Loxapine Succinate

Name: Loxapine Succinate

Clinical pharmacology

Pharmacodynamics

Pharmacologically, loxapine (loxapine (loxapine (loxapine succinate) succinate) succinate) is an antipsychotic for which the exact mode of action has not been established. However, changes in the level of excitability of subcortical inhibitory areas have been observed in several animal species in association with such manifestations of tranquilization as calming effects and suppression of aggressive behavior.

In normal human volunteers, signs of sedation were seen within 20 to 30 minutes after administration, were most pronounced within one and one-half to three hours, and lasted through 12 hours. Similar timing of primary pharmacologic effects was seen in animals.

Absorption, Distribution, Metabolism, and Excretion

Absorption of loxapine (loxapine (loxapine (loxapine succinate) succinate) succinate) following oral or parenteral administration is virtually complete. The drug is removed rapidly from the plasma and distributed in tissues. Animal studies suggest an initial preferential distribution in lungs, brain, spleen, heart, and kidney. Loxapine (loxapine (loxapine (loxapine succinate) succinate) succinate) is metabolized extensively and is excreted mainly in the first 24 hours. Metabolites are excreted in the urine in the form of conjugates and in the feces unconjugated.

What should i avoid while taking loxapine (loxitane)?

Loxapine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Avoid drinking alcohol. You should not take loxapine if you are under the effects of alcohol.

Avoid becoming overheated or dehydrated during exercise and in hot weather. Loxapine can decrease perspiration and you may be more prone to heat stroke.

Where can i get more information?

Your pharmacist can provide more information about loxapine.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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Uses for Loxapine Succinate

Psychotic Disorders

Symptomatic management of psychotic disorders (i.e., schizophrenia).a b e g h i j q r

Has been used in the management of refractory or treatment-resistant schizophrenia.b s v

Mental Retardation

Efficacy not established for the management of behavioral complications in patients with mental retardation.a b g h

Loxapine Succinate Dosage and Administration

General

  • Adjust dosage carefully according to individual requirements and response; use the lowest possible effective dosage.a b g h j q r v

  • Periodically evaluate patients receiving long-term therapy to determine whether maintenance dosage can be decreased or drug therapy discontinued.a g h aa (See Tardive Dyskinesia under Cautions.)

  • For symptomatic relief of psychotic disorders, initial therapeutic response to antipsychotic therapy usually occurs within 2–4 weeks and optimum therapeutic response occurs within 6 months or longer.b i q aa v

Administration

Oral Administration

Loxapine succinate is administered orally, usually in divided doses 2–4 times daily.a b g h j v Loxapine hydrochloride has been given orally and parenterally, but no longer is commercially available in the US.b e j k

Dosage

Available as loxapine succinate; dosage expressed in terms of loxapine.a b g h k

Adults

Psychotic Disorders Oral

Initially, 10 mg given twice daily.a b g h j q r v

In severely schizophrenic patients, an initial dosage of up to 50 mg daily may be preferable.a b g h j q r v

May increase dosage fairly rapidly during the first 7–10 days of therapy according to patient response and tolerance.a b g h j q r v

Usual maintenance dosage: 60–100 mg daily; some patients respond to a lower dosage and others require a higher dosage.a b g h i j q r t v For severely ill patients with chronic schizophrenia, some clinicians recommend maintenance dosages of 100–200 mg daily.b

Prescribing Limits

Adults

Psychotic Disorders Oral

Maximum 250 mg daily.a b g h v

Special Populations

Geriatric Patients

No specific dosage recommendations for geriatric patients, but generally select dosage at the lower end of recommended range; increase dosage more gradually and monitor closely.i j r aa dd (See Geriatric Use under Cautions.)

Interactions for Loxapine Succinate

Drugs Affecting Hepatic Microsomal Enzymes

Pharmacokinetic interactions with inhibitors of CYP2D6, CYP3A4, or CYP1A2 are possible.s

Specific Drugs

Drug

Interaction

Comments

Alcohol

Potential additive CNS depressant effectsa b g h j q r v

Use with cautiona b g h

Anticholinergic drugs

Possible potentiated anticholinergic effectsa b g h

Use with cautiona b g h

Anticonvulsants (e.g., carbamazepine, phenobarbital, phenytoin)

Anticonvulsants may decrease plasma loxapine concentrationss

Loxapine may lower seizure thresholda b g h j q r

Phenytoin: Loxapine may decrease serum phenytoin concentrationsq r

Dosage adjustment of anticonvulsants may be necessary during concomitant usej s

Beta-blockers (e.g., propranolol)

Possible further lowering of BPr v

Use with caution and consider reduced loxapine dosager v

CNS depressants (e.g., antihistamines, barbiturates, general anesthetics, opiate analgesics, sedative/hypnotics)

Possible additive effects or potentiated action of other CNS depressantsa b g h j q r

Use with caution to avoid excessive sedation or CNS depressiona b g h r

Epinephrine or dopamine

Possible further lowering of BPa b g h aa

Do not use epinephrine or dopamine for loxapine-induced hypotensiona b g h aa (see Cardiovascular Effects under Cautions)

Lithium

An acute encephalopathic syndrome reported occasionally, especially when high serum lithium concentrations present j aa

Observe patients receiving combined therapy for evidence of adverse neurologic effects; promptly discontinue if such signs or symptoms appearaa

Lorazepam

Possible respiratory depression, stupor, and/or hypotensiona g h p s

Advice to Patients

  • Importance of advising patients and caregivers that geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death.122 126 ee Inform patients and caregivers that loxapine is not approved for treating geriatric patients with dementia-related psychosis.126 ee

  • Potential for drug to impair mental alertness or physical coordination; use caution when driving or operating machinery until effects on individual are known.a g h

  • Importance of avoiding alcohol during loxapine therapy.a g h r

  • Importance of clinicians informing patients in whom chronic use is contemplated of risk of tardive dyskinesia, taking into account clinical circumstances and competency of patient to understand information provided.a g h

  • Importance of clinicians informing patients of risk of extrapyramidal reactions and providing reassurance that these reactions usually can be controlled by administration of antiparkinsonian drugs (e.g., benztropine) and by subsequent dosage reduction.a g h aa

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., cardiovascular disease, seizure disorder).a g h

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.a g h Importance of clinicians informing patients about the benefits and risks of taking antipsychotics during pregnancy (see Pregnancy under Cautions).129 Importance of advising patients not to stop taking loxapine if they become pregnant without consulting their clinician; abruptly stopping antipsychotic agents may cause complications.129

  • Importance of informing patients of other important precautionary information.a g h (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Loxapine Succinate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

5 mg (of loxapine)*

Loxapine Succinate Capsules

Amide, Mylan, Watson

Loxitane

Watson

10 mg (of loxapine)*

Loxapine Succinate Capsules

Amide, Mylan, Watson

Loxitane

Watson

25 mg (of loxapine)*

Loxapine Succinate Capsules

Amide, Mylan, Watson

Loxitane

Watson

50 mg (of loxapine)*

Loxapine Succinate Capsules

Amide, Mylan, Watson

Loxitane

Watson

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