Adasuve
loxapine · Aerosol, Powder · Respiratory (inhalation)
Uses
1 INDICATIONS AND USAGE ADASUVE is indicated for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults [see Clinical Studies (14) ] . ADASUVE is an atypical antipsychotic indicated for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults ( 1 ). Limitations of Use: ADASUVE must be administered only in a certified healthcare setting ( 1 ). Limitations of Use: As part of the ADASUVE REMS Program to mitigate the risk of bronchospasm, ADASUVE must be administered only in a certified healthcare setting [see Warnings and Precautions (5.2) ] .
Dosage and administration
Must be administered only by a healthcare professional ( 2.1 ) 10 mg by oral inhalation using an inhaler ( 2.1 ) Administer only a single dose within any 24-hour period ( 2.1 ) Prior to administering, screen all patients for a history of pulmonary disease, and assess patients (including chest auscultation) for respiratory abnormalities (e.g. wheezing) ( 2.2 ) Refer to Full Prescribing Information for important instructions on use of the ADASUVE inhaler ( 2.3 ) After administration, monitor patients for signs and symptoms of bronchospasm for at least one hour ( 2.4 ) 2.1 Dosing Information ADASUVE must be administered only by a healthcare professional. ADASUVE is administered by oral inhalation only. The recommended dose for acute agitation is 10 mg administered by oral inhalation, using a single-use inhaler. Administer only a single dose within a 24-hour period [see Warnings and Precautions (5.1) ] . 2.2 Required Examination Prior to Dosing Prior to administering ADASUVE, screen all patients for a history of asthma, COPD, or other pulmonary disease, and assess patients (including chest auscultation) for respiratory signs (e.g. wheezing) [see Warnings and Precautions (5.1) ] . 2.3 Important Administration Instructions Read all of these instructions prior to administering ADASUVE. Step 1. Open the Pouch When ready to use, tear open the foil pouch and remove the inhaler from the package (see Figure 1 ). Figure 1. Tearing the pouch When the ADASUVE inhaler is removed from the pouch, the indicator light is off (see Figure 2 ). Figure 2. ADASUVE Inhaler with Indicator Light Step 2. Pull Tab Firmly pull the plastic tab from the rear of the inhaler (see Figure 3 ). Check that the green light turns on. This indicates that the inhaler is ready for use. Use the inhaler within 15 minutes after removing the tab to prevent automatic deactivation of the inhaler. The green light will turn off, indicating that the inhaler is not usable. Discard the inhaler after one use. Figure 3. Step 3. Explain Procedures to the Patient Explain the administration procedures to the patient prior to use, and advise the patient that it is important to follow the instructions. Inform the patient that the inhaler may produce a flash of light and a clicking sound, and it may become warm during use. These are normal. Step 4. Instruct the Patient to Exhale Instruct the patient to hold the inhaler away from the mouth and breathe out fully to empty the lungs (see Figure 4 ). Figure 4. Exhale Step 5. Instruct the Patient to Inhale Instruct the patient to put the mouthpiece of the inhaler between the lips, close the lips, and inhale through the mouthpiece with a steady deep breath (see Figure 5 ). Check that the green light turns off indicating that the dose has been delivered. Figure 5. Inhale Step 6. Instruct the Patient to Hold Breath Instruct the patient to remove the mouthpiece from the mouth and hold the breath for as long as possible, up to 10 seconds (see Figure 6 ). Figure 6. Hold Breath Important: If the green light remains on after the patient inhales, the dose of ADASUVE has NOT been delivered. Instruct the patient to repeat Step 4, Step 5, and Step 6 up to 2 additional times. If the green light still does not turn off, discard the inhaler and use a new one. Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 2.4 Monitoring to Assess Safety Monitor the patient for signs and symptoms of bronchospasm after ADASUVE administration for at least one hour [see Warnings and Precautions (5.1) ] .
Dosage forms and strengths
3 DOSAGE FORMS AND STRENGTHS ADASUVE is an inhalation powder supplied in a single-use, disposable inhaler containing 10 mg of loxapine base. Inhalation powder: 10 mg unit in a single-use inhaler ( 3 )
Contraindications
4 CONTRAINDICATIONS ADASUVE is contraindicated in patients with the following: Current diagnosis or history of asthma, COPD, or other lung disease associated with bronchospasm [see Warnings and Precautions (5.1) ] Acute respiratory symptoms or signs (e.g., wheezing) [see Warnings and Precautions (5.1) ] Current use of medications to treat airways disease, such as asthma or COPD [see Warnings and Precautions (5.1) ] History of bronchospasm following ADASUVE treatment [see Warnings and Precautions (5.1) ] Known hypersensitivity to loxapine or amoxapine. Serious skin reactions have occurred with oral loxapine and amoxapine. Current diagnosis or history of asthma, chronic obstructive pulmonary disease (COPD), or other lung disease associated with bronchospasm ( 4 ) Acute respiratory signs/symptoms (e.g., wheezing) ( 4 ) Current use of medications to treat airways disease, such as asthma or COPD ( 4 ) History of bronchospasm following ADASUVE treatment ( 4 ) Known hypersensitivity to loxapine or amoxapine ( 4 )
Warnings and precautions
Neuroleptic Malignant Syndrome : May develop in patients treated with antipsychotic drugs. Discontinue treatment ( 5.4 ) Hypotension and Syncope : Use with caution in patients with known cardiovascular or cerebrovascular disease ( 5.5 ) Seizure : Use with caution in patients with a history of seizures or with conditions that lower the seizure threshold ( 5.7 ) Potential for Cognitive and Motor Impairment : Use caution when driving or operating machinery ( 5.8 ) Cerebrovascular Adverse Reactions : Increased incidence of stroke and transient ischemic attack in elderly patients with dementia-related psychosis treated with antipsychotic drugs ( 5.9 ) 5.1 Bronchospasm ADASUVE can cause bronchospasm that has the potential to lead to respiratory distress and respiratory arrest [see Adverse Reactions (6.1) ] . Administer ADASUVE only in a certified healthcare setting that has immediate access on site to supplies and healthcare professionals competent in the management of acute bronchospasm and access to emergency assistance for symptoms that require immediate medical attention. Certified healthcare settings must have a short-acting bronchodilator (e.g. albuterol) available for the immediate treatment of bronchospasm; this short-acting bronchodilator can be delivered by inhaler (with spacer) or nebulizer [see Boxed Warning and Warnings and Precautions (5.2) ] . Prior to administering ADASUVE, screen patients regarding a current diagnosis or history of asthma, COPD, and other lung disease associated with bronchospasm, acute respiratory symptoms or signs, current use of medications to treat airways disease, such as asthma or COPD; and assess patients (including chest auscultation) for respiratory abnormalities (e.g., wheezing) [See Dosage and Administration (2.2) and Contraindications (4) ] . Monitor patients for symptoms and signs of bronchospasm for a minimum of one hour following treatment with ADASUVE [see Dosage and Administration (2.4) ] . ADASUVE can cause sedation, which can mask the symptoms of bronchospasm. Because clinical trials in patients with asthma or COPD demonstrated that the degree of bronchospasm, as indicated by changes in forced expiratory volume in 1 second (FEV1), was greater following a second dose of ADASUVE, limit ADASUVE use to a single dose within a 24-hour period. Advise all patients of the risk of bronchospasm. Advise them to inform the healthcare professional if they develop any breathing problems such as wheezing, shortness of breath, chest tightness, or cough following treatment with ADASUVE. 5.2 ADASUVE REMS to Mitigate Bronchospasm Because of the risk of bronchospasm, ADASUVE is available only through a restricted program under a REMS called the ADASUVE REMS [see Boxed Warning and Warnings and Precautions (5.1) ] . Required components of the ADASUVE REMS are: Healthcare settings that dispense and administer ADASUVE must be certified and comply with the REMS requirements. Certified healthcare settings must be able to provide immediate access on site to supplies and healthcare professionals competent in the management of acute bronchospasm and access to emergency assistance for symptoms that require immediate medical attention. Settings must have a short-acting bronchodilator (e.g. albuterol) available for the immediate treatment of bronchospasm; this short-acting bronchodilator can be delivered by inhaler (with spacer) or nebulizer. Wholesalers and distributors that distribute ADASUVE must distribute only to certified healthcare settings. Further information is available at www.adasuverems.com or 1-855-755-0492. 5.3 Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at 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 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 cases 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 can be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. ADASUVE is not approved for the treatment of elderly patients with dementia-related psychosis [see Boxed Warning ] . 5.4 Neuroleptic Malignant Syndrome Antipsychotic drugs can cause a potentially fatal symptom complex termed Neuroleptic Malignant Syndrome (NMS). Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Associated features can include elevated serum creatine phosphokinase (CPK) concentration, rhabdomyolysis, elevated serum and urine myoglobin concentration, and renal failure. NMS did not occur in the ADASUVE clinical program. The diagnostic evaluation of patients with this syndrome is complicated. It is important to consider the presence of other serious medical conditions (e.g., pneumonia, systemic infection, heat stroke, primary CNS pathology, central anticholinergic toxicity, extrapyramidal symptoms, or drug fever). The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs that may contribute to the underlying disorder, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems.
Side effects
The following adverse reactions are discussed in more detail in other sections of the labeling: Hypersensitivity (serious skin reactions) [see Contraindications (4) ] Bronchospasm [see Warnings and Precautions (5.1) ] Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Warnings and Precautions (5.3) ] Neuroleptic Malignant Syndrome [see Warnings and Precautions (5.4) ] Hypotension and syncope [see Warnings and Precautions (5.5) ] Falls [see Warnings and Precautions (5.6) ] Seizure [see Warnings and Precautions (5.7) ] Potential for Cognitive and Motor Impairment [see Warnings and Precautions (5.8) ] Cerebrovascular Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis [see Warnings and Precautions (5.9) ] Anticholinergic Reactions Including Exacerbation of Glaucoma and Urinary Retention [see Warnings and Precautions (5.10) ] Most common adverse reactions (incidence ≥ 2% and greater than placebo) were dysgeusia, sedation, and throat irritation ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS contact Alexza Pharmaceuticals, Inc. at 1-800-284-0062 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The following findings are based on pooled data from three short-term (24-hour), randomized, double-blind, placebo-controlled clinical trials (Studies 1, 2, and 3) of ADASUVE 10 mg in the treatment of patients with acute agitation associated with schizophrenia or bipolar I disorder. In the 3 trials, 259 patients received ADASUVE 10 mg, and 263 received placebo [see Clinical Studies (14) ] . Commonly Observed Adverse Reactions : In the 3 trials in acute agitation, the most common adverse reactions were dysgeusia, sedation, and throat irritation. These reactions occurred at a rate of at least 2% of the ADASUVE group and at a rate greater than in the placebo group. (Refer to Table 1). Table 1. Adverse Reactions in 3 Pooled Short-Term, Placebo-Controlled Trials (Studies 1, 2, and 3) in Patients with Schizophrenia or Bipolar Disorder Adverse Reaction Placebo (n = 263) ADASUVE (n = 259) Dysgeusia 5% 14% Sedation 10% 12% Throat Irritation 0% 3% Airway Adverse Reactions in the 3 Trials in Acute Agitation Agitated patients with Schizophrenia or Bipolar Disorder: In the 3 short-term (24-hour), placebo-controlled trials in patients with agitation associated with schizophrenia or bipolar disorder (Studies 1, 2, and 3), bronchospasm (which includes reports of wheezing, shortness of breath and cough) occurred more frequently in the ADASUVE group, compared to the placebo group: 0% (0/263) in the placebo group and 0.8% (2/259) in the ADASUVE 10 mg group. One patient with schizophrenia, without a history of pulmonary disease, had significant bronchospasm requiring rescue treatment with a bronchodilator and oxygen. Bronchospasm and Airway Adverse Reactions in Pulmonary Safety Trials Clinical pulmonary safety trials demonstrated that ADASUVE can cause bronchospasm as measured by FEV1, and as indicated by respiratory signs and symptoms in the trials. In addition, the trials demonstrated that patients with asthma or other pulmonary diseases, such as COPD are at increased risk of bronchospasm. The effect of ADASUVE on pulmonary function was evaluated in 3 randomized, double-blind, placebo-controlled clinical pulmonary safety trials in healthy volunteers, patients with asthma, and patients with COPD. Pulmonary function was assessed by serial FEV1 tests, and respiratory signs and symptoms were assessed. In the asthma and COPD trials, patients with respiratory symptoms or FEV1 decrease of ≥ 20% were administered rescue treatment with albuterol (metered dose inhaler or nebulizer) as required. These patients were not eligible for a second dose; however, they had continued FEV1 monitoring in the trial. Healthy Volunteers : In the healthy volunteer crossover trial, 30 subjects received 2 doses of either ADASUVE or placebo 8 hours apart, and 2 doses of the alternate treatment at least 4 days later. The results for maximum decrease in FEV1 are presented in Table 2. No subjects in this trial developed airway related adverse reactions (cough, wheezing, chest tightness, or dyspnea). Asthma Patients: In the asthma trial, 52 patients with mild-moderate persistent asthma (with FEV1 ≥ 60% of predicted) were randomized to treatment with 2 doses of ADASUVE 10 mg or placebo. The second dose was to be administered 10 hours after the first dose. Approximately 67% of these patients had a baseline FEV1 ≥ 80% of predicted. The remaining patients had an FEV1 60-80% of predicted. Nine patients (17%) were former smokers. As shown in Table 2 and Figure 7, there was a marked decrease in FEV1 immediately following the first dose (maximum mean decreases in FEV1 and % predicted FEV1 were 303 mL and 9.1%, respectively). Furthermore, the effect on FEV1 was greater following the second dose (maximum mean decreases in FEV1 and % predicted FEV1 were 537 mL and 14.7%, respectively). Respiratory-related adverse reactions (bronchospasm, chest discomfort, cough, dyspnea, throat tightness, and wheezing) occurred in 54% of ADASUVE-treated patients and 12% of placebo-treated patients. There were no serious adverse events. Nine of 26 (35%) patients in the ADASUVE group, compared to one of 26 (4%) in the placebo group, did not receive a second dose of study medication, because they had a ≥ 20% decrease in FEV1 or they developed respiratory symptoms after the first dose.
Drug interactions
7.1 CNS Depressants ADASUVE is a central nervous system (CNS) depressant. The concurrent use of ADASUVE with other CNS depressants (e.g., alcohol, opioid analgesics, benzodiazepines, tricyclic antidepressants, general anesthetics, phenothiazines, sedative/hypnotics, muscle relaxants, and/or illicit CNS depressants) can increase the risk of respiratory depression, hypotension, profound sedation, and syncope. Therefore, consider reducing the dose of CNS depressants if used concomitantly with ADASUVE. 7.2 Anticholinergic Drugs ADASUVE has anticholinergic activity. The concomitant use of ADASUVE and other anticholinergic drugs can increase the risk of anticholinergic adverse reactions including exacerbation of glaucoma and urinary retention.
Use in specific populations
Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure ( 8.1 ). 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. Risk Summary Neonates exposed to antipsychotic drugs, including ADASUVE, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations ). The available data from published case reports and pharmacovigilance cases with loxapine, the active ingredient in ADASUVE, in pregnant women are insufficient to determine a drug-associated risk for major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother associated with untreated schizophrenia or bipolar I disorder, and with exposure to antipsychotics, including ADASUVE, during pregnancy (see Clinical Considerations ) . In animal reproduction studies, increased embryofetal toxicity and death in rat fetuses and offspring were observed when pregnant rats were orally administered loxapine, during the period of organogenesis, at doses approximately less than or equal to the maximum recommended human dose (MRHD) based on mg/m 2 body surface area (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs, including ADASUVE, during the third trimester of pregnancy. These symptoms have varied in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Data Animal Data Pregnant rats were administered oral doses of 1, 4, and 12 mg/kg/day loxapine (~1, 4, and 12 times the MRHD of 10 mg/day based on mg/m 2 body surface area, respectively) during the period of organogenesis. Embryofetal toxicity (increased fetal resorptions, reduced weights, and hydronephrosis with hydroureter) was observed at doses equal to the MRHD and higher based on mg/m 2 body surface area. Pregnant rabbits were administered oral doses of 20 and 60 mg/kg/day loxapine (~40 and 120 times the MRHD based on mg/m 2 body surface area) during the period of organogenesis. Loxapine did not cause adverse developmental effects in rabbits at doses up to 120 times the MRHD based on mg/m 2 body surface area. Pregnant rats were administered oral doses of 0.21, 0.62, and 1.86 mg/kg/day loxapine (~0.2, 0.6, and 1.8 times the MRHD based on mg/m 2 body surface area) during the period of organogenesis and through lactation. Fetal toxicity (increased prenatal death, decreased postnatal survival, reduced fetal weights, delayed ossification, and/or distended renal pelvis with reduced or absent papillae) was observed at doses of 0.6 times the MRHD and higher based on mg/m 2 body surface area. 8.2 Lactation Risk Summary There is no available information on the presence of loxapine in human milk, the effects of loxapine on the breastfed infant, or the effects of loxapine on milk production. Loxapine is present in the milk of lactating dogs. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ADASUVE and any potential adverse effects on the breastfed child from ADASUVE or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of ADASUVE in pediatric patients have not been established. 8.5 Geriatric Use Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death [see Boxed Warning and Warnings and Precautions (5.3) ] . ADASUVE is not approved for the treatment of dementia-related psychosis. Placebo-controlled studies of ADASUVE in patients with agitation associated with schizophrenia or bipolar disorder did not include patients over 65 years of age.
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. Risk Summary Neonates exposed to antipsychotic drugs, including ADASUVE, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations ). The available data from published case reports and pharmacovigilance cases with loxapine, the active ingredient in ADASUVE, in pregnant women are insufficient to determine a drug-associated risk for major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother associated with untreated schizophrenia or bipolar I disorder, and with exposure to antipsychotics, including ADASUVE, during pregnancy (see Clinical Considerations ) . In animal reproduction studies, increased embryofetal toxicity and death in rat fetuses and offspring were observed when pregnant rats were orally administered loxapine, during the period of organogenesis, at doses approximately less than or equal to the maximum recommended human dose (MRHD) based on mg/m 2 body surface area (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs, including ADASUVE, during the third trimester of pregnancy. These symptoms have varied in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Data Animal Data Pregnant rats were administered oral doses of 1, 4, and 12 mg/kg/day loxapine (~1, 4, and 12 times the MRHD of 10 mg/day based on mg/m 2 body surface area, respectively) during the period of organogenesis. Embryofetal toxicity (increased fetal resorptions, reduced weights, and hydronephrosis with hydroureter) was observed at doses equal to the MRHD and higher based on mg/m 2 body surface area. Pregnant rabbits were administered oral doses of 20 and 60 mg/kg/day loxapine (~40 and 120 times the MRHD based on mg/m 2 body surface area) during the period of organogenesis. Loxapine did not cause adverse developmental effects in rabbits at doses up to 120 times the MRHD based on mg/m 2 body surface area. Pregnant rats were administered oral doses of 0.21, 0.62, and 1.86 mg/kg/day loxapine (~0.2, 0.6, and 1.8 times the MRHD based on mg/m 2 body surface area) during the period of organogenesis and through lactation. Fetal toxicity (increased prenatal death, decreased postnatal survival, reduced fetal weights, delayed ossification, and/or distended renal pelvis with reduced or absent papillae) was observed at doses of 0.6 times the MRHD and higher based on mg/m 2 body surface area.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of ADASUVE in pediatric patients have not been established.
Geriatric use
8.5 Geriatric Use Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death [see Boxed Warning and Warnings and Precautions (5.3) ] . ADASUVE is not approved for the treatment of dementia-related psychosis. Placebo-controlled studies of ADASUVE in patients with agitation associated with schizophrenia or bipolar disorder did not include patients over 65 years of age.
Overdosage
Signs and Symptoms of Overdosage As would be expected from the pharmacologic actions of loxapine, the clinical findings may include CNS depression, unconsciousness, profound hypotension, respiratory depression, extrapyramidal symptoms, and seizure. Management of Overdosage For the most up to date information on the management of ADASUVE overdosage, contact a certified poison control center (1-800-222-1222 or www.poison.org). Provide supportive care including close medical supervision and monitoring. Treatment should consist of general measures employed in the management of overdosage with any drug. Consider the possibility of multiple drug overdosage. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. Use supportive and symptomatic measures.
Description
11 DESCRIPTION ADASUVE, an atypical antipsychotic, is an inhalation powder of loxapine supplied in a single-use, disposable inhaler containing 10 mg of loxapine base. ADASUVE is a drug-device combination product. Active Ingredient: Loxapine (base). Loxapine, a dibenzoxazepine compound, represents a subclass of tricyclic antipsychotic agents, chemically distinct from the thioxanthenes, butyrophenones, and phenothiazines. Chemically, it is 2-Chloro-11-(4-methyl-1-piperazinyl) dibenz [b,f] [1,4] oxazepine. ADASUVE is a single-use, drug-device combination product that provides rapid systemic delivery by inhalation of a thermally-generated aerosol of loxapine. Oral inhalation through the product initiates the controlled rapid heating of a thin film of excipient-free loxapine to form a thermally-generated drug vapor. The vapor condenses into aerosol particles that are dispersed into the airstream created by the patient inhaling through the mouthpiece. Each product is packaged inside a sealed foil pouch. The product is a white to off-white plastic unit, with a mouthpiece on one end and a pull-tab protruding from the other end. Removal of a pull-tab from the product renders it ready for use, as indicated by illumination of a green light. After inhalation through the mouthpiece, successful dosing is signaled by the green light turning off. Under standardized in vitro test conditions, ADASUVE, 10 mg delivers 9.1 mg of loxapine out of the mouthpiece. Chemical Structure
Mechanism of action
12.1 Mechanism of Action The mechanism of action of loxapine in the treatment of agitation associated with schizophrenia and bipolar I disorder is unclear. However, its efficacy could be mediated through a combination of antagonism of central serotonin and dopamine receptors.
How supplied
16.1 How Supplied ADASUVE ® (loxapine) inhalation powder is supplied as: ADASUVE 10 mg (NDC 51097-001-01) is a single-use, disposable inhaler containing 10 mg of loxapine, provided in a sealed foil pouch. ADASUVE, 10 mg is supplied in a carton of 5 units per carton (NDC 51097-001-02). 16.2 Restricted Access ADASUVE is only available through a restricted program called the ADASUVE REMS Program [see Warnings and Precautions (5.2) ] . 16.3 Storage and Handling Store ADASUVE at room temperature, 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Keep out of reach of children. Keep ADASUVE in pouch until time of use. ADASUVE contains a lithium battery. Dispose of ADASUVE in accordance with all federal, state and local laws.
Storage
16.3 Storage and Handling Store ADASUVE at room temperature, 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Keep out of reach of children. Keep ADASUVE in pouch until time of use. ADASUVE contains a lithium battery. Dispose of ADASUVE in accordance with all federal, state and local laws.
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Bronchospasm Advise patients and caregivers that there is a risk of bronchospasm. Advise patients to inform their healthcare professional if they develop any breathing problems such as wheezing, shortness of breath, chest tightness, or cough following treatment with ADASUVE [see Boxed Warning and Warnings and Precautions (5.1) ] . Interference with Cognitive and Motor Performance Caution patients and caregivers about performing activities requiring mental alertness, such as operating hazardous machinery or operating a motor vehicle, until they are reasonably certain that ADASUVE has not affected them adversely [see Warnings and Precautions (5.8) ] . Caution patients and caregivers about the potential for sedation, especially when used concurrently with other CNS depressants (e.g., alcohol, opioid analgesics, benzodiazepines, tricyclic antidepressants, general anesthetics, phenothiazines, sedative/hypnotics, muscle relaxants, and/or illicit CNS depressants). Neuroleptic Malignant Syndrome Patients and caregivers should be counseled that a potentially fatal symptom complex sometimes referred to as NMS has been reported in association with administration of antipsychotic drugs. Signs and symptoms of NMS include hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia) [see Warnings and Precautions (5.4) ] . Hypotension and Syncope Advise patients and caregivers of the risk of hypotension or orthostatic hypotension (symptoms include feeling dizzy or lightheaded upon standing) [see Warnings and Precautions (5.5) ] . Anticholinergic Reactions Counsel patients and caregivers about the potential risks of anticholinergic reactions, such as exacerbation of glaucoma and urinary retention [see Warnings and Precautions (5.10) ] . Pregnancy Advise pregnant women to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with ADASUVE. Advise patients that ADASUVE may cause extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder) in a neonate. Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADASUVE during pregnancy [see Use in Specific Populations (8.1) ] .
Label text from the FDA structured product label by Alexza Pharmaceuticals, Inc. (revised Jul 6, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Loxapine in 1 product
Adasuve NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 51097-001 | Loxapine 10 mg/1 Aerosol, Powder | Alexza Pharmaceuticals, Inc. | NDA |
Frequently asked questions
What is Adasuve used for?
1 INDICATIONS AND USAGE ADASUVE is indicated for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults [see Clinical Studies (14) ] . ADASUVE is an atypical antipsychotic indicated for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults ( 1 ). Limitations of Use: ADASUVE must be administered only in a certified…
What are the side effects of Adasuve?
The following adverse reactions are discussed in more detail in other sections of the labeling: Hypersensitivity (serious skin reactions) [see Contraindications (4) ] Bronchospasm [see Warnings and Precautions (5.1) ] Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Warnings and Precautions (5.3) ] Neuroleptic Malignant Syndrome [see Warnings and Precautions (5.4) ]… See the full label for the complete list.
Who makes Adasuve?
Adasuve is listed by 1 labeler in the FDA NDC directory, including Alexza Pharmaceuticals, Inc..