Chlordiazepoxide Hydrochloride 25 MG Oral Capsule

WARNINGS

Concomitant use of benzodiazepines, including chlordiazepoxide, 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 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.

In patients already receiving an opioid analgesic, prescribe a lower initial dose of chlordiazepoxide than indicated in the absence of an opioid and titrate based on clinical response.

If an opioid is initiated in a patient already taking chlordiazepoxide, prescribe a lower initial dose of the opioid and titrate based upon clinical response.

Advise both patients and caregivers about the risks of respiratory depression and sedation when chlordiazepoxide is used with opioids.

Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined (see DRUG INTERACTIONS).

Chlordiazepoxide HCl may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a vehicle or operating machinery.

Similarly, it may impair mental alertness in children.

The concomitant use of alcohol or other central nervous system depressants may have an additive effect.

PATIENTS SHOULD BE WARNED ACCORDINGLY.

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 monitor patients closely for respiratory depression and sedation.

OVERDOSAGE

Manifestations of chlordiazepoxide overdosage includes 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 HCl overdosage.

General supportive measures should be employed, along with immediate gastric lavage.

Intravenous fluids should be administered and an adequate airway maintained.

Hypotension may be combated by the use of norepinephrine or metaraminol.

Dialysis is of limited value.

There have been occasional reports of excitation in patients following chlordiazepoxide HCl overdosage; if this occurs 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.

Flumazenil, a specific benzodiazepine-receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when an overdose with a benzodiazepine is known or suspected.

Prior to the administration of flumazenil, necessary measures should be instituted to secure airway, ventilation and intravenous access.

Flumazenil is intended as an adjunct to, not as a substitute for, proper management of benzodiazepine overdose.

Patients treated with flumazenil should be monitored for resedation, respiratory depression and other residual benzodiazepine effects for an appropriate period after treatment.

The prescriber should be aware of a risk of seizure in association with flumazenil treatment, particularly in long term benzodiazepine users and in cyclic antidepressant overdose.

The complete flumazenil package insert, including CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS, should be consulted prior to use.

DESCRIPTION

Chlordiazepoxide hydrochloride is the prototype for the benzodiazepine compounds.

It is a versatile therapeutic agent of proven value for the relief of anxiety.

Chlordiazepoxide hydrochloride is among the safer of the effective psychopharmacologic compounds available, as demonstrated by extensive clinical evidence.

Chlordiazepoxide hydrochloride is 7-chloro-2- (methylamino)-5-phenyl-3H-1,4-benzodiazepine 4-oxide hydrochloride.

A white to practically white crystalline substance, it is soluble in water.

It is unstable in solution and the powder must be protected from light.

The structural formula is: C16H14ClN3O • HCl M.W.

336.22 Each capsule, for oral administration, contains either 5 mg, 10 mg or 25 mg of chlordiazepoxide hydrochloride, USP and has the following inactive ingredients: anhydrous lactose, D&C yellow no.

10, FD&C blue no.

1, FD&C blue no.

1 aluminum lake, gelatin, hydrogenated vegetable oil, microcrystalline cellulose, pharmaceutical glaze, and titanium dioxide.

The 5 mg and 25 mg also contain D&C yellow no.

10 aluminum lake, FD&C blue no.

2 aluminum lake, FD&C red no.

40 aluminum lake, propylene glycol, and synthetic black iron oxide.

In addition, the 5 mg contains D&C red no.

33 and the 10 mg also contains butyl paraben, edetate calcium disodium, dimethyl polysiloxane, ethylene glycol monoethyl ether, FD&C red no.

40, methyl paraben, propyl paraben, sodium, sodium lauryl sulfate, sodium propionate, and soya lecithin.

Chlordiazepoxide hydrochloride structural formula

HOW SUPPLIED

Product: 50090-0328

INDICATIONS AND USAGE

Chlordiazepoxide HCl capsules are indicated for the management of anxiety disorders or for the short term relief of symptoms of anxiety, withdrawal symptoms of acute alcoholism, and preoperative apprehension and anxiety.

Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.

The effectiveness of chlordiazepoxide HCl capsules in long term use, that is, more than 4 months, has not been assessed by systematic clinical studies.

The physician should periodically reassess the usefulness of the drug for the individual patient.

PEDIATRIC USE

Pediatric Use Because of the varied response of pediatric patients to CNS-acting drugs, therapy should be initiated with the lowest dose and increased as required (see DOSAGE AND ADMINISTRATION).

Since clinical experience with chlordiazepoxide HCl in pediatric patients under 6 years of age is limited, use in this age group is not recommended.

Hyperactive aggressive pediatric patients should be monitored for paradoxical reactions to chlordiazepoxide HCl (see PRECAUTIONS).

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, DRUG INTERACTIONS].

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 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 wide range of clinical indications for chlordiazepoxide HCl, the optimum dosage varies with the diagnosis and response of the individual patient.

The dosage, therefore, should be individualized for maximum beneficial effects.

ADULTS USUAL DAILY DOSE Relief of Mild and Moderate Anxiety Disorders and Symptoms of Anxiety 5 mg or 10 mg, 3 or 4 times daily Relief of Severe Anxiety Disorders and Symptoms of Anxiety 20 mg or 25 mg, 3 or 4 times daily Geriatric Patients, or in the presence of debilitating disease.

5 mg, 2 to 4 times daily Preoperative Apprehension and Anxiety On days preceding surgery, 5 to 10 mg orally, 3 or 4 times daily.

If used as preoperative medication, 50 to 100 mg IM 1 hour prior to surgery.

PEDIATRIC PATIENTS USUAL DAILY DOSE Because of the varied response of pediatric patients to CNS-acting drugs, therapy should be initiated with the lowest dose and increased as required.

Since clinical experience in pediatric patients under 6 years of age is limited, the use of the drug in this age group is not recommended.

5 mg, 2 to 4 times daily (may be increased in some pediatric patients to 10 mg, 2 to 3 times daily) For the relief of withdrawal symptoms of acute alcoholism, the parenteral form is usually used initially.

If the drug is administered orally, the suggested initial dose is 50 to 100 mg, to be followed by repeated doses as needed until agitation is controlled — up to 300 mg per day.

Dosage should then be reduced to maintenance levels..