CHLORDIAZEPOXIDE

brands

Class

• Neuroscience-based Nomenclature: GABA positive allosteric modulator (GABA-PAM)
• Benzodiazepine (anxiolytic)

CHLORDIAZEPOXIDE commonly prescribed for

(Bold for FDA approved)

How CHLORDIAZEPOXIDE works

• Binds to benzodiazepine receptors at the GABA-A ligand-gated chloride channel complex

• Enhances the inhibitory effects of GABA

• Boosts chloride conductance through GABA-regulated channels

• Inhibits neuronal activity presumably in amygdala-centered fear circuits to provide therapeutic benefits in anxiety disorders

How long until CHLORDIAZEPOXIDE works

• Some immediate relief with first dosing is common; can take several weeks with daily dosing for maximal therapeutic benefit

Notable Side Effects

• Sedation, fatigue, depression

• Dizziness, ataxia, slurred speech, weakness

• Forgetfulness, confusion

• Hyperexcitability, nervousness

• Rare hallucinations, mania

• Rare hypotension

• Hypersalivation, dry mouth

Life Threatening Side Effects

• Respiratory depression, especially when taken with CNS depressants in overdose

• Rare hepatic dysfunction, renal dysfunction, blood dyscrasias

weight gain

unusual

sedation

common

What to do about CHLORDIAZEPOXIDE side effects

• Wait

• Wait

• Wait

• Lower the dose

• Take largest dose at bedtime to avoid sedative effects during the day

• Switch to another agent

• Administer flumazenil if side effects are severe or life-threatening

usual dosage range

• Mild to moderate anxiety: 15–40 mg/day in 3–4 doses

• Severe anxiety: 60–100 mg/day in 3–4 doses

Dosage Forms

• Capsule 2.5 mg, 5 mg, 10 mg, 25 mg

long term use

• Evidence of efficacy for up to 16 weeks

• Risk of dependence, particularly for treatment periods longer than 12 weeks, and especially in patients with past or current polysubstance abuse

habit forming

• Chlordiazepoxide is a Schedule IV drug

• Patients may develop dependence and/or tolerance with long-term use

Renal Impairment

• Initial 10–20 mg/day in 2–4 doses; increase as needed

Hepatic Impairment

• Initial 10–20 mg/day in 2–4 doses; increase as needed

Cardiac Impairment

• Benzodiazepines have been used to treat anxiety associated with acute myocardial infarction

Elderly

• Initial 10–20 mg/day in 2–4 doses; increase as needed

• Elderly patients may be more sensitive to sedative effects

Children and Adolescents

• Not recommended for use in children under age 6

• Initial 10–20 mg/day in 2–4 doses; may increase to 20–30 mg/day in 2–3 doses if ineffective

• Hyperactive children should be monitored for paradoxical effects

• Long-term effects of chlordiazepoxide in children/adolescents are unknown

• Should generally receive lower doses and be more closely monitored

Pregnancy

• Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001

• Possible increased risk of birth defects when benzodiazepines are taken during pregnancy

• Because of the potential risks, chlordiazepoxide is not generally recommended as treatment for anxiety during pregnancy, especially during first trimester

• Drug should be tapered if discontinued

• Infants whose mothers received a benzodiazepine late in pregnancy may experience withdrawal effects

• Neonatal flaccidity has been reported in infants whose mothers took a benzodiazepine during pregnancy

• Seizures, even mild seizures, may cause harm to the embryo/fetus

Breast Feeding

Unknown if chlordiazepoxide is secreted in human breast milk, but all psychotropics are assumed to be secreted in breast milk

• Recommended either to discontinue drug or bottle feed

• Effects of benzodiazepines on nursing infants have been reported and include feeding difficulties, sedation, and weight loss