Loxapine (Loxitane, Adasuve)
FGA • Last reviewed 2025-09-26
General information
Loxapine is a mid-potency first-generation antipsychotic available as oral capsules, oral solution, and an inhaled powder (Adasuve) for acute agitation in schizophrenia or bipolar disorder.
Structurally similar to clozapine, loxapine exhibits mixed dopamine and serotonin antagonism with a balanced EPS and sedation profile.
Inhaled loxapine is restricted by a REMS program due to bronchospasm risk; contraindicated in asthma or COPD.
Oral loxapine is rarely used as first-line therapy today but remains an option when sedation is desirable or when patients have previously responded.
Dosing & administration
Oral: start 10 mg twice daily; titrate to 60–100 mg/day divided 2–4 times (max 250 mg/day).
Inhaled: 10 mg per dose via single-use inhaler; may repeat once after 2 hours (max 20 mg/24 h).
Bedtime dosing may improve tolerability due to sedation.
Dose adjustments
- Elderly/debilitated
- Start 5 mg twice daily; titrate cautiously.
- Acute agitation (inhaled)
- 10 mg single dose; monitor respiratory status.
Mechanism of action
Loxapine antagonizes dopamine D2 and serotonin 5-HT2A receptors, producing antipsychotic effects with moderate EPS risk.
It also blocks histamine H1, muscarinic M1, and α1 receptors, contributing to sedation, anticholinergic effects, and orthostasis.
Metabolism & pharmacokinetics
Oral loxapine peaks within 1–3 hours and is extensively metabolized via CYP1A2, CYP3A4, and CYP2D6 to active metabolites (e.g., amoxapine).
Half-life is 4–8 hours for the parent and up to 12 hours for metabolites. Inhaled loxapine reaches peak concentration within minutes, with effects in 10 minutes.
Metabolites are eliminated via urine and feces; protein binding ~96%.
- Tmax (oral)
- 1–3 hours
- Half-life
- 4–8 hours (parent)
- Metabolism
- CYP1A2, CYP3A4, CYP2D6
Drug interactions
CYP1A2 inhibitors increase loxapine exposure; adjust dose.
CYP inducers (carbamazepine, smoking) may reduce efficacy.
CNS depressants heighten sedation.
Inhaled formulation contraindicated in airway disease.
| Mechanism | Agents / factors | Management |
|---|---|---|
| CYP1A2 inhibition | Fluvoxamine, ciprofloxacin | Lower dose; monitor sedation. |
| CYP induction | Carbamazepine, tobacco smoke | Monitor efficacy; adjust dose. |
| CNS depression | Benzodiazepines, opioids | Monitor respiratory status, especially inhaled. |
Monitoring & safety checks
Weight, lipids, glucose
Baseline, annually • Metabolic changes
EPS monitoring
Each visit • Moderate EPS risk
Airway assessment (inhaled)
Before each dose • Bronchospasm risk
Vital signs
Baseline and post-dose • Orthostasis
Ensure REMS enrollment for inhaled product and availability of short-acting bronchodilator.
Discontinuation guidance
Taper gradually over weeks to limit relapse and cholinergic rebound.
Adverse effects
Common: somnolence, dry mouth, dizziness, EPS.
Inhaled: bronchospasm, cough, dysgeusia.
References
- Loxapine hydrochloride — Prescribing Information — FDA (2023)
- Adasuve (loxapine) REMS — FDA (2019)
- Clinical review of loxapine — Ther Adv Psychopharmacol (2020) DOI: 10.1177/2045125320969818
Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.