FDA

Librax

Approved 1 Sept 1966OralCapsule

Indications

Librax is indicated to control emotional and somatic factors in gastrointestinal disorders. Librax may also be used as adjunctive therapy in the treatment of peptic ulcer and in the treatment of the irritable bowel syndrome (irritable colon, spastic colon, mucous colitis) and acute enterocolitis.

Contraindications

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.

Warnings and precautions

Risks From Concomitant Use with Opioids Concomitant use of benzodiazepines, including Librax, and opioids may result in profound sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of these drugs - 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 Librax 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 both patients and caregivers about the risks of respiratory depression and sedation when Librax is used with opioids (see PRECAUTIONS ). Abuse, Misuse, and Addiction The use of benzodiazepines, including chlordiazepoxide hydrochloride, a component of Librax, exposes users to the risks of abuse, misuse, and addiction, which can lead to overdose or death.

Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death (see DRUG ABUSE AND DEPENDENCE ). Before prescribing Librax and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool).

Use of Librax, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of Librax along with monitoring for signs and symptoms of abuse, misuse, and addiction. Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug.

At a glance

Brand name: Librax
Active substance: chlordiazepoxide hydrochloride
Route: Oral
Dosage form: Capsule
Applicant: Bausch
Status: Prescription
FDA approval: 1 Sept 1966
Application: NDA012750-001

Contraindications

Warnings and precautions

Interactions

Drug Interactions Opioids The concomitant use of benzodiazepines, including chlordiazepoxide hydrochloride, a component of Librax, and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABA A 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 Librax and opioids, and follow patients closely for respiratory depression and sedation. Oral Anticoagulants 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, a component of Librax.

Pregnancy Risk Summary Chlordiazepoxide Hydrochloride Neonates born to mothers using benzodiazepines during the later stages of pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal (see WARNINGS, Neonatal Sedation and Withdrawal Syndrome and PRECAUTIONS: Clinical Considerations ). Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects (see Data).

Clidinium Bromide Over decades of use, there is an absence of published data on orally administered clidinium bromide in pregnant women, including an absence of any reports of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia and sedation in neonates. Monitor neonates exposed to Librax, which contains a benzodiazepine (chlordiazepoxide hydrochloride), during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems.

Monitor neonates exposed to Librax during pregnancy for signs of withdrawal. Manage these neonates accordingly (see WARNINGS, Neonatal Sedation and Withdrawal Syndrome). Data Human Data Published data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. Although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted.

In addition, the majority of more recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol. Tobacco and other medications, have not confirmed these findings. Animal Data Oral daily doses of 2.5 mg/kg chlordiazepoxide hydrochloride with 1.25 mg/kg clidinium bromide or 25 mg/kg chlordiazepoxide hydrochloride with 12.5 mg/kg clidinium bromide (0.6 and 6.1 times, respectively, the maximum recommended clinical dose for both drugs, based on body surface area) were administered to rats in a reproduction study through two successive matings.

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. 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.

Nursing Mothers Chlordiazepoxide Hydrochloride There are no data on the presence of chlordiazepoxide in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. However, there are reports of sedation, poor feeding and poor weight gain in infants exposed to other benzodiazepines through breast milk. Reproduction studies in rats fed chlordiazepoxide hydrochloride, 10, 20 and 80 mg/kg daily (2.4, 4.8 and 19.4 times respectively, the maximum recommended clinical dose of 40 mg/day, based on body surface area), and bred through one or two matings showed no adverse effects on lactation of the dams.

Clidinium Bromide There are no data on the presence of clidinium in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. As with other anticholinergic drugs, clidinium may cause suppression of lactation. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Librax and any potential adverse effects on the breastfed infant from Librax.

Infants exposed to Librax through breast milk should be monitored for sedation, poor feeding and poor weight gain. Pediatric Use Safety and effectiveness in pediatric patients have not been established.

Adverse reactions

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

Adverse effects reported with use of Librax are those typical of anticholinergic agents, i.e., 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. To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Librax

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Librax

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Interactions

Adverse reactions

Composition

Official product information