Overdose
Manifestations of Librium (chlordiazepoxide) 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 (chlordiazepoxide) 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 HCI 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
Librium (chlordiazepoxide) is contraindicated in patients with known hypersensitivity to the
drug.
Undesirable 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 (chlordiazepoxide) treatment.
Blood dyscrasias (including agranulocytosis), jaundice and hepatic dysfunction have occasionally been reported during therapy. When Librium (chlordiazepoxide) treatment is protracted, periodic blood counts and liver function tests are advisable.
DRUG ABUSE AND DEPENDENCE: Chlordiazepoxide hydrochloride capsules are
classified by the Drug Enforcement Administration as a Schedule IV controlled
substance.
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. Generally
milder withdrawal symptoms (eg, 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.
Therapeutic indications
Librium (chlordiazepoxide) 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 (chlordiazepoxide) 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.
Special warnings and precautions for use
WARNINGS
Chlordiazepoxide HCI 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.
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.
Withdrawal symptoms of the barbiturate type have occurred after the discontinuation
of benzodiazepines. (See DRUG ABUSE AND DEPENDENCE
section.)
PRECAUTIONS
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 (chlordiazepoxide)
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 (chlordiazepoxide) therapy. The usual precautions are
indicated when Librium (chlordiazepoxide) 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: 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 Librium (chlordiazepoxide) 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 Librium (chlordiazepoxide)
(see PRECAUTIONS).
Dosage (Posology) and method of administration
Because of the wide range of clinical indications for Librium (chlordiazepoxide) , 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.
* See package insert for Injectable Librium (chlordiazepoxide HCI).
Interaction with other medicinal products and other forms of interaction
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 (chlordiazepoxide) treatment.
Blood dyscrasias (including agranulocytosis), jaundice and hepatic dysfunction have occasionally been reported during therapy. When Librium (chlordiazepoxide) treatment is protracted, periodic blood counts and liver function tests are advisable.
DRUG ABUSE AND DEPENDENCE: Chlordiazepoxide hydrochloride capsules are
classified by the Drug Enforcement Administration as a Schedule IV controlled
substance.
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. Generally
milder withdrawal symptoms (eg, 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.
DRUG INTERACTIONS
No information provided.
