loxapine
Last reviewed 2025-12-29
Reviewed by PsychMed Editorial Team.
Brands: Loxitane, Adasuve
Sources updated 2025 • 4 references
General Information
Loxapine is a mid-potency first-generation antipsychotic with serotonergic antagonism resembling second-generation antipsychotics (SGAs), available orally and as inhaled powder for acute agitation.
Used in adult schizophrenia and bipolar agitation (inhaled formulation under REMS protocols).
The compare tool and loxapine evidence feed can help evaluate EPS, metabolic burden, and inhaled versus oral strategies when considering switches or Adasuve use.
Inhaled loxapine is not a “take-home” rescue medication; it is a facility-based option for selected patients when rapid calming is needed and airway risk has been screened.
U.S. approvals
- Schizophrenia (oral) (1975)
- Acute agitation in schizophrenia/bipolar I (inhaled) (2012)
Formulations & strengths
- Oral capsules: 5–50 mg; oral concentrate 5 mg/mL.
- Inhaled powder (Adasuve) 10 mg single-use device.
Generic availability
- Oral products available generically; inhaled formulation remains brand-only (REMS).
Selected for cost-sensitive maintenance regimens or when inhaled rapid-acting therapy is desirable, especially in bipolar agitation where avoidance of injections improves adherence; Adasuve’s bronchospasm risk and REMS observation requirements shape patient selection and follow-up using the bipolar disorder hub.
View labelExactMechanism of Action
Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.
Antagonizes dopamine D2/D3 and serotonin 5-HT2A receptors, blending FGA potency with SGA-like serotonergic effects.
Additional antagonism at histamine H1, adrenergic α1, and muscarinic receptors mediates sedation and anticholinergic effects.
- Antagonist at dopamine D2/D3 and serotonin 5-HT2A/5-HT2C receptors.
- Antagonist at histamine H1 and adrenergic α1 receptors.
- Moderate muscarinic antagonism.
Metabolism and Pharmacokinetics
- Peak plasma levels ~1–3 h (oral); highly lipophilic with extensive distribution.
- Metabolized via CYP1A2 and CYP3A4 to active metabolite amoxapine.
- Half-life ~4 h (longer for metabolites); eliminated renally as metabolites.
- Smoking and CYP1A2 induction can reduce exposure; dose changes may be needed when smoking status changes during hospitalization or after discharge.
Dosing and Administration
- Oral: start 10 mg BID; titrate to 60–100 mg/day divided (max 250 mg/day).
- Inhaled (Adasuve): 10 mg per administration; may repeat once ≥2 h later (max 20 mg/day) under REMS monitoring.
Monitoring & Labs
- Baseline airway screening (asthma/COPD history, active wheeze) before inhaled dosing; avoid Adasuve when bronchospasm risk is present.
- Post-inhalation observation ≥1 hour with pulse oximetry and rescue bronchodilator immediately available; document respiratory symptoms and response.
- EPS monitoring during titration and AIMS screening every 3–6 months for tardive dyskinesia, especially with long-term oral use.
- Weight/BMI and metabolic labs at baseline and periodically, even if risk is lower than olanzapine; sedation and appetite changes still affect weight.
- Orthostatic vitals and falls risk during initiation and after dose increases; adjust dose timing to bedtime when dizziness or sedation is problematic.
- ECG monitoring when cardiac risk factors or QT-active co-medications are present.
- Smoking status and CYP1A2 modulators that can change exposure; reassess dose needs after smoking cessation or restart.
Monitoring differs by formulation: inhaled loxapine requires airway observation under REMS, while oral maintenance follows standard antipsychotic safety monitoring with an emphasis on EPS and orthostasis, and staff readiness.
Adverse Effects
FDA boxed warnings
- Increased mortality in elderly patients with dementia-related psychosis.
Common side effects (≥10%)
- Sedation: Frequent due to H1 blockade.
- Dizziness: Notable during initiation.
- Orthostatic hypotension: From α1 antagonism.
- Anticholinergic effects: Dry mouth and constipation.
- Extrapyramidal symptoms: Dose dependent (~10–15%).
Other notable effects
- Weight gain is typically moderate; metabolic monitoring remains standard.
- Seizure threshold reduction at high doses.
- Inhaled loxapine may cause bronchospasm—screening for asthma/COPD and observation with rescue bronchodilator availability are required.
- Neuroleptic malignant syndrome and tardive dyskinesia are rare but serious antipsychotic-class risks; education for patients and caregivers often covers early warning signs, and AIMS screening cadence is commonly documented.
Interactions
- CYP1A2/CYP3A4 inhibitors increase levels; smoking or enzyme inducers reduce exposure.
- Additive CNS depression with alcohol or benzodiazepines.
- Potentiates antihypertensives via α1 blockade.
Other Useful Information
- EPS and metabolic monitoring often follow patterns used for other antipsychotics.
- REMS certification required for Adasuve; patients are observed ≥1 h post dose for bronchospasm.
- SGAs are often considered if metabolic or EPS burden is problematic long-term.
- For agitation pathways, define the full protocol (eligibility screening, post-dose observation, rescue bronchodilator availability, and transition-to-maintenance plan) rather than relying on repeat PRN dosing.