LOXITANE IM

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LOXITANE IM (LOXITANE IM).

How it works

LOXITANE IM (loxapine) is a dibenzoxazepine antipsychotic. Its mechanism of action is not fully established but is thought to be mediated via antagonism of central dopamine D2 and serotonin 5-HT2A receptors. It has high affinity for D2, D3, D4, and 5-HT2A receptors and low affinity for D1 receptors. It also has moderate affinity for histamine H1 and alpha1-adrenergic receptors.

What the body does with it

Metabolism	Loxapine undergoes extensive hepatic metabolism, primarily via cytochrome P450 (CYP) isoenzymes CYP1A2, CYP2D6, and CYP3A4. The major metabolic pathways include hydroxylation, N-oxidation, and N-demethylation. The active metabolite, 7-hydroxyloxapine (amoxapine), contributes to clinical effects.
Excretion	Primarily renal: 70% as metabolites; biliary/fecal: 30% as metabolites and unchanged drug.
Half-life	Terminal elimination half-life: 8-12 hours. Clinically, steady-state reached in 2-3 days; dosing interval based on q6-12h.
Protein binding	92% bound, primarily to albumin and α1-acid glycoprotein.
Volume of Distribution	Vd: 7-15 L/kg (extensive tissue distribution).
Bioavailability	IM: 100% (complete absorption).
Onset of Action	IM: 15-30 minutes for acute psychotic symptoms.
Duration of Action	IM: 6-12 hours. Clinical effects may persist longer due to active metabolites.

Classification & Brands

Dosing & administration

Adults: 12.5-50 mg IM every 4-6 hours as needed, not to exceed 150 mg/day.

Dosage form	INJECTABLE
Renal impairment	No specific guidelines; use with caution in severe renal impairment (CrCl <10 mL/min) due to potential for accumulation.
Liver impairment	Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild to moderate (Child-Pugh A or B), reduce initial dose by 50% and titrate cautiously.
Pediatric use	Not established for IM use; safety and efficacy in pediatric patients have not been determined.
Geriatric use	Initial dose: 3.75-7.5 mg IM every 4-6 hours as needed; increase cautiously due to increased sensitivity and risk of hypotension, sedation, 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 LOXITANE IM (LOXITANE IM).

Breastfeeding	Loxapine is excreted into breast milk in low concentrations (M/P ratio approximately 0.5). Monitor infant for sedation, irritability, and poor feeding. Consider risk versus benefit.
Teratogenic Risk	First trimester: Limited human data; animal studies show no consistent teratogenicity. Second and third trimesters: Risk of extrapyramidal symptoms and/or withdrawal in neonates following late third-trimester exposure.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. LOXITANE IM is not approved for the treatment of dementia-related psychosis.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Comatose states","Severe central nervous system depression","Known hypersensitivity to loxapine or any component of the formulation","Circulatory collapse"]

Clinical Precautions

Precautions

["Increased mortality in elderly patients with dementia-related psychosis","Neuroleptic Malignant Syndrome (NMS): potentially fatal, discontinue if suspected","Tardive Dyskinesia: risk increases with cumulative dose and duration of treatment","QT prolongation: use caution in patients with risk factors for QT prolongation","Seizures: may lower seizure threshold, use caution in patients with seizure disorders","Hypotension: orthostatic hypotension can occur, especially with IM administration","Leukopenia/Neutropenia/Agranulocytosis: monitor CBCs if signs of infection occur","Cognitive and motor impairment: caution when operating machinery","Hyperprolactinemia: may cause galactorrhea, gynecomastia, sexual dysfunction","Dysphagia: may increase risk of aspiration pneumonia"]

Clinical Tips & Counseling

Drug interactions

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LOXITANE IM

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LOXITANE IM (LOXITANE IM).

How it works

What the body does with it

Metabolism	Loxapine undergoes extensive hepatic metabolism, primarily via cytochrome P450 (CYP) isoenzymes CYP1A2, CYP2D6, and CYP3A4. The major metabolic pathways include hydroxylation, N-oxidation, and N-demethylation. The active metabolite, 7-hydroxyloxapine (amoxapine), contributes to clinical effects.
Excretion	Primarily renal: 70% as metabolites; biliary/fecal: 30% as metabolites and unchanged drug.
Half-life	Terminal elimination half-life: 8-12 hours. Clinically, steady-state reached in 2-3 days; dosing interval based on q6-12h.
Protein binding	92% bound, primarily to albumin and α1-acid glycoprotein.
Volume of Distribution	Vd: 7-15 L/kg (extensive tissue distribution).
Bioavailability	IM: 100% (complete absorption).
Onset of Action	IM: 15-30 minutes for acute psychotic symptoms.
Duration of Action	IM: 6-12 hours. Clinical effects may persist longer due to active metabolites.

Classification & Brands

Dosing & administration

Adults: 12.5-50 mg IM every 4-6 hours as needed, not to exceed 150 mg/day.

Dosage form	INJECTABLE
Renal impairment	No specific guidelines; use with caution in severe renal impairment (CrCl <10 mL/min) due to potential for accumulation.
Liver impairment	Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild to moderate (Child-Pugh A or B), reduce initial dose by 50% and titrate cautiously.
Pediatric use	Not established for IM use; safety and efficacy in pediatric patients have not been determined.
Geriatric use	Initial dose: 3.75-7.5 mg IM every 4-6 hours as needed; increase cautiously due to increased sensitivity and risk of hypotension, sedation, 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 LOXITANE IM (LOXITANE IM).

Breastfeeding	Loxapine is excreted into breast milk in low concentrations (M/P ratio approximately 0.5). Monitor infant for sedation, irritability, and poor feeding. Consider risk versus benefit.
Teratogenic Risk	First trimester: Limited human data; animal studies show no consistent teratogenicity. Second and third trimesters: Risk of extrapyramidal symptoms and/or withdrawal in neonates following late third-trimester exposure.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. LOXITANE IM is not approved for the treatment of dementia-related psychosis.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Comatose states","Severe central nervous system depression","Known hypersensitivity to loxapine or any component of the formulation","Circulatory collapse"]