TRANXENE SD

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TRANXENE SD (TRANXENE SD).

How it works

Benzodiazepine that enhances GABA-A receptor activity by increasing the frequency of chloride channel opening, leading to neuronal inhibition.

What the body does with it

Metabolism	Hepatic via conjugation and oxidative metabolism; primary metabolite is desmethyldiazepam (active); CYP450 involvement (CYP3A4 and CYP2C19).
Excretion	Renal excretion of conjugated metabolites, with less than 1% unchanged drug; approximately 30% excreted in feces via biliary elimination.
Half-life	Terminal elimination half-life of nordazepam (active metabolite) is 30–100 hours (mean 50 hours); clorazepate itself has a short half-life (~2 hours) due to rapid conversion.
Protein binding	97–98% bound to albumin; nordazepam is highly protein-bound.
Volume of Distribution	0.9–1.4 L/kg for clorazepate; nordazepam Vd approximately 0.8–1.2 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral: 100% (prodrug fully converted); no parenteral formulation.
Onset of Action	Oral: 1–2 hours for anxiolytic effect; peak plasma concentrations of nordazepam at 1–2 hours after oral dose.
Duration of Action	12–24 hours for anxiolytic effect; sustained action due to long-lived active metabolite nordazepam.

Classification & Brands

Dosing & administration

Oral: 11.25-22.5 mg once daily (sustained-release formulation).

Dosage form	TABLET
Renal impairment	GFR <10 mL/min: Reduce dose by 25-50% and consider avoidance due to accumulation of active metabolites.
Liver impairment	Child-Pugh Class B or C: Reduce dose by 50% or avoid use; monitor for excessive sedation.
Pediatric use	Not recommended for patients <18 years due to lack of safety and efficacy data.
Geriatric use	Reduce initial dose by 50% (e.g., 11.25 mg once daily or less), titrate slowly, and monitor for falls and cognitive impairment.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TRANXENE SD (TRANXENE SD).

Breastfeeding	Clorazepate is excreted into breast milk; M/P ratio approximately 0.2. Infant exposure likely low but may cause sedation. Use with caution; monitor infant for drowsiness and poor feeding. Consider alternative if high maternal doses or prolonged use.
Teratogenic Risk	First trimester: Increased risk of congenital malformations (oral clefts) reported with benzodiazepine use; data specifically for clorazepate limited but class effect assumed. Second/third trimester: Exposure may cause fetal CNS depression, hypotonia, respiratory depression, and withdrawal symptoms (e.g., jitteriness, hypertonia) in neonates.

Warnings & precautions

■ FDA Black Box Warning

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to clorazepate or other benzodiazepines","Acute narrow-angle glaucoma","Severe respiratory insufficiency","Myasthenia gravis","Concomitant use with opioids (in some contexts)"]

Clinical Precautions

Precautions

["Risk of abuse, misuse, and addiction","Dependence and withdrawal reactions","CNS depressant effects (impairment of driving/operating machinery)","Respiratory depression (especially with opioids)","Glaucoma (narrow-angle) use cautiously","Suicidal ideation (pre-existing depression)"]

Clinical Tips & Counseling

Drug interactions

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TRANXENE SD

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TRANXENE SD (TRANXENE SD).

How it works

Benzodiazepine that enhances GABA-A receptor activity by increasing the frequency of chloride channel opening, leading to neuronal inhibition.

What the body does with it

Metabolism	Hepatic via conjugation and oxidative metabolism; primary metabolite is desmethyldiazepam (active); CYP450 involvement (CYP3A4 and CYP2C19).
Excretion	Renal excretion of conjugated metabolites, with less than 1% unchanged drug; approximately 30% excreted in feces via biliary elimination.
Half-life	Terminal elimination half-life of nordazepam (active metabolite) is 30–100 hours (mean 50 hours); clorazepate itself has a short half-life (~2 hours) due to rapid conversion.
Protein binding	97–98% bound to albumin; nordazepam is highly protein-bound.
Volume of Distribution	0.9–1.4 L/kg for clorazepate; nordazepam Vd approximately 0.8–1.2 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral: 100% (prodrug fully converted); no parenteral formulation.
Onset of Action	Oral: 1–2 hours for anxiolytic effect; peak plasma concentrations of nordazepam at 1–2 hours after oral dose.
Duration of Action	12–24 hours for anxiolytic effect; sustained action due to long-lived active metabolite nordazepam.

Classification & Brands

Dosing & administration

Oral: 11.25-22.5 mg once daily (sustained-release formulation).

Dosage form	TABLET
Renal impairment	GFR <10 mL/min: Reduce dose by 25-50% and consider avoidance due to accumulation of active metabolites.
Liver impairment	Child-Pugh Class B or C: Reduce dose by 50% or avoid use; monitor for excessive sedation.
Pediatric use	Not recommended for patients <18 years due to lack of safety and efficacy data.
Geriatric use	Reduce initial dose by 50% (e.g., 11.25 mg once daily or less), titrate slowly, and monitor for falls and cognitive impairment.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TRANXENE SD (TRANXENE SD).

Breastfeeding	Clorazepate is excreted into breast milk; M/P ratio approximately 0.2. Infant exposure likely low but may cause sedation. Use with caution; monitor infant for drowsiness and poor feeding. Consider alternative if high maternal doses or prolonged use.
Teratogenic Risk	First trimester: Increased risk of congenital malformations (oral clefts) reported with benzodiazepine use; data specifically for clorazepate limited but class effect assumed. Second/third trimester: Exposure may cause fetal CNS depression, hypotonia, respiratory depression, and withdrawal symptoms (e.g., jitteriness, hypertonia) in neonates.

Warnings & precautions

■ FDA Black Box Warning

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to clorazepate or other benzodiazepines","Acute narrow-angle glaucoma","Severe respiratory insufficiency","Myasthenia gravis","Concomitant use with opioids (in some contexts)"]