INDICATION AND USES:
Librium is 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 Librium 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.
DOSAGE AND ADMINISTRATION
| 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 initiatied 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 10mg, 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.
SIDE EFFECTS:
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 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 Librium treatment.
Blood dyscrasias (including agranulocytosis), jaundice and hepatic dysfunction have occasionally been reported during therapy. When Librium treatment is protracted, periodic blood counts and liver function tests are advisable.
CONTRAINDICATIONS:
Librium is contraindicated in patients with known hypersensitivity to the drug.
WARNINGS AND PRECAUTIONS:
- Concomitant use of benzodiazepines, including Librium, and opioids may result in profound sedation, respiratory depression, coma, and death.
- 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 Librium 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 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.
- 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.
- Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines. (See DRUG ABUSE AND DEPENDENCE section.)
- In elderly and debilitated patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia or oversedation (10 mg or less per day initially, to be increased gradually as needed and tolerated).
- In general, the concomitant administration of Librium 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 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, eg, excitement, stimulation and acute rage, have been reported in psychiatric patients and in hyperactive aggressive pediatric patients, and should be watched for during Librium therapy.
- The usual precautions are indicated when Librium 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 Librium.
- In view of isolated reports associating chlordiazepoxide with exacerbation of porphyria, caution should be exercised in prescribing chlordiazepoxide to patients suffering from this disease.
- Pediatric Use: Since clinical experience with Librium in pediatric patients under 6 years of age is limited, use in this age group is not recommended.
- Drug abuse and dependence
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.
OVERDOSE:
Manifestations of Librium 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 Librium 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 Levophed® (norepinephrine) or Aramine (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.
- Uses
-
INDICATION AND USES:
Librium is 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 Librium 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.
DOSAGE AND ADMINISTRATION
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 initiatied 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 10mg, 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.
- Side Effects
-
SIDE EFFECTS:
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 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 Librium treatment.
Blood dyscrasias (including agranulocytosis), jaundice and hepatic dysfunction have occasionally been reported during therapy. When Librium treatment is protracted, periodic blood counts and liver function tests are advisable.
- Precautions
-
CONTRAINDICATIONS:
Librium is contraindicated in patients with known hypersensitivity to the drug.
WARNINGS AND PRECAUTIONS:
- Concomitant use of benzodiazepines, including Librium, and opioids may result in profound sedation, respiratory depression, coma, and death.
- 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 Librium 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 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.
- 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.
- Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines. (See DRUG ABUSE AND DEPENDENCE section.)
- In elderly and debilitated patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia or oversedation (10 mg or less per day initially, to be increased gradually as needed and tolerated).
- In general, the concomitant administration of Librium 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 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, eg, excitement, stimulation and acute rage, have been reported in psychiatric patients and in hyperactive aggressive pediatric patients, and should be watched for during Librium therapy.
- The usual precautions are indicated when Librium 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 Librium.
- In view of isolated reports associating chlordiazepoxide with exacerbation of porphyria, caution should be exercised in prescribing chlordiazepoxide to patients suffering from this disease.
- Pediatric Use: Since clinical experience with Librium in pediatric patients under 6 years of age is limited, use in this age group is not recommended.
- Drug abuse and dependence
- 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 monitor patients closely for respiratory depression and sedation.
- Overdose
-
OVERDOSE:
Manifestations of Librium 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 Librium 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 Levophed® (norepinephrine) or Aramine (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.