Maximum Dose of Loxapine for Agitation
The maximum recommended dose of loxapine depends on the formulation: for oral loxapine, the FDA-approved maximum is 250 mg daily (though doses above this are not recommended), while for inhaled loxapine (Adasuve), the maximum is a single 10 mg dose in 24 hours. 1, 2
Inhaled Loxapine (Adasuve) - Preferred for Acute Agitation
For acute agitation in schizophrenia or bipolar disorder, inhaled loxapine 10 mg is the dominant dose choice, administered as a single dose with a strict maximum of one dose per 24 hours. 3
Dosing Specifics:
- 10 mg is the preferred dose based on superior effect sizes (0.60 for schizophrenia, 0.94 for bipolar disorder) compared to 5 mg 3
- 5 mg is an alternative for patients who may require lower dosing, though less robust efficacy 3, 4
- Onset of action occurs within 10 minutes (first measurable timepoint), with peak plasma concentrations at 2 minutes 5, 3
- Absolute maximum: one dose in 24 hours per FDA Risk Evaluation and Mitigation Strategy (REMS) requirements 2, 3
Critical Safety Restrictions:
- Contraindicated in patients with any airways disease including asthma, COPD, or acute respiratory symptoms 5, 2
- Requires 1-hour post-dose monitoring for bronchospasm in hospital settings only 2
- Must pre-screen all patients for pulmonary disease before administration 2
Oral Loxapine - For Chronic Management
For ongoing management of psychotic symptoms with agitation, oral loxapine has an FDA-approved maximum of 250 mg daily, though this is rarely necessary. 1
Dosing Algorithm:
- Initial dosing: 10 mg twice daily (20 mg/day total) for most patients 1
- Severely disturbed patients: Up to 50 mg/day initially may be used 1
- Titration: Increase rapidly over 7-10 days to achieve symptom control 1
- Usual therapeutic range: 60-100 mg daily in divided doses (2-4 times daily) 1
- Maintenance range: 20-60 mg daily once stabilized 1
- Absolute maximum: 250 mg daily, with doses above this not recommended 1
Context from Guidelines:
- Loxapine is classified as a typical antipsychotic with an "in-between" side effect profile 6
- Should be considered second-line to atypical antipsychotics due to higher risk of extrapyramidal symptoms and tardive dyskinesia (50% risk in elderly after 2 years of continuous use) 6
- Dosing "varies by agent" in guideline tables, reflecting the need for individualized titration within the FDA-approved range 6
Key Clinical Pitfalls:
Do not confuse formulations: Inhaled loxapine is strictly limited to one dose per 24 hours for acute agitation, while oral loxapine can be dosed multiple times daily for chronic management 1, 2
Do not use inhaled loxapine without pulmonary screening: The REMS program exists because Phase I studies showed common respiratory symptoms in patients with asthma or COPD 2, 3
Do not exceed 250 mg daily of oral loxapine: The FDA label explicitly states this is not recommended, and lower maintenance doses (20-60 mg/day) are typically sufficient 1