Adasuve

Name: Adasuve

Commonly used brand name(s)

In the U.S.

  • Adasuve

Available Dosage Forms:

  • Powder

Therapeutic Class: Antipsychotic

Chemical Class: Dibenzoxazepine

What do I need to tell my doctor BEFORE I take Adasuve?

  • If you have an allergy to loxapine or any other part of this medicine.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are very sleepy.
  • If you have recently drunk a lot of alcohol or taken a big amount of drugs that may slow your actions like phenobarbital or some pain drugs like oxycodone.
  • If you have trouble breathing.
  • If you are taking any drugs to treat lung or breathing problems like asthma or COPD.

This is not a list of all drugs or health problems that interact with Adasuve.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take Adasuve?

  • Tell all of your health care providers that you take Adasuve. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • Avoid drinking alcohol while taking Adasuve.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Low white blood cell counts have happened with drugs like this one. This may lead to a higher chance of getting an infection. Deadly infections have rarely happened. Tell your doctor if you have ever had a low white blood cell count. Call your doctor right away if you have signs of infection like fever, chills, or sore throat. Talk with your doctor.
  • Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
  • Have an eye exam as you have been told by your doctor.
  • Dizziness, sleepiness, and feeling less stable may happen with this medicine. These may lead to falling. Broken bones or other health problems can happen from falling. Talk with the doctor.
  • Older adults with dementia taking drugs like this one have had a higher number of strokes. Sometimes these strokes have been deadly. This drug is not approved to treat mental problems caused by dementia. Talk with your doctor.
  • If you are 65 or older, use Adasuve with care. You could have more side effects.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
  • Taking Adasuve in the third trimester of pregnancy may lead to muscle movements that cannot be controlled and withdrawal in the newborn. Talk with the doctor.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Dosage and administration

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 examine 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.

2.4 Monitoring to Assess Safety

Monitor the patient for signs and symptoms of bronchospasm after Adasuve administration. Perform a physical examination, including chest auscultation, at least every 15 minutes for at least one hour after Adasuve administration [see Warnings and Precautions (5.1)].

Warnings and precautions

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 an enrolled healthcare facility that has immediate access on site to supplies and personnel trained to manage acute bronchospasm and ready access to emergency response services. Facilities must have a short-acting bronchodilator (e.g. albuterol), including a nebulizer and inhalation solution, for the immediate treatment of bronchospasm [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 examine 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 (i.e., vital signs and chest auscultation) at least every 15 minutes 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 facilities that dispense and administer Adasuve must be enrolled and comply with the REMS requirements. Certified healthcare facilities must be able to provide immediate access on site to supplies and personnel trained to manage acute bronchospasm and ready access to emergency response services. Facilities must have a short-acting bronchodilator (e.g. albuterol), including a nebulizer and inhalation solution, for the immediate treatment of bronchospasm.

• Wholesalers and distributors that distribute Adasuve must distribute only to enrolled healthcare facilities.

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. There is no general agreement about specific pharmacological treatment regimens for NMS.

If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported. 

5.5 Hypotension and Syncope

Adasuve can cause hypotension, orthostatic hypotension, and syncope. Use Adasuve with caution in patients with known cardiovascular disease (history of myocardial infarction or ischemic heart disease, heart failure or conduction abnormalities), cerebrovascular disease, or conditions that would predispose patients to hypotension (dehydration, hypovolemia, or treatment with antihypertensive medications or other drugs that affect blood pressure or reduce heart rate).

In the presence of severe hypotension requiring vasopressor therapy, the preferred drugs may be norepinephrine or phenylephrine. Epinephrine should not be used, because beta stimulation may worsen hypotension in the setting of Adasuve-induced partial alpha blockade.

In short-term (24-hour) placebo-controlled trials of patients with agitation associated with schizophrenia or bipolar I disorder, hypotension occurred in 0.4% and 0.8% in the Adasuve 10 mg and placebo groups, respectively. There were no cases of orthostatic hypotension, postural symptoms, presyncope or syncope. A systolic blood pressure ≤ 90 mm Hg with a decrease of ≥ 20 mm Hg occurred in 1.5% and 0.8% of the Adasuve 10 mg and placebo groups, respectively. A diastolic blood pressure ≤ 50 mm Hg with a decrease of ≥15 mm Hg occurred in 0.8% and 0.4% of the Adasuve 10 mg and placebo groups, respectively.

In 5 Phase 1 studies in normal volunteers, the incidence of hypotension was 3% and 0% in Adasuve 10 mg and the placebo groups, respectively. The incidence of syncope or presyncope in normal volunteers was 2.3% and 0% in the Adasuve and placebo groups, respectively. In normal volunteers, a systolic blood pressure ≤ 90 mm Hg with a decrease of ≥ 20 mm Hg occurred in 5.3% and 1.1% in the Adasuve and placebo groups, respectively. A diastolic blood pressure ≤ 50 mm Hg with a decrease of ≥ 15 mm Hg occurred in 7.5% and 3.3% in the Adasuve and placebo groups, respectively.

5.6 Falls

Adasuve may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.

5.7 Seizures

Adasuve lowers the seizure threshold. Seizures have occurred in patients treated with oral loxapine. Seizures can occur in epileptic patients even during antiepileptic drug maintenance therapy. In short term (24 hour), placebo-controlled trials of Adasuve, there were no reports of seizures.

5.8 Potential for Cognitive and Motor Impairment

Adasuve can impair judgment, thinking, and motor skills. In short-term, placebo-controlled trials, sedation and/or somnolence were reported in 12% and 10% in the Adasuve and placebo groups, respectively. No patients discontinued treatment because of sedation or somnolence.

The potential for cognitive and motor impairment is increased when Adasuve is administered concurrently with other CNS depressants [see Drug Interactions (7.1)]. Caution patients about operating hazardous machinery, including automobiles, until they are reasonably certain that therapy with Adasuve does not affect them adversely. 

5.9 Cerebrovascular Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis

In placebo-controlled trials with atypical antipsychotics in elderly patients with dementia-related psychosis, there was a higher incidence of cerebrovascular adverse reactions (stroke and transient ischemic attacks), including fatalities, compared to placebo-treated patients. Adasuve is not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning and Warnings and Precautions (5.3)].

5.10 Anticholinergic Reactions Including Exacerbation of Glaucoma and Urinary Retention

Adasuve has anticholinergic activity, and it has the potential to cause anticholinergic adverse reactions including exacerbation of glaucoma or urinary retention. The concomitant use of other anticholinergic drugs (e.g., antiparkinson drugs) with Adasuve could have additive effects.

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.

How supplied/storage and handling

16.1 How Supplied

Adasuve® (loxapine) inhalation powder is supplied as:

Adasuve 10 mg (NDC 57844-510-11) 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 57844-510-55).

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.

  • Bipolar Disorder
  • Schizophrenia
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