CHLORDIAZEPOXIDE HYDROCHLORIDE AND CLIDINIUM BROMIDE
Clinical safety rating: avoid
CNS depressants including alcohol and opioids increase sedation risk Abrupt discontinuation can cause withdrawal symptoms.
Chlordiazepoxide is a benzodiazepine that enhances GABA-A receptor activity, increasing chloride ion influx and causing CNS depression. Clidinium bromide is an anticholinergic that blocks muscarinic acetylcholine receptors, reducing GI motility and secretions.
| Metabolism | Chlordiazepoxide is metabolized by hepatic CYP450 enzymes (primarily CYP3A4) to active metabolites (desmethylchlordiazepoxide, demoxepam, nordazepam, oxazepam). Clidinium is not extensively metabolized. |
| Excretion | Chlordiazepoxide is extensively metabolized in the liver to active metabolites (e.g., desmethylchlordiazepoxide, demoxepam). Renal excretion accounts for approximately 20% of unchanged drug; the remainder is excreted as metabolites in urine (80-90%) and feces (10-20%). Clidinium is excreted primarily unchanged in urine (75%) and feces (25%). |
| Half-life | Chlordiazepoxide has a terminal elimination half-life of 5-30 hours (mean ~24 hours) in adults; its active metabolite desmethylchlordiazepoxide has a half-life of 10-30 hours. Accumulation occurs with repeated dosing. In elderly or hepatic impairment, half-life may be prolonged significantly. Clidinium has a half-life of 10-12 hours. |
| Protein binding | Chlordiazepoxide is 96-98% bound to plasma proteins (primarily albumin and alpha-1-acid glycoprotein). Clidinium is approximately 50% bound to plasma proteins. |
| Volume of Distribution | Chlordiazepoxide: apparent Vd of 0.3-0.6 L/kg (approximately 20-40 L in adults), indicating extensive tissue distribution. Clidinium: Vd approximately 1-2 L/kg, reflecting distribution into peripheral tissues. |
| Bioavailability | Oral bioavailability of chlordiazepoxide is 80-90% (high, due to complete absorption but first-pass metabolism). Clidinium has poor oral bioavailability (~10-20%) due to extensive first-pass metabolism and incomplete absorption; the combination product is formulated to deliver both drugs. |
| Onset of Action | Oral: 15-45 minutes for chlordiazepoxide's anxiolytic effect; clidinium's anticholinergic effect begins within 1 hour. Peak plasma concentrations occur at 1-4 hours. |
| Duration of Action | Anxiolytic and sedative effects of chlordiazepoxide last 4-8 hours after a single dose, but active metabolites prolong clinical duration. Anticholinergic effects of clidinium persist 6-8 hours. Steady-state is reached within 3-7 days. |
Each tablet contains chlordiazepoxide HCl 5 mg and clidinium bromide 2.5 mg. Typical adult dose: 1-2 tablets orally 3-4 times daily before meals and at bedtime. Max 8 tablets daily.
| Dosage form | CAPSULE |
| Renal impairment | GFR 50-80 mL/min: No adjustment. GFR 10-50 mL/min: Administer 50-75% of normal dose. GFR <10 mL/min: Avoid use due to risk of accumulation. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Avoid use. |
| Pediatric use | Not recommended for children under 6 years. For children 6-12 years: chlordiazepoxide 5 mg and clidinium 2.5 mg orally 2-4 times daily, adjust based on weight (0.5 mg/kg/day chlordiazepoxide equivalent divided into 3-4 doses). |
| Geriatric use | Initially 1 tablet (5 mg/2.5 mg) orally 1-2 times daily, titrate slowly. Avoid doses ≥ 4 tablets daily due to increased sensitivity to CNS effects and anticholinergic side effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants including alcohol and opioids increase sedation risk Abrupt discontinuation can cause withdrawal symptoms.
| FDA category | Positive |
| Breastfeeding | Excreted into breast milk; M/P ratio not reported for chlordiazepoxide. Clidinium bromide enteric absorption minimal. Potential for infant sedation, poor feeding, and weight loss. Use only if benefit outweighs risk; monitor infant for lethargy and respiratory depression. |
| Teratogenic Risk |
■ FDA Black Box Warning
None
| Common Effects | alcohol withdrawal |
| Serious Effects |
["Hypersensitivity to chlordiazepoxide, clidinium, or any component","Myasthenia gravis","Narrow-angle glaucoma","Obstructive uropathy (e.g., prostatic hypertrophy)","Severe hepatic disease","Concomitant use with strong CYP3A4 inhibitors or inducers (caution)"]
| Precautions | ["Risk of dependence, tolerance, and withdrawal with prolonged use of chlordiazepoxide","May impair cognitive and motor function; avoid driving or operating machinery","Concomitant use with opioids may cause profound sedation, respiratory depression, coma, and death","Use cautiously in elderly, debilitated patients, and those with hepatic or renal impairment","Anticholinergic effects of clidinium may cause urinary retention, constipation, blurred vision, and heat intolerance"] |
| Food/Dietary |
Loading safety data…
| First trimester: Increased risk of congenital malformations (e.g., cleft lip/palate, cardiac defects) based on benzodiazepine data. Second and third trimesters: Risk of hypotonia, respiratory depression, withdrawal symptoms (e.g., irritability, hypertonia) in neonates after chronic exposure. Avoid use during pregnancy, especially first trimester. |
| Fetal Monitoring | Maternal: liver function tests, CBC, and renal function periodically. Fetal: ultrasound for growth and anatomy if used during first trimester. Neonatal: Apgar scores, respiratory status, and withdrawal signs (e.g., modified Finnegan scoring) for 24–48 hours after delivery if chronic maternal use. |
| Fertility Effects | No specific human data for chlordiazepoxide/clidinium. Benzodiazepines may cause menstrual irregularity, anovulation, or decreased libido; effects on fertility are uncertain. Clidinium is anticholinergic with unknown reproductive impact. |
| Avoid alcohol and products containing alcohol (e.g., some mouthwashes, cough syrups) as they potentiate CNS depression. Grapefruit juice may theoretically increase benzodiazepine absorption but is not a major concern with chlordiazepoxide. No significant food interactions are reported for clidinium; however, high-fiber meals may reduce gastrointestinal motility and anticholinergic absorption. Maintain adequate fluid intake to counteract anticholinergic-induced constipation. |
| Clinical Pearls | Chlordiazepoxide/clidinium (Librax) combines a benzodiazepine anxiolytic with an anticholinergic/antispasmodic. It is primarily used for irritable bowel syndrome (IBS) and peptic ulcer disease. Due to the benzodiazepine component, avoid use in patients with severe hepatic impairment, narrow-angle glaucoma, or concurrent CNS depressants. The anticholinergic component may exacerbate urinary retention, constipation, and hyperthermia. Elderly patients are at increased risk for falls, cognitive impairment, and anticholinergic side effects; consider deprescribing. Monitor for paradoxical reactions and dependence with prolonged use. |
| Patient Advice | This medication may cause drowsiness or dizziness; avoid driving or operating heavy machinery until you know how it affects you. · Do not drink alcohol while taking this medication; it can increase the sedative effects. · Report any signs of an allergic reaction, such as rash, itching, or swelling, especially of the face or throat. · Avoid use in combination with other sedatives, muscle relaxants, or opioids unless directed by your doctor. · If you become pregnant or plan to become pregnant, consult your doctor immediately; use during pregnancy may harm the baby. · Do not stop taking this medication abruptly; it may cause withdrawal symptoms such as anxiety, insomnia, or seizures. · Notify your doctor if you develop blurred vision, difficulty urinating, constipation, or confusion. · Take this medication exactly as prescribed; do not increase the dose or frequency without medical advice. |