Adasuve

Name: Adasuve

Indications

ADASUVE is a typical antipsychotic indicated for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults.

“Psychomotor agitation” is defined in DSM-IV as “excessive motor activity associated with a feeling of inner tension.” Patients experiencing agitation often manifest behaviors that interfere with their care (e.g., threatening behaviors, escalating or urgently distressing behavior, self-exhausting behavior), leading clinicians to the use of rapidly absorbed antipsychotic medications to achieve immediate control of the agitation [see Clinical Studies].

The efficacy of ADASUVE was established in one study of acute agitation in patients with schizophrenia and one study of acute agitation in patients with bipolar I disorder [see Clinical Studies].

Limitations Of Use

As part of the ADASUVE REMS Program to mitigate the risk of bronchospasm, ADASUVE must be administered only in an enrolled healthcare facility [see WARNINGS AND PRECAUTIONS].

Warnings

Included as part of the PRECAUTIONS section.

Uses For Adasuve

Inhaled loxapine is used to treat acute agitation in adult patients with schizophrenia or bipolar I disorder (type of depression). It works in the brain to increase levels of dopamine and serotonin, which are chemicals that help regulate agitation, schizophrenia, and depression. Loxapine is an antipsychotic medicine.

This medicine is available only under a special restricted distribution program called the AdasuveĀ® REMS program.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.
  • This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time Adasuve is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Adasuve or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Adasuve. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Dosage forms and strengths

Adasuve is an inhalation powder supplied in a single-use, disposable inhaler containing 10 mg of loxapine base.

Adverse reactions

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)]
  • 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)]

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. Rescue medication (albuterol via metered dose inhaler or nebulizer) was administered to 54% of patients in the Adasuve group [7 patients (27%) after the first dose and 7 of the remaining 17 patients (41%) after the second dose] and 12% in the placebo group (1 patient after the first dose and 2 patients after the second dose).

COPD Patients: In the COPD trial, 53 patients with mild to severe COPD (with FEV1 ≥ 40% 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 57% of these patients had moderate COPD [Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage II]; 32% had severe disease (GOLD Stage III); and 11% had mild disease (GOLD Stage I). As illustrated in Table 2 there was a decrease in FEV1 soon after the first dose (maximum mean decreases in FEV1 and % predicted FEV1 were 96 mL and 3.5%, respectively), and the effect on FEV1 was greater following the second dose (maximum mean decreases in FEV1 and % predicted FEV1 were 125 mL and 4.5%, respectively). Respiratory adverse reactions occurred more frequently in the Adasuve group (19%) than in the placebo group (11%). There were no serious adverse events. Seven of 25 (28%) patients in the Adasuve group and 1of 27 (4%) in the placebo group did not receive a second dose of study medication because of a ≥ 20% decrease in FEV1 or the development of respiratory symptoms after the first dose. Rescue medication (albuterol via MDI or nebulizer) was administered to 23% of patients in the Adasuve group: 8% of patients after the first dose and 21% of patients after the second dose, and to 15% of patients in the placebo group.

Table 2: Maximum Decrease in FEV1 from Baseline in the Healthy Volunteer, Asthma, and COPD Trials
Healthy Volunteer Asthma COPD
Maximum % FEV ↓ Placebo
n (%)
Adasuve 10 mg
n (%)
Placebo
n (%)
Adasuve 10 mg
n (%)
Placebo
n (%)
Adasuve 10 mg
n (%)
After any Dose N=26 N=26 N=26 N=26 N=27 N=25
≥10 7 (27) 7 (27) 3 (12) 22 (85) 18 (67) 20 (80)
≥15 1 (4) 5 (19) 1 (4) 16 (62) 9 (33) 14 (56)
≥20 0 1 (4) 1 (4) 11 (42) 3 (11) 10 (40)
After Dose 1 N=26 N=26 N=26 N=26 N=27 N=25
≥10 4 (15) 5 (19) 2 (8) 16 (62) 8 (30) 16 (64)
≥15 1 (4) 2 (8) 1 (4) 8 (31) 4 (15) 10 (40)
≥20 0 0 1 (4) 6 (23) 2 (7) 9 (36)
After Dose 2 N=26 N=25 N=25 N=17 N=26 N=19
≥10 5 (19) 6 (24) 3 (12) 12 (71) 15 (58) 12 (63)
≥15 0 5 (20) 1 (4) 9 (53) 6 (23) 10 (53)
≥20 0 1 (4) 1 (4) 5 (30) 1 (4) 5 (26)

FEV1 categories are cumulative; i.e. a subject with a maximum decrease of 21% is included in all 3 categories. Patients with a ≥ 20% decrease in FEV1 did not receive a second dose of study drug.

Figure 7: LS Mean Change from Baseline in FEV1 in Patients with Asthma

Patients with a ≥ 20% decrease in FEV1 did not receive a second dose of study drug and are not included in the curves beyond hour 10.

Extrapyramidal Symptoms (EPS): Extrapyramidal reactions have occurred during the administration of oral loxapine. In most patients, these reactions involved parkinsonian symptoms such as tremor, rigidity, and masked facies. Akathisia (motor restlessness) has also occurred.

In the 3 short-term (24-hour), placebo-controlled trials of Adasuve in 259 patients with agitation associated with schizophrenia or bipolar disorder, extrapyramidal reactions occurred. One patient (0.4%) treated with Adasuve developed neck dystonia and oculogyration. The incidence of akathisia was 0% and 0.4% in the placebo and Adasuve groups, respectively.

Dystonia (Antipsychotic Class Effect): Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during treatment with Adasuve. Dystonic symptoms include spasm of the neck muscles, sometimes progressing to tightness of the throat, difficulty swallowing or breathing, and/or protrusion of the tongue.

Acute dystonia tends to be dose-related, but can occur at low doses, and occurs more frequently with first generation antipsychotic drugs such as Adasuve. The risk is greater in males and younger age groups.

Cardiovascular Reactions: Tachycardia, hypotension, hypertension, orthostatic hypotension, lightheadedness, and syncope have been reported with oral administration of loxapine.

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.

Patient counseling 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

Counsel patients and caregivers regarding the potential risk to the fetus or neonate [see Use in Specific Populations (8.1)].

Nursing Mothers

Counsel patients and caregivers regarding the potential risk to the infant [see Use in Specific Populations (8.3)].

Manufactured by: Alexza Pharmaceuticals, Inc., Mountain View, CA 94043

MEDICATION GUIDE

Adasuve® (AD-uh-soov)

(loxapine)

Inhalation Powder

Read this Medication Guide before you start taking Adasuve and each time it is given to you. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or your treatment. You should share this information with your family members and caregivers.

What is the most important information I should know about Adasuve? 

Adasuve is available only through the Adasuve Risk Evaluation and Mitigation Strategy (REMS) Program. The healthcare facility must be enrolled in the Adasuve REMS Program before you can be given Adasuve.

Adasuve may cause serious side effects, including:

  • Narrowing of the airways (bronchospasm) that can cause you to have problems breathing or to stop breathing. People who have asthma or other airway or lung problems, such as chronic obstructive pulmonary disease (COPD), have a higher risk of bronchospasm when taking Adasuve. Symptoms of bronchospasm may include:
    ○ wheezing
    ○ coughing
    ○ chest tightness
    ○ shortness of breath

Tell your healthcare provider right away if you have any of these symptoms of bronchospasm after taking Adasuve.

Your healthcare provider should check you for breathing problems before and after you take Adasuve.

  • Increased risk of death in elderly patients with dementia-related psychosis.  Medicines like Adasuve can raise the risk of death in elderly people who have lost touch with reality (psychosis) due to confusion and memory loss (dementia). Adasuve is not approved for the treatment of patients with dementia-related psychosis.   

What is Adasuve?

Adasuve is a prescription medicine that is inhaled through your mouth and is used to treat acute agitation in adults with schizophrenia or bipolar I disorder.

It is not known if Adasuve is safe and effective in children.  

Who should not take Adasuve?

Do not take Adasuve if you:

  • have or have had asthma, chronic obstructive pulmonary disease (COPD), or other airway or lung problems that can cause bronchospasm
  • are having problems with wheezing, coughing, chest tightness, or shortness of breath
  • are taking medicines to treat asthma or COPD
  • have taken Adasuve before and had bronchospasm
  • are allergic to loxapine or amoxapine

What should I tell my healthcare provider before taking Adasuve?

Before you take Adasuve, tell your healthcare provider if you:

  • have high or low blood pressure 
  • have or have had heart problems or stroke
  • have or have had seizures (convulsions)
  • drink alcohol or use street drugs
  • have any other medical conditions
  • are pregnant or plan to become pregnant.  It is not known if Adasuve will harm your unborn baby.
  • are breastfeeding or plan to breastfeed.  It is not known if Adasuve passes into your breast milk.  You and your healthcare provider should decide if you will take Adasuve if you are breastfeeding.  

Tell your doctor about all medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

  • Adasuve and other medicines may affect each other causing side effects. Adasuve may affect the way other medicines work, and other medicines may affect the way Adasuve works.

Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure.

Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine.

How should I take Adasuve? 

  • Your healthcare provider will show you how to take Adasuve right before you take it.
  • Take Adasuve exactly as your healthcare provider shows you to take it.
  • Adasuve is for oral inhalation only.

What should I avoid while taking Adasuve?

  • Do not drive, operate heavy machinery, or do other dangerous activities until you know how Adasuve affects you.
  • Do not drink alcohol while taking Adasuve. It can increase your chances of getting serious side effects.

What are the possible side effects of Adasuve?

Adasuve can cause serious side effects, including:

  • See “What is the most important information I should know about Adasuve?”
  • neuroleptic malignant syndrome (NMS). NMS is a rare but serious condition that may cause death. Symptoms of NMS may include:
    ○ high fever
    ○ stiff muscles
    ○ confusion
    ○ sweating
    ○ changes in pulse, heart rate, and blood pressure

Tell your healthcare provider right away if you have any of these symptoms of NMS after taking Adasuve.

  • low blood pressure (hypotension), lightheadedness, or fainting
  • seizures (convulsions)
  • severe sleepiness and difficulty with potentially dangerous activities such as driving
  • worsening of glaucoma
  • difficulty urinating

The most common side effects of Adasuve include:

  • bad, bitter, or metallic taste in your mouth (dysgeusia)
  • sleepiness (especially when used with other drugs that cause sleepiness)
  • sore throat

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Adasuve.  For more information ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects.  You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of Adasuve.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide.

This Medication Guide summarizes the most important information about Adasuve.  If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about Adasuve that is written for health professionals.

For more information, go to www.Adasuve.com or call 1-800-284-0062.

What are the ingredients in Adasuve?

Active Ingredient: loxapine
Inactive Ingredients: none

This Medication Guide has been approved by the U.S. Food and Drug Administration

Manufactured by:Alexza Pharmaceuticals, Inc., Mountain View, CA 94043

Rev.1/2017

PRINCIPAL DISPLAY PANEL

NDC 57844-510-55
Adasuve
(loxapine) inhalation powder
5 single dose units per carton
10 mg
Rx Only

PRINCIPAL DISPLAY PANEL

NDC 57844-510-55
Adasuve
(loxapine) inhalation powder
5 single dose units per carton
10 mg
Rx Only

PRINCIPAL DISPLAY PANEL

NDC 57844-510-55
Adasuve
(loxapine) inhalation powder
5 single dose units per carton
10 mg
Rx Only

PRINCIPAL DISPLAY PANEL

NDC 57844-510-55
Adasuve
(loxapine) inhalation powder
5 single dose units per carton
10 mg
Rx Only

PRINCIPAL DISPLAY PANEL

NDC 57844-510-55
Adasuve
(loxapine) inhalation powder
5 single dose units per carton
10 mg
Rx Only

Adasuve 
loxapine aerosol, powder
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:57844-510
Route of Administration RESPIRATORY (INHALATION) DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
LOXAPINE (LOXAPINE) LOXAPINE 10 mg
Packaging
# Item Code Package Description
1 NDC:57844-510-55 5 POUCH in 1 CARTON
1 NDC:57844-510-11 1 AEROSOL, POWDER in 1 POUCH
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA022549 01/22/2014
Labeler - Teva Select Brands (001627975)
Revised: 01/2017   Teva Select Brands
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