Chlordiazepoxide Hydrochloride 5 MG / Clidinium bromide 2.5 MG Oral Capsule
WARNINGS
Concomitant use of benzodiazepines, including Chlordiazepoxide Hydrochloride/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/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/Clidinium Bromide is used with opioids (see PRECAUTIONS ).
As in the case of other preparations containing CNS-acting drugs, patients receiving Chlordiazepoxide Hydrochloride/Clidinium Bromide 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 ).
DRUG INTERACTIONS
Drug Interactions The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration.
Benzodiazepines interact at GABAA sites and opioids interact primarily at mu receptors.
When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists.
Limit dosage and duration of concomitant use of benzodiazepines and opioids, and follow patients closely for respiratory depression and sedation.
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/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 ).
DESCRIPTION
Chlordiazepoxide Hydrochloride/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/Clidinium Bromide capsule contains active ingredients 5 mg chlordiazepoxide hydrochloride and 2.5 mg clidinium bromide.
Each capsule also contains 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: Chemical Structure Chemical Structure
HOW SUPPLIED
Chlordiazepoxide Hydrochloride/Clidinium Bromide capsules are light green opaque capsules with “VP302” imprinted on the cap of capsule, each containing 5 mg chlordiazepoxide hydrochloride and 2.5 mg clidinium bromide.
Bottle of 100 capsules (NDC 76439-302-10).
Rx only Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
GERIATRIC USE
Geriatric Use Geriatric subjects may be particularly prone to experiencing drowsiness, ataxia and confusion while receiving Chlordiazepoxide Hydrochloride/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 ).
INDICATIONS AND USAGE
Chlordiazepoxide Hydrochloride/Clidinium Bromide is indicated to control the emotional and somatic factors in gastrointestinal disorders.
Chlordiazepoxide Hydrochloride/Clidinium Bromide may also be used as adjunctive therapy in the treatment of peptic ulcer and in the treatment of irritable bowel syndrome (irritable colon, spastic colon, mucous colitis) and acute enterocolitis.
PEDIATRIC USE
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
BOXED WARNING
WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death (see WARNINGS and PRECAUTIONS ).
• Reserve concomitant prescribing of these drugs for use 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.
INFORMATION FOR PATIENTS
Information for Patients Inform patients and caregivers that potentially fatal additive effects may occur if Chlordiazepoxide Hydrochloride/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.
DOSAGE AND ADMINISTRATION
Because of the varied individual responses to tranquilizers and anticholinergics, the optimum dosage of Chlordiazepoxide Hydrochloride/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/Clidinium Bromide capsules per day, to be increased gradually as needed and tolerated.