NAVANE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for NAVANE (NAVANE).

How it works

Thioxanthene neuroleptic; blocks postsynaptic dopamine D1 and D2 receptors in the brain; also exhibits anticholinergic, alpha-adrenergic blocking, and sedative effects.

What the body does with it

Metabolism	Hepatic via CYP450 enzymes (primarily CYP2D6, with minor contributions from CYP1A2, CYP3A4).
Excretion	Primarily hepatic metabolism; approximately 20-30% excreted renally as metabolites, <1% unchanged. Biliary/fecal excretion accounts for ~50% of metabolites.
Half-life	Terminal elimination half-life is approximately 20-24 hours, allowing for once-daily dosing. Steady-state reached in 4-5 days.
Protein binding	>99% bound, primarily to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	10-15 L/kg, indicating extensive tissue distribution and high lipophilicity.
Bioavailability	Oral: ~30-40% due to first-pass metabolism; IM: 100%.
Onset of Action	Oral: 30-60 minutes; IM: 15-30 minutes.
Duration of Action	Oral: 12-24 hours; IM: 24-48 hours. Clinical effects may persist longer due to active metabolites.

Classification & Brands

Dosing & administration

Oral: 10-20 mg three times daily; maximum 160 mg/day. IM (acute): 5-10 mg every 4-6 hours; maximum 30 mg/day.

Dosage form	CONCENTRATE
Renal impairment	No specific guidelines; use caution in severe impairment (GFR <30 mL/min) with 50% dose reduction.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: avoid use.
Pediatric use	Not recommended for use in children; safety and efficacy not established.
Geriatric use	Initiate at 5 mg/day with gradual titration; monitor for hypotension and extrapyramidal symptoms.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for NAVANE (NAVANE).

Breastfeeding	Thiothixene is excreted in human milk. M/P ratio not established. Potential for serious adverse reactions in nursing infants; decision to discontinue nursing or drug should be based on importance of drug to mother. Caution advised.
Teratogenic Risk	Pregnancy Category C. First trimester: Risk of congenital malformations not established; animal studies show fetal harm. Second and third trimesters: Neonates exposed late in pregnancy may exhibit extrapyramidal symptoms, jaundice, and hyperbilirubinemia. Maternal seizures may occur if drug withdrawn abruptly.

Warnings & precautions

■ FDA Black Box Warning

Increased mortality in elderly patients with dementia-related psychosis; risk of fatal stroke.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Comatose states","CNS depression (e.g., from alcohol, barbiturates, opioids)","Blood dyscrasias","Hepatic damage","Hypersensitivity to thioxanthenes or any component"]

Clinical Precautions

Precautions

["Tardive dyskinesia risk with prolonged use","Neuroleptic malignant syndrome (NMS)","QT prolongation and arrhythmias","Orthostatic hypotension","Leukopenia, neutropenia, agranulocytosis","Seizure threshold lowering","Anticholinergic effects (constipation, urinary retention, blurred vision)","Hyperprolactinemia"]

Clinical Tips & Counseling

Drug interactions

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NAVANE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for NAVANE (NAVANE).

How it works

Thioxanthene neuroleptic; blocks postsynaptic dopamine D1 and D2 receptors in the brain; also exhibits anticholinergic, alpha-adrenergic blocking, and sedative effects.

What the body does with it

Metabolism	Hepatic via CYP450 enzymes (primarily CYP2D6, with minor contributions from CYP1A2, CYP3A4).
Excretion	Primarily hepatic metabolism; approximately 20-30% excreted renally as metabolites, <1% unchanged. Biliary/fecal excretion accounts for ~50% of metabolites.
Half-life	Terminal elimination half-life is approximately 20-24 hours, allowing for once-daily dosing. Steady-state reached in 4-5 days.
Protein binding	>99% bound, primarily to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	10-15 L/kg, indicating extensive tissue distribution and high lipophilicity.
Bioavailability	Oral: ~30-40% due to first-pass metabolism; IM: 100%.
Onset of Action	Oral: 30-60 minutes; IM: 15-30 minutes.
Duration of Action	Oral: 12-24 hours; IM: 24-48 hours. Clinical effects may persist longer due to active metabolites.

Classification & Brands

Dosing & administration

Oral: 10-20 mg three times daily; maximum 160 mg/day. IM (acute): 5-10 mg every 4-6 hours; maximum 30 mg/day.

Dosage form	CONCENTRATE
Renal impairment	No specific guidelines; use caution in severe impairment (GFR <30 mL/min) with 50% dose reduction.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: avoid use.
Pediatric use	Not recommended for use in children; safety and efficacy not established.
Geriatric use	Initiate at 5 mg/day with gradual titration; monitor for hypotension and extrapyramidal symptoms.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for NAVANE (NAVANE).

Breastfeeding	Thiothixene is excreted in human milk. M/P ratio not established. Potential for serious adverse reactions in nursing infants; decision to discontinue nursing or drug should be based on importance of drug to mother. Caution advised.
Teratogenic Risk	Pregnancy Category C. First trimester: Risk of congenital malformations not established; animal studies show fetal harm. Second and third trimesters: Neonates exposed late in pregnancy may exhibit extrapyramidal symptoms, jaundice, and hyperbilirubinemia. Maternal seizures may occur if drug withdrawn abruptly.

Warnings & precautions

■ FDA Black Box Warning

Increased mortality in elderly patients with dementia-related psychosis; risk of fatal stroke.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Comatose states","CNS depression (e.g., from alcohol, barbiturates, opioids)","Blood dyscrasias","Hepatic damage","Hypersensitivity to thioxanthenes or any component"]