loxapine (Rx)

Frequency Not Defined

Common

• Hypotension, Orthostatic hypotension
• Akathisia, dizziness, drug-induced tardive dystonia, dystonia, extrapyramidal disease, parkinsonian, somnolence, tardive dyskinesia
• Diminished sweating
• Constipation, xerostomia
• Blurred vision
• Urinary retention
• Nasal congestion

Serious

• Prolonged QT interval, torsades de pointes
• Ineffective thermoregulation, heatstroke or hypothermia (rare), neuroleptic malignant syndrome (rare), seizure (rare)
• Paralytic ileus (rare)
• Agranulocytosis (rare), disorder of hematopoietic structure (rare), leukopenia (rare), thrombocytopenia (rare)
• Cholestatic jaundice syndrome (rare)
• Drug-induced lupus erythematosus, systemic (rare)
• Priapism (rare)

Postmarketing Reports

Falls

Contraindications

Documented hypersensitivity; severe CNS depression; severe liver or cardiac disease, bone marrow suppression; narrow-angle glaucoma

CNS depression (including coma), neuroleptic malignant syndrome (NMS), poorly controlled seizure disorder

Cautions

Caution in patients with cardiovascular disease or seizures; watch for hypotension if administering IM; in patients taking benzodiazepines, loxapine should be preceded by stopping benzodiazepine therapy for 2 weeks to avoid drug interactions capable of respiratory depression

May cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries; perform complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy

FDA Warning regarding off-label use for dementia in elderly

Can cause bronchospasm that has potential to lead to respiratory distress and respiratory arrest (See BBW)

REMS to Mitigate Bronchospasm

• Available only through restricted program under a REMS called the ADASUVE REMS
• Healthcare facilities that dispense and administer therapy must be enrolled and comply with REMS requirements; certified healthcare facilities must be able to provide immediate access on site to supplies and personnel trained to manage acute bronchospasm, and ready access to emergency response services
• Facilities must have a short-acting bronchodilator (e.g., albuterol), including nebulizers and inhalation solutions, for immediate treatment of bronchospasm
• Wholesalers and distributors must distribute only to enrolled healthcare facilities

Pregnancy Category: C

Neonates exposed to antipsychotic drugs during the 3rd trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery

These complications vary in severity; in some cases, symptoms have been self-limited, while in other cases neonates have required intensive care unit support and prolonged hospitalization

Lactation: avoid in breastfeeding

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Dibenzoxazepine antipsychotic; blocks mesolimbic D1 and D2 receptors in the brain; also has anti-serotonin 5HT2 activity

Pharmacokinetics

Half-Life: 4-12 hr

Duration: 12 hr

Onset: 20-30 min

Peak plasma time: 1-2 hr (PO); 5 hr (IM)

Peak plasma concentration: 0.006-0.013 mcg/mL

Metabolism: Aromatic hydroxylation, N-demethylation, N-oxidation

Metabolites: 8-hydroxyloxapine, 7-hydroxyloxapine

Excretion: Urine (56-70%), feces