LOXITANE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LOXITANE (LOXITANE).

How it works

Loxapine is a typical antipsychotic that exerts its effects primarily by blocking dopamine D2 receptors in the mesolimbic pathway. It also has affinity for serotonin 5-HT2A, histamine H1, alpha1-adrenergic, and muscarinic receptors.

What the body does with it

Metabolism	Hepatic metabolism primarily via CYP1A2 and CYP3A4 isoenzymes, with minor contributions from CYP2D6. Metabolites include 8-hydroxyloxapine and loxapine N-oxide.
Excretion	Renal excretion accounts for 50-60% (primarily as metabolites, <1% unchanged). Fecal/biliary elimination accounts for 25-35% (via bile).
Half-life	12-18 hours (terminal). Steady state achieved within 3-5 days; dosing adjustments for renal/hepatic impairment.
Protein binding	92% (primarily to albumin and alpha-1-acid glycoprotein).
Volume of Distribution	7-20 L/kg (extensive tissue distribution; large Vd indicates accumulation in tissues).
Bioavailability	Oral: 20-40% (extensive first-pass metabolism). IM: 100% (bioequivalent to IV).
Onset of Action	Oral: 30-60 minutes. IM: 15-30 minutes.
Duration of Action	8-12 hours (oral); 6-8 hours (IM). Clinical effects may persist for up to 24 hours due to active metabolites.

Classification & Brands

Dosing & administration

Oral: Initial 10 mg twice daily; may increase up to 250 mg/day in divided doses. IM: 12.5-50 mg every 4-6 hours.

Dosage form	TABLET
Renal impairment	No specific dose adjustment guidelines available; use caution in severe renal impairment.
Liver impairment	No specific Child-Pugh based guidelines; use caution in severe hepatic impairment.
Pediatric use	Not recommended for children under 12 years; safety and efficacy not established.
Geriatric use	Start with lower doses (e.g., 5-10 mg/day oral) and titrate slowly due to increased sensitivity and risk of 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 LOXITANE (LOXITANE).

Breastfeeding	Loxapine is excreted into breast milk; M/P ratio unknown. Data are limited, but risk of adverse effects (e.g., sedation, EPS) in the infant exists. Consider benefits of breastfeeding and potential risks; monitor for infant drowsiness, irritability, and feeding problems. Alternative agents (e.g., haloperidol) may be preferred.
Teratogenic Risk	Loxapine is pregnancy category D. First trimester: human data limited, but known risk of teratogenic effects (e.g., CNS malformations) based on animal studies and other antipsychotics; avoid unless essential. Second/third trimesters: risk of extrapyramidal symptoms (EPS) and withdrawal in neonates (e.g., agitation, hypertonia, tremors, feeding difficulties). Use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

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

Side Effect Profile

Serious Effects

Absolute Contraindications

Absolute: Known hypersensitivity to loxapine, severe CNS depression, comatose states. Relative: Concurrent use of illicit opioids or alcohol, pre-existing bone marrow suppression, narrow-angle glaucoma, urinary retention.

Clinical Precautions

Precautions

Neuroleptic Malignant Syndrome (NMS), tardive dyskinesia, orthostatic hypotension, leukopenia/neutropenia, agranulocytosis, QT prolongation, seizures, hyperglycemia, dyslipidemia, weight gain, aspiration pneumonia (inhalation formulation).

Clinical Tips & Counseling

Drug interactions

Loading safety data…

LOXITANE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LOXITANE (LOXITANE).

How it works

What the body does with it

Metabolism	Hepatic metabolism primarily via CYP1A2 and CYP3A4 isoenzymes, with minor contributions from CYP2D6. Metabolites include 8-hydroxyloxapine and loxapine N-oxide.
Excretion	Renal excretion accounts for 50-60% (primarily as metabolites, <1% unchanged). Fecal/biliary elimination accounts for 25-35% (via bile).
Half-life	12-18 hours (terminal). Steady state achieved within 3-5 days; dosing adjustments for renal/hepatic impairment.
Protein binding	92% (primarily to albumin and alpha-1-acid glycoprotein).
Volume of Distribution	7-20 L/kg (extensive tissue distribution; large Vd indicates accumulation in tissues).
Bioavailability	Oral: 20-40% (extensive first-pass metabolism). IM: 100% (bioequivalent to IV).
Onset of Action	Oral: 30-60 minutes. IM: 15-30 minutes.
Duration of Action	8-12 hours (oral); 6-8 hours (IM). Clinical effects may persist for up to 24 hours due to active metabolites.

Classification & Brands

Dosing & administration

Oral: Initial 10 mg twice daily; may increase up to 250 mg/day in divided doses. IM: 12.5-50 mg every 4-6 hours.

Dosage form	TABLET
Renal impairment	No specific dose adjustment guidelines available; use caution in severe renal impairment.
Liver impairment	No specific Child-Pugh based guidelines; use caution in severe hepatic impairment.
Pediatric use	Not recommended for children under 12 years; safety and efficacy not established.
Geriatric use	Start with lower doses (e.g., 5-10 mg/day oral) and titrate slowly due to increased sensitivity and risk of 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 LOXITANE (LOXITANE).

Breastfeeding	Loxapine is excreted into breast milk; M/P ratio unknown. Data are limited, but risk of adverse effects (e.g., sedation, EPS) in the infant exists. Consider benefits of breastfeeding and potential risks; monitor for infant drowsiness, irritability, and feeding problems. Alternative agents (e.g., haloperidol) may be preferred.
Teratogenic Risk	Loxapine is pregnancy category D. First trimester: human data limited, but known risk of teratogenic effects (e.g., CNS malformations) based on animal studies and other antipsychotics; avoid unless essential. Second/third trimesters: risk of extrapyramidal symptoms (EPS) and withdrawal in neonates (e.g., agitation, hypertonia, tremors, feeding difficulties). Use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

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