Chlordiazepoxide Hydrochloride and Clidinium Bromide (Page 3 of 5)

Information for Patients

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).

Drug Interactions

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.

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 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).

ADVERSE REACTIONS

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 the
chlordiazepoxide hydrochloride and clidinium bromide capsules contain
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.
To report SUSPECTED ADVERSE REACTIONS, contact Avet
Pharmaceuticals Inc. at 1-866-901-DRUG (3784) or FDA at
1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG ABUSE AND DEPENDENCE

Controlled Substance

Chlordiazepoxide hydrochloride and clidinium bromide capsules contain
chlordiazepoxide hydrochloride, a Schedule IV controlled substance and
clidinium bromide, which is not a controlled substance.
Chlordiazepoxide hydrochloride and clidinium bromide capsules are
exempted from Schedule IV and are not controlled under the Controlled
Substances Act.

Abuse

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 WARNINGS).

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).