ZAXOPAM

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZAXOPAM (ZAXOPAM).

How it works

Zaxopam is a benzodiazepine that enhances GABA-A receptor activity by binding to the benzodiazepine site, increasing chloride ion influx and causing neuronal hyperpolarization.

What the body does with it

Metabolism	Hepatic via CYP3A4 and CYP2C19 isoenzymes; major metabolites include active metabolites (e.g., desalkylzaxopam).
Excretion	Renal excretion accounts for approximately 80% of the administered dose, predominantly as conjugated metabolites; biliary/fecal excretion accounts for the remaining 20%.
Half-life	Terminal elimination half-life is 12-15 hours, allowing for once-daily dosing in most patients.
Protein binding	95-98% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	0.8-1.2 L/kg, indicating moderate distribution into total body water and tissues.
Bioavailability	Oral: 80-90% due to minimal first-pass metabolism; intravenous: 100%.
Onset of Action	Oral: 30-60 minutes; intravenous: 1-3 minutes.
Duration of Action	Oral: 6-8 hours; intravenous: 2-4 hours. Extended duration possible with hepatic impairment.

Classification & Brands

Dosing & administration

10 mg orally twice daily, titrated to a maximum of 30 mg twice daily based on response and tolerability; oral route.

Dosage form	CAPSULE
Renal impairment	eGFR 30-59 mL/min: administer 50% of usual dose; eGFR <30 mL/min: not recommended.
Liver impairment	Child-Pugh Class A: no adjustment; Child-Pugh Class B: initiate at 50% of usual dose; Child-Pugh Class C: contraindicated.
Pediatric use	Not approved for use in pediatric patients; safety and efficacy not established.
Geriatric use	Initiate at 5 mg orally twice daily; increase cautiously with careful monitoring for adverse effects.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ZAXOPAM (ZAXOPAM).

Breastfeeding

ZAXOPAM is excreted into breast milk. Milk-to-plasma ratio (M/P) approximately 0.2-0.5. Infant exposure via breastfeeding is low but may cause sedation and poor feeding in neonates. American Academy of Pediatrics recommends caution; avoid use in breastfeeding mothers if possible, or monitor infant for drowsiness and weight gain.

Teratogenic Risk

ZAXOPAM is a benzodiazepine. First trimester: associated with increased risk of congenital malformations (cleft palate, inguinal hernia, cardiac defects) based on observational studies; relative risk approximately 2.0. Second and third trimesters: exposure may cause fetal central nervous system depression, hypotonia, withdrawal symptoms (floppy infant syndrome), and respiratory depression at delivery.

Warnings & precautions

■ FDA Black Box Warning

Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant use for patients without alternative treatment options.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to zaxopam or other benzodiazepines; severe respiratory insufficiency; sleep apnea; myasthenia gravis; narrow-angle glaucoma; concurrent use with opioids in non-tolerant patients.

Clinical Precautions

Precautions

Risk of dependence and withdrawal reactions; tolerance may develop; caution in hepatic impairment; risk of anterograde amnesia; monitor for respiratory depression, especially in elderly or debilitated patients.

Clinical Tips & Counseling

Drug interactions

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ZAXOPAM

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZAXOPAM (ZAXOPAM).

How it works

Zaxopam is a benzodiazepine that enhances GABA-A receptor activity by binding to the benzodiazepine site, increasing chloride ion influx and causing neuronal hyperpolarization.

What the body does with it

Metabolism	Hepatic via CYP3A4 and CYP2C19 isoenzymes; major metabolites include active metabolites (e.g., desalkylzaxopam).
Excretion	Renal excretion accounts for approximately 80% of the administered dose, predominantly as conjugated metabolites; biliary/fecal excretion accounts for the remaining 20%.
Half-life	Terminal elimination half-life is 12-15 hours, allowing for once-daily dosing in most patients.
Protein binding	95-98% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	0.8-1.2 L/kg, indicating moderate distribution into total body water and tissues.
Bioavailability	Oral: 80-90% due to minimal first-pass metabolism; intravenous: 100%.
Onset of Action	Oral: 30-60 minutes; intravenous: 1-3 minutes.
Duration of Action	Oral: 6-8 hours; intravenous: 2-4 hours. Extended duration possible with hepatic impairment.

Classification & Brands

Dosing & administration

10 mg orally twice daily, titrated to a maximum of 30 mg twice daily based on response and tolerability; oral route.

Dosage form	CAPSULE
Renal impairment	eGFR 30-59 mL/min: administer 50% of usual dose; eGFR <30 mL/min: not recommended.
Liver impairment	Child-Pugh Class A: no adjustment; Child-Pugh Class B: initiate at 50% of usual dose; Child-Pugh Class C: contraindicated.
Pediatric use	Not approved for use in pediatric patients; safety and efficacy not established.
Geriatric use	Initiate at 5 mg orally twice daily; increase cautiously with careful monitoring for adverse effects.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ZAXOPAM (ZAXOPAM).

Breastfeeding

Teratogenic Risk

Warnings & precautions

■ FDA Black Box Warning

Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant use for patients without alternative treatment options.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to zaxopam or other benzodiazepines; severe respiratory insufficiency; sleep apnea; myasthenia gravis; narrow-angle glaucoma; concurrent use with opioids in non-tolerant patients.