employing dosages of 2.5 and 10 mg/kg daily in each experiment. in the first experiment, clidinium bromide was administered for a 9-week interval prior to mating; no untoward effect on fertilization or gestation was noted. the offspring were taken by caesarean section and did not show a significant incidence of congenital anomalies when compared to control animals. in the second experiment, adult animals were given clidinium bromide for 10 days prior to and through two mating cycles. no significant effects were observed on fertility, gestation, viability of offspring or lactation, as compared to control animals, nor was there a significant incidence of congenital anomalies in the offspring derived from these experiments. a reproduction study of chlordiazepoxide hydrochloride and clidinium bromide capsules was carried out in rats through two successive matings. oral daily doses were administered in two concentrations: 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. 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. as with all anticholinergic drugs, an inhibiting effect on lactation may occur. 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. additional animal reproduction studies are in progress.

ients 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 is 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 ).