LOXITANE C
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LOXITANE C (LOXITANE C).
Loxapine, a dibenzoxazepine antipsychotic, acts primarily by blocking dopamine D2 receptors in the brain. It also exhibits affinity for serotonin 5-HT2A receptors, alpha-adrenergic, histaminergic, and muscarinic receptors, contributing to its antipsychotic and sedative effects.
| Metabolism | Primarily hepatic via cytochrome P450 enzymes (CYP1A2, CYP3A4, CYP2D6) to active metabolites including 7-hydroxy-loxapine, 8-hydroxy-loxapine, and amoxapine |
| Excretion | Approximately 70% renal (mainly as conjugated metabolites, <1% unchanged), 30% fecal via biliary excretion. |
| Half-life | Terminal elimination half-life is 4-8 hours (mean 6 hours). Clinical context: Requires multiple daily dosing; stable plasma levels achieved by second day. |
| Protein binding | 92-96% bound to albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | Vd: 1.5-2.5 L/kg (mean 2.0 L/kg). Extensive tissue distribution, including brain. |
| Bioavailability | Oral: 30-40% due to extensive first-pass metabolism; IM: 100%. |
| Onset of Action | Oral: 30-60 minutes for sedation; 2-3 weeks for full antipsychotic effect. |
| Duration of Action | Oral: 8-12 hours for sedation; prolonged antipsychotic effect persists for days after discontinuation. |
10 mg orally twice daily initially; may increase by 10 mg/day every 3–4 days; usual therapeutic range 60–100 mg/day; maximum 250 mg/day.
| Dosage form | CONCENTRATE |
| Renal impairment | No specific guidelines; use with caution in severe impairment (CrCl <10 mL/min) with reduced initial dose and slow titration. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | Not recommended for use in children <16 years due to lack of safety data. |
| Geriatric use | Initial dose 5 mg orally twice daily; increase slowly by 5 mg/day; maximum 100 mg/day; monitor for orthostatic hypotension and QT prolongation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LOXITANE C (LOXITANE C).
| Breastfeeding | Loxapine and its metabolites are excreted in human milk; M/P ratio not established. Potential for serious adverse reactions in nursing infants (e.g., sedation, extrapyramidal symptoms). Decision to discontinue nursing or drug based on importance of drug to mother. |
| Teratogenic Risk | Pregnancy Category C. First trimester: Limited human data, animal studies show increased fetal resorptions and malformations at high doses. Second and third trimesters: Risk of extrapyramidal symptoms and/or withdrawal symptoms in neonates following maternal use. Not recommended unless benefit outweighs risk. |
■ 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.
| Serious Effects |
Hypersensitivity to loxapine or any component of the formulation, severe central nervous system depression, comatose states, and concurrent use with alcohol or other CNS depressants
| Precautions | Neuroleptic malignant syndrome (NMS), tardive dyskinesia, hyperglycemia and diabetes mellitus, orthostatic hypotension, leukopenia/neutropenia, agranulocytosis, QT prolongation, seizures, body temperature dysregulation, and dysphagia |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and extrapyramidal symptoms. In neonates, observe for abnormal muscle movements, sedation, respiratory distress, and feeding difficulties. Consider fetal growth ultrasound if prolonged use. |
| Fertility Effects | May cause hyperprolactinemia leading to menstrual irregularities, galactorrhea, and decreased libido in females; reversible upon discontinuation. In males, potential for erectile dysfunction and gynecomastia. Animal studies: no direct impairment of fertility. |