d within 25 minutes after dosing. Consequently, patients receiving ADASUVE should be observed as appropriate following dosing. ADASUVE has not been investigated in patients with other forms of lung disease. Should bronchospasm occur after treatment with ADASUVE, it can be treated with a short-acting beta-agonist bronchodilator, e.g., salbutamol (see sections 4.2 and 4.8). ADASUVE should not be re-administered in patients who develop any respiratory signs/symptoms (see section 4.3).
Hypoventilation
Given the primary Central Nervous System (CNS) effects of loxapine, ADASUVE should be used with caution in patients with compromised respiration, such as hypovigilant patients or patients with CNS-depression due to alcohol or other centrally acting medicinal products, e.g., anxiolytics, most antipsychotics, hypnotics, opiates, etc. (see section 4.5).
Elderly patients with dementia-related psychosis
ADASUVE has not been studied in elderly patients, including those with dementia-related psychosis. Clinical studies with both atypical and convetional antipsychotic medicinal products have demonstrated that elderly patients with dementia-related psychosis are at an increased risk of death compared to placebo. ADASUVE is not indicated for the treatment of patients with dementia-related psychosis.
Extrapyramidal symptoms
Extrapyramidal symptoms (including acute dystonia) are known class effects for antipsychotics. ADASUVE should be used with caution in patients with a known history of extrapyramidal symptoms.
Tardive dyskinesia
If signs and symptoms of tardive dyskinesia appear in a patient being treated with loxapine, discontinuation should be considered. These symptoms can temporally worsen or can even arise after discontinuation of treatment.
Neuroleptic malignant syndrome (NMS)
Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, ADASUVE must be discontinued.
Hypotension
Mild hypotension was reported in short-term (24-hour), placebo-controlled trials in agitated patients administered ADASUVE. If vasopressor therapy is required, noradrenaline or phenylephrine is preferred. Adrenaline should not be used, since beta-adrenoceptor stimulation may worsen hypotension in the setting of loxapine-induced partial alpha-adrenoceptor blockade (see section 4.5).
Cardiovascular
No data are available on the use of ADASUVE in patients with underlying cardiovascular diseases. ADASUVE is not recommended in patient populations with known cardiovascular disease (history of myocardial infarction or ischemic heart disease, heart failure or conduction abnormalities), cerebrovascular disease, or conditions which would predispose patients to hypotension (dehydration, hypovolaemia, and treatment with antihypertensive medicinal products).
QT interval
Clinically relevant QT prolongation does not appear to be associated with single and repeat doses of ADASUVE. Caution should be exercised when ADASUVE is administered in patients with known cardiovascul |
