loxapine hydrochloride
Loxitane C, Loxitane IM

loxapine succinate
Loxitane, Loxapac ◆

Pharmacologic classification: dibenzoxazepine
Therapeutic classification: antipsychotic
Pregnancy risk category NR

Available forms
Available by prescription only
Capsules: 5 mg, 10 mg, 25 mg, 50 mg
Injection: 50 mg/ml
Oral concentrate: 25 mg/ml

Indications and dosages
 Psychotic disorders. Adults: Initially, 10 mg P.O. b.i.d. (in severe schizophrenia, 50 mg P.O. daily); usual therapeutic and maintenance dosage is 60 to 100 mg P.O. daily b.i.d. to q.i.d. (dose varies from patient to patient) or 12.5 to 50 mg I.M. q 4 to 6 hours or longer. Maximum daily dose is 250 mg. After desired symptom control, change to oral therapy. Don’t administer drug I.V.

Antipsychotic action: Loxapine is the only tricyclic antipsychotic; it’s structurally similar to amoxapine. Loxapine is thought to exert its antipsychotic effects by postsynaptic blockade of CNS dopamine receptors, thus inhibiting dopamine-mediated effects. Loxapine has many other central and peripheral effects; its most prominent adverse reactions are extrapyramidal.

Absorption: Absorbed rapidly and completely from the GI tract. First-pass metabolism results in lower systemic availability.
Distribution: Distributed widely throughout the body, including breast milk. Steady state serum level is achieved within 3 to 4 days. Drug is 91% to 99% protein-bound.
Metabolism: Metabolized extensively by the liver, forming a few active metabolites; duration of action is 12 hours.
Excretion: Mostly excreted as metabolites in urine; some is excreted in feces by way of the biliary tract. About 50% is excreted in urine and feces within 24 hours.

Route Onset Peak Duration
P.O., I.M. 1/2 hr 1 1/2-3 hr 12 hr

Contraindications and precautions
Contraindicated in patients hypersensitive to dibenzoxazepines and in patients experiencing coma, severe CNS depression, or drug-induced depressed states. Use cautiously in patients with seizure or CV disorders, glaucoma, or history of urine retention.

Drug-drug. Aluminum- and magnesium-containing antacids and antidiarrheals: Decreases loxapine absorption and therapeutic effects. Separate administration times.
Antiarrhythmics, disopyramide, quinidine, procainamide: Increases risk of arrhythmias and conduction defects. Use together cautiously.
Anticholinergics, including antidepressants, antihistamines, antiparkinsonians, atropine, MAO inhibitors, meperidine, phenothiazines: Causes oversedation, paralytic ileus, visual changes, and severe constipation. Avoid use together.
Beta blockers: May inhibit loxapine metabolism, increasing plasma levels and toxicity. Use together cautiously.
Bromocriptine: May antagonize therapeutic effect of bromocriptine on prolactin secretion. Monitor patient for effect.
Centrally acting antihypertensives, such as clonidine, guanabenz, guanadrel, guanethidine, methyldopa, and reserpine: May inhibit blood pressure response. Use together cautiously.
CNS depressants, including analgesics, anesthetics (general, spinal, and epidural), barbiturates, narcotics, tranquilizers, and parenteral magnesium sulfate: May cause additive effects. Use together cautiously.
Dopamine: Decreases vasoconstricting effects of high-dose dopamine. Avoid use together.
Levodopa: Decreases effectiveness and increases toxicity of levodopa (by dopamine blockade). Avoid use together.
Lithium: May cause severe neurologic toxicity with an encephalitis-like syndrome and a decreased therapeutic response to loxapine. Avoid use together.
Nitrates: May cause hypotension. Use together cautiously.
Sympathomimetics, including ephedrine, epinephrine, and phenylephrine (often found in nasal sprays), appetite suppressants: Decreases stimulatory and pressor effects. Loxapine may cause epinephrine reversal, an inhibition of the vasopressor effect of epinephrine. Use together cautiously.
Drug-lifestyle. Alcohol use: May cause additive effects. Discourage alcohol use.

Adverse reactions
CNS: extrapyramidal reactions, sedation, drowsiness, seizures, numbness, confusion, syncope, tardive dyskinesia, neuroleptic malignant syndrome, pseudoparkinsonism, EEG changes, dizziness.
CV: orthostatic hypotension, tachycardia, ECG changes, hypertension.
EENT: blurred vision, nasal congestion.
GI: dry mouth, constipation, nausea, vomiting, paralytic ileus.
GU: urine retention, menstrual irregularities.
Hematologic: leukopenia, agranulocytosis, thrombocytopenia.
Hepatic: jaundice.
Metabolic: weight gain.
Skin: mild photosensitivity, allergic reactions, rash, pruritus.
Other: gynecomastia.

Effects on lab test results
• May increase liver function test values. May decrease WBC, granulocyte, and platelet counts.

Overdose and treatment
CNS depression is characterized by deep, unarousable sleep and possible coma, hypotension or hypertension, extrapyramidal symptoms, abnormal involuntary muscle movements, agitation, seizures, arrhythmias, ECG changes, hypothermia or hyperthermia, and autonomic nervous system dysfunction. Treatment is symptomatic and supportive, including maintaining vital signs, airway, stable body temperature, and fluid and electrolyte balance.
 Don’t induce vomiting: drug inhibits cough reflex, and aspiration may occur. Use gastric lavage, then activated charcoal and saline cathartics; hemodialysis may be helpful. Regulate body temperature as needed. Treat hypotension with I.V. fluids; don’t give epinephrine. Treat seizures with parenteral diazepam or barbiturates; arrhythmias with parenteral phenytoin (1 mg/kg with rate adjusted to blood pressure); and extrapyramidal reactions with benztropine 1 to 2 mg or parenteral diphenhydramine 10 to 50 mg.

Special considerations
• Obtain baseline blood pressure measurements before starting therapy and monitor regularly.
• Tardive dyskinesia may occur, usually after prolonged use. It may not appear until months or years after treatment and may disappear spontaneously or persist for life.
• Patient should avoid combining drug with alcohol or other depressants.
• Dilute liquid concentrate with orange or grapefruit juice just before administering.
• Dose of 10 mg is therapeutic equivalent of 100 mg chlorpromazine.
• Periodically assess patient for abnormal body movement.
• Periodic ophthalmic testing should be performed.
• Photosensitivity may occur.
• Drug causes false-positive test results for urinary porphyrins, urobilinogen, amylase, and 5-hydroxyindoleacetic acid because of darkening of urine by metabolites; it also causes false-positive urine pregnancy test results using human chorionic gonadotropin.
Pediatric patients
• Drug isn’t recommended for children younger than age 16.
Geriatric patients
• Elderly patients are highly sensitive to antimuscarinic, hypotensive, and sedative effects of drug and have a higher risk of extrapyramidal adverse reactions, such as parkinsonism and tardive dyskinesia.
• Higher plasma levels develop in these patients; therefore, they require lower initial dosage and more gradual dosage adjustment.

Patient education
• Warn patient against activities that require alertness and good psychomotor coordination until CNS response to drug is determined. Drowsiness and dizziness usually subside after first few weeks.
• Recommend sugarless gum or candy, mouthwash, ice chips, or artificial saliva to alleviate dry mouth.
• Advise patient to get up slowly to avoid orthostatic hypotension.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use