What is an overview of loxapine, an (antipsychotic medication)?

Overview of Loxapine

Loxapine is a dibenzoxazepine tricyclic antipsychotic medication that is effective for treating psychotic symptoms in schizophrenia and bipolar disorder, with a side effect profile similar to typical antipsychotics, particularly at higher doses. 1

Pharmacology and Mechanism of Action

• Classification: Loxapine is chemically distinct from other antipsychotics (thioxanthenes, butyrophenones, and phenothiazines) 1
• Chemical structure: 2-Chloro-11-(4-methyl-1-piperazinyl)dibenz[b,f]1, 4oxazepine 1
• Mechanism of action:
  • Exact mode of action not fully established
  • Acts by changing excitability levels in subcortical inhibitory areas 1
  • Has D2/D3 receptor antagonist activity with higher affinity for D3 than D2 receptors 2

Pharmacokinetics

• Absorption: Virtually complete after oral administration 1
• Distribution: Rapidly removed from plasma and distributed in tissues 1
• Metabolism: Extensively metabolized 1
• Excretion: Primarily within first 24 hours; metabolites excreted in urine as conjugates and in feces unconjugated 1
• Onset of action:
  • Oral: Signs of sedation within 20-30 minutes
  • Peak effects: 1.5-3 hours
  • Duration: Effects last up to 12 hours 1
  • Inhaled: Maximum plasma concentrations reached in median of 2 minutes 3

Available Formulations

1. Oral capsules: Available in strengths of 5 mg, 10 mg, 25 mg, and 50 mg 1
2. Intramuscular injection: For acute administration 4
3. Inhalation powder (Adasuve®):
   • Recently approved for acute treatment of agitation
   • Delivered via hand-held, single-dose device using Staccato® delivery system
   • Provides rapid onset of action (within 10 minutes) 3

Clinical Efficacy

• Schizophrenia:

  • As effective as chlorpromazine, haloperidol, trifluoperazine, and thiothixene when evaluated after 4-12 weeks 5
  • In a study of 75 adolescents with schizophrenia, loxapine was superior to placebo but did not differ from haloperidol 6

• Acute agitation:

  • Inhaled loxapine significantly reduces agitation in patients with bipolar I disorder or schizophrenia 3
  • Onset of effect seen within 10 minutes of administration 3

Side Effects and Safety Profile

• Common side effects:

  • Extrapyramidal symptoms (high incidence, similar to typical antipsychotics) 5
  • Sedation (especially during early treatment) 5
  • Dysgeusia (with inhaled formulation) 3

• Less common side effects:

  • Anticholinergic effects (dry mouth, blurred vision)
  • Hypotension
  • Tachycardia
  • Precipitation of epileptic seizures 5

• Contraindications:

  • Inhaled loxapine is contraindicated in patients with airways disease associated with bronchospasm or acute respiratory signs/symptoms 3

Clinical Use Guidelines

• Dosing: Should be administered for 4-6 weeks at therapeutic doses before determining efficacy 6

• Monitoring:

  • Document target symptoms before initiating treatment
  • Monitor for extrapyramidal symptoms, sedation, tardive dyskinesia
  • Regular laboratory monitoring based on specific medication requirements 7

• Treatment algorithm:

  1. Start with lower doses and titrate based on response and tolerability
  2. Evaluate efficacy after 4-6 weeks of adequate dosing
  3. If insufficient response, consider switching to a different antipsychotic 6

Special Considerations

• Inhaled loxapine:

  • Provides a rapid, non-invasive option for acute agitation
  • Should be used with caution due to potential respiratory effects
  • Requires proper screening for pulmonary disease before administration 8

• Depot formulations:

  • Not recommended for children with very early onset schizophrenia
  • Should only be considered in adolescents with documented chronic psychotic symptoms and poor medication compliance 6

Comparison to Other Antipsychotics

• Efficacy: Similar to typical antipsychotics and some atypical antipsychotics 4, 2
• Side effects: Profile comparable to typical antipsychotics at high doses for chronic treatment 4
• Potential advantages:
  • Multiple formulations available (oral, IM, inhaled)
  • Rapid onset with inhaled formulation for acute agitation 3

Loxapine remains a clinically useful antipsychotic with established efficacy, particularly valuable in its inhaled formulation for rapid treatment of acute agitation in patients with schizophrenia or bipolar disorder.