No

Antipsychotic Agent, Dibenzoxazepine

Management of psychotic disorders

C

Hypersensitivity to loxapine or any component; severe CNS depression and coma

May cause hypotension, particularly with I.M. administration. Moderately sedating, use with caution in disorders where CNS depression is a feature. Use with caution in Parkinson's disease. Caution in patients with hemodynamic instability; bone marrow suppression; predisposition to seizures; subcortical brain damage; severe cardiac, hepatic, renal or respiratory disease. Esophageal dysmotility and aspiration have been associated with antipsychotic use - use with caution in patients at risk of pneumonia (ie, Alzheimer's disease). Caution in breast cancer or other prolactin-dependent tumors (may elevate prolactin levels). May alter temperature regulation or mask toxicity of other drugs due to antiemetic effects. May alter cardiac conduction; life-threatening arrhythmias have occurred with therapeutic doses of phenothiazines. May cause orthostatic hypotension - use with caution in patients at risk of this effect or those who would tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, or other medications which may predispose). Safety and effectiveness of loxapine in pediatric patients have not been established.

May cause extrapyramidal reactions, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is moderate-high relative to other neuroleptics). May be associated with neuroleptic malignant syndrome (NMS) or pigmentary retinopathy.

Cardiovascular: Orthostatic hypotension, tachycardia, arrhythmias, abnormal T-waves with prolonged ventricular repolarization, hypertension, hypotension, lightheadedness, syncope

Central nervous system: Drowsiness, extrapyramidal reactions (dystonia, akathisia, pseudoparkinsonism, tardive dyskinesia, akinesia), dizziness, faintness, ataxia, insomnia, agitation, tension, seizures, slurred speech, confusion, headache, neuroleptic malignant syndrome (NMS), altered central temperature regulation

Dermatologic: Rash, pruritus, photosensitivity, dermatitis, alopecia, seborrhea

Endocrine & metabolic: Enlargement of breasts, galactorrhea, amenorrhea, gynecomastia, menstrual irregularity

Gastrointestinal: Xerostomia, constipation, nausea, vomiting, nasal congestion, weight gain or loss, adynamic ileus, polydipsia

Genitourinary: Urinary retention, sexual dysfunction

Hematologic: Agranulocytosis, leukopenia, thrombocytopenia

Neuromuscular & skeletal: Weakness

Ocular: Blurred vision

Symptoms of overdose include deep sleep, dystonia, agitation, dysrhythmias, extrapyramidal symptoms, hypotension, seizures

Following initiation of essential overdose management, toxic symptom treatment and supportive treatment should be initiated. Hypotension usually responds to I.V. fluids or Trendelenburg positioning. If unresponsive to these measures, the use of a parenteral inotrope may be required (eg, norepinephrine 0.1-0.2 mcg/kg/minute titrated to response). Seizures commonly respond to diazepam (I.V. 5-10 mg bolus in adults every 15 minutes if needed up to a total of 30 mg; I.V. 0.25-0.4 mg/kg/dose up to a total of 10 mg in children) or to phenytoin or phenobarbital. Critical cardiac arrhythmias often respond to I.V. phenytoin (15 mg/kg up to 1 g), while other antiarrhythmics can be used. Neuroleptics often cause extrapyramidal symptoms (eg, dystonic reactions) requiring management with diphenhydramine 1-2 mg/kg (adults) up to a maximum of 50 mg I.M. or I.V. slow push followed by a maintenance dose for 48-72 hours. When these reactions are unresponsive to diphenhydramine, benztropine mesylate I.V. 1-2 mg (adults) may be effective. These agents are generally effective within 2-5 minutes.

Antipsychotics inhibit the ability of bromocriptine to lower serum prolactin concentrations

Benztropine (and other anticholinergics) may inhibit the therapeutic response to loxapine and excess anticholinergic effects may occur

Chloroquine may increase loxapine concentrations

Cigarette smoking may enhance the hepatic metabolism of loxapine. Larger doses may be required compared to a nonsmoker.

Concurrent use of loxapine with an antihypertensive may produce additive hypotensive effects

Concurrent use with TCA may produce increased toxicity or altered therapeutic response

Loxapine may inhibit the antiparkinsonian effect of levodopa

Loxapine plus lithium may rarely produce neurotoxicity

Barbiturates may reduce loxapine concentrations

Propranolol may increase loxapine concentrations

Sulfadoxine-pyrimethamine may increase loxapine concentrations

Loxapine and possibly other low potency antipsychotic may reverse the pressor effects of epinephrine

Loxapine and CNS depressants (ethanol, narcotics) may produce additive CNS depressant effects

Loxapine and trazodone may produce additive hypotensive effects

There are rare reports of significant respiratory depression, stupor, and/or hypotension with the concomitant use of loxapine and lorazepam; use caution if the concomitant administration of loxapine and CNS drugs is required

Protect from light; dispense in amber or opaque vials

Blocks postsynaptic mesolimbic D1 and D2 receptors in the brain, and also possesses serotonin 5HT2 blocking activity

Onset of neuroleptic effect: Oral: Within 20-30 minutes

Peak effect: 1.5-3 hours

Duration: ~12 hours

Metabolism: Hepatic to glucuronide conjugates

Half-life, biphasic: Initial: 5 hours; Terminal: 12-19 hours

Elimination: In urine, and to a smaller degree, feces

Adults:

Elderly: 20-60 mg/day

I.M.: 12.5-50 mg every 4-6 hours or longer as needed and change to oral therapy as soon as possible

Rapid tranquilization of agitated patient:

Oral: 25 mg

I.M.: 10-15 mg

Average total dose for tranquilization: 30-60 mg

Alcohol: Additive CNS effect, avoid use

False-positives for phenylketonuria, amylase, uroporphyrins, urobilinogen, liver function tests

Most pharmacology textbooks state that in presence of phenothiazines, systemic doses of epinephrine paradoxically decrease the blood pressure. This is the so called "epinephrine reversal" phenomenon. This has never been observed when epinephrine is given by infiltration as part of the anesthesia procedure.

>10% of patients experience dry mouth. Significant hypotension may occur, especially when the drug is administered parenterally; orthostatic hypotension is due to alpha-receptor blockade, the elderly are at greater risk for orthostatic hypotension

Extrapyramidal reactions are more common in elderly with up to 50% developing these reactions after 60 years of age; drug-induced Parkinson's syndrome occurs often; Akathisia is the most common extrapyramidal reaction in elderly

Increased confusion, memory loss, psychotic behavior, and agitation frequently occur as a consequence of anticholinergic effects

Antipsychotic associated sedation in nonpsychotic patients is extremely unpleasant due to feelings of depersonalization, derealization, and dysphoria

Use exactly as directed (do not increase dose or frequency); may cause physical and/or psychological dependence. It may take 2-3 weeks to achieve desired results; do not discontinue without consulting prescriber. Dilute oral concentration with water or juice. Do not take within 2 hours of any antacid. Avoid excess alcohol or caffeine and other prescription or OTC medications not approved by prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience excess drowsiness, restlessness, dizziness, or blurred vision (use caution driving or when engaging in tasks requiring alertness until response to drug is known); nausea, vomiting (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, or dietary fruit and fiber may help); postural hypotension (use caution climbing stairs or when changing position from lying or sitting to standing); urinary retention (void before taking medication); or decreased perspiration (avoid strenuous exercise in hot environments). Report persistent CNS effects (eg, trembling fingers, altered gait or balance, excessive sedation, seizures, unusual movements, anxiety, abnormal thoughts, confusion, personality changes); chest pain, palpitations, rapid heartbeat, severe dizziness; unresolved urinary retention or changes in urinary pattern; vision changes; skin rash or yellowing of skin; difficulty breathing; or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Injectable is for I.M. use only; dilute the oral concentrate with water or juice before administration; avoid skin contact with oral suspension or solution; may cause contact dermatitis

Monitor orthostatic blood pressures 3-5 days after initiation of therapy or a dose increase; observe for tremor and abnormal movement or posturing (extrapyramidal symptoms)

Capsule, as succinate: 5 mg, 10 mg, 25 mg, 50 mg

Concentrate, oral, as hydrochloride: 25 mg/mL (120 mL dropper bottle)

Injection, as hydrochloride: 50 mg/mL (1 mL)

Browne JL, Tsuang MT, and Perry PJ, "Amoxapine Neurotoxicity: A Case Report With Long-Term Follow-Up," Drug Intell Clin Pharm, 1982, 16(5):404-7.

Peabody CA, Warner MD, Whiteford HA, et al, "Neuroleptics and the Elderly," J Am Geriatr Soc, 1987, 35(3):233-8.

Peterson CD, "Seizures Induced by Acute Loxapine Overdose," Am J Psychiatry, 1981, 138(8):1089-91.

Risse SC and Barnes R, "Pharmacologic Treatment of Agitation Associated With Dementia," J Am Geriatr Soc, 1986, 34(5):368-76.

Saltz BL, Woerner MG, Kane JM, et al, "Prospective Study of Tardive Dyskinesia Incidence in the Elderly," JAMA, 1991, 266(17):2402-6.

Seifert RD, "Therapeutic Drug Monitoring: Psychotropic Drugs," J Pharm Pract, 1984, 6:403-16.

Tam CW, Olin BR 3d, and Ruiz AE, "Loxapine-Associated Rhabdomyolysis and Acute Renal Failure," Arch Intern Med, 1980, 140(7):975-6.