Loxapine

Pronunciation

Pronunciation: LOX-a-peen
Class: Dibenzapine derivative

Trade Names

Loxitane
- Capsules, oral 5 mg
- Capsules, oral 10 mg
- Capsules, oral 25 mg
- Capsules, oral 50 mg

Apo-Loxapine (Canada)
Loxapac IM (Canada)
PMS-Loxapine (Canada)

Pharmacology

Unknown. Changes level of excitability of subcortical inhibitory areas in some animals.

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Pharmacokinetics

Absorption

Virtually complete absorption.

Distribution

Removed rapidly from plasma and distributed into tissue.

Metabolism

Extensively metabolized.

Elimination

Excreted mainly in first 24 h. Metabolites excreted in urine in the form of conjugates and in feces unconjugated.

Indications and Usage

Treatment of schizophrenia.

Contraindications

Comatose or severe drug-induced depressed states (eg, barbiturates); hypersensitivity to dibenzoxazepines.

Dosage and Administration

Adults Initial dose

PO 10 mg twice daily, up to 50 mg/day, titrated fairly rapidly over first 7 to 10 days until symptoms are controlled (max, 250 mg/day).

Maintenance dose

Reduce dosage to lowest amount compatible with symptom control. Usual range is 60 to 100 mg/day; many patients have been maintained satisfactorily at a dosage range of 20 to 60 mg/day. Dosages higher than 250 mg/day are not recommended.

General Advice

  • Administer in divided doses, 2 to 4 times per day.
  • Administer without regard to meals. Administer with food if GI upset occurs.
  • Reduce dosage to lowest amount compatible with symptom control.

Storage/Stability

Store between 68° and 77°F.

Drug Interactions

Anticholinergics (eg, benztropine)

Coadministration may cause additive anticholinergic toxicity. Use with caution.

Epinephrine

Loxapine may reverse the beta-adrenergic effects of epinephrine, producing hypotension and tachycardia.

Ethanol

Sedative effects of loxapine may be enhanced by ethanol.

Lorazepam

There have been rare reports of significant respiratory depression, stupor, or hypotension with the concomitant use of loxapine and lorazepam.

Metoclopramide

Coadministration may increase the risk of extrapyramidal reactions. Coadministration is not recommended.

Sodium oxybate

Concurrent use may increase sleep duration and CNS depression. Sodium oxybate is contraindicated in patients receiving other sedative-hypnotics.

Tramadol

Coadministration may cause CNS toxicity, primarily an increased risk of seizures. Coadministration is not recommended.

Adverse Reactions

Cardiovascular

ECG changes, hypertension, hypotension, orthostatic hypotension, syncope, tachycardia.

CNS

Agitation, akathisia, akinesia, dizziness, dystonic (eg, muscle spasms of the neck and face) and dyskinetic reactions (eg, choreoathetoid movements), extrapyramidal effects (eg, parkinsonian-like symptoms, tremor, rigidity, excessive salivation, masked facies), faintness, headache, insomnia, light-headedness, mental confusion, muscle twitching, NMS, numbness, paresthesia, sedation, seizures, shuffling gait, slurred speech, staggering gait, tardive dyskinesia, tension, transient drowsiness, weakness.

Dermatologic

Alopecia, dermatitis, edema (puffiness of face), pruritus, rash, seborrhea.

EENT

Blurred vision, nasal congestion.

GI

Constipation, dry mouth, nausea, paralytic ileus, vomiting.

Genitourinary

Amenorrhea, galactorrhea, gynecomastia, menstrual irregularity, urinary retention.

Hematologic

Agranulocytosis, leukopenia, thrombocytopenia.

Hepatic

Hepatitis, hepatocellular injury, jaundice.

Metabolic

Weight gain or loss.

Respiratory

Dyspnea.

Miscellaneous

Facial flushing, hyperpyrexia, polydipsia, prolactin levels increased, ptosis.

Precautions

Warnings

Increased mortality in elderly patients with dementia-related psychosis

Elderly patients with dementia-related psychosis who are treated with antipsychotic drugs are at an increased risk of death. During the course of a typical 10-week trial, the rate of death in drug-treated patients was approximately 4.5% compared with a rate of approximately 2.6% in the placebo group. Although the causes of death varied, most of the deaths appeared to be CV (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature.

Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. Loxapine is not approved for the treatment of patients with dementia-related psychosis.


Monitor

Monitor CBC frequently during the first few months of therapy in patients with a history of clinically significant low WBC or drug-induced leukopenia/neutropenia. Monitor patients with neutropenia for fever or other symptoms or signs of infection. If a patient requires loxapine treatment after recovery from NMS, carefully monitor the patient because recurrences of NMS have been reported.


Pregnancy

Category undetermined . Neonates exposed to antipsychotics during the third trimester of pregnancy are at risk of extrapyramidal and/or withdrawal symptoms.

Lactation

Undetermined.

Children

Safety and efficacy not established.

Special Risk Patients

Use with caution in patients with a history of CV disease, glaucoma, or tendency for urinary retention.

Antiemetic effect

Because loxapine may have an antiemetic effect, signs and symptoms of overdosage with certain drugs or conditions (eg, brain tumor, intestinal obstruction) may be masked.

Cognitive and motor performance

Judgment, thinking, or motor skills may be impaired.

Hematologic effects

Leukopenia, neutropenia, and agranulocytosis have been reported.

Hyperprolactinemia

Prolactin levels may be elevated.

NMS

This potentially fatal condition has been reported in association with antipsychotic agents. Signs and symptoms include hyperpyrexia, muscle rigidity, altered mental status, irregular pulse or BP, tachycardia, diaphoresis, and cardiac arrhythmias.

Ophthalmic effects

Carefully observe patient for pigmentary retinopathy and lenticular pigmentation.

Seizures

May occur; use with caution in patients with a history of seizures or other conditions that potentially lower the seizure threshold.

Tardive dyskinesia

This syndrome of potentially irreversible, involuntary, dyskinetic movements may develop. Prevalence is higher in elderly patients, especially women. Use lowest effective dose for shortest period of time needed.

Overdosage

Symptoms

CV and CNS depression, extrapyramidal symptoms, profound hypotension, renal failure, respiratory depression, seizures, unconsciousness.

Patient Information

  • Explain name, dose, action, and potential side effects of drug, including risk of developing tardive dyskinesia.
  • Advise patients that dose will be started low and then increased until max benefit is achieved; advise patient not to take more than prescribed or increase the dose more rapidly than advised.
  • Advise patients to take prescribed dose without regard to meals, but to take with food if stomach upset occurs.
  • Instruct patients not to change the dose or stop taking unless advised by health care provider.
  • Instruct patients not to stop taking loxapine when symptoms have improved.
  • Tell patients to immediately report high fever, muscle rigidity, involuntary body or facial movements, altered mental status, irregular pulse, or sweating to their health care provider.
  • Instruct patients to avoid alcohol and other CNS depressant medications.
  • Advise patients to take sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
  • Advise patients that loxapine may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Advise patients to notify their health care provider if excessive drowsiness occurs.
  • Advise patients not to breast-feed during therapy.
  • Advise patients to notify their health care provider if they become pregnant or intend to become pregnant during treatment.

Copyright © 2009 Wolters Kluwer Health.

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