NDC 0276-0500 Not Applicable

Chlordiazepoxide Hydrochloride And Clidinium Bromide Capsules

NDC Product Code 0276-0500

NDC 0276-0500-10

Package Description: 100 CAPSULE in 1 BOTTLE

NDC Product Information

Not Applicable with NDC 0276-0500 is a a human prescription drug product labeled by Misemer Pharmaceuticals, Inc. The generic name of Not Applicable is chlordiazepoxide hydrochloride and clidinium bromide capsules. The product's dosage form is capsule and is administered via oral form.

Labeler Name: Misemer Pharmaceuticals, Inc

Dosage Form: Capsule - A solid oral dosage form consisting of a shell and a filling. The shell is composed of a single sealed enclosure, or two halves that fit together and which are sometimes sealed with a band. Capsule shells may be made from gelatin, starch, or cellulose, or other suitable materials, may be soft or hard, and are filled with solid or liquid ingredients that can be poured or squeezed.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

DEA Schedule: Schedule IV (CIV) Substances What is the Drug Enforcement Administration (DEA) CIV Schedule?
The controlled substances in the CIV schedule have an abuse potential and dependence liability less than those listed in CIII and have an accepted medical use in the United States.

Not Applicable Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • CHLORDIAZEPOXIDE 5 mg/1
  • CLIDINIUM BROMIDE 2.5 1/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • STARCH, PREGELATINIZED CORN (UNII: O8232NY3SJ)
  • TALC (UNII: 7SEV7J4R1U)
  • LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)
  • GELATIN (UNII: 2G86QN327L)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.
  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Benzodiazepine - [EPC] (Established Pharmacologic Class)
  • Benzodiazepines - [CS]
  • Anticholinergic - [EPC] (Established Pharmacologic Class)
  • Decreased Parasympathetic Acetylcholine Activity - [PE] (Physiologic Effect)
  • GI Motility Alteration - [PE] (Physiologic Effect)
  • Digestive/GI System Activity Alteration - [PE] (Physiologic Effect)
  • Cholinergic Antagonists - [MoA] (Mechanism of Action)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Misemer Pharmaceuticals, Inc
Labeler Code: 0276
FDA Application Number: ANDA210579 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 09-03-2020 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Not Applicable Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Description

Chlordiazepoxide Hydrochloride and Clidinium Bromide combines in a single capsule formulation the antianxiety action of chlordiazepoxide hydrochloride and the anticholinergic/spasmolytic effects of clidinium bromide.Each Chlordiazepoxide Hydrochloride and Clidinium Bromide capsule contains the active ingredients 5 mg chlordiazepoxide hydrochloride and 2.5 mg clidinium bromide.Each capsule also contains the inactive ingredients lactose monohydrate, pregelatinized starch, talc. Gelatin capsule shells may contain titanium dioxide with the following dye systems: D&C Yellow #10, FD&C Green #3 and gelatin.Chlordiazepoxide hydrochloride is a versatile, therapeutic agent of proven value for the relief of anxiety and tension. It is indicated when anxiety, tension or apprehension are significant components of the clinical profile. It is among the safer of the effective psychopharmacologic compounds.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 a pronounced antispasmodic and antisecretory effect on the gastrointestinal tract. Structurally clidinium bromide is:

Animal Pharmacology

Chlordiazepoxide hydrochloride has been studied extensively in many species of animals and these studies are suggestive of action on the limbic system of the brain, which recent evidence indicates is involved in emotional responses.Hostile monkeys were made tame by oral drug doses, which did not cause sedation. Chlordiazepoxide hydrochloride revealed a taming-action with the elimination of fear and aggression. The taming effect of chlordiazepoxide hydrochloride was further demonstrated in rats made vicious by lesions in the septal area of the brain. The drug dosage which effectively blocked the vicious reaction was well below the dose which caused sedation in these animals.The oral LD50 of single doses of chlordiazepoxide hydrochloride, calculated according to the method of Miller and Tainter, is 720 ± 51 mg/kg as determined in mice observed over a period of 5 days following dosage.Clidinium bromide is an effective anticholinergic agent with activity 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 LD50 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 was carried out in rats through two successive mating. 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.

Indications And Usage

Chlordiazepoxide Hydrochloride and Clidinium Bromide is indicated to control emotional and somatic factors in gastrointestinal disorders. Chlordiazepoxide Hydrochloride and Clidinium Bromide 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.

Contraindications

Chlordiazepoxide Hydrochloride and Clidinium Bromide 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.

Warnings

Concomitant use of benzodiazepines, including Chlordiazepoxide Hydrochloride and Clidinium Bromide, and opioids may result in profound sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. If a decision is made to prescribe Chlordiazepoxide Hydrochloride and Clidinium Bromide 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 is used with opioids (see PRECAUTIONS).As in the case of other preparations containing CNS-acting drugs, patients receiving chlordiazepoxide hydrochloride and clidinium bromide should be cautioned about possible combined effects with 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, 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).

Overdosage

Manifestations of chlordiazepoxide hydrochloride overdosage include somnolence, confusion, coma and diminished reflexes. Respiration, pulse and blood pressure should be monitored, as in all cases of drug overdosage, although, in general, these effects have been minimal following chlordiazepoxide hydrochloride overdosage.While the signs and symptoms of Chlordiazepoxide Hydrochloride and Clidinium Bromide overdosage may be produced by either of its components, usually such symptoms will be overshadowed by the anticholinergic actions of clidinium bromide. The symptoms of overdosage of clidinium bromide are excessive dryness of mouth, blurring of vision, urinary hesitancy and constipation.General supportive measures should be employed, along with immediate gastric lavage. Administer physostigmine 0.5 to 2 mg at a rate of no more than 1 mg per minute. This may be repeated in 1 to 4 mg doses if arrhythmias, convulsions or deep coma recur. Intravenous fluids should be administered and an adequate airway maintained. Hypotension may be combated by the use of levarterenol or metaraminol. Methylphenidate or caffeine and sodium benzoate may be given to combat CNS-depressive effects. Dialysis is of limited value. Should excitation occur, barbiturates should not be used. As with the management of intentional overdosage with any drug, it should be borne in mind that multiple agents may have been ingested.Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines (see DRUG ABUSE AND DEPENDENCE).

Precautions

In 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 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 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. 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.

Information For Patients

Inform patients and caregivers that potentially fatal additive effects may occur if Chlordiazepoxide Hydrochloride and Clidinium Bromide 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).To assure the safe and effective use of benzodiazepines, patients should be informed that, since benzodiazepines may produce psychological and physical dependence, it is advisable that they consult with their physician before either increasing the dose or abruptly discontinuing this drug.Drug InteractionsThe concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABAA sites and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and follow patients closely for respiratory depression and sedation

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Geriatric subjects may be particularly prone to experiencing drowsiness, ataxia and confusion while receiving Chlordiazepoxide Hydrochloride and Clidinium Bromide. 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/Clidinium Bromide is contraindicated in the presence of glaucoma, prostatic hypertrophy and benign bladder neck obstruction (see CONTRAINDICATIONS).

Adverse Reactions

No side effects or manifestation not seen with either compound alone have been reported with the administration of Chlordiazepoxide Hydrochloride and Clidinium Bromide. However, since the Chlordiazepoxide Hydrochloride and Clidinium Bromide capsule 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 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 therapy has been combined with other spasmolytic agents and/or low residue diet.To report SUSPECTED ADVERSE REACTIONS, contact Misemer Pharmaceuticals, Inc at 1-732-762-6577 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Drug Abuse And Dependence

Withdrawal symptoms, similar in character to those noted with barbiturates and alcohol (convulsions, tremor, abdominal and muscle cramps, vomiting and sweating), have occurred following abrupt discontinuance of chlordiazepoxide. The more severe withdrawal symptoms have usually been limited to those patients who had received excessive doses over an extended period of time. General milder withdrawal symptoms (e.g., dysphoria and insomnia) have been reported following abrupt discontinuance of benzodiazepines taken continuously at therapeutic levels for several months. Consequently, after extended therapy, abrupt discontinuation should generally be avoided and a gradual dosage tapering schedule followed. Addiction-prone individuals (such as drug addicts or alcoholics) should be under careful surveillance when receiving chlordiazepoxide or other psychotropic agents because of the predisposition of such patients to habituation and dependence.

Dosage And Administration

Because of the varied individual responses to tranquilizers and anticholinergics, the optimum dosage of Chlordiazepoxide Hydrochloride and Clidinium Bromide 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.

Geriatric Dosing

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.

How Supplied

Chlordiazepoxide Hydrochloride and Clidinium Bromide capsules are available in light green opaque capsules, with “VP302” imprinted on the cap of capsule, each containing 5 mg chlordiazepoxide hydrochloride and 2.5 mg clidinium bromide - bottles of 100 capsules (NDC 62250-652-10), with “VP302” imprinted on the cap of capsule.Store at 25°C (77°F): excursions permitted to 15° to 30°C (59° to 86°F).Keep out of reach of children. Dispense in a tight, light-resistant container as defined in the USP/NF.Manufactured for:Mismer Pharmaceuticals IncRipley, MS 38663.D-2020

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