Adasuve

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

 

 

 



 

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1. NAME OF THE MEDICINAL PRODUCT 

 

ADASUVE 4.5 mg inhalation powder, pre-dispensed 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each single-dose inhaler contains 5 mg loxapine and delivers 4.5 mg loxapine. 

 

 

3. PHARMACEUTICAL FORM 

 

Inhalation powder, pre-dispensed (inhalation powder). 

 

White device with a mouthpiece on one end and a pull-tab protruding from the other end. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

ADASUVE is indicated for the rapid control of mild-to-moderate agitation in adult patients with 

schizophrenia or bipolar disorder. Patients should receive regular treatment immediately after control 

of acute agitation symptoms. 

 

 

4.2 Posology and method of administration 

 

ADASUVE should only be administered in a hospital-setting under the supervision of a healthcare 

professional. 

 

Short-acting beta-agonist bronchodilator treatment should be available for treatment of possible 

severe respiratory side-effects (bronchospasm).  

 

Posology 

 

The recommended initial dose of ADASUVE is 9.1 mg. As this dose cannot be reach with this 

presentation (ADASUVE 4.5 mg), the presentation ADASUVE 9.1 mg should be used initially. A 

second dose can be given after 2 hours, if necessary. No more than two doses should be administered.  

 

A lower dose of 4.5 mg may be given if the 9.1 mg dose was not previously tolerated by the patient or 

if the physician decides a lower dose is more appropriate.   

 

Patient should be observed during the first hour after each dose for signs and symptoms of 

bronchospasm. 

 

  

Elderly 

The safety and efficacy of ADASUVE in patients older than 65 years of age have not been established. 

No data are available. 

 

Renal and/or hepatic impairment 

ADASUVE has not been studied in patients with renal or hepatic impairment. No data are available. 



 

3 

 

Paediatric population 

The safety and efficacy of ADASUVE in children (less than 18 years of age) have not been 

established. No data are available. 

Method of administration  

 

Inhalation use. The product is packaged in a sealed pouch.  

 

When needed, the product is removed from the pouch. Once the pull-tab is removed, a green light 

turns on, indicating the product is ready for use (Note: the product must be used within 15 minutes of 

pulling the tab). To deliver the medicinal product, the patient inhales through the mouthpiece with a 

steady deep breath. Upon completion of the inhalation, the patient removes the mouthpiece from 

mouth and holds breath briefly. The medicinal product has been delivered when the green light turns 

off. The device exterior may become warm during use. This is normal. 

 

For complete instructions on how to use ADASUVE see information for the healthcare professional 

section of the package leaflet. 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance, or to amoxapine. 

 

Patients with acute respiratory signs/symptoms (e.g., wheezing) or with active airways disease (such 

as patients with asthma or chronic obstructive pulmonary disease [COPD] (see section 4.4). 

 

4.4 Special warnings and precautions for use 

 

Correct use of ADASUVE inhaler is important for administration of the full dose of loxapine. 

Healthcare professionals should ensure the patient will use the inhaler properly. 

 

ADASUVE may have limited effectiveness when patients are on concomitant medicinal products, 

predominantly other antipsychotics.  

 

Bronchospasm 

 

In placebo-controlled clinical trials in subjects with asthma or COPD, bronchospasm was very 

commonly observed. When it occurred, it was typically reported 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 conventional antipsychotic medicinal products have 



 

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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 

cardiovascular disease or family history of QT prolongation, and in concomitant use with other 

medicinal products known to prolong the QT interval. The potential risk of QTc prolongation due to 

interaction with medicinal products known to prolong QTc interval is unknown.  

 

Seizures / convulsions 

 

Loxapine should be used with caution in patients with a history of convulsive disorders since it lowers 

the convulsive threshold. Seizures have been reported in patients receiving oral loxapine at 

antipsychotic dose levels, and may occur in epileptic patients even with maintenance of routine 

anticonvulsant drug therapy (see section 4.5). 

 



 

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Anticholinergic activity 

 

Because of anticholinergic action, ADASUVE should be used cautiously in patients with glaucoma or 

a tendency to urinary retention, particularly with concomitant administration of anticholinergic-type 

antiparkinson medicinal products. 

 

Intoxication or physical disease (delirium) 

 

The safety and efficacy of ADASUVE has not been evaluated in patients with agitation due to 

intoxication or physical disease (delirium). ADASUVE should be used with caution in patients who 

are intoxicated or delirious (see section 4.5). 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Concomitant administration of benzodiazepines or other hypnosedatives or respiratory depressants 

may be associated with excessive sedation and respiratory depression or respiratory failure. If 

benzodiazepine therapy is deemed necessary in addition to loxapine, patients should be monitored for 

excessive sedation and for orthostatic hypotension.  

 

A study of inhaled loxapine and intramuscular lorazepam 1 mg in combination found no significant 

effects on respiratory rate, pulse oximetry, blood pressure, or heart rate compared with either drug 

administered alone. Higher doses of lorazepam have not been studied. The effects of the combination 

on sedation appeared to be additive. 

 

Potential for ADASUVE to affect other medicinal products 

 

Loxapine is not expected to cause clinically important pharmacokinetic interactions with medicinal 

products that are either metabolised by cytochrome P450 (CYP450) isozymes or glucuronidated by 

human uridine 5’-diphosphoglucuronosyl transferases (UGTs).  

 

Caution is advised if loxapine is combined with other medicinal products known to lower the seizure 

threshold, e.g. phenothiazines or butyrophenones, clozapine, tricyclics or selective serotonine reuptake 

inhibitors (SSRIs), tramadol, mefloquine (see section 4.4). 

 

In vitro studies indicated that loxapine was not a substrate for P-glycoprotein (P-gp), but does inhibit 

P-gp. At therapeutic concentrations, however, it is not expected to inhibit P-gp-mediated transport of 

other medicinal products in a clinically significant manner. 

 

Given the primary CNS effects of loxapine, ADASUVE should be used with caution in combination 

with alcohol or other centrally acting medicinal products, e.g., anxiolytics, most antipsychotics, 

hypnotics, opiates, etc. The use of loxapine in patients with alcohol or medicinal product intoxication 

(either with prescribed or illicit medicinal products) has not been evaluated. Loxapine may cause 

severe respiratory depression if combined with other CNS-depressants (see section 4.4). 

 

Potential for other medicinal products to affect ADASUVE 

 

Loxapine is a substrate for flavin-containing mono-oxygenases (FMOs), and for several CYP450 

isozymes (see section 5.2). Therefore, the risk of metabolic interactions caused by an effect on an 

individual isoform is limited. Caution should be used in patients receiving concomitant treatment with 

other medicinal products that are either inhibitors or inducers of these enzymes, particularly if the 

concomitant medicinal product is known to inhibit or induce several of the enzymes involved in 

loxapine metabolism. Such medicinal products may modify efficacy and safety of ADASUVE in an 

irregular manner. Concomitant use of CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin, enoxacin, 

propranolol and refecoxib) should be avoided, if possible. 

 



 

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Adrenaline 

 

Co-administration of loxapine and adrenaline may cause worsening of hypotension (see section 4.4). 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

 

New-born infants exposed repeatedly to antipsychotics during the third trimester of pregnancy are at 

risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in 

severity and duration following delivery. There have been reports of agitation, hypertonia, hypotonia, 

tremor, somnolence, respiratory distress, or feeding disorder. Consequently, monitoring of new-borns 

should be considered. ADASUVE should be used during pregnancy only if the potential benefit 

justifies the potential risk to the foetus. 

 

Breast-feeding 

 

The extent of the excretion of loxapine or its metabolites in human milk is not known. However, 

loxapine and its metabolites have been shown to be transported into the milk of lactating dogs. 

Patients should be advised not to breast feed for a period of 48 hours after receiving loxapine and 

discard the milk produced in the meantime. 

 

Fertility 

 

No loxapine specific human data on fertility are available. It is known that in humans, long-term 

treatment with antipsychotics may lead to loss of libido and amenorrhoea. In female rats, reproductive 

effects have been observed (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 

 

 ADASUVE has major influence on the ability to drive and use machines. Because of the potential for 

sedation/somnolence, fatigue, or dizziness, patients should not operate hazardous machines, including 

motor vehicles, until they are reasonably certain that loxapine has not affected them adversely (see 

section 4.8).  

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

Assessment of adverse reactions from clinical study data is based on two Phase 3 and one Phase 2A 

short-term (24-hour) placebo-controlled clinical trials enrolling 524 adult patients with agitation 

associated with schizophrenia (including 27 patients with schizoaffective disorder) or bipolar disorder, 

treated with ADASUVE 4.5 mg (265 patients) or ADASUVE 9.1 mg (259 patients). 

 

In studies in agitated patients, bronchospasm was reported as an uncommon, but serious adverse 

reaction, while in subjects with active airways disease, bronchospasm was commonly reported and 

often required treatment with a short-acting beta-agonist bronchodilator. The most commonly reported 

adverse reactions during treatment with ADASUVE were dysgeusia, sedation/somnolence and 

dizziness (dizziness was more common after placebo treatment than loxapine treatment).  

 

Tabulated list of adverse reactions 

 

The adverse reactions listed below are categorized using the following convention: Very common (≥ 

1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); 

very rare (< 1/10,000). 

 



 

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Table 1: Adverse reactions 

MedDRA system organ classification 

Nervous system disorders 

Very common: sedation/somnolence 

Common: dizziness 

Uncommon: dystonia, dyskinesia, oculogyration, tremor, akathisia/restlessness 

Vascular disorders 

Uncommon: hypotension 

Respiratory, thoracic and mediastinal disorders 

Common: throat irritation 

Uncommon: bronchospasm (including shortness of breath) 

Gastrointestinal disorders 

Very common: dysgeusia 

Common: dry mouth 

General disorders and administration site conditions 

Common: fatigue 

 

Description of selected adverse reactions 

 

Bronchospasm 

 

In short-term (24-hour), placebo-controlled trials in patients with agitation associated with 

schizophrenia or bipolar disorder without active airways disease, bronchospasm (which includes 

reports of wheezing, shortness of breath or cough) was uncommon in patients treated with 

ADASUVE. However, in placebo-controlled clinical trials in subjects with mild-to-moderate 

persistent asthma or moderate-to-severe COPD, adverse reactions of bronchospasm were reported very 

commonly. Most of these events occurred within 25 minutes of dosing, were mild to moderate in 

severity, and could be relieved with an inhaled bronchodilator. 

 

Adverse reactions seen with chronic oral loxapine use 

 

With chronic oral administration of loxapine, the reported adverse reactions include sedation and 

drowsiness; extrapyramidal symptoms (e.g., tremor, akathisia, rigidity, and dystonia); cardiovascular 

effects (e.g., tachycardia, hypotension, hypertension, orthostatic hypotension, light-headedness, and 

syncope); and anticholinergic effects (e.g., dry eyes, blurred vision, and urinary retention). 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 

 

No cases of overdosage of ADASUVE were reported in clinical studies. 

 

Symptoms  

 

In the event of accidental overdosage, signs and symptoms will depend on the number of units taken 

and individual patient tolerance. As would be expected from the pharmacologic actions of loxapine, 

the clinical findings may range from mild depression of the CNS and cardiovascular systems to 

profound hypotension, respiratory depression, and unconsciousness (see section 4.4). The possibility 

of occurrence of extrapyramidal symptoms and/or convulsive seizures should be kept in mind. Renal 

failure following oral loxapine overdosage has also been reported.  



 

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Management 

 

The treatment of overdosage is essentially symptomatic and supportive. Severe hypotension might be 

expected to respond to the administration of noradrenaline or phenylephrine. Adrenaline should not be 

used since its use in a patient with partial adrenergic blockage may further lower the blood pressure 

(see sections 4.4 and 4.5). Severe extrapyramidal reactions should be treated with anticholinergic 

antiparkinson medicinal products or diphenhydramine hydrochloride, and anticonvulsant therapy 

should be initiated as indicated. Additional measures include oxygen and intravenous fluids. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 

 

Pharmacotherapeutic group: psycholeptics, antipsychotics; ATC code: N05AH01 

 

The efficacy of loxapine is proposed to be mediated through high affinity antagonism of dopamine D2 

receptors and serotonin 5-HT2A receptors. Loxapine binds with noradrenergic, histaminergic, and 

cholinergic receptors, and its interaction with these systems may influence the spectrum of its 

pharmacological effects. 

 

Changes in the level of excitability of subcortical inhibitory areas have been observed in several 

animal species, associated with calming effects and suppression of aggressive behaviour. 

 

Clinical efficacy  

 

In the two Phase 3 studies patients were enrolled who had acute agitation of at least moderate level (14 

or higher on Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) scale (poor 

impulse control, tension, hostility, uncooperativeness, and excitement). Inclusion in Study 004-301 

required a diagnosis of schizophrenia. Inclusion in Study 004-302 required a diagnosis of bipolar 

disorder (current episode manic or mixed). Patients had significant and long-standing psychiatric 

disease (Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)), based on 

years since diagnosis and previous hospitalizations. Patients were randomised to placebo, ADASUVE 

4.5 mg and ADASUVE 9.1 mg.  

 

The mean age of randomized patients was 43.1 years in Study 004-301 and 40.8 years in Study 

004-302: young adults (18-25 years old) were scarcely (7.3%) represented in either trial. Women in 

the schizophrenia trial were scarcely represented (26.5%), and about half of the patients were male 

(49.7%) in Study 004-302. About 35% of the patients with schizophrenia were taking concomitant 

antipsychotics at the time of dosing while approximately 13% of the patients with bipolar disorder 

were taking these drugs. A majority of the patients in both Phase 3 studies were smokers with about 

82% of the patients with schizophrenia and 74% of the patients with bipolar disorder currently 

smoking. 

 

After the first dose, a second dose was administered at least 2 hours later if the agitation had not 

subsided sufficiently. A third dose was administered if needed after at least 4 hours after dose 2. 

Rescue medication (intramuscular lorazepam) was given if medically required. Primary endpoint was 

absolute change in PEC score from baseline to 2 hours following Dose 1 for both doses of ADASUVE 

compared with placebo. Among the other endpoints were PEC and Clinical Global Impression – 

Improvement (CGI-I) responders at 2 hours after dose 1, and total number of patients per group who 

received 1, 2, or 3 doses of study medication with and without rescue medication. Responders were 

considered patients with a ≥40% decrease from baseline in the total PEC score or patients with CGI-I 

score of 1 (very much improved) or 2 (much improved). 

 



 

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Decreased agitation was evident 10 minutes after Dose 1, the first assessment time, and at all 

subsequent assessments during the 24 hour evaluation period, for both 4.5 mg and 9.1 mg doses in 

both schizophrenia and bipolar disorder patients. 

 

Examination of population subsets (age, race, and gender) did not reveal any differential 

responsiveness on the basis of these subgroupings. 

 

For the main results, see the table below. 

Main results of the pivotal efficacy studies: comparisons between ADASUVE 4.5 mg, 9.1 mg, 

and placebo 

 

Study 

Patients 

004-301 

Schizophrenia 

004-302 

Bipolar Disorder 

Treatment 

N 

PBO 

115 

4.5 mg 

116 

9.1 mg 

112 

PBO 

105 

4.5 mg 

104 

9.1 mg 

105 

P
E

C
 

C
h

a
n

g
e 

Baseline  17.4 17.8 17.6 17.7 17.4 17.3 

Change at 2 hr 

post dose 
-5.5 -8.1+ -8.6* -4.9 -8.1* -9.0* 

SD 4.9 5.2 4.4 4.8 4.9 4.7 

P
E

C
 

R
es

p
o

n
d

er
s 

30 min post dose 27.8% 46.6% 57.1% 23.8% 59.6% 61.9% 

2 hr post dose 38.3% 62.9% 69.6% 27.6% 62.5% 73.3% 

C
G

I-
I 

R
es

p
o

n
d

er
 

% CGI-I 

Responders 
35.7% 57.4% 67.0% 27.6% 66.3% 74.3% 

#
 D

o
se

s 
N

ee
d

ed
 One 46.1% 54.4% 60.9% 26.7% 41.3% 61.5% 

Two 29.6% 30.7% 26.4% 41.0% 44.2% 26.0% 

Three 8.7% 8.8% 7.3% 11.4% 5.8% 3.8% 

Rescue 15.6% 6.1% 5.4% 21.0% 8.6% 8.6% 

*= p<0.0001 += p<0.01 

PEC Responders = > 40% change from PEC Baseline;  

CGI-I Responders = Score of 1 (Very Much Improved) or 2 (Much Improved) 

PBO = placebo SD=Standard Deviation 

 

 

In a supportive Phase 2 single dose study enrolling a total of 129 patients with schizophrenia and 

schizoaffective disorder the decrease in PEC change after 2 hours was -5.0 for placebo, -6.7 for 

ADASUVE 4.5 mg, and -8.6 (p<0.001) for ADASUVE 9.1 mg. Rescue medication was administered 

in respectively 32.6%, 11.1 % and 14.6 % of patients. 

 

Paediatric population 

 

The European Medicines Agency has waived the obligation to submit the results of studies with 

ADASUVE in the subset of the paediatric population from birth to less than 12 years of age for the 



 

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treatment of schizophrenia and in the subset from birth to less than 10 years of age for the treatment of 

bipolar disorder (see section 4.2 for information on paediatric use). 

 

The European Medicines Agency has deferred the obligation to submit the results of studies with 

ADASUVE in the subset of the paediatric population from 12 to less than 18 years of age for the 

treatment of schizophrenia and in the subset from 10 years to less than 18 years of age in bipolar 

disorder (see section 4.2 for information on paediatric use). 

 

5.2 Pharmacokinetic properties 

 

Absorption 

 

Administration of ADASUVE resulted in rapid absorption of loxapine with a median time of 

maximum plasma concentration (Tmax) by 2 minutes. Loxapine exposure in the first 2 hours after 

administration (AUC0-2h, a measure of early exposure that is relevant to the onset of therapeutic effect) 

was 25.6 ng*h/mL for the 4.5 mg dose and 66.7 ng*h/mL for the 9.1 mg dose in healthy subjects.  

 

The pharmacokinetic parameters of loxapine were determined in subjects on chronic, stable 

antipsychotic regimens following repeat administration of ADASUVE every 4 hours for a total of 3 

doses (either 4.5 mg or 9.1 mg). Mean peak plasma concentrations were similar after the first and third 

dose of ADASUVE, indicating minimal accumulation during the 4-hour dosing interval. 

 

Distribution 

 

Loxapine is removed rapidly from the plasma and distributed in tissues. Animal studies following oral 

administration suggest an initial preferential distribution in the lungs, brain, spleen, heart and kidney. 

Loxapine is 96.6% bound to human plasma proteins. 

 

Biotransformation 

 

Loxapine is metabolised extensively in the liver, with multiple metabolites formed. The main 

metabolic pathways include hydroxylation to form 8-OH-loxapine and 7-OH-loxapine, N-oxidation to 

form loxapine N-oxide, and de-methylation to form amoxapine. For ADASUVE, the order of 

metabolites observed in humans (based on systemic exposure) was 8-OH-loxapine >> loxapine N 

oxide > 7-OH-loxapine > amoxapine, with plasma levels of 8-OH-loxapine similar to the parent 

compound. 8-OH-loxapine is not pharmacologically active at the D2 receptor while the minor 

metabolite, 7-OH-loxapine, has high binding affinity to D2 receptors. 

 

Loxapine is a substrate for several CYP450 isozymes; in vitro studies demonstrated that 7-OH-

loxapine is formed mainly by CYPs 3A4 and 2D6, 8-OH-loxapine is formed mainly by CYP1A2, 

amoxapine is formed mainly by CYP3A4, 2C19, and 2C8, and loxapine N-oxide is formed by FMOs. 

 

The potential for loxapine and its metabolites (amoxapine, 7-OH-loxapine, 8-OH-loxapine, and 

loxapine-N-oxide) to inhibit CYP450 - mediated drug metabolism has been examined in vitro for 

CYPs 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4. No significant inhibition was 

observed. In vitro studies indicate that loxapine and 8-OH-loxapine are not inducers of CYP1A2, 2B6 

or 3A4 enzymes at clinically relevant concentrations. In addition, in vitro studies indicate that loxapine 

and 8-OH loxapine are not inhibitors of UGT1A1, 1A3, 1A4, 2B7 and 2B15. 

 

Elimination 

 

Loxapine excretion occurs mainly in the first 24 hours. Metabolites are excreted in the urine in the 

form of conjugates and in the faeces unconjugated. The terminal elimination half-life (T½) ranged 

from 6 to 8 hours. 

 



 

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Linearity/non-linearity 

 

The mean plasma loxapine concentrations following administration of ADASUVE were linear over 

the clinical dose range. AUC0-2h, AUCinf, and Cmax increased in a dose-dependent manner. 

 

Pharmacokinetics in special patient populations 

 

Smokers 

 

A population pharmacokinetic analysis that compared exposures in smokers versus non-smokers 

indicated that smoking, which induces CYP1A2, had a minimal effect on the exposure to ADASUVE. 

No dosage adjustment is recommended based on smoking status. 

 

In female smokers exposure (AUCinf) to ADASUVE and its active metabolite 7-OH-loxapine is lower 

than in female non-smokers (84% vs 109% 7-OH-loxapine/Loxapine Ratio), which is probably due to 

an increase in loxapine clearance in smokers. 

 

Demographics 

 

There were no important differences in the exposure or disposition of loxapine following 

administration of ADASUVE due to age, gender, race, weight, or body mass index (BMI). 

 

5.3 Preclinical safety data 

 

Non-clinical safety data revealed no special hazard for humans based on conventional studies of safety 

pharmacology, repeat-dose toxicity, and genotoxicity, except for changes to reproductive tissues 

related to the extended pharmacology of loxapine. Similar changes, e.g., gynecomastia, are known in 

humans, but only after long-term administration of medicines causing hyperprolactinaemia. 

 

Female rats did not mate due to persistent diestrus after oral treatment with loxapine. Embryo/fetal 

developmental and perinatal studies have shown indications of developmental delay (reduced weights, 

delayed ossification, hydronephrosis, hydrourether, and/or distended renal pelvis with reduced or 

absent papillae) as well as increased numbers of perinatal and neonatal deaths in offspring of rats 

treated from mid-pregnancy with oral doses below the maximum recommended human dose for 

ADASUVE on a mg/m2 basis (see section 4.6). 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

None 

 

6.2 Incompatibilities 

 

Not applicable 

 

6.3 Shelf life 

 

3 years 

 

6.4 Special precautions for storage 

 

Store in the original pouch until ready for use in order to protect from light and moisture. 

 

This medicinal product does not require any special temperature storage conditions. 



 

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6.5 Nature and contents of container  

 

The white inhaler (housing) is molded from a medical-grade polycarbonate. 

Each inhaler is provided in a sealed, multilaminate aluminum foil pouch.  

ADASUVE 4.5 mg is supplied in a carton of 1 or 5 units.  

 

Not all pack-sized may be marketed. 

 

6.6 Special precautions for disposal 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Ferrer Internacional, S.A. 

Gran Vía Carlos III, 94 

08028- Barcelona 

España 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/823/001 (5 single-dose inhalers) 

EU/1/13/823/003 (1 single-dose inhaler) 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 20 February 2013 

Date of latest renewal: 

 

10. DATE OF REVISION OF THE TEXT 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 



 

13 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADASUVE 9.1 mg inhalation powder, pre-dispensed 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each single-dose inhaler contains 10 mg loxapine and delivers 9.1 mg loxapine. 

 

 

3. PHARMACEUTICAL FORM 

 

Inhalation powder, pre-dispensed (inhalation powder). 

 

White device with a mouthpiece on one end and a pull-tab protruding from the other end. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

ADASUVE is indicated for the rapid control of mild-to-moderate agitation in adult patients with 

schizophrenia or bipolar disorder. Patients should receive regular treatment immediately after control 

of acute agitation symptoms. 

 

 

4.2 Posology and method of administration 

 

ADASUVE should only be administered in a hospital-setting under the supervision of a healthcare 

professional. 

 

Short-acting beta-agonist bronchodilator treatment should be available for treatment of possible 

severe respiratory side-effects (bronchospasm).  

 

Posology 

 

The recommended initial dose of ADASUVE is 9.1 mg. A second dose can be given after 2 hours, if 

necessary. No more than two doses should be administered.  

 

A lower dose of 4.5 mg may be given if the 9.1 mg dose was not previously tolerated by the patient or 

if the physician decides a lower dose is more appropriate.   

 

Patient should be observed during the first hour after each dose for signs and symptoms of 

bronchospasm. 

 

  

Elderly 

The safety and efficacy of ADASUVE in patients older than 65 years of age have not been established. 

No data are available. 

 

Renal and/or hepatic impairment 

ADASUVE has not been studied in patients with renal or hepatic impairment. No data are available. 

 



 

14 

Paediatric population 

The safety and efficacy of ADASUVE in children (less than 18 years of age) have not been 

established. No data are available. 

Method of administration  

 

Inhalation use. The product is packaged in a sealed pouch.  

 

When needed, the product is removed from the pouch. Once the pull-tab is removed, a green light 

turns on, indicating the product is ready for use (Note: the product must be used within 15 minutes of 

pulling the tab). To deliver the medicinal product, the patient inhales through the mouthpiece with a 

steady deep breath. Upon completion of the inhalation, the patient removes the mouthpiece from 

mouth and holds breath briefly. The medicinal product has been delivered when the green light turns 

off. The device exterior may become warm during use. This is normal. 

 

For complete instructions on how to use ADASUVE see information for the healthcare professional 

section of the package leaflet. 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance, or to amoxapine. 

 

Patients with acute respiratory signs/symptoms (e.g., wheezing) or with active airways disease (such 

as patients with asthma or chronic obstructive pulmonary disease [COPD] (see section 4.4). 

 

4.4 Special warnings and precautions for use 

 

Correct use of ADASUVE inhaler is important for administration of the full dose of loxapine. 

Healthcare professionals should ensure the patient will use the inhaler properly. 

 

ADASUVE may have limited effectiveness when patients are on concomitant medicinal products, 

predominantly other antipsychotics.  

 

Bronchospasm 

 

In placebo-controlled clinical trials in subjects with asthma or COPD, bronchospasm was very 

commonly observed. When it occurred, it was typically reported 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 conventional antipsychotic medicinal products have 

demonstrated that elderly patients with dementia-related psychosis are at an increased risk of death 



 

15 

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 

cardiovascular disease or family history of QT prolongation, and in concomitant use with other 

medicinal products known to prolong the QT interval. The potential risk of QTc prolongation due to 

interaction with medicinal products known to prolong QTc interval is unknown.  

 

Seizures / convulsions 

 

Loxapine should be used with caution in patients with a history of convulsive disorders since it lowers 

the convulsive threshold. Seizures have been reported in patients receiving oral loxapine at 

antipsychotic dose levels, and may occur in epileptic patients even with maintenance of routine 

anticonvulsant drug therapy (see section 4.5). 

 



 

16 

Anticholinergic activity 

 

Because of anticholinergic action, ADASUVE should be used cautiously in patients with glaucoma or 

a tendency to urinary retention, particularly with concomitant administration of anticholinergic-type 

antiparkinson medicinal products. 

 

Intoxication or physical disease (delirium) 

 

The safety and efficacy of ADASUVE has not been evaluated in patients with agitation due to 

intoxication or physical disease (delirium). ADASUVE should be used with caution in patients who 

are intoxicated or delirious (see section 4.5). 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Concomitant administration of benzodiazepines or other hypnosedatives or respiratory depressants 

may be associated with excessive sedation and respiratory depression or respiratory failure. If 

benzodiazepine therapy is deemed necessary in addition to loxapine, patients should be monitored for 

excessive sedation and for orthostatic hypotension.  

 

A study of inhaled loxapine and intramuscular lorazepam 1 mg in combination found no significant 

effects on respiratory rate, pulse oximetry, blood pressure, or heart rate compared with either drug 

administered alone. Higher doses of lorazepam have not been studied. The effects of the combination 

on sedation appeared to be additive. 

 

Potential for ADASUVE to affect other medicinal products 

 

Loxapine is not expected to cause clinically important pharmacokinetic interactions with medicinal 

products that are either metabolised by cytochrome P450 (CYP450) isozymes or glucuronidated by 

human uridine 5’-diphosphoglucuronosyl transferases (UGTs) .  

 

Caution is advised if loxapine is combined with other medicinal products known to lower the seizure 

threshold, e.g. phenothiazines or butyrophenones, clozapine, tricyclics or selective serotonine reuptake 

inhibitors (SSRIs), tramadol, mefloquine (see section 4.4). 

 

In vitro studies indicated that loxapine was not a substrate for P-glycoprotein (P-gp), but does inhibit 

P-gp. At therapeutic concentrations, however, it is not expected to inhibit P-gp-mediated transport of 

other medicinal products in a clinically significant manner. 

 

Given the primary CNS effects of loxapine, ADASUVE should be used with caution in combination 

with alcohol or other centrally acting medicinal products, e.g., anxiolytics, most antipsychotics, 

hypnotics, opiates, etc. The use of loxapine in patients with alcohol or medicinal product intoxication 

(either with prescribed or illicit medicinal products) has not been evaluated. Loxapine may cause 

severe respiratory depression if combined with other CNS-depressants (see section 4.4). 

 

Potential for other medicinal products to affect ADASUVE 

 

Loxapine is a substrate for flavin-containing mono-oxygenases (FMOs), and for several CYP450 

isozymes (see section 5.2). Therefore, the risk of metabolic interactions caused by an effect on an 

individual isoform is limited. Caution should be used in patients receiving concomitant treatment with 

other medicinal products that are either inhibitors or inducers of these enzymes, particularly if the 

concomitant medicinal product is known to inhibit or induce several of the enzymes involved in 

loxapine metabolism. Such medicinal products may modify efficacy and safety of ADASUVE in an 

irregular manner. Concomitant use of CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin, enoxacin, 

propranolol and refecoxib) should be avoided, if possible. 

 



 

17 

Adrenaline 

 

Co-administration of loxapine and adrenaline may cause worsening of hypotension (see section 4.4). 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

 

New-born infants exposed repeatedly to antipsychotics during the third trimester of pregnancy are at 

risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in 

severity and duration following delivery. There have been reports of agitation, hypertonia, hypotonia, 

tremor, somnolence, respiratory distress, or feeding disorder. Consequently, monitoring of new-borns 

should be considered. ADASUVE should be used during pregnancy only if the potential benefit 

justifies the potential risk to the foetus. 

 

Breast-feeding 

 

The extent of the excretion of loxapine or its metabolites in human milk is not known. However, 

loxapine and its metabolites have been shown to be transported into the milk of lactating dogs. 

Patients should be advised not to breast feed for a period of 48 hours after receiving loxapine and 

discard the milk produced in the meantime. 

 

Fertility 

 

No loxapine specific human data on fertility are available. It is known that in humans, long-term 

treatment with antipsychotics may lead to loss of libido and amenorrhoea. In female rats, reproductive 

effects have been observed (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 

 

ADASUVE has major influence on the ability to drive and use machines. Because of the potential for 

sedation/somnolence, fatigue, or dizziness, patients should not operate hazardous machines, including 

motor vehicles, until they are reasonably certain that loxapine has not affected them adversely (see 

section 4.8).  

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

Assessment of adverse reactions from clinical study data is based on two Phase 3 and one Phase 2A 

short-term (24-hour) placebo-controlled clinical trials enrolling 524 adult patients with agitation 

associated with schizophrenia (including 27 patients with schizoaffective disorder) or bipolar disorder, 

treated with ADASUVE 4.5 mg (265 patients) or ADASUVE 9.1 mg (259 patients). 

 

In studies in agitated patients, bronchospasm was reported as an uncommon, but serious adverse 

reaction, while in subjects with active airways disease, bronchospasm was commonly reported and 

often required treatment with a short-acting beta-agonist bronchodilator. The most commonly reported 

adverse reactions during treatment with ADASUVE were dysgeusia, sedation/somnolence and 

dizziness (dizziness was more common after placebo treatment than loxapine treatment).  

 

Tabulated list of adverse reactions 

 

The adverse reactions listed below are categorized using the following convention: Very common (≥ 

1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); 

very rare (< 1/10,000). 

 



 

18 

Table 1: Adverse reactions 

MedDRA system organ classification 

Nervous system disorders 

Very common: sedation/somnolence 

Common: dizziness 

Uncommon: dystonia, dyskinesia, oculogyration, tremor, akathisia/restlessness 

Vascular disorders 

Uncommon: hypotension 

Respiratory, thoracic and mediastinal disorders 

Common: throat irritation 

Uncommon: bronchospasm (including shortness of breath) 

Gastrointestinal disorders 

Very common: dysgeusia 

Common: dry mouth 

General disorders and administration site conditions 

Common: fatigue 

 

Description of selected adverse reactions 

 

Bronchospasm 

 

In short-term (24-hour), placebo-controlled trials in patients with agitation associated with 

schizophrenia or bipolar disorder without active airways disease, bronchospasm (which includes 

reports of wheezing, shortness of breath or cough) was uncommon in patients treated with 

ADASUVE. However, in placebo-controlled clinical trials in subjects with mild-to-moderate 

persistent asthma or moderate-to-severe COPD, adverse reactions of bronchospasm were reported very 

commonly. Most of these events occurred within 25 minutes of dosing, were mild to moderate in 

severity, and could be relieved with an inhaled bronchodilator. 

 

Adverse reactions seen with chronic oral loxapine use 

 

With chronic oral administration of loxapine, the reported adverse reactions include sedation and 

drowsiness; extrapyramidal symptoms (e.g., tremor, akathisia, rigidity, and dystonia); cardiovascular 

effects (e.g., tachycardia, hypotension, hypertension, orthostatic hypotension, light-headedness, and 

syncope); and anticholinergic effects (e.g., dry eyes, blurred vision, and urinary retention). 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V . 

 

4.9 Overdose 

 

No cases of overdosage of ADASUVE were reported in clinical studies. 

 

Symptoms 

 

In the event of accidental overdosage, signs and symptoms will depend on the number of units taken 

and individual patient tolerance. As would be expected from the pharmacologic actions of loxapine, 

the clinical findings may range from mild depression of the CNS and cardiovascular systems to 

profound hypotension, respiratory depression, and unconsciousness (see section 4.4). The possibility 

of occurrence of extrapyramidal symptoms and/or convulsive seizures should be kept in mind. Renal 

failure following oral loxapine overdosage has also been reported.  



 

19 

 

Management 

 

The treatment of overdosage is essentially symptomatic and supportive. Severe hypotension might be 

expected to respond to the administration of noradrenaline or phenylephrine. Adrenaline should not be 

used since its use in a patient with partial adrenergic blockage may further lower the blood pressure 

(see sections 4.4 and 4.5). Severe extrapyramidal reactions should be treated with anticholinergic 

antiparkinson medicinal products or diphenhydramine hydrochloride, and anticonvulsant therapy 

should be initiated as indicated. Additional measures include oxygen and intravenous fluids. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 

 

Pharmacotherapeutic group: psycholeptics, antipsychotics; ATC code: N05AH01 

 

The efficacy of loxapine is proposed to be mediated through high affinity antagonism of dopamine D2 

receptors and serotonin 5-HT2A receptors. Loxapine binds with noradrenergic, histaminergic, and 

cholinergic receptors, and its interaction with these systems may influence the spectrum of its 

pharmacological effects. 

 

Changes in the level of excitability of subcortical inhibitory areas have been observed in several 

animal species, associated with calming effects and suppression of aggressive behaviour. 

 

Clinical efficacy  

 

In the two Phase 3 studies patients were enrolled who had acute agitation of at least moderate level (14 

or higher on Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) scale (poor 

impulse control, tension, hostility, uncooperativeness, and excitement). Inclusion in Study 004-301 

required a diagnosis of schizophrenia. Inclusion in Study 004-302 required a diagnosis of bipolar 

disorder (current episode manic or mixed). Patients had significant and long-standing psychiatric 

disease (Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)), based on 

years since diagnosis and previous hospitalizations. Patients were randomised to placebo, ADASUVE 

4.5 mg and ADASUVE 9.1 mg.  

 

The mean age of randomized patients was 43.1 years in Study 004-301 and 40.8 years in Study 

004-302: young adults (18-25 years old) were scarcely (7.3%) represented in either trial. Women in 

the schizophrenia trial were scarcely represented (26.5%), and about half of the patients were male 

(49.7%) in Study 004-302. About 35% of the patients with schizophrenia were taking concomitant 

antipsychotics at the time of dosing while approximately 13% of the patients with bipolar disorder 

were taking these drugs. A majority of the patients in both Phase 3 studies were smokers with about 

82% of the patients with schizophrenia and 74% of the patients with bipolar disorder currently 

smoking. 

 

After the first dose, a second dose was administered at least 2 hours later if the agitation had not 

subsided sufficiently. A third dose was administered if needed after at least 4 hours after dose 2. 

Rescue medication (intramuscular lorazepam) was given if medically required. Primary endpoint was 

absolute change in PEC score from baseline to 2 hours following Dose 1 for both doses of ADASUVE 

compared with placebo. Among the other endpoints were PEC and Clinical Global Impression – 

Improvement (CGI-I) responders at 2 hours after dose 1, and total number of patients per group who 

received 1, 2, or 3 doses of study medication with and without rescue medication. Responders were 

considered patients with a ≥40% decrease from baseline in the total PEC score or patients with CGI-I 

score of 1 (very much improved) or 2 (much improved). 

 



 

20 

Decreased agitation was evident 10 minutes after Dose 1, the first assessment time, and at all 

subsequent assessments during the 24 hour evaluation period, for both 4.5 mg and 9.1 mg doses in 

both schizophrenia and bipolar disorder patients. 

 

Examination of population subsets (age, race, and gender) did not reveal any differential 

responsiveness on the basis of these subgroupings. 

 

For the main results, see the table below.Main results of the pivotal efficacy studies: comparisons 

between ADASUVE 4.5 mg, 9.1 mg, and placebo 

 

Study 

Patients 

004-301 

Schizophrenia 

004-302 

Bipolar Disorder 

Treatment 

N 

PBO 

115 

4.5 mg 

116 

9.1 mg 

112 

PBO 

105 

4.5 mg 

104 

9.1 mg 

105 

P
E

C
 

C
h

a
n

g
e 

Baseline  17.4 17.8 17.6 17.7 17.4 17.3 

Change at 2 hr 

post dose 
-5.5 -8.1+ -8.6* -4.9 -8.1* -9.0* 

SD 4.9 5.2 4.4 4.8 4.9 4.7 

P
E

C
 

R
es

p
o

n
d

er
s 

30 min post dose 27.8% 46.6% 57.1% 23.8% 59.6% 61.9% 

2 hr post dose 38.3% 62.9% 69.6% 27.6% 62.5% 73.3% 

C
G

I-
I 

R
es

p
o

n
d

er
 

% CGI-I 

Responders 
35.7% 57.4% 67.0% 27.6% 66.3% 74.3% 

#
 D

o
se

s 
N

ee
d

ed
 One 46.1% 54.4% 60.9% 26.7% 41.3% 61.5% 

Two 29.6% 30.7% 26.4% 41.0% 44.2% 26.0% 

Three 8.7% 8.8% 7.3% 11.4% 5.8% 3.8% 

Rescue 15.6% 6.1% 5.4% 21.0% 8.6% 8.6% 

*= p<0.0001 += p<0.01 

PEC Responders = > 40% change from PEC Baseline;  

CGI-I Responders = Score of 1 (Very Much Improved) or 2 (Much Improved) 

PBO = placebo SD=Standard Deviation 

 

 

In a supportive Phase 2 single dose study enrolling a total of 129 patients with schizophrenia and 

schizoaffective disorder the decrease in PEC change after 2 hours was -5.0 for placebo, -6.7 for 

ADASUVE 4.5 mg, and -8.6 (p<0.001) for ADASUVE 9.1 mg. Rescue medication was administered 

in respectively 32.6%, 11.1 % and 14.6 % of patients. 

 

Paediatric population 

 

The European Medicines Agency has waived the obligation to submit the results of studies with 

ADASUVE in the subset of the paediatric population from birth to less than 12 years of age for the 

treatment of schizophrenia and in the subset from birth to less than 10 years of age for the treatment of 

bipolar disorder (see section 4.2 for information on paediatric use). 



 

21 

 

The European Medicines Agency has deferred the obligation to submit the results of studies with 

ADASUVE in the subset of the paediatric population from 12 to less than 18 years of age for the 

treatment of schizophrenia and in the subset from 10 years to less than 18 years of age in bipolar 

disorder (see section 4.2 for information on paediatric use). 

 

5.2 Pharmacokinetic properties 

 

Absorption 

 

Administration of ADASUVE resulted in rapid absorption of loxapine with a median time of 

maximum plasma concentration (Tmax) by 2 minutes. Loxapine exposure in the first 2 hours after 

administration (AUC0-2h, a measure of early exposure that is relevant to the onset of therapeutic effect) 

was 25.6 ng*h/mL for the 4.5 mg dose and 66.7 ng*h/mL for the 9.1 mg dose in healthy subjects.  

 

The pharmacokinetic parameters of loxapine were determined in subjects on chronic, stable 

antipsychotic regimens following repeat administration of ADASUVE every 4 hours for a total of 3 

doses (either 4.5 mg or 9.1 mg). Mean peak plasma concentrations were similar after the first and third 

dose of ADASUVE, indicating minimal accumulation during the 4-hour dosing interval. 

 

Distribution 

 

Loxapine is removed rapidly from the plasma and distributed in tissues. Animal studies following oral 

administration suggest an initial preferential distribution in the lungs, brain, spleen, heart and kidney. 

Loxapine is 96.6% bound to human plasma proteins. 

 

Biotransformation 

 

Loxapine is metabolised extensively in the liver, with multiple metabolites formed. The main 

metabolic pathways include hydroxylation to form 8-OH-loxapine and 7-OH-loxapine, N-oxidation to 

form loxapine N-oxide, and de-methylation to form amoxapine. For ADASUVE, the order of 

metabolites observed in humans (based on systemic exposure) was 8-OH-loxapine >> loxapine N 

oxide > 7-OH-loxapine > amoxapine, with plasma levels of 8-OH-loxapine similar to the parent 

compound. 8-OH-loxapine is not pharmacologically active at the D2 receptor while the minor 

metabolite, 7-OH-loxapine, has high binding affinity to D2 receptors. 

 

Loxapine is a substrate for several CYP450 isozymes; in vitro studies demonstrated that 7-OH-

loxapine is formed mainly by CYPs 3A4 and 2D6, 8-OH-loxapine is formed mainly by CYP1A2, 

amoxapine is formed mainly by CYP3A4, 2C19, and 2C8, and loxapine N-oxide is formed by FMOs. 

 

The potential for loxapine and its metabolites (amoxapine, 7-OH-loxapine, 8-OH-loxapine, and 

loxapine-N-oxide) to inhibit CYP450 - mediated drug metabolism has been examined in vitro for 

CYPs 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4. No significant inhibition was 

observed. In vitro studies indicate that loxapine and 8-OH-loxapine are not inducers of CYP1A2, 2B6 

or 3A4 enzymes at clinically relevant concentrations. In addition, in vitro studies indicate that loxapine 

and 8-OH loxapine are not inhibitors of UGT1A1, 1A3, 1A4, 2B7 and 2B15. 

 

Elimination 

 

Loxapine excretion occurs mainly in the first 24 hours. Metabolites are excreted in the urine in the 

form of conjugates and in the faeces unconjugated. The terminal elimination half-life (T½) ranged 

from 6 to 8 hours. 

 

Linearity/non-linearity 

 



 

22 

The mean plasma loxapine concentrations following administration of ADASUVE were linear over 

the clinical dose range. AUC0-2h, AUCinf, and Cmax increased in a dose-dependent manner. 

 

Pharmacokinetics in special patient populations 

 

Smokers 

 

A population pharmacokinetic analysis that compared exposures in smokers versus non-smokers 

indicated that smoking, which induces CYP1A2, had a minimal effect on the exposure to ADASUVE. 

No dosage adjustment is recommended based on smoking status. 

 

In female smokers exposure (AUCinf) to ADASUVE and its active metabolite 7-OH-loxapine is lower 

than in female non-smokers (84% vs 109% 7-OH-loxapine/Loxapine Ratio), which is probably due to 

an increase in loxapine clearance in smokers. 

 

Demographics 

 

There were no important differences in the exposure or disposition of loxapine following 

administration of ADASUVE due to age, gender, race, weight, or body mass index (BMI). 

 

5.3 Preclinical safety data 

 

Non-clinical safety data revealed no special hazard for humans based on conventional studies of safety 

pharmacology, repeat-dose toxicity, and genotoxicity, except for changes to reproductive tissues 

related to the extended pharmacology of loxapine. Similar changes, e.g., gynecomastia, are known in 

humans, but only after long-term administration of medicines causing hyperprolactinaemia. 

 

Female rats did not mate due to persistent diestrus after oral treatment with loxapine. Embryo/fetal 

developmental and perinatal studies have shown indications of developmental delay (reduced weights, 

delayed ossification, hydronephrosis, hydrourether, and/or distended renal pelvis with reduced or 

absent papillae) as well as increased numbers of perinatal and neonatal deaths in offspring of rats 

treated from mid-pregnancy with oral doses below the maximum recommended human dose for 

ADASUVE on a mg/m2 basis (see section 4.6). 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

None 

 

6.2 Incompatibilities 

 

Not applicable 

 

6.3 Shelf life 

 

4 years 

 

6.4 Special precautions for storage 

 

Store in the original pouch until ready for use in order to protect from light and moisture. 

 

This medicinal product does not require any special temperature storage conditions. 

 

6.5 Nature and contents of container  



 

23 

 

The white inhaler (housing) is molded from a medical-grade polycarbonate. 

 

Each inhaler is provided in a sealed, multilaminate aluminum foil pouch. ADASUVE 9.1 mg is 

supplied in a carton of 1 or 5 units. 

 

Not all pack-sized may be marketed. 

 

6.6 Special precautions for disposal 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Ferrer Internacional, S.A. 

Gran Vía Carlos III, 94 

08028- Barcelona 

España 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/823/002 (5 single-dose inhalers) 

EU/1/13/823/004 (1 single-dose inhaler)  

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 20 February 2013 

Date of latest renewal: 

 

10. DATE OF REVISION OF THE TEXT 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

  



 

24 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 

 

 



 

25 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer responsible for batch release 

 

FERRER INTERNACIONAL, S.A. 

Joan Buscalla, 1-9, 08173 Sant Cugat del Vallès, Barcelona, Spain 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  

 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

 Periodic safety update reports 

 

The requirements for submission of periodic safety update reports for this medicinal product are set 

out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 

2001/83/EC and any subsequent updates published on the European medicines web-portal. 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 Risk Management Plan (RMP) 

 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 

agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 

updates of the RMP. 

An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 

 Whenever the risk management system is modified, especially as the result of new 
information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 

 Addtional risk minimisation measures 

 

Prior to launch in each Member State the Marketing Authorisation Holder (MAH) shall agree an 

educational programme with the National Competent Authority. 

 

The MAH shall ensure that, following discussion and agreement with the National Competent 

Authorities in each Member State where ADASUVE is marketed, at launch and after launch, all 

healthcare professionals who are expected to use ADASUVE are provided with an information pack 

containing the following items: 

 

 Summary of Product Characteristics (SmPC) and Package Leaflet and Labelling 

 Educational material for the healthcare professionals 

 

Key elements to be included in the educational materials: 



 

26 

 

General: 

 Introductory statement on the purpose of the educational material 

 Statement on acute setting of indication 

 

Risk of bronchospasm: 

 Mention of contra-indications and related warnings 

 A clear recommendation not to start ADASUVE treatment in patients with a respiratory medical 

history 

 Treatment with ADASUVE to be limited to a hospital setting 

 Availabilty of rescue medications (short acting beta agonist bronchodilator) during treatment 

 Observation of patients for 1 hour after each dose of ADASUVE 

 

Risk of QT prolongation: 

 Administration of a maximum of 2 doses 

 Caution to be exercised when ADASUVE is administered in patients with known 

cardiovascular disease or a family history of QT prolongation, and in cases of concomitant use 

with other medicial products known to prolong the QT interval 

 

 

 

  



 

27 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



 

28 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

 

  



 

29 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADASUVE 4.5 mg inhalation powder, pre-dispensed 

loxapine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each inhaler delivers 4.5 mg loxapine. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Inhalation powder, pre-dispensed 

 

1 single dose inhaler 

 

5 single-dose inhalers 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use 

 

Inhalation use 

 

For single use only 

 

This product is packaged in a sealed pouch and should remain in the pouch until ready to use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

 



 

30 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store in the original pouch until ready for use in order to protect from light and moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Ferrer Internacional, S.A. 

Gran Vía Carlos III, 94 

08028- Barcelona 

España  

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/823/001 (5 single-dose inhalers) 

EU/1/13/823/003 (1 single-dose inhaler) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 



 

31 

PC: {number} 

SN: {number} 

NN: {number} 

 

 



 

32 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

POUCH 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADASUVE 4.5 mg inhalation powder 

loxapine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each inhaler delivers 4.5 mg loxapine. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Inhalation powder 

 

One single-dose inhaler 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Directions for use inside 

 

Read the package leaflet before use 

 

Inhalation use 

 

Directions for use 

 

Read the following 5 steps before administering ADASUVE to a patient: 

 

1.  Open pouch. Do not open pouch until ready to use. 

 

Tear open the foil pouch and remove the inhaler from the package. 

 

2.  Pull tab.  Firmly pull the plastic tab from the rear of the inhaler.  The green light turns on 

indicating that the inhaler is ready for use.   

 



 

33 

 

Use within 15 minutes after removing the tab (or until the green light turns off) to prevent 

automatic deactivation of the inhaler. 

 

 

Instruct the patient to: 

 

3.  Exhale.  Hold the inhaler away from the mouth and breathe out fully to empty lungs. 

 

 

 

4.  Inhale.  Inhale through the mouthpiece with a steady, deep breath. 

 

IMPORTANT:  Check that the green light turns off after the patient inhales. 

 

 

 

 

 

 

 

 

 

5.  Hold Breath.  Remove the mouthpiece from the mouth and hold breath briefly.  

 

 

 

 

 

 

 

 

 

Note:  If the green light stays on after the patient inhales, instruct the patient to repeat 

steps 3 to 5. 

 

 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 



 

34 

Keep out of the sight and reach of children 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

Do not use in patients with asthma or COPD or acute respiratory symptoms 

 

A short-acting beta-agonist bronchodilator should be available for treatment of possible 

bronchospasm. 

 

Patients should be observed during the first hour after each dose for signs and symptoms of 

bronchospasm. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store in the original pouch until ready for use in order to protect from light and moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Ferrer Internacional, S.A. 

Gran Vía Carlos III, 94 

08028- Barcelona 

España  

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/823/001 (5 single-dose inhalers) 

EU/1/13/823/003 (1 single-dose inhaler) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 



 

35 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 



 

36 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

DEVICE HOUSING 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

ADASUVE 4.5 mg inhalation powder 

loxapine 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

4.5 mg 

 

 

6. OTHER 

 

 

 

  



 

37 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADASUVE 9.1 mg inhalation powder, pre-dispensed 

loxapine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each inhaler delivers 9.1 mg loxapine. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Inhalation powder, pre-dispensed 

 

1 single dose inhaler 

 

5 single-dose inhalers 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use 

 

Inhalation use 

 

For single use only 

 

This product is packaged in a sealed pouch and should remain in the pouch until ready to use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

 



 

38 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store in the original pouch until ready for use in order to protect from light and moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Ferrer Internacional, S.A. 

Gran Vía Carlos III, 94 

08028- Barcelona 

España  

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/823/002 (5 single-dose inhalers) 

EU/1/13/823/004 (1 single-dose inhaler) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC: {number} 



 

39 

SN: {number} 

NN: {number} 

 

 



 

40 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

POUCH 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADASUVE 9.1 mg inhalation powder 

loxapine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each inhaler delivers 9.1 mg loxapine. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Inhalation powder 

 

One single-dose inhaler 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Directions for use inside 

 

Read the package leaflet before use 

 

Inhalation use 

 

Directions for use 

 

Read the following 5 steps before administering ADASUVE to a patient: 

 

1.  Open pouch. Do not open pouch until ready to use. 

 

Tear open the foil pouch and remove the inhaler from the package. 

 

2.  Pull tab.  Firmly pull the plastic tab from the rear of the inhaler.  The green light turns on 

indicating that the inhaler is ready for use.   

 



 

41 

 

Use within 15 minutes after removing the tab (or until the green light turns off) to prevent 

automatic deactivation of the inhaler. 

 

 

Instruct the patient to: 

 

3.  Exhale.  Hold the inhaler away from the mouth and breathe out fully to empty lungs. 

 

 

 

4.  Inhale.  Inhale through the mouthpiece with a steady, deep breath. 

 

IMPORTANT:  Check that the green light turns off after the patient inhales. 

 

 

 

 

 

 

 

 

 

5.  Hold Breath.  Remove the mouthpiece from the mouth and hold breath briefly.  

 

 

 

 

 

 

 

 

 

Note:  If the green light stays on after the patient inhales, instruct the patient to repeat 

steps 3 to 5. 

 

 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 



 

42 

Keep out of the sight and reach of children 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

Do not use in patients with asthma or COPD or acute respiratory symptoms 

 

A short-acting beta-agonist bronchodilator should be available for treatment of possible 

bronchospasm. 

 

Patients should be observed during the first hour after each dose for signs and symptoms of 

bronchospasm. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store in the original pouch until ready for use in order to protect from light and moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Ferrer Internacional, S.A. 

Gran Vía Carlos III, 94 

08028- Barcelona 

España  

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/823/002 (5 single-dose inhalers) 

EU/1/13/823/004 (1 single-dose inhaler) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 



 

43 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 



 

44 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

DEVICE HOUSING 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

ADASUVE 9.1 mg inhalation powder 

loxapine 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

9.1 mg 

 

 

6. OTHER 

 

 

 

  



 

45 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



 

46 

Package leaflet: Information for the user 

 

ADASUVE 4.5 mg inhalation powder, pre-dispensed 

loxapine 

 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor or nurse.  

- If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 

listed in this leaflet. See section 4. 

 

What is in this leaflet 

 

1. What ADASUVE is and what it is used for 

2. What you need to know before you use ADASUVE 

3. How to use ADASUVE 

4. Possible side effects 

5. How to store ADASUVE 

6. Contents of the pack and other information 

 

1. What ADASUVE is and what it is used for 

 

ADASUVE contains the active substance loxapine, which belongs to a group of medicines called 

antipsychotics. ADASUVE works by blocking certain chemicals in the brain (neurotransmitters) such 

as dopamine and serotonin thus causing calming effects and relieving aggressive behaviour. 

 

ADASUVE is used to treat acute symptoms of mild-to-moderate agitation that may occur in adult 

patients who have schizophrenia or bipolar disorder. These are diseases characterised by symptoms 

such as: 

 

• (Schizophrenia) Hearing, seeing, or sensing things which are not there, suspiciousness, mistaken 
beliefs, incoherent speech and behaviour and emotional flatness. People with this condition may 

also feel depressed, guilty, anxious or tense. 

• (Bipolar disorder) Feeling “high”, having excessive amounts of energy, needing much less sleep 
than usual, talking very quickly with racing ideas, and sometimes severe irritability. 

 

 

2. What you need to know before you use ADASUVE  

 

Do not use ADASUVE 

• if you are allergic to loxapine or amoxapine; 
• if you have symptoms of wheezing or shortness of breath; 
• if you have lung problems like asthma or chronic obstructive pulmonary disease (which your 

doctor may have called “COPD”). 

 

Warnings and precautions 

Your doctor or nurse will talk to you before you use ADASUVE and determine whether it is 

appropriate for you. 

 

• ADASUVE may cause narrowing of the airways (bronchospasm) and may cause you to wheeze, 
cough, feel chest tightness or have shortness of breath. Typically, this will occur within 25 minutes 

of use. 

• Neuroleptic Malignant Syndrome (NMS) is a set of symptoms that can occur if you are taking 
antipsychotic medicines, including ADASUVE. These symptoms can be high fever, rigid muscles, 



 

47 

irregular or fast heart rate or pulse. NMS can cause death. Do not use ADASUVE again if NMS 

occurs. 

• Antipsychotic medicines like ADASUVE can cause movements that you may not be able to 
control including making faces, sticking out your tongue, smacking or puckering your lips, 

blinking rapidly, or moving your legs, arms or fingers rapidly. Treatment with ADASUVE may 

have to be stopped if this occurs. 

• ADASUVE should be used with caution in patients who are intoxicated or delirious. 
 

 

Before treatment with ADASUVE, tell your doctor or nurse if you: 

• have or had breathing problems like asthma or other chronic lung diseases such as bronchitis or 
emphysema 

• have or had heart problems or stroke 
• have or had low or high blood pressure 
• have or had seizures (convulsions) 
• have or had glaucoma (increased pressure in the eye) 
• have or had urinary retention (incomplete emptying of the bladder) 
• already used ADASUVE and you developed symptoms of wheezing or shortness of breath 
• ever had muscle or eye movements you can’t control, lack of coordination, sustained muscle 

contraction, or feeling restless or unable to sit still 

• are an older person with dementia (loss of memory and other mental abilities). 
 

 

 

Children and adolescents 

ADASUVE is not for use in children and adolescents under 18 years. 

 

Other medicines and ADASUVE 

Tell your doctor if you are using or have recently used or might use any other medicines, including: 

• adrenaline 
• medicines to treat a breathing problem 
• medicines that may put you at a risk for seizures (for example, clozapine, tricyclics or SSRIs, 

tramadol, mefloquine) 

• medicines to treat Parkinson’s disease 
• lorazepam or other centrally acting medicines (to treat anxiety, depression, pain, or to help you 

sleep) or any other medicines that cause sleepiness 

• recreational (illegal) drugs 
• medicines like fluvoxamine, propranolol, and enoxacin and other medicines that inhibit a certain 

liver enzyme called “CYP450 1A2.” 

• medicines to treat schizophrenia, depression, or pain since you may be more at risk for seizures 
Using ADASUVE and adrenaline together may cause your blood pressure to drop. 

 

ADASUVE with alcohol 

Because ADASUVE affects the nervous system, alcohol should be avoided when using ADASUVE. 

 

Pregnancy and breast-feeding 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor for advice before using this medicine. You should not breast-feed for a period of 48 hours 

after receiving ADASUVE and should discard the milk produced in the meantime. 

 

The following symptoms may occur in newborn babies of mothers that have repeatedly used 

antipsychotic medicines in the last three months of their pregnancy: shaking, muscle stiffness and/or 

weakness, sleepiness, agitation, breathing problems, and difficulty in feeding. If your baby develops 

any of these symptoms you may need to contact your doctor. 

 



 

48 

Driving and using machines 

Do not drive or use any tools or machines after using ADASUVE until you know how ADASUVE 

affects you since dizziness, sedation, and sleepiness have been reported as a potential side effect of 

ADASUVE. 

 

 

3. How to use ADASUVE 

 

Always use this medicine exactly as your doctor or nurse has told you. Check with your doctor or 

nurse if you are not sure. 

 

The recommended initial dose is 9.1 mg. After 2 hours, your doctor may prescribe a second dose after 

carefully considering your condition and your dose may be reduced to 4.5 mg if your doctor believes 

that this is a more appropriate dose to treat your condition. 

 

You will use ADASUVE under the supervision of a doctor or nurse. 

 

ADASUVE is for inhalation use. After the doctor or nurse has prepared ADASUVE for you to use, 

you will be asked to take the device in your hand, exhale and then put the mouthpiece in your mouth, 

inhale the medicine through the device and then hold your breath briefly.  

 

If you use more ADASUVE than you should 

 

If you are concerned that you are given more ADASUVE than you feel necessary, tell your doctor or 

nurse of your concern. Patients who have been given more ADASUVE than they should may 

experience any of the following symptoms: extreme tiredness or sleepiness, trouble breathing, low 

blood pressure, throat irritation or a bad taste in the mouth, muscle or eye movements you can’t 

control.  

 

If you have any further questions on the use of this medicine, ask your doctor or nurse. 

 

 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

If you get any of the following side effects, talk to your doctor immediately and stop taking the 

medicine:  

• any breathing symptoms such as wheezing, cough, shortness of breath, or chest tightness, as these 
could mean that the medicine is irritating your airways (uncommon occurrence unless you have 

asthma or COPD); 

• light-headedness or fainting, as these could mean that the medicine is lowering your blood 
pressure (uncommon occurrence); 

• worsening agitation or confusion, especially combined with fever or muscle stiffness (rare 
occurrence). These can be associated with a severe condition called neuroleptic malignant 

syndrome (NMS)  

 

Also talk to your doctor if you have any of the following side effects that could also happen with 

other forms of this medicine: 

 

Very common (may affect more than 1 in 10 people): bad taste in the mouth or sleepiness. 

 

Common (may affect up to 1 in 10 people): dizziness, throat irritation, dry mouth or tiredness. 

 

Uncommon (may affect up to 1 in 100 people): muscle or eye movements you can’t control, lack of 

coordination, sustained muscle contraction, or feeling restless or unable to sit still. 

 



 

49 

 

Additional side effects which have been related to long term use of loxapine by mouth and which may 

be relevant for ADASUVE include faintness upon standing, increased heart rate, increased blood 

pressure, blurred vision, dry eyes, and decreased urination.  

 

Reporting of side effects 

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 

listed in this leaflet. You can also report side effects directly via the national reporting system listed in 

Appendix V. By reporting side effects you can help provide more information on the safety of this 

medicine. 

 

 

5. How to store ADASUVE 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use ADASUVE after the expiry date which is stated on the product label. The expiry date 

refers to the last day of that month. 

 

Store in the original pouch until ready for use in order to protect from light and moisture. 

 

Do not use ADASUVE if you notice an open or torn pouch or any signs of physical damage to the 

medicine. 

 

Do not throw away any medicines via household waste. Ask your pharmacist how to throw away 

medicines you no longer use. These measures will help protect the environment. 

 

 

6. Contents of the pack and other information 

 

What ADASUVE contains  

The active substance is loxapine. Each single-dose inhaler contains 5 mg loxapine and delivers 4.5 mg 

of loxapine. 

 

What ADASUVE looks like and contents of the pack 

ADASUVE 4.5 mg inhalation powder, pre-dispensed consists of a single-dose, disposable white 

plastic inhaler that contains loxapine. Each inhaler is packaged in a sealed foil pouch. ADASUVE 4.5 

mg is supplied in a carton of 1 or 5 single dose inhalers. 

 

Marketing Authorisation Holder 

Ferrer Internacional, S.A. 

Gran Vía Carlos III, 94 

08028- Barcelona 

España 

 

Manufacturer 

Ferrer Internacional, S.A. 

Joan Buscalla, 1-9, 08173 Sant Cugat del Vallès 

Barcelona, Spain 

 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien  

Ferrer Internacional, S.A. 

Tél/Tel: +34 93 600 37 00 

Lietuva  

AOP Orphan Pharmaceuticals AG LT 

Tel +370 672 12222 



 

50 

   

България  

AOP Orphan Pharmaceuticals AG BG 

Teл.: +35 988 6666096 

 

Luxembourg/Luxemburg  

Ferrer Internacional, S.A. 

Tél/Tel: +34 93 600 37 00 

 

Česká republika  

AOP Orphan Pharmaceuticals AG CZ 

Tel: +420 251 512 947 

 

Magyarország  

AOP Orphan Pharmaceuticals AG HU 

Tel.: +36 1 3192633 

 

Danmark  

Ferrer Internacional, S.A. 

Tlf: +34 93 600 37 00 

 

Malta  

Ferrer Internacional, S.A. 

Tel.: +34 93 600 37 00 

 

Deutschland  

Ferrer Deutschland GmbH 

Tel: +49 (0) 2407 502311 0 

 

Nederland  

Ferrer Internacional, S.A. 

Tel.: +34 93 600 37 00 

 

Eesti  

AOP Orphan Pharmaceuticals AG LT 

Tel: +370 672 12222 

 

 

Norge  

Ferrer Internacional, S.A. 

Tlf: +34 93 600 37 00 

 

Ελλάδα  

Ferrer Galenica S.A. 

Τηλ: +30 210 52 81 700 

 

Österreich  

AOP Orphan Pharmaceuticals AG 

Tel: +43 1 5037244-0 

 

España  

Ferrer Farma, S.A. 

Tel.: +34 93 600 37 00 

 

Polska  

AOP Orphan Pharmaceuticals S.A. PL 

Tel: +48 22 5424068 

 

France  

Ferrer Internacional, S.A. 

Tél: +34 93 600 37 00 

 

Portugal  

Ferrer Portugal, S.A. 

Tel: +351 214449600 

 

Hrvatska  

AOP Orphan Pharmaceuticals AG 

Tel: +43 1 5037244-0 

 

România  

Galenica S.A. 

Tel: +30 210 52 81 700 

 

Ireland  

Ferrer Internacional, S.A. 

Tel.: +34 93 600 37 00 

Slovenija  

AOP Orphan Pharmaceuticals AG 

Tel: +43 1 5037244-0 

 

Ísland  

Ferrer Internacional, S.A. 

Sími: +34 93 600 37 00 

 

Slovenská republika  

AOP Orphan Pharmaceuticals AG SK 

Tel: +421 31 5502271 

 

Italia  

Angelini S.p.A. 

Tel: +39 06 780531 

 

Suomi/Finland  

Ferrer Internacional, S.A. 

Puh/Tel: +34 93 600 37 00 

 

Κύπρος  

Τhespis Pharmaceutical Ltd Tηλ: 

++357 22 67 77 10 

 

Sverige  

Ferrer Internacional, S.A. 

Tel: +34 93 600 37 00 

 

Latvija  

AOP Orphan Pharmaceuticals AG LT 

United Kingdom  

Ferrer Internacional, S.A. 



 

51 

Tel +370 672 12222 

 
Tel.: +34 93 600 37 00 

 

 

 

 

This leaflet was last revised in  

 

Other sources of information 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu.  

 

 

The following information is intended for healthcare professionals only: 

 

 

Read all instructions before use. See the SmPC for more information. 

 

Becoming familiar with ADASUVE: The pictures below show the important features of ADASUVE.  

 

 
 

 ADASUVE is provided in a sealed pouch. 

 When ADASUVE is removed from the pouch, the indicator light is off. 

 The indicator light turns on (green) when the tab is pulled out. The inhaler is then ready for use. 

 The indicator light automatically turns off again when the medicine is inhaled. 

Read the following 5 steps before administering ADASUVE to a patient. 

 



 

52 

 

 

1. Open pouch 

Do not open the pouch until ready to use. Tear open the foil 

pouch and remove the inhaler from the package. 

  

 

 

2. Pull tab 

Firmly pull the plastic tab from the rear of the inhaler. The green 

light turns on indicating that the inhaler is ready for use.  

 

Use within 15 minutes after removing the tab (or until the 

green light turns off) to prevent automatic deactivation of 

the inhaler. 

  

Instruct the patient to: 

 

 

 

3. Exhale 

Hold the inhaler away from the mouth and breathe out fully to 

empty lungs. 

 

 

4. Inhale 

Inhale through the mouthpiece with a steady deep breath. 

 

IMPORTANT: Check that the green light turns off after 

the patient inhales. 
 

 

5. Hold breath 

Remove the mouthpiece from the mouth and hold breath briefly. 

NOTE: If the green light stays on after the patient inhales, instruct the patient to repeat steps 3-5. 

 



 

53 

Package leaflet: Information for the user 

 

ADASUVE 9.1 mg inhalation powder, pre-dispensed 

loxapine 

 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor or nurse.  

- If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 

listed in this leaflet. See section 4. 

 

What is in this leaflet 

 

1. What ADASUVE is and what it is used for 

2. What you need to know before you use ADASUVE 

3. How to use ADASUVE 

4. Possible side effects 

5. How to store ADASUVE 

6. Contents of the pack and other information 

 

1. What ADASUVE is and what it is used for 

 

ADASUVE contains the active substance loxapine, which belongs to a group of medicines called 

antipsychotics. ADASUVE works by blocking certain chemicals in the brain (neurotransmitters) such 

as dopamine and serotonin thus causing calming effects and relieving aggressive behaviour. 

 

ADASUVE is used to treat acute symptoms of mild-to-moderate agitation that may occur in adult 

patients who have schizophrenia or bipolar disorder. These are diseases characterised by symptoms 

such as: 

 

• (Schizophrenia) Hearing, seeing, or sensing things which are not there, suspiciousness, mistaken 
beliefs, incoherent speech and behaviour and emotional flatness. People with this condition may 

also feel depressed, guilty, anxious or tense. 

• (Bipolar disorder) Feeling “high”, having excessive amounts of energy, needing much less sleep 
than usual, talking very quickly with racing ideas, and sometimes severe irritability. 

 

 

2. What you need to know before you use ADASUVE  

 

Do not use ADASUVE 

• if you are allergic to loxapine or amoxapine; 
• if you have symptoms of wheezing or shortness of breath; 
• if you have lung problems like asthma or chronic obstructive pulmonary disease (which your 

doctor may have called “COPD”). 

 

Warnings and precautions 

Your doctor or nurse will talk to you before you use ADASUVE and determine whether it is 

appropriate for you. 

 

• ADASUVE may cause narrowing of the airways (bronchospasm) and may cause you to wheeze, 
cough, feel chest tightness or have shortness of breath. Typically, this will occur within 25 minutes 

of use. 

• Neuroleptic Malignant Syndrome (NMS) is a set of symptoms that can occur if you are taking 
antipsychotic medicines, including ADASUVE. These symptoms can be high fever, rigid muscles, 



 

54 

irregular or fast heart rate or pulse. NMS can cause death. Do not use ADASUVE again if NMS 

occurs. 

• Antipsychotic medicines like ADASUVE can cause movements that you may not be able to 
control including making faces, sticking out your tongue, smacking or puckering your lips, 

blinking rapidly, or moving your legs, arms or fingers rapidly. Treatment with ADASUVE may 

have to be stopped if this occurs. 

• ADASUVE should be used with caution in patients who are intoxicated or delirious. 
 

 

Before treatment with ADASUVE, tell your doctor or nurse if you: 

• have or had breathing problems like asthma or other chronic lung diseases such as bronchitis or 
emphysema 

• have or had heart problems or stroke 
• have or had low or high blood pressure 
• have or had seizures (convulsions) 
• have or had glaucoma (increased pressure in the eye) 
• have or had urinary retention (incomplete emptying of the bladder) 
• already used ADASUVE and you developed symptoms of wheezing or shortness of breath 
• ever had muscle or eye movements you can’t control, lack of coordination, sustained muscle 

contraction, or feeling restless or unable to sit still 

• are an older person with dementia (loss of memory and other mental abilities). 
 

 

Children and adolescents 

ADASUVE is not for use in children and adolescents under 18 years. 

 

Other medicines and ADASUVE 

Tell your doctor if you are using or have recently used or might use any other medicines, including: 

• adrenaline 
• medicines to treat a breathing problem 
• medicines that may put you at a risk for seizures (for example, clozapine, tricyclics or SSRIs, 

tramadol, mefloquine) 

• medicines to treat Parkinson’s disease 
• lorazepam or other centrally acting medicines (to treat anxiety, depression, pain, or to help you 

sleep) or any other medicines that cause sleepiness 

• recreational (illegal) drugs 
• medicines like fluvoxamine, propranolol, and enoxacin and other medicines that inhibit a certain 

liver enzyme called “CYP450 1A2.” 

• medicines to treat schizophrenia, depression, or pain since you may be more at risk for seizures 
Using ADASUVE and adrenaline together may cause your blood pressure to drop. 

 

ADASUVE with alcohol 

Because ADASUVE affects the nervous system, alcohol should be avoided when using ADASUVE. 

 

Pregnancy and breast-feeding 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor for advice before using this medicine. You should not breast-feed for a period of 48 hours 

after receiving ADASUVE and should discard the milk produced in the meantime. 

 

The following symptoms may occur in newborn babies of mothers that have repeatedly used 

antipsychotic medicines in the last three months of their pregnancy: shaking, muscle stiffness and/or 

weakness, sleepiness, agitation, breathing problems, and difficulty in feeding. If your baby develops 

any of these symptoms you may need to contact your doctor. 

 



 

55 

Driving and using machines 

Do not drive or use any tools or machines after using ADASUVE until you know how ADASUVE 

affects you since dizziness, sedation, and sleepiness have been reported as a potential side effect of 

ADASUVE. 

 

 

3. How to use ADASUVE 

 

Always use this medicine exactly as your doctor or nurse has told you. Check with your doctor or 

nurse if you are not sure. 

 

The recommended initial dose is 9.1 mg. After 2 hours, your doctor may prescribe a second dose after 

carefully considering your condition and your dose may be reduced to 4.5 mg if your doctor believes 

that this is a more appropriate dose to treat your condition. 

 

You will use ADASUVE under the supervision of a doctor or nurse. 

 

ADASUVE is for inhalation use. After the doctor or nurse has prepared ADASUVE for you to use, 

you will be asked to take the device in your hand, exhale and then put the mouthpiece in your mouth, 

inhale the medicine through the device and then hold your breath briefly.  

 

If you use more ADASUVE than you should 

 

If you are concerned that you are given more ADASUVE than you feel necessary, tell your doctor or 

nurse of your concern. Patients who have been given more ADASUVE than they should may 

experience any of the following symptoms: extreme tiredness or sleepiness, trouble breathing, low 

blood pressure, throat irritation or a bad taste in the mouth, muscle or eye movements you can’t 

control.  

 

If you have any further questions on the use of this medicine, ask your doctor or nurse. 

 

 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

If you get any of the following side effects, talk to your doctor immediately and stop taking the 

medicine:  

• any breathing symptoms such as wheezing, cough, shortness of breath, or chest tightness, as these 
could mean that the medicine is irritating your airways (uncommon occurrence unless you have 

asthma or COPD); 

• light-headedness or fainting, as these could mean that the medicine is lowering your blood 
pressure (uncommon occurrence); 

• worsening agitation or confusion, especially combined with fever or muscle stiffness (rare 
occurrence). These can be associated with a severe condition called neuroleptic malignant 

syndrome (NMS)  

 

Also talk to your doctor if you have any of the following side effects that could also happen with 

other forms of this medicine: 

 

Very common (may affect more than 1 in 10 people): bad taste in the mouth or sleepiness. 

 

Common (may affect up to 1 in 10 people): dizziness, throat irritation, dry mouth or tiredness. 

 

Uncommon (may affect up to 1 in 100 people): muscle or eye movements you can’t control, lack of 

coordination, sustained muscle contraction, or feeling restless or unable to sit still. 

 



 

56 

 

Additional side effects which have been related to long term use of loxapine by mouth and which may 

be relevant for ADASUVE include faintness upon standing, increased heart rate, increased blood 

pressure, blurred vision, dry eyes, and decreased urination. 

 

Reporting of side effects 

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 

listed in this leaflet. You can also report side effects directly via the national reporting system listed in 

Appendix V. By reporting side effects you can help provide more information on the safety of this 

medicine. 

 

 

5. How to store ADASUVE 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use ADASUVE after the expiry date which is stated on the product label. The expiry date 

refers to the last day of that month. 

 

Store in the original pouch until ready for use in order to protect from light and moisture. 

 

Do not use ADASUVE if you notice an open or torn pouch or any signs of physical damage to the 

medicine. 

 

Do not throw away any medicines via household waste. Ask your pharmacist how to throw away 

medicines you no longer use. These measures will help protect the environment. 

 

 

6. Contents of the pack and other information 

 

What ADASUVE contains  

The active substance is loxapine. Each single-dose inhaler contains 10 mg loxapine and delivers 9.1 

mg of loxapine. 

 

What ADASUVE looks like and contents of the pack 

ADASUVE 9.1 mg inhalation powder, pre-dispensed consists of a single-dose, disposable white 

plastic inhaler that contains loxapine. Each inhaler is packaged in a sealed foil pouch. ADASUVE 9.1 

mg is supplied in a carton of 1 or 5 single dose inhalers. 

 

Marketing Authorisation Holder   

Ferrer Internacional, S.A. 

Gran Vía Carlos III, 94 

08028- Barcelona 

España 

 

Manufacturer 

Ferrer Internacional, S.A. 

Joan Buscalla, 1-9, 08173 Sant Cugat del Vallès 

Barcelona, Spain 

 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien  

Ferrer Internacional, S.A. 

Tél/Tel: +34 93 600 37 00 

Lietuva  

AOP Orphan Pharmaceuticals AG LT 

Tel +370 672 12222 



 

57 

   

България  

AOP Orphan Pharmaceuticals AG BG 

Teл.: +35 988 6666096 

 

Luxembourg/Luxemburg  

Ferrer Internacional, S.A. 

Tél/Tel: +34 93 600 37 00 

 

Česká republika  

AOP Orphan Pharmaceuticals AG CZ 

Tel: +420 251 512 947 

 

Magyarország  

AOP Orphan Pharmaceuticals AG HU 

Tel.: +36 1 3192633 

 

Danmark  

Ferrer Internacional, S.A. 

Tlf: +34 93 600 37 00 

 

Malta  

Ferrer Internacional, S.A. 

Tel.: +34 93 600 37 00 

 

Deutschland  

Ferrer Deutschland GmbH 

Tel: +49 (0) 2407 502311 0 

 

Nederland  

Ferrer Internacional, S.A. 

Tel.: +34 93 600 37 00 

 

Eesti  

AOP Orphan Pharmaceuticals AG LT 

Tel: +370 672 12222 

 

 

Norge  

Ferrer Internacional, S.A. 

Tlf: +34 93 600 37 00 

 

Ελλάδα  

Ferrer Galenica S.A. 

Τηλ: +30 210 52 81 700 

 

Österreich  

AOP Orphan Pharmaceuticals AG 

Tel: +43 1 5037244-0 

 

España  

Ferrer Farma, S.A. 

Tel.: +34 93 600 37 00 

 

Polska  

AOP Orphan Pharmaceuticals S.A. PL 

Tel: +48 22 5424068 

 

France  

Ferrer Internacional, S.A. 

Tél: +34 93 600 37 00 

 

Portugal  

Ferrer Portugal, S.A. 

Tel: +351 214449600 

 

Hrvatska  

AOP Orphan Pharmaceuticals AG 

Tel: +43 1 5037244-0 

 

România  

Galenica S.A. 

Tel: +30 210 52 81 700 

 

Ireland  

Ferrer Internacional, S.A. 

Tel.: +34 93 600 37 00 

Slovenija  

AOP Orphan Pharmaceuticals AG 

Tel: +43 1 5037244-0 

 

Ísland  

Ferrer Internacional, S.A. 

Sími: +34 93 600 37 00 

 

Slovenská republika  

AOP Orphan Pharmaceuticals AG SK 

Tel: +421 31 5502271 

 

Italia  

Angelini S.p.A. 

Tel: +39 06 780531 

 

Suomi/Finland  

Ferrer Internacional, S.A. 

Puh/Tel: +34 93 600 37 00 

 

Κύπρος  

Τhespis Pharmaceutical Ltd 

Tηλ: ++357 22 67 77 10 

 

Sverige  

Ferrer Internacional, S.A. 

Tel: +34 93 600 37 00 

 

Latvija  

AOP Orphan Pharmaceuticals AG LT 

United Kingdom  

Ferrer Internacional, S.A. 



 

58 

Tel +370 672 12222 

 
Tel.: +34 93 600 37 00 

 

 

 

 

This leaflet was last revised in  

 

Other sources of information 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu.  

 

 

The following information is intended for healthcare professionals only: 

 

 

Read all instructions before use. See the SmPC for more information. 

 

Becoming familiar with ADASUVE: The pictures below show the important features of ADASUVE.  

 

 
 

 ADASUVE is provided in a sealed pouch. 

 When ADASUVE is removed from the pouch, the indicator light is off. 

 The indicator light turns on (green) when the tab is pulled out. The inhaler is then ready for use. 

 The indicator light automatically turns off again when the medicine is inhaled. 

Read the following 5 steps before administering ADASUVE to a patient. 

 



 

59 

 

 

1. Open pouch 

Do not open the pouch until ready to use. Tear open the foil 

pouch and remove the inhaler from the package. 

  

 

 

2. Pull tab 

Firmly pull the plastic tab from the rear of the inhaler. The green 

light turns on indicating that the inhaler is ready for use.  

 

Use within 15 minutes after removing the tab (or until the 

green light turns off) to prevent automatic deactivation of 

the inhaler. 

  

Instruct the patient to: 

 

 

 

3. Exhale 

Hold the inhaler away from the mouth and breathe out fully to 

empty lungs. 

 

 

4. Inhale 

Inhale through the mouthpiece with a steady deep breath. 

 

IMPORTANT: Check that the green light turns off after 

the patient inhales. 
 

 

5. Hold breath 

Remove the mouthpiece from the mouth and hold breath briefly. 

NOTE: If the green light stays on after the patient inhales, instruct the patient to repeat steps 3-5. 

 


	ANNEX I
	SUMMARY OF PRODUCT CHARACTERISTICS
	1. NAME OF THE MEDICINAL PRODUCT
	2. QUALITATIVE AND QUANTITATIVE COMPOSITION
	3. PHARMACEUTICAL FORM
	4. CLINICAL PARTICULARS
	4.1 Therapeutic indications
	4.2 Posology and method of administration
	4.3 Contraindications
	4.4 Special warnings and precautions for use
	4.5 Interaction with other medicinal products and other forms of interaction
	4.6 Fertility, pregnancy and lactation
	4.7 Effects on ability to drive and use machines
	4.8 Undesirable effects
	4.9 Overdose
	5. PHARMACOLOGICAL PROPERTIES
	5.1  Pharmacodynamic properties
	Clinical efficacy
	Paediatric population
	5.2 Pharmacokinetic properties
	Absorption
	Distribution
	Biotransformation
	Elimination
	Linearity/non-linearity
	Pharmacokinetics in special patient populations
	Smokers
	Demographics
	5.3 Preclinical safety data
	6. PHARMACEUTICAL PARTICULARS
	6.1 List of excipients
	6.2 Incompatibilities
	6.3 Shelf life
	6.4 Special precautions for storage
	6.5 Nature and contents of container
	6.6 Special precautions for disposal
	7. MARKETING AUTHORISATION HOLDER
	8. MARKETING AUTHORISATION NUMBER(S)
	9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
	10. DATE OF REVISION OF THE TEXT
	2. QUALITATIVE AND QUANTITATIVE COMPOSITION
	3. PHARMACEUTICAL FORM
	4. CLINICAL PARTICULARS
	4.1 Therapeutic indications
	4.2 Posology and method of administration
	4.3 Contraindications
	4.4 Special warnings and precautions for use
	4.5 Interaction with other medicinal products and other forms of interaction
	4.6 Fertility, pregnancy and lactation
	4.7 Effects on ability to drive and use machines
	4.8 Undesirable effects
	4.9 Overdose
	5. PHARMACOLOGICAL PROPERTIES
	5.1  Pharmacodynamic properties
	Clinical efficacy
	Paediatric population
	5.2 Pharmacokinetic properties
	Absorption
	Distribution
	Biotransformation
	Elimination
	Linearity/non-linearity
	Pharmacokinetics in special patient populations
	Smokers
	Demographics
	5.3 Preclinical safety data
	6. PHARMACEUTICAL PARTICULARS
	6.1 List of excipients
	6.2 Incompatibilities
	6.3 Shelf life
	6.4 Special precautions for storage
	6.5 Nature and contents of container
	6.6 Special precautions for disposal
	7. MARKETING AUTHORISATION HOLDER
	8. MARKETING AUTHORISATION NUMBER(S)
	9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
	10. DATE OF REVISION OF THE TEXT
	Name and address of the manufacturer responsible for batch release
	ANNEX III
	LABELLING AND PACKAGE LEAFLET
	A. LABELLING
	PARTICULARS TO APPEAR ON THE OUTER PACKAGING  CARTON
	1. NAME OF THE MEDICINAL PRODUCT
	2. STATEMENT OF ACTIVE SUBSTANCE(S)
	3. LIST OF EXCIPIENTS
	4. PHARMACEUTICAL FORM AND CONTENTS
	5. METHOD AND ROUTE(S) OF ADMINISTRATION
	6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN
	7. OTHER SPECIAL WARNING(S), IF NECESSARY
	8. EXPIRY DATE
	9. SPECIAL STORAGE CONDITIONS
	10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE
	11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
	12. MARKETING AUTHORISATION NUMBER(S)
	13. BATCH NUMBER
	14. GENERAL CLASSIFICATION FOR SUPPLY
	15. INSTRUCTIONS ON USE
	16. INFORMATION IN BRAILLE
	17. UNIQUE IDENTIFIER – 2D BARCODE
	18. UNIQUE IDENTIFIER – HUMAN READABLE DATA
	PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING  POUCH
	1. NAME OF THE MEDICINAL PRODUCT
	2. STATEMENT OF ACTIVE SUBSTANCE(S)
	3. LIST OF EXCIPIENTS
	4. PHARMACEUTICAL FORM AND CONTENTS
	5. METHOD AND ROUTE(S) OF ADMINISTRATION
	6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN
	7. OTHER SPECIAL WARNING(S), IF NECESSARY
	8. EXPIRY DATE
	9. SPECIAL STORAGE CONDITIONS
	10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE
	11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
	12. MARKETING AUTHORISATION NUMBER(S)
	13. BATCH NUMBER
	14. GENERAL CLASSIFICATION FOR SUPPLY
	15. INSTRUCTIONS ON USE
	16. INFORMATION IN BRAILLE
	17. UNIQUE IDENTIFIER – 2D BARCODE
	18. UNIQUE IDENTIFIER – HUMAN READABLE DATA
	MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  DEVICE HOUSING
	1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION
	2. METHOD OF ADMINISTRATION
	3. EXPIRY DATE
	4. BATCH NUMBER
	5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
	6. OTHER
	PARTICULARS TO APPEAR ON THE OUTER PACKAGING  CARTON
	1. NAME OF THE MEDICINAL PRODUCT
	2. STATEMENT OF ACTIVE SUBSTANCE(S)
	3. LIST OF EXCIPIENTS
	4. PHARMACEUTICAL FORM AND CONTENTS
	5. METHOD AND ROUTE(S) OF ADMINISTRATION
	6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN
	7. OTHER SPECIAL WARNING(S), IF NECESSARY
	8. EXPIRY DATE
	9. SPECIAL STORAGE CONDITIONS
	10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE
	11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
	12. MARKETING AUTHORISATION NUMBER(S)
	13. BATCH NUMBER
	14. GENERAL CLASSIFICATION FOR SUPPLY
	15. INSTRUCTIONS ON USE
	16. INFORMATION IN BRAILLE
	17. UNIQUE IDENTIFIER – 2D BARCODE
	18. UNIQUE IDENTIFIER – HUMAN READABLE DATA
	PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING  POUCH
	1. NAME OF THE MEDICINAL PRODUCT
	2. STATEMENT OF ACTIVE SUBSTANCE(S)
	3. LIST OF EXCIPIENTS
	4. PHARMACEUTICAL FORM AND CONTENTS
	5. METHOD AND ROUTE(S) OF ADMINISTRATION
	6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN
	7. OTHER SPECIAL WARNING(S), IF NECESSARY
	8. EXPIRY DATE
	9. SPECIAL STORAGE CONDITIONS
	10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE
	11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
	12. MARKETING AUTHORISATION NUMBER(S)
	13. BATCH NUMBER
	14. GENERAL CLASSIFICATION FOR SUPPLY
	15. INSTRUCTIONS ON USE
	16. INFORMATION IN BRAILLE
	17. UNIQUE IDENTIFIER – 2D BARCODE
	18. UNIQUE IDENTIFIER – HUMAN READABLE DATA
	MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  DEVICE HOUSING
	1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION
	2. METHOD OF ADMINISTRATION
	3. EXPIRY DATE
	4. BATCH NUMBER
	5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
	6. OTHER
	B. PACKAGE LEAFLET
	1. What ADASUVE is and what it is used for
	2. What you need to know before you use ADASUVE
	3. How to use ADASUVE
	4. Possible side effects
	5. How to store ADASUVE
	6. Contents of the pack and other information
	1. What ADASUVE is and what it is used for
	2. What you need to know before you use ADASUVE
	3. How to use ADASUVE
	4. Possible side effects
	5. How to store ADASUVE
	6. Contents of the pack and other information