Librium, the original chlordiazepoxide HCI and prototype for the benzodiazepine compounds, was synthesized and developed at Hoffmann-La Roche Inc. It is a versatile therapeutic agent of proven value for the relief of anxiety. Librium is among the safer of the effective psychopharmacologic compounds available, as demonstrated by extensive clinical evidence.

Librium is available as capsules containing 5 mg, 10 mg or 25 mg chlordiazepoxide HCI. Each capsule also contains corn starch, lactose and talc. Gelatin capsule shells may contain methyl.and propyl parabens and potassium sorbater with the following dye systems: 5-mg capsules - FD&C Yellow No. 6 plus D&C Yellow No. 10 and either FD&C Blue No. 1 or FD&C Green No. 3. 10-mg capsules - D&C Yellow No. 10 and either FD&C Blue No. 1 plus FD&C Red No. 3 or FD&C Green No. 3 plus FD&C Red No. 40. 25-mg capsules- D&C Yellow No. 10 and either FD&C Green No. 3 or FD&C Blue No. 1.

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 molecular weight is 336.22. The structural formula of chlordiazepoxide hydrochloride is as follows:

Last updated on RxList: 3/20/2008

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.

Because of the wide range of clinical indications for Librium, the optimum dosage varies with the diagnosis and response of the individual patient. The dosage, therefore, should be individualized for maximum beneficial effects.

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.

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).

Librium (chlordiazepoxide HCI) Capsules are available in the following presentations:

5 mg hard gelatin capsules in bottles of 100 (NDC-0187- 3750-10), with LIBRIUM 5 imprinted on the opaque green cap and ICN imprinted on the opaque yellow body.
10 mg hard gelatin capsules in bottles of 100 (NDC-0187- 3751-10), with LIBRIUM 10 imprinted on the opaque black cap and ICN imprinted on the opaque green body.
25 mg hard gelatin capsules in bottles of 100 (NDC-0187- 3758-10), with LIBRIUM 25 imprinted on the opaque green cap and ICN imprinted on the opaque white body.

Store at 25°C (77°F); excursions permitted to 15°C - 30°C (59°F - 86°F).

Vaieant Pharmaceuticals International Costa Mesa, CA 92626. Rev. July 2005. FDA rev date: 9/6/2002

Last updated on RxList: 3/20/2008

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.

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.

No information provided.

Last updated on RxList: 3/20/2008

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.)

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: 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 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 (see PRECAUTIONS).

Last updated on RxList: 3/20/2008

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 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, WARNINGS and PRECAUTIONS, should be consulted prior to use.

Librium is contraindicated in patients with known hypersensitivity to the drug.

Last updated on RxList: 3/20/2008

Librium (chlordiazepoxide HCI) has antianxiety, sedative, appetite-stimulating and weak analgesic actions. The precise mechanism of action is not known. The drug blocks EEG arousal from stimulation of the brain stem reticular formation. It takes several hours for peak blood levels to be reached and the half-life of the drug is between 24 and 48 hours. After the drug is discontinued plasma levels decline slowly over a period of several days. Chlordiazepoxide is excreted in the urine, with 1% to 2% unchanged and 3% to 6% as conjugate.

Animal Pharmacology: The drug has been studied extensively in many species of animals and these studies are suggestive of action on the limbic system of the brain, which recent evidence indicates is involved in emotional responses.

Hostile monkeys were made tame by oral drug doses which did not cause sedation. Chlordiazepoxide HCI revealed a "taming" action with the elimination of fear and aggression. The taming effect of chlordiazepoxide HCI was further demonstrated in rats made vicious by lesions in the septal area of the brain. The drug dosage which effectively blocked the vicious reaction was well below the dose which caused sedation in these animals.

The LDM of parenterally administered chlordiazepoxide HCI was determined in mice (72 hours) and rats (5 days), and calculated according to the method of Miller and Tainter, with the following results: mice, IV, 123+12mg/kg; mice, IM, 366±7mg/kg; rats, IV, 120±7 mg/kg; rats, IM, > 160 mg/kg.

Effects on Reproduction: Reproduction studies in rats fed 10, 20 and 80 mg/kg daily and bred through one or two matings showed no congenital anomalies, nor were there adverse effects on lactation of the dams or growth of the newborn. However, in another study at 100 mg/kg daily there was noted a significant decrease in the fertilization rate and a marked decrease in the viability and body weight of off-spring which may be attributable to sedative activity, thus resulting in lack of interest in mating and lessened

maternal nursing and care of the young. One neonate in each of the first and second matings in the rat reproduction study at the 100 mg/kg dose exhibited major skeletal defects. Further studies are in progress to determine the significance of these findings.

Last updated on RxList: 3/20/2008

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.

Last updated on RxList: 3/20/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

CHLORDIAZEPOXIDE - ORAL

(KLOR-dye-AZ-e-POX-ide)

COMMON BRAND NAME(S): Librium

USES: Chlordiazepoxide is used to treat anxiety and acute alcohol withdrawal. It is also used to relieve fear and anxiety before surgery. This medication belongs to a class of drugs called benzodiazepines which act on the brain and nerves (central nervous system) to produce a calming effect. It works by enhancing the effects of a certain natural chemical in the body (GABA).

HOW TO USE: Take this medication by mouth as directed by your doctor. The dosage is based on your medical condition and response to therapy.

Use this medication exactly as prescribed. Do not increase your dose, take it more frequently or use it for a longer period of time than prescribed because this drug can be habit-forming. Also, if used for an extended period of time, do not suddenly stop using this drug without your doctor's approval. Some conditions may become worse when the drug is abruptly stopped. Your dose may need to be gradually decreased to avoid side effects such as seizures.

When used for an extended period, this medication may not work as well and may require different dosing. Talk with your doctor if this medication stops working well.

SIDE EFFECTS: Drowsiness, dizziness, nausea, constipation, blurred vision, or headache may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: mental/mood changes, slurred speech, clumsiness, trouble walking, decreased/increased interest in sex, tremor, uncontrollable movements, facial or muscle twitching, trouble urinating, sleep disturbances.

Tell your doctor immediately if any of these highly unlikely but very serious side effects occur: fainting, stomach/abdominal pain, persistent nausea, vomiting, fatigue, yellowing eyes or skin, dark urine, persistent sore throat or fever.

A serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, kidney disease, lung/breathing problems (e.g., COPD, sleep apnea), blood disorder (porphyria), drug or alcohol abuse, any allergies.

This drug may make you dizzy, drowsy or cause blurred vision; use caution engaging in activities requiring alertness such as driving or using machinery. Avoid alcoholic beverages.

Caution is advised when using this drug in the elderly because they may be more sensitive to the effects of the drug, especially the drowsiness effect.

This medication is not recommended for use during pregnancy due to the potential for harm to an unborn baby. If you become pregnant or think you may be pregnant, inform your doctor immediately. Consult your doctor for more details.

Based on information from related drugs, this drug may pass into breast milk and may have undesirable effects on a nursing infant. Therefore, breast-feeding while using this medication is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medication because a very serious interaction may occur: sodium oxybate.

If you are currently using this medication, tell your doctor or pharmacist before starting chlordiazepoxide.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: antacids, certain anti-depressants (e.g., fluoxetine, fluvoxamine, nefazodone), cimetidine, clozapine, digoxin, disulfiram, kava, levodopa.

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: antihistamines that cause drowsiness (e.g., diphenhydramine), anti-seizure drugs (e.g., carbamazepine), medicine for sleep (e.g., sedatives), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., phenothiazines such as chlorpromazine, or tricyclics such as amitriptyline), tranquilizers.

Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain drowsiness-causing ingredients. Ask your pharmacist about the safe use of those products.

This product can affect the results of certain lab tests. Make sure laboratory personnel and your doctors know you use this drug.

Smoking can decrease the effectiveness of this drug (through liver enzyme induction). Tell your doctor if you smoke or if you have recently stopped smoking because your dose may need to be adjusted.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include: severe drowsiness, slowed/reduced reflexes, slowed breathing, fainting, loss of consciousness.

NOTES: Do not share this medication with others. It is against the law.

If this drug is used for an extended period of time, laboratory and/or medical tests (e.g., liver function tests, complete blood count) may be performed periodically to check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59 and 86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For enrollment information call MedicAlert at 1-800-854- 1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.