Usual Adult Dose for Schizophrenia

Initial Dose: 10 mg orally twice a day

• Initial doses of up to 50 mg a day may be needed in severely disturbed patients

Titrate rapidly over the first 7 to 10 days until symptoms are effectively controlled
Maintenance Dose: 60 mg to 100 mg daily in divided doses, 2 to 4 times a day
Maximum dose: 250 mg/day

Comments:

• Daily dosage should be adjusted to the individual patient's needs based on severity of symptoms and previous antipsychotic drug response.
• Usual therapeutic and maintenance range is 60 to 100 mg daily; however, some patients may respond to lower, and others higher, doses.
• For maintenance therapy, 20 to 60 mg has been satisfactory for a majority of patients.

Use: For the treatment of schizophrenia

Usual Adult Dose for Agitated State

10 mg by oral inhalation once within a 24-hour period

Comments:

• To mitigate the risk of bronchospasm, all patients must undergo screening and examination prior to administration.
• This drug must be administered by a healthcare professional only in an enrolled healthcare facility.

Use: For the acute treatment of agitation associated with schizophrenia or bipolar I disorder

Renal Dose Adjustments

Inhalation: No dosage adjustment necessary

Oral: Data not available

Liver Dose Adjustments

Inhalation: No dosage adjustment necessary

Oral: Data not available

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for Adasuve(R) Inhalation powder. The REMS consists of a communication plan, elements to assure safe use, and an implementation system. Additional information is available at www.fda.gov/REMS.

US BOXED WARNINGS:
INCREASED MORTALITY in ELDERLY PATIENTS with DEMENTIA-RELATED PSYCHOSIS:

• Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Loxapine succinate is not approved for the treatment of patients with dementia-related psychosis.

BRONCHOSPASM:

• This drug can cause bronchospasm that has the potential to lead to respiratory distress and respiratory arrest. This drug is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Adasuve REMS. Administer only in an enrolled healthcare facility that has immediate access on-site to equipment and personnel trained to manage acute bronchospasm, including advanced airway management (intubation and mechanical ventilation).

Safety and efficacy have not been established in pediatric patients.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Take capsules with or without food

Inhaler:

• Do not administer more than 1 dose within a 24-hour period
• For preparation of inhaler, see below
• Explain to patient that it is normal for the inhaler to produce a flash of light, a clicking sound, and become warm during use.
• To administer dose, patient should breathe out fully to empty the lungs; place mouthpiece between lips, close lips, and inhale with a steady deep breath through the mouthpiece; remove mouthpiece and hold breath as long as possible up to 10 seconds.
• Check that the green light turns off as this will indicate that a dose has been delivered; if the green light remains on, the dose has not been delivered; may repeat administration up to 2 additional times; if still, the green light does not turn off, discard the inhaler and start over with a new one.

Storage requirements:

• Keep inhaler in pouch until ready to use
• The inhaler contains a lithium battery; dispose of in accordance with all federal, state, and local laws.

Preparation techniques:

• Tear open pouch to remove the inhaler; the indicator light should be off.
• Firmly pull the plastic tab from the rear of the inhaler; the green light should turn on indicating the inhaler is ready for use; the inhaler will automatically deactivate if not used within 15 minutes (the green light will turn off and the inhaler is not useable).
• Discard inhaler after 1 use.

General:

• Psychomotor agitation is defined in DSM-IV as "excessive motor activity associated with a feeling of inner tension".
• Patients exposed chronically to antipsychotics should understand the risk of tardive dyskinesia
• During chronic therapy, patients should be periodically reassessed to determine continued need for treatment.

Monitoring:

• Chronic use: Patients with preexisting low WBC and/or a prior history of drug-induced leukopenia or neutropenia should monitor CBC frequently during the first few months.
• For patients using inhaler, monitor for signs and symptoms of bronchospasm at least every 15 minutes and for at least 1 hour after use; monitoring should include chest auscultation.

Patient advice:

• This drug may impair judgment, thinking, or motor skills; have patient avoid driving or operating machinery until adverse effects are determined.
• Advise patient to speak to physician or health care professional if pregnant, intend to become pregnant, or are breastfeeding.
• Patients should be aware of signs and symptoms of neuroleptic malignant syndrome and be instructed to contact health care provider right away if symptoms are present.
• Patients should be advised to report signs/symptoms of bronchospasm (e.g., wheezing, shortness of breath, chest tightness, cough).