loxapine LOXITANE

Class: First Generation Antipsychotic/​Dibenzoxazepine
FDA Indications: Schizophrenia, Agitation Associated With Schizophrenia Or Bipolar I Disorder In Adults (ADASUVE Inhalation Powder)
Off-Label Use: Reversal Of Antipsychotic-Induced Metabolic Disturbances, Irritability In Autism Spectrum Disorders
Prescribing
Forms: 5, 10, 25, 50mg tablet; 10mg single-use, disposable inhaler (Adasuve); 25mg/ml po soln; 50mg/ml IM
Dose Range: 20-250 mg/day
Starting: 10 mg bid. Dosage should then be increased fairly rapidly over the first seven to ten days until there is effective control of symptoms of schizophrenia. The usual therapeutic and maintenance range is 60 mg to 100 mg daily.
Stopping: Taper 6-8 weeks, rapid d/c can lead to rebound psychosis
Monitoring:

NAMI drug fact sheet

Precautions
Contraindications: Contraindicated in severe central nervous system depression (alcohol, barbiturates, narcotics, etc.) or comatose states
Serious Side Effects: , , Neutropenia and/or Agranulocytosis (rare), Hyperprolactinemia
Side Effects: constipation, xerostomia, akathisia, EPS, drowsiness
Pharmacodynamics
1° MOA: 5HT2A–D2 antagonist
Target: D2 (very high), D4 (very high), 5HT2A (high), α1 (moderate), H1 (moderate), M1 (low)
Pharmacokinetics
t½: 4 (1-14)° TMAX:
Substrate of: 1A2, 2D6, 3A4, FMO
Inhibits: ∅ ; Induces:
Active Metabolites: amoxapine, 7-OH-loxapine
DDIs
  • - 1A2, 2D6 & 3A4 inhibitors can ↑ levels; 1A2, 2D6 & 3A4 inducers can ↓ levels
  • - caution when co-prescribed with other medications that can lower blood pressure
  • - caution when co-prescribed with other CNS depressants
  • - caution when co-prescribed with other medications that can lower seizure threshold
Misc
  • - exhibits atypicality at low doses
  • - minimial weight gain
  • - its chemical structure is similar to clozapine
  • - receptor binding profile, especially its high 5HT2/D2 ratio, is more characteristic of atypical antipsychotics (similar binding profile as clozapine and olanzapine)
  • - binds with higher affinity to D4 than the other dopaminergic receptors (again similar to clozapine)
  • - IM formulation has longer t½ (12°) and Tmax (5°) than PO and inhaled form
  • - one of its 2° metabolites is the tetracyclic antidepressant, amoxapine
Special Populations

Category C—Although the human pregnancy experience with loxapine is very limited, structural anomalies have not been associated with other agents in this subclass. Because of the very limited human pregnancy experience with atypical antipsychotics, ACOG does not recommend the routine use of these agents in pregnancy, but a risk-benefit assessment may indicate that such use is appropriate. A 1996 review on the management of psychiatric illness concluded that patients with histories of chronic psychosis represent a high-risk group (for both the mother and the fetus) and should be maintained on pharmacologic therapy before and during pregnancy.

No reports describing the use during human lactation have been located. The relatively low molecular weight of loxapine (about 328) suggests that the drug are excreted into breast milk. The effect of this exposure on a nursing infant is unknown. In 2001, the American Academy of Pediatrics classified antipsychotics as drugs whose effect on the nursing infant is unknown but may be of concern. Because of the very limited human experience with antipsychotics, the ACOG does not recommend the routine use of these agents during lactation, but a risk-benefit assessment may indicate that such use is appropriate.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Elderly and debilitated patients should be started on lower dosage.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Although specific dosage guidelines are not available for oral loxapine, adjustments may be needed depending upon clinical response and the degree of hepatic impairment due to extensive metabolism of loxapine in the liver.

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Last updated August 27 2018 18:45:06. Disclaimer: This website does not provide medical advice, nor is it a substitute for clinical judgment.