Librax combines in a single capsule formulation the antianxiety action of chlordiazepoxide hydrochloride and the anticholinergic/spasmolytic effects of clidinium bromide, both exclusive developments of Roche research.

Each Librax capsule contains 5 mg chlordiazepoxide hydrochloride and 2.5 mg clidinium bromide. Each capsule also contains corn starch, lactose and talc. Gelatin capsule shells may contain methyl and propyl parabens and potassium sorbate, with the following dye systems: D&C Yellow No. 10 and either FD&C Blue No. 1 or FD&C Green No. 3.

Chlordiazepoxide hydrochloride is a versatile, therapeutic agent of proven value for the relief of anxiety and tension. It is indicated when anxiety, tension or apprehension are significant components of the clinical profile. It is among the safer of the effective psychopharmacologic compounds.

Chlordiazepoxide hydrochloride is 7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine 4-oxide hydrochloride. A colorless, 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:

Clidinium bromide is a synthetic anticholinergic agent which has been shown in experimental and clinical studies to have a pronounced antispasmodic and antisecretory effect on the gastrointestinal tract. Structurally clidinium bromide is:

Last updated on RxList: 3/18/2009

Because of the varied individual responses to tranquilizers and anticholinergics, the optimum dosage of Librax varies with the diagnosis and response of the individual patient. The dosage, therefore, should be individualized for maximum beneficial effects. The usual maintenance dose is 1 or 2 capsules, 3 or 4 times a day administered before meals and at bedtime.

Geriatric Dosing

Dosage should be limited to the smallest effective amount to preclude the development of ataxia, oversedation or confusion. The initial dose should not exceed 2 Librax capsules per day, to be increased gradually as needed and tolerated.

Librax is available in green capsules, each containing 5 mg chlordiazepoxide hydrochloride and 2.5 mg clidinium bromide — bottles of 100 (NDC 0187-4100-10).

Valeant Pharmaceuticals International, Costa Mesa, CA92626. Rev. Jun. 05.

Last updated on RxList: 3/18/2009

No side effects or manifestations not seen with either compound alone have been reported with the administration of Librax. However, since Librax contains 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 chlor-diazepoxide 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 chlor-diazepoxide hydrochloride treatment.

Blood dyscrasias, including agranulocytosis, jaundice and hepatic dysfunction have occasionally been reported during therapy with chlordiazepoxide hydrochloride. When chlor-diazepoxide hydrochloride treatment is protracted, periodic blood counts and liver function tests are advisable.

Adverse effects reported with use of Librax are those typical of anticolinergic agents, ie, dryness of the mouth, blurring of vision, urinary hesitancy and constipation. Constipation has occurred most often when Librax therapy has been combined with other spasmolytic agents and/or a low residue diet.

Drug Abuse And Dependence

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: 3/18/2009

As in the case of other preparations containing CNS-acting drugs, patients receiving Librax should be cautioned about possible combined effects with alcohol and other CNS depressants. For the same reason, they should be cautioned against hazardous occupations requiring complete mental alertness such as operating machinery or driving a motor vehicle.

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.

As with all anticholinergic drugs, an inhibiting effect on lactation may occur (see Animal Pharmacology).

In debilitated patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia, oversedation or confusion (not more than 2 Librax capsules per day initially, to be increased gradually as needed and tolerated). In general, the concomitant administration of Librax 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 the 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 to chlordiazepoxide hydrochloride, eg, excitement, stimulation and acute rage, have been reported in psychiatric patients and should be watched for during Librax therapy. The usual precautions are indicated when chlordiazepoxide hydrochloride 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 chlordiazepoxide hydrochloride.

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 Librax. 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). Librax is contraindicated in the presence of glaucoma, prostatic hypertrophy and benign bladder neck obstruction (see CONTRAINDICATIONS).

Last updated on RxList: 3/18/2009

Manifestations of chlordiazepoxide hydrochloride 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 chlordiazepoxide hydrochloride overdosage.

While the signs and symptoms of Librax overdosage may be produced by either of its components, usually such symptoms will be overshadowed by the anticholinergic actions of clidinium bromide. The symptoms of overdosage of clidinium bromide are excessive dryness of mouth, blurring of vision, urinary hesitancy and constipation.

General supportive measures should be employed, along with immediate gastric lavage. Administer physostigmine 0.5 to 2 mg at a rate of no more than 1 mg per minute. This may be repeated in 1 to 4 mg doses if arrhythmias, convulsions or deep coma recur. Intravenous fluids should be administered and an adequate airway maintained. Hypotension may be combated by the use of levarterenol or metaraminol. Methylphenidate or caffeine and sodium ben-zoate may be given to combat CNS-depressive effects. Dialysis is of limited value. Should excitation occur, 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.

Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines (see Drug Abuse And Dependence section).

Librax is contraindicated in the presence of glaucoma (since the anticholinergic component may produce some degree of mydriasis) and in patients with prostatic hypertrophy and benign bladder neck obstruction. It is contraindicated in patients with known hypersensitivity to chlordiazepoxide hydrochloride and/or clidinium bromide.

Last updated on RxList: 3/18/2009

Animal Pharmacology

Chlordiazepoxide hydrochloride 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 hydrochloride revealed a “taming” action with the elimination of fear and aggression. The taming effect of chlordiazepoxide hydrochloride 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 oral LD₅₀ of single doses of chlordiazepoxide hydrochloride, calculated according to the method of Miller and Tainter, is 720 ±51 mg/kg as determined in mice observed over a period of 5 days following dosage.

Clidinium bromide is an effective anticholinergic agent with activity approximating that of atropine sulfate against acetyl-choline-induced spasms in isolated intestinal strips. On oral administration in mice it proved an effective antisialagogue in preventing pilocarpine-induced salivation. Spontaneous intestinal motility in both rats and dogs is reduced following oral dosing with 0.1 to 0.25 mg/kg. Potent cholinergic gan-glionic blocking effects (vagal) are produced with intravenous usage in anesthetized dogs.

Oral doses of 2.5 mg/kg to dogs produced signs of nasal dryness and slight pupillary dilation. In two other species, monkeys and rabbits, doses of 5 mg/kg, po, given three times daily for 5 days did not produce apparent secretory or visual changes.

The oral LD₅₀ of single doses of clidinium bromide is 860 ±57 mg/kg as determined in mice observed over a period of 5 days following dosage; the calculations were made according to the method of Miller and Tainter.

Effects on Reproduction

Reproduction studies in rats fed chlordiazepoxide hydrochloride, 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 offspring 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.

Two series of reproduction experiments with clidinium bromide were carried out in rats, employing dosages of 2.5 and 10 mg/kg daily in each experiment. In the first experiment cli-dinium bromide was administered for a 9-week interval prior to mating; no untoward effect on fertilization or gestation was noted. The offspring were taken by caesarean section and did not show a significant incidence of congenital anomalies when compared to control animals. In the second experiment adult animals were given clidinium bromide for 10 days prior to and through two mating cycles. No significant effects were observed on fertility, gestation, viability of offspring or lactation, as compared to control animals, nor was there a significant incidence of congenital anomalies in the offspring derived from these experiments.

A reproduction study of Librax was carried out in rats through two successive matings. Oral daily doses were administered in two concentrations: 2.5 mg/kg chlor-diazepoxide hydrochloride with 1.25 mg/kg clidinium bromide or 25 mg/kg chlordiazepoxide hydrochloride with 12.5 mg/kg clidinium bromide. In the first mating no significant differences were noted between the control or the treated groups, with the exception of a slight decrease in the number of animals surviving during lactation among those receiving the highest dosage. As with all anticholinergic drugs, an inhibiting effect on lactation may occur. In the second mating similar results were obtained except for a slight decrease in the number of pregnant females and in the percentage of offspring surviving until weaning. No congenital anomalies were observed in both matings in either the control or treated groups. Additional animal reproduction studies are in progress.

Last updated on RxList: 3/18/2009

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: 3/18/2009

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.

CLIDINIUM/CHLORDIAZEPOXIDE - ORAL

(klor-dye-azz-eh-POX-ide/klye-DIN-ee-um)

COMMON BRAND NAME(S): Librax

USES: This medication is used along with medications that treat stomach ulcers. This combination product contains 2 medicines, chlordiazepoxide and clidinium. Chlordiazepoxide belongs to a class of drugs known as benzodiazepine anxiolytics. It works by relieving anxiety. Clidinium belongs to a class of drugs known as anticholinergics. It may help symptoms of cramping and abdominal/stomach pain by decreasing stomach acid, and slowing the intestines.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This drug may also be used for relief of symptoms from irritable bowel syndrome.

HOW TO USE: Take this medication by mouth, usually 3-4 times daily or as directed by your doctor.

Dosage is based on your medical condition and response to therapy.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.

This medication may cause dependence, especially if it has been used regularly for an extended time or if it has been used in high doses. In such cases, withdrawal reactions (e.g., shakiness, sweating, nausea, seizures) may occur if you suddenly stop this drug. To prevent withdrawal reactions when stopping extended, regular treatment with this drug, gradually reduce the dosage as directed. Consult your doctor or pharmacist for more details, and report any withdrawal reactions immediately.

Though very unlikely, abnormal drug-seeking behavior (addiction) is possible with this medication. Do not increase your dose, take it more frequently, or take it for a longer time than prescribed. Properly stop the medication when so directed.

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.

Inform your doctor if your condition persists or worsens after 7 days.

SIDE EFFECTS: Drowsiness, blurred vision, dry mouth, dry eyes, constipation, or increased heartbeat may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

To relieve dry mouth, suck on hard candy or ice chips, chew gum, drink water, or use a saliva substitute.

To prevent constipation, maintain a diet adequate in fiber, and drink plenty of water. If you become constipated while using this drug, consult your pharmacist for help in selecting a laxative (e.g., stimulant-type with stool softener).

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: fast/irregular heartbeat, weakness, slurred speech, headache, mental/mood changes (e.g., nervousness, confusion, trouble thinking clearly, depression), loss of taste, nausea, vomiting, decreased sweating, reduced tolerance of heat/strenuous exercise, decreased ability to start urination, decreased sexual ability/desire.

For more details about heat tolerance, see Precautions section.

Tell your doctor immediately if any of these rare but very serious side effects occur: memory problems, signs of severe infection (e.g., fever, persistent sore throat, shaking chills), easy bruising/bleeding, signs of anemia (low red blood cells) (e.g., severe tiredness, weakness, fainting, pale lips/nails/skin, fast heartbeat at rest, fast breathing), signs of severe liver problems (e.g., appetite loss, persistent nausea, vomiting, stomach/abdominal pain, severe tiredness, dark urine, yellowing eyes/skin, aching muscles, joint pain).

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: 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 taking this product, tell your doctor or pharmacist if you are allergic to chlordiazepoxide or clidinium; or to other benzodiazepines (e.g., diazepam, lorazepam); or to other anticholinergics (e.g., atropine); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: glaucoma, urine blockage due to enlarged prostate, blockage or narrowing in the stomach/intestines, severe slowing or stoppage of the intestines (e.g., intestinal atony, paralytic ileus), any condition that causes immobility (being bedridden), severe bleeding, a certain severe form of an intestinal disease (ulcerative colitis), a certain muscle disease (myasthenia gravis).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: mental/mood disorders (e.g., depression, psychosis, schizophrenia, thoughts of suicide), sleep apnea, previous heatstroke, liver problems, kidney problems, ulcerative colitis, heart disease (e.g., angina, previous heart attack, chronic heart failure, heart rhythm problems), overactive thyroid (hyperthyroidism), high blood pressure, nerve problems that cause slowing of the intestines (autonomic neuropathy), hiatal hernia with heartburn.

This drug may make you dizzy or drowsy. Use caution while driving, using machinery, or doing any activity that requires alertness. Avoid alcoholic beverages.

This drug may make you sweat less, causing you to be more likely to develop a severe condition caused by becoming overheated (heatstroke). Use caution in hot temperatures and during strenuous exercise. Drink plenty of fluids and dress lightly while in hot weather or when exercising. Check carefully for signs of decreased sweating. If this occurs, stop exercising and promptly seek cooler shelter. Seek immediate medical attention if your body temperature is above normal or if you have mental/mood changes, headache, or dizziness.

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

This medication is not recommended for use during pregnancy. It may harm an unborn baby. Consult your doctor for more details and to discuss reliable forms of birth control. If you become pregnant while taking this medication, notify your doctor immediately.

This medication passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding. This medication may also decrease the amount of breast milk that you make.

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 your doctor or pharmacist first.

This drug should not be used with the following medications because very serious interactions may occur: sodium oxybate, pramlintide.

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting chlordiazepoxide/clidinium.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: alcohol, fluoxetine, nefazodone, fluvoxamine, cimetidine, certain mental/mood medications (e.g., clozapine, chlorpromazine), certain antidepressants (e.g., amitriptyline, nortriptyline, trazodone), certain antihistamines (e.g., diphenhydramine, chlorpheniramine), potassium tablets/capsules.

Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain ingredients that have similar side effects as this medication (e.g., drowsiness, dry eyes, dry mouth, constipation, urination problems). Ask your pharmacist about using those products safely.

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as anti-seizure drugs (e.g., phenobarbital, carbamazepine), medicine for sleep or anxiety (e.g., alprazolam, diazepam, zolpidem, secobarbital), muscle relaxants (e.g., methocarbamol), narcotic pain relievers (e.g., codeine).

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 should call the US National Poison Hotline at 1-800-222-1222. Canada residents should call a provincial poison control center. Symptoms of overdose may include: restlessness, unusual behavior, excitability, fainting, slowed breathing, inability to move (paralysis), inability to wake up (coma).

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

Laboratory and/or medical tests (e.g., blood counts, test for blood in your stools) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take 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 at 77 degrees F (25 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.

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