INAPSINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for INAPSINE (INAPSINE).

How it works

Butyrophenone antipsychotic; antagonizes dopamine D2 receptors in the CNS, also exhibits alpha-adrenergic blocking activity.

What the body does with it

Metabolism	Primarily hepatic via oxidation and conjugation; major enzyme: CYP3A4 (minor involvement of CYP2D6); elimination half-life: 24-72 hours.
Excretion	Primarily renal (50-70% as unchanged drug and metabolites); biliary/fecal excretion accounts for approximately 20-30%.
Half-life	Terminal elimination half-life is 10-22 hours (mean 14.5 hours) in adults; may be prolonged in elderly or patients with hepatic impairment.
Protein binding	Approximately 88-92%, primarily to albumin and alpha-1 acid glycoprotein.
Volume of Distribution	5.5-13.5 L/kg (mean 10 L/kg), indicating extensive tissue distribution and high lipophilicity.
Bioavailability	Oral: 40-50% (due to first-pass metabolism); Intramuscular: 70-80% (assumed).
Onset of Action	Intravenous: 3-5 minutes; Intramuscular: 10-15 minutes; Oral: 30-60 minutes.
Duration of Action	Intravenous: 2-4 hours (dose-dependent); Intramuscular: 4-6 hours; Oral: 6-12 hours. Clinical effects (neuroleptic) may persist longer due to active metabolites.

Classification & Brands

Dosing & administration

IM: 2.5-10 mg every 3-4 hours as needed; IV: 2.5-10 mg slow IV push (over 2-3 minutes), repeat every 30-60 minutes as needed; maximum total dose 20 mg.

Dosage form	INJECTABLE
Renal impairment	No specific dose adjustment required for renal impairment; use with caution in severe impairment (CrCl <30 mL/min) due to potential for increased sedation and hypotension.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25-50%; Child-Pugh C: contraindicated or use with extreme caution, consider alternative agent.
Pediatric use	Not approved for pediatric use; safety and efficacy not established.
Geriatric use	Initial dose: 1-2.5 mg IM/IV; titrate cautiously due to increased sensitivity to CNS effects and higher risk of falls, 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 INAPSINE (INAPSINE).

Breastfeeding	Present in human milk; M/P ratio not established. American Academy of Pediatrics considers compatible with breastfeeding but monitor infant for potential adverse effects: bleeding, jaundice, and kernicterus due to vitamin K antagonism. Use with caution, especially in premature or high-risk infants.
Teratogenic Risk	Pregnancy Category C. Animal studies show fetal harm; no adequate human studies. First trimester: potential increased risk of congenital malformations, especially neural tube defects (NTDs) based on folate antagonism. Second/third trimesters: risk of neonatal hemorrhage (vitamin K antagonism) and respiratory depression if used near term. Avoid use during pregnancy unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Increased mortality in elderly patients with dementia-related psychosis; risk of QT prolongation and torsades de pointes, especially with IV administration.

Side Effect Profile

Serious Effects

Absolute Contraindications

Known hypersensitivity to droperidol; patients with pre-existing QT prolongation (QTc >450 ms), recent MI, uncompensated heart failure, hypokalemia, hypomagnesemia; concurrent use with drugs that prolong QT interval; Parkinson disease; severe CNS depression.

Clinical Precautions

Precautions

May cause QT prolongation; avoid use with other QT-prolonging drugs. Use with caution in patients with electrolyte disturbances, bradycardia, or cardiac disease. May cause tardive dyskinesia, neuroleptic malignant syndrome, and hypotension (especially orthostatic).

Clinical Tips & Counseling

Drug interactions

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INAPSINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for INAPSINE (INAPSINE).

How it works

Butyrophenone antipsychotic; antagonizes dopamine D2 receptors in the CNS, also exhibits alpha-adrenergic blocking activity.

What the body does with it

Metabolism	Primarily hepatic via oxidation and conjugation; major enzyme: CYP3A4 (minor involvement of CYP2D6); elimination half-life: 24-72 hours.
Excretion	Primarily renal (50-70% as unchanged drug and metabolites); biliary/fecal excretion accounts for approximately 20-30%.
Half-life	Terminal elimination half-life is 10-22 hours (mean 14.5 hours) in adults; may be prolonged in elderly or patients with hepatic impairment.
Protein binding	Approximately 88-92%, primarily to albumin and alpha-1 acid glycoprotein.
Volume of Distribution	5.5-13.5 L/kg (mean 10 L/kg), indicating extensive tissue distribution and high lipophilicity.
Bioavailability	Oral: 40-50% (due to first-pass metabolism); Intramuscular: 70-80% (assumed).
Onset of Action	Intravenous: 3-5 minutes; Intramuscular: 10-15 minutes; Oral: 30-60 minutes.
Duration of Action	Intravenous: 2-4 hours (dose-dependent); Intramuscular: 4-6 hours; Oral: 6-12 hours. Clinical effects (neuroleptic) may persist longer due to active metabolites.

Classification & Brands

Dosing & administration

IM: 2.5-10 mg every 3-4 hours as needed; IV: 2.5-10 mg slow IV push (over 2-3 minutes), repeat every 30-60 minutes as needed; maximum total dose 20 mg.

Dosage form	INJECTABLE
Renal impairment	No specific dose adjustment required for renal impairment; use with caution in severe impairment (CrCl <30 mL/min) due to potential for increased sedation and hypotension.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25-50%; Child-Pugh C: contraindicated or use with extreme caution, consider alternative agent.
Pediatric use	Not approved for pediatric use; safety and efficacy not established.
Geriatric use	Initial dose: 1-2.5 mg IM/IV; titrate cautiously due to increased sensitivity to CNS effects and higher risk of falls, 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 INAPSINE (INAPSINE).

Breastfeeding	Present in human milk; M/P ratio not established. American Academy of Pediatrics considers compatible with breastfeeding but monitor infant for potential adverse effects: bleeding, jaundice, and kernicterus due to vitamin K antagonism. Use with caution, especially in premature or high-risk infants.
Teratogenic Risk	Pregnancy Category C. Animal studies show fetal harm; no adequate human studies. First trimester: potential increased risk of congenital malformations, especially neural tube defects (NTDs) based on folate antagonism. Second/third trimesters: risk of neonatal hemorrhage (vitamin K antagonism) and respiratory depression if used near term. Avoid use during pregnancy unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Increased mortality in elderly patients with dementia-related psychosis; risk of QT prolongation and torsades de pointes, especially with IV administration.