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Chlordiazepoxide (Librium) - Uses, Dose, Side effects

Chlordiazepoxide is a benzodiazepine that inhibits the stimulation of excitatory neurons by enhancing the action of GABA receptors in the central nervous system. It is used to treat the following disorders:

Treatment of acute alcohol withdrawal
Treatment of anxiety disorders or the short-term relief of symptoms of anxiety.
Treatment of preoperative apprehension and anxiety

Chlordiazepoxide (Librium) Dose in Adults

Chlordiazepoxide (Librium) Dose in Acute alcohol withdrawal:

50 to 100 mg initially that may be increased as necessary to a maximum dose of 300 mg/day.

Chlordiazepoxide Dose in Anxiety:

Mild-moderate anxiety:
- 5 to 10 mg Thrice of four times a day.
Severe anxiety:
- 20 to 25 mg three or four times a day.
Debilitated patients:
- 5 mg 2 - 4 times a day.

Chlordiazepoxide Dose in Preoperative anxiety:

5 - 10 mg thrice or four times a day on the days preceding surgery.

Chlordiazepoxide (Librium) Dose in Children

Chlordiazepoxide Dose in Anxiety:

Children older than 6 years of age and Adolescents:
- 5 mg 2 - 4 times a day. The dose may be increased to 10 mg twice or thrice daily.

Note: Newer benzodiazepines have replaced chlordiazepoxide in the treatment of anxiety [Ref].

Chlordiazepoxide Pregnancy Risk Factor D

The placental barrier is crossed by chlordiazepoxide and teratogenic effects were observed in human studies using benzodiazepines during the first trimester.
Low birth weight, premature births and neonatal hypoglycemia have all been linked to maternal benzodiazepines use.
Reports of Floppy Infant Syndrome have been made in connection with late-term maternal use of benzodiazepines.

Use of chlordiazepoxide during breastfeeding

After maternal use of benzodiazepines, chlordiazepoxide can enter breast milk. It may cause drowsiness or lethargy in nursing infants.

Chlordiazepoxide (Librium) renal dose:

Although the manufacturer has not advised any dose adjustment for patients with kidney disease, the following guidelines may be used to guide treatment and adjust doses [ Ref]
- CrCl >=10mL/minuteThere is no need to adjust the dose
- CrCl 10mL/minuteHalf the recommended dose should be taken
- Peritoneal dialysisHalf the recommended dose should be taken.

Chlordiazepoxide Dose in Liver disease:

The manufacturer has not recommended any dose adjustment in patients with liver disease, however, because of the risks of hepatic encephalopathy, it should be used with caution.

Common Side Effects of Chlordiazepoxide (Librium):

Cardiovascular:
- Edema
- Syncope
Central nervous system:
- Abnormal electroencephalogram
- Ataxia
- Confusion
- Drowsiness
- Druginduced extrapyramidal reaction
Dermatologic:
- Skin rash
Endocrine & metabolic:
- Change in libido
- Menstrual disease
Gastrointestinal:
- Constipation
- Nausea
Hematologic & oncologic:
- Agranulocytosis
- Bone marrow depression
Hepatic:
- Hepatic insufficiency
- Jaundice
Miscellaneous:
- Paradoxical reaction

Contraindications to Chlordiazepoxide (Librium):

Allergy or sensitivity to chlordiazepoxide, or any component of this formulation

Warnings and Precautions

Anterograde amnesia
- Amnesia may occur from Benzodiazepines , including chlordiazepoxide.
Depression in the CNS:
- CNS depression can result, which may cause impairments in mental or physical abilities.
- Before initiating treatment with benzodiazepines, individuals who are required to be alert for tasks such as driving or operating heavy machinery should be advised.
Paradoxical reactions
- Adolescents and older patients may experience paradoxical reactions to alcohol withdrawal.
- These reactions can manifest as aggression or hyperactivity.
Activities that are sleep-related:
- Sleep-related disorders have been linked to the use of benzodiazepines, including sleepwalking, sleeping while driving, and making phone calls.
Depression
- Patients with depression may be more likely to suicidal thoughts.
Use of drugs:
- Long-term use of marijuana has been linked to psychological and physical dependence.
Hepatic impairment
- Patients suffering from liver disease should be cautious when taking the drug.
Porphyria
- Patients suffering from porphyria are advised to take the drug with caution.
Renal impairment
- Patients suffering from kidney disease should be cautious when using the drug.
Respiratory disease
- Patients suffering from chronic respiratory conditions should be cautious about taking the drug as it can cause respiratory depression.

Chlordiazepoxide: Drug Interaction

Note: Drug Interaction Categories:

Risk Factor C: Monitor When Using Combination
Risk Factor D: Consider Treatment Modification
Risk Factor X: Avoid Concomitant Use

Notice: Drug Interaction Categories

Risk Factor C (Monitor therapy).
Alcohol (Ethyl).	CNS Depressants can increase the CNS depressant effects of Alcohol (Ethyl).
Alizapride	CNS Depressants may increase the CNS depressant effects.
Aprepitant	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Bosentan	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Brexanolone	CNS Depressants can increase the CNS depressant effects of Brexanolone.
Brimonidine	CNS Depressants may increase the CNS depressant effects.
Bromopride	CNS Depressants may increase the CNS depressant effects.
Cannabidiol	CNS Depressants may increase the CNS depressant effects.
Cannabis	CNS Depressants may increase the CNS depressant effects.
Chlorphenesin Carbamate	CNS Depressants may have an adverse/toxic effect that can be exacerbated by them.
Clofazimine	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
CNS Depressants	Can increase the toxic/adverse effects of CNS Depressants.
Moderate CYP3A4 Inducers	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Moderate CYP3A4 inhibitors	Might decrease metabolism of CYP3A4 substrates (High Risk with Inhibitors).
Deferasirox	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Dimethindene (Topical).	CNS Depressants may increase the CNS depressant effects.
Disulfiram	Might increase serum ChlordiazePOXIDE concentrations.
Doxylamine	CNS Depressants may have a greater CNS depressant effect if taken with other CNS Depressants. Management: Diclegis (doxylamine/pyridoxine), which is intended for pregnancy, has specifically stated that it should not be used with any other CNS depressants.
Dronabinol	CNS Depressants may increase the CNS depressant effects.
Duvelisib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Erdafitinib	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Erdafitinib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Esketamine	CNS Depressants may increase the CNS depressant effects.
Fosaprepitant	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Fosnetupitant	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
HydrOXYzine	CNS Depressants may increase the CNS depressant effects.
Ivosidenib	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Kava Kava	CNS Depressants may have an adverse/toxic effect that can be exacerbated by them.
Larotrectinib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Lofexidine	CNS Depressants may have a greater depressant effect on the brain. Management: Separate drug interaction monographs are available for drugs listed as an exception to this monograph.
Magnesium Sulfate	CNS Depressants may increase the CNS depressant effects.
Melatonin	May increase the sedative effects of Benzodiazepines.
MetyroSINE	MetyroSINE may have a sedative effect that can be enhanced by CNS depressants.
Minocycline	CNS Depressants may increase the CNS depressant effects.
Mirtazapine	CNS Depressants can increase the CNS depressant effects of Mirtazapine.
Nabilone	CNS Depressants may increase the CNS depressant effects.
Netupitant	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Palbociclib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Piribedil	CNS Depressants could increase the CNS depressant effects of Piribedil.
Pramipexole	Pramipexole may have a greater sedative effect if it is combined with CNS depressants.
ROPINIRole	CNS Depressants can increase the sedative effects of ROPINIRole.
Rotigotine	CNS Depressants can increase the sedative effects of Rotigotine.
Rufinamide	CNS Depressants may have an adverse/toxic effect that can be exacerbated by this. Particularly, dizziness and sleepiness may be increased.
Sarilumab	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Selective Serotonin Reuptake inhibitors	CNS Depressants can increase the toxic/adverse effects of Selective Serotonin Resuptake Inhibitors. Particularly, psychomotor impairment could be increased.
Siltuximab	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Simeprevir	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Teduglutide	May increase serum concentrations of Benzodiazepines.
Tetrahydrocannabinol	CNS Depressants may increase the CNS depressant effects.
Tetrahydrocannabinol, and Cannabidiol	CNS Depressants may increase the CNS depressant effects.
Tocilizumab	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Trimeprazine	CNS Depressants may increase the CNS depressant effects.
Yohimbine	Antianxiety agents may have a less therapeutic effect.
Risk Factor D (Regard therapy modification)
Blonanserin	CNS Depressants can increase the CNS depressant effects of Blonanserin.
Buprenorphine	CNS Depressants can increase the CNS depressant effects of buprenorphine. Management: Reduced doses of CNS depressants should be considered and avoidance of such drugs for patients at high risk for buprenorphine self-injection/overuse. Buprenorphine patches (Butrans) should be initiated at 5 mg/hr for adults, when taken with other CNS depression drugs.
Chlormethiazole	CNS Depressants may increase the CNS depressant effects. Monitoring: Look out for signs of CNS depression. If a combination of chlormethiazole and other drugs is required, a reduced dose should be used.
CloZAPine	CloZAPine's toxic/adverse effects may be exacerbated by benzodiazepines. Management: Before starting clozapine, reduce or discontinue your benzodiazepines.
Strong CYP3A4 Inducers	May increase metabolism of CYP3A4 substrates (High Risk with Inducers). Management: You may consider a different drug to replace one of the interacting drugs. Some combinations might be contraindicated. Refer to the manufacturer's label.
Strong CYP3A4 inhibitors	Might decrease metabolism of CYP3A4 substrates (High Risk with Inhibitors).
Dabrafenib	High risk of Inducers causing a decrease in serum CYP3A4 substrates. Management: If possible, seek alternatives to the CYP3A4 substrate. Concomitant therapy should be avoided if possible. Monitor the clinical effects of the substrate carefully (especially therapeutic effects).
Droperidol	CNS Depressants may increase the CNS depressant effects. Management: Droperidol and other CNS agents, such as opioids, may be reduced or used in combination with droperidol. Separate drug interaction monographs provide more detail on exceptions to this monograph.
Enzalutamide	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Management: Avoid concurrent use of enzalutamide and CYP3A4 substrates with a narrow therapeutic index. You should exercise caution when using enzalutamide or any other CYP3A4 sub-substance.
Flunitrazepam	CNS Depressants can increase the CNS depressant effects of Flunitrazepam.
HYDROcodone	CNS Depressants can increase the CNS depressant effects of HYDROcodone. When possible, avoid concomitant use with hydrocodone, benzodiazepines, or other CNS depressionants. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
Lorlatinib	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Management: Do not use lorlatinib concurrently with any CYP3A4 Substrates. Even a slight decrease in serum concentrations could cause therapeutic failure or serious clinical consequences.
Methadone	Methadone's CNS depressant effects may be exacerbated by benzodiazepines. Methadone and benzodiazepines should not be used in combination by doctors. Any such combination should be done with extreme caution.
Methotrimeprazine	Methotrimeprazine may have a higher CNS depressant activity than CNS Depressants. Methotrimeprazine can increase the CNS depressant effects of CNS Depressants. Management: Lower the adult dose of CNS Depressants by 50% and start concomitant methotrimeprazine treatment. After clinically proven efficacy of methotrimeprazine, further CNS depressant dose adjustments should only be made.
MiFEPRIStone	High risk of Inhibitors causing an increase in serum concentrations of CYP3A4 substrates. Management: Reduce CYP3A4 Substrates and monitor for elevated concentrations/toxicity during and after treatment with mifepristone. Avoid dihydroergotamine and ergotamine.
Mitotane	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Treatment: Patients receiving mitotane may require significant adjustments in the dosage of CYP3A4 Substrates.
Opioid Agonists	CNS Depressants can increase the CNS depressant effects of Opioid Aggonists. Management: When possible, avoid concomitant use opioid agonists and other CNS depressants. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
OxyCODONE	CNS Depressants can increase OxyCODONE's CNS depressant effects. When possible, avoid the simultaneous use of oxycodone, benzodiazepines, or other CNS depression drugs. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
Perampanel	CNS Depressants may have a greater CNS depressant effect. Perampanel and any other CNS depressant drug should be used in combination. Patients who take perampanel together with other drugs that have CNS depressant activity should not engage in complex or high-risk activities until they are familiar with the combination.
Pitolisant	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates Management: Avoid combining pitolisant and a CYP3A4 substrat with a low therapeutic index. Pitolisant should not be combined with other CYP3A4 sub-substances.
St John's Wort	High risk of Inducers causing a decrease in serum CYP3A4 Substrates. Management: You may consider a different drug to replace one of the interacting drugs. Some combinations might be contraindicated. Refer to the manufacturer's label.
Stiripentol	High risk of Inhibitors causing an increase in serum concentrations of CYP3A4 substrates. Management: Avoid stiripentol use with CYP3A4 Substrates that have a narrow therapeutic Index. This is to avoid adverse effects and toxicities. Monitoring of any CYP3A4 substrate that is used with stiripentol should be closely done.
Suvorexant	CNS Depressants can increase the CNS depressant effects of Suvorexant. Management: Suvorexant or any other CNS depressionant can be reduced in doses. Suvorexant should not be taken with alcohol. It is also not recommended to take suvorexant along with any other drugs for insomnia.
Tapentadol	CNS Depressants may increase the CNS depressant effects. Tapentadol, benzodiazepines and other CNS depressants should be avoided when possible. Combining these agents is not recommended unless there are other options. Limit the amount and duration of each drug when combined.
Theophylline Derivatives	This may reduce the therapeutic effects of Benzodiazepines.
Zolpidem	CNS Depressants can increase the CNS depressant effects of Zolpidem. Management: For men who also take CNS depressants, reduce the adult Intermezzo brand sublingual Zolpidem dose to 1.75mg. For women, no dose adjustment is advised. Avoid using CNS depressants at night; do not use alcohol.
Risk Factor X (Avoid the combination)
Azelastine (Nasal).	CNS Depressants could increase the CNS depressant effects of Azelastine.
Bromperidol	CNS Depressants may increase the CNS depressant effects.
Conivaptan	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Fusidic Acid (Systemic).	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Idelalisib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
OLANZapine	May increase the toxic/adverse effects of Benzodiazepines. Management: Avoid the concurrent use of parenteral benzodiazepines or IM olanzapine. There are risks of additional adverse events, such as cardiorespiratory depression. The prescribing information for Olanzapine does not include any recommendations for oral administration.
Orphenadrine	Orphenadrine may be more effective against CNS depression than other drugs.
Oxomemazine	CNS Depressants may increase the CNS depressant effects.
Paraldehyde	Paraldehyde may be enhanced by CNS depressants.
Sodium Oxybate	Benzodiazepines can increase the CNS depressant effects of Sodium Oxybate.
Thalidomide	CNS Depressants can increase Thalidomide's CNS depressant effects.

Monitoring parameters:

Mental status changes
Cardiac and Respiratory status
Postural hypotension
Paradoxical reactions, and
Features of ethanol withdrawal if used for alcohol withdrawal

How to take Chlordiazepoxide (Librium)?

It may be taken without regard to meals. Abrupt withdrawal should be avoided.

Mechanism of action of Chlordiazepoxide (Librium):

It binds to the CNS benzodiazepine receptors, including the limbic and Reticular systems.
Hyperpolarization is caused by the transfer of the chloride Ions into excitable neuronal excitable cells.
This results in stabilization or inhibition of excitable neuronal activity.

96% of the drug's total isProtein boundIt is widely used.

MetabolizedThe liver.

TheEliminating half-lifeIt takes between 24 and 48 hours, depending on the time of day.

Peak serum concentrationIt takes between 0.5 and 2 hours.

Chlordiazepoxide Brand Names (International):

Benpine
Cetabrium
Chlordiazepoxid L.F.M.
Chlordiazepoxidum
Cozep
Dipoxido
Elenium
Eposal
Equilibrium
Huberplex
Klopoxid
Klorpo
Liberty
Librium
Nova-Pam
O.C.M.
Paxium
Peast C
Psicodex
Radepur
Retcol
Risolid
Seren
Sophiamin
Trakipearl

Chlordiazepoxide Brand Names in Pakistan:

Chlordiazepoxide 5 mg Tablets
ALIUM	AMROS PHARMACEUTICALS.
CHLOBRIUM	UNEXO LABS (PVT) LTD.
ELENIUM	KRKA-PAK PHARMACEUTICAL & CHEMICAL WORKS

Chlordiazepoxide 10 mg Tablets
CHLOBRIUM	UNEXO LABS (PVT) LTD.
CHLORDIAZEPOXIDE	STAR LABORATORIES (PVT) LTD.
ELENIUM	KRKA-PAK PHARMACEUTICAL & CHEMICAL WORKS