CHLORDIAZEPOXIDE

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Created Mar 2019 | Updated Nov 2020

CHLORDIAZEPOXIDE

  • [LIBRIUM]
  • [LIBRITABS]
  • [LIMBITROL]
  • [SK-LYGEN]

DEA CODE 2744: Schedule 4

  • Chlordiazepoxide (trade name Librium) is a sedative and hypnotic medication of the benzodiazepine class. 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 in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies.
  • Chlordiazepoxide acts on benzodiazepine allosteric sites that are part of the GABAA receptor/ion-channel complex and this results in an increased binding of the inhibitory neurotransmitter GABA to the GABAA receptor thereby producing inhibitory effects on the central nervous system and body similar to the effects of other benzodiazepines. The withdrawal of chlordiazepoxide during pregnancy and breastfeeding is recommended, as chlordiazepoxide rapidly crosses the placenta and also is excreted in breast milk.
  • Chlordiazepoxide is a long-acting benzodiazepine drug. The half-life of Chlordiazepoxide is 5 - 30 hours but has an active benzodiazepine metabolite (desmethyldiazepam), which has a half-life of 36 - 200 hours. 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.

Chlordiazepoxide is the most prescribed drug for alcohol withdrawal

This is due to its long half-life, which means that some of its active metabolites are still in effect even after two days of prior of intake. The drug's very long half-life makes it ideal for relieving symptoms of alcohol withdrawal. However, elderly people require special precaution, as there are risks of drug accumulation and prolonged action, which, in turn, may lead to cases of drug abuse, dependence, or overdose. Similarly, pregnant and lactating women must first consult a healthcare provider prior to the drug's intake or continuation of use.

Chlordiazepoxide is a prescription medication that acts as a central nervous system depressant. Alcohol is also considered as a depressant. Both substances slow down the activity of the brain, and together, they make a rather powerful CNS depressant that can cause adverse side effects. If you are taking chlordiazepoxide for alcohol withdrawal treatment, alcohol consumption should be avoided altogether to ensure safe and continuous recovery.


Liver:
As with other benzodiazepines, chlordiazepoxide therapy is not associated with serum aminotransferase or alkaline phosphatase elevations, and clinically apparent liver injury from chlordiazepoxide has been reported, but is very rare.

Chlordiazepoxide Hepatotoxicity:
Chlordiazepoxide, as with other benzodiazepines, is rarely associated with serum ALT elevations, and clinically apparent liver injury from its use is rare. There have been several case reports of acute liver injury from chlordiazepoxide, published largely before 1980. The latency to onset of acute liver injury was 1 to 4 months, and the pattern of liver enzyme elevations varied from hepatocellular to cholestatic and mixed. The injury was usually mild-to-moderate in severity and self-limited. Fever and rash were uncommon, as was autoantibody formation.

D Likelihood score: D (Possible, rare cause of clniically apparent liver injury).


Pediatric:
Appropriate studies have not been performed on the relationship of age to the effects of chlordiazepoxide in children below 6 years of age.

Safety and efficacy have not been established.

Geriatric:
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of chlordiazepoxide in the elderly. However, severe drowsiness, dizziness, confusion, clumsiness, or unsteadiness are more likely to occur in the elderly, who are usually more sensitive than younger adults to the effects of chlordiazepoxide.

Elderly patients may require a lower dose to help reduce unwanted effects.

Other Interactions:

  • Ethanol

Other Medical Problems:
Make sure you tell your doctor if you have any other medical problems, especially:

  • Kidney disease
  • Liver disease - Use with caution. The effects may be increased because of slower removal of the medicine from the body
  • Porphyria (genetic disorder) - Use with caution. May make this condition worse

Breastfeeding:

Summary of Use During Lactation:
No information is available on the use of chlordiazepoxide during breastfeeding.

Because the drug and metabolites could accumulate in the breastfed infant, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.

Drug Levels:
Chlordiazepoxide is metabolized to active compounds including demoxepam, desmethylchlordiazepoxide, desmethyldiazepam, and oxazepam.

Chlordiazepoxide has a long half-life of 5 to 30 hours, and the half-lives of its metabolites range from 14 to 100 hours.

Alternate Drugs to Consider:

Librium
Duration:

A medium-acting benzodiazepine drug prescribed mostly for sleep purposes. Sedative and hypnotic, it may cause lowered inhibitions and amnesia in high doses.

NOTE: 25mg of Librium is approximately equal to 10mg of Diazepam.

RouteOnsetDurationAfter Effects
Tripsit Factsheets
All ROAs:20-40 minutes6-10 hours1-14 hours
Librium Duration
Avoid:
All other CNS depressants.
Effects:
Anxiolytic, Sedative, Muscle Relaxant, Amnesia, Dystaxia, Hypnotic.

Important Information:
Chlordiazepoxide may be habit-forming. Misuse of habit-forming medicine can cause addiction, overdose, or death. Selling or giving away chlordiazepoxide is against the law.

Avoid drinking alcohol. Dangerous side effects could occur.

Chlordiazepoxide may impair your thinking or reactions. Avoid driving or operating machinery until you know how chlordiazepoxide will affect you. Dizziness or severe drowsiness can cause falls or other accidents.

Interactions:

Drug Interactions (409) Alcohol/Food Interactions (2) Disease Interactions (11)


What other drugs will affect Chlordiazepoxide?
Taking chlordiazepoxide with other drugs that make you sleepy or slow your breathing can cause dangerous side effects or death. Ask your doctor before taking a sleeping pill, narcotic pain medicine, prescription cough medicine, a muscle relaxer, or medicine for anxiety, depression, or seizures.

Other drugs may interact with chlordiazepoxide, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

A total of 409 drugs are known to interact with Chlordiazepoxide.

  • 27 major drug interactions
  • 346 moderate drug interactions
  • 36 minor drug interactions

Chlordiazepoxide:

It was the first benzodiazepine to be synthesized. Three years later chlordiazepoxide was marketed as a therapeutic benzodiazepine medication under the brand name Librium. Three years after that diazepam hit the market under the brand name Valium as a "simplified" version of chlordiazepoxide, primarily to counteract anxiety symptoms.

  • A sedative and hypnotic medication of the benzodiazepine class
  • Used to treat anxiety, insomnia and symptoms of withdrawal from alcohol and other drugs
  • Medium to long half-life but its active metabolite has a very long half-life. Half-life of Chlordiazepoxide is 5 - 30 hours but has an active benzodiazepine metabolite (desmethyldiazepam), which has a half-life of 36 - 200 hours
  • It has amnesic, anticonvulsant, anxiolytic, hypnotic, sedative and skeletal muscle relaxant properties
  • Patented in 1958
  • Approved for medical use in 1960

Chlordiazepoxide is generally considered an inappropriate benzodiazepine for the elderly due to its long elimination half-life and the risks of accumulation. The half-life of chlordiazepoxide increases significantly in the elderly, which may result in prolonged action as well as accumulation of the drug during repeated administration.

  
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