Adasuve

Package leaflet: Information for the user

ADASUVE 4.5 mg inhalation powder in single-dose container

loxapine
Please 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 questions, ask your doctor or nurse.
• If you get any side effects, including those not listed in this leaflet, talk to your doctor or nurse. See section 4.

Contents of this leaflet

1. What ADASUVE is and what it is used for
2. What you need to know before using 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, thereby producing calming effects and reducing aggressive behaviour.
ADASUVE is used to treat acute mild to moderate agitation symptoms that may occur in adult patients suffering from schizophrenia or bipolar disorder. These are conditions characterised by symptoms such as:

• (Schizophrenia): Hearing, seeing or sensing things that are not there, suspiciousness, false beliefs, disorganised speech and behaviour, and emotional blunting. People affected by this condition may also feel depressed, guilty, anxious or tense.
• (Bipolar disorder): Feeling overly elated, excessive amounts of energy, reduced need for sleep, talking very rapidly with racing thoughts, and sometimes being highly irritable.

2. What you should know before using ADASUVE

Do not use ADASUVE

• if you are allergic to loxapine or amoxapine;
• if you experience symptoms such as wheezing or shortness of breath;
• if you have lung problems such as asthma or chronic obstructive pulmonary disease (which your doctor may refer to as COPD).

Warnings and precautions
Your doctor or nurse will speak with you before you use ADASUVE and will determine whether this
medicine is suitable for you.

• ADASUVE may cause narrowing of the airways (bronchospasm) and wheezing, coughing, chest tightness, or shortness of breath. This usually occurs within 25 minutes after use.
• Neuroleptic Malignant Syndrome (NMS) is a group of symptoms that may occur when taking antipsychotic medicines, including ADASUVE. These symptoms may include high fever, muscle stiffness, irregular or rapid heartbeat or pulse. NMS can be fatal. Do not use ADASUVE again if NMS occurs.
• Antipsychotic medicines such as ADASUVE may cause movements that you may not be able to control, including facial grimacing, sticking out the tongue, lip smacking or puckering, rapid blinking, or fast movements of the legs, arms, or fingers. If this occurs, it may be necessary to stop treatment with ADASUVE.
• ADASUVE should be used with caution in patients who are intoxicated or delirious.
• Serious skin reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), have been reported in association with loxapine treatment. Seek immediate medical attention if, after using ADASUVE, you notice any of the following symptoms: widespread rash, high body temperature, or swollen lymph nodes.

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

• have or have had breathing problems, such as asthma or other chronic lung diseases, such as bronchitis or emphysema
• have or have had heart problems or stroke
• have or have had low or high blood pressure
• have or have had seizures
• have or have had glaucoma (increased pressure in the eye)
• have or have had urinary retention (incomplete emptying of the bladder)
• have previously used ADASUVE and developed symptoms such as wheezing or shortness of breath
• have experienced uncontrolled muscle or eye movements, lack of coordination, prolonged muscle contractions, or feelings of restlessness or inability to remain still
• are an elderly patient with dementia (loss of memory and other mental abilities)
• have had a severe widespread rash, high body temperature, and swollen lymph nodes after taking loxapine

Children and adolescents
ADASUVE must not be used in children and adolescents under 18 years of age.
Other medicines and ADASUVE
Inform your doctor if you are currently using, have recently used, or might use any other medicines, including:

• adrenaline
• medicines used to treat breathing problems
• medicines that may increase your risk of seizures (e.g., clozapine, tricyclic antidepressants, or selective serotonin reuptake inhibitors (SSRIs), tramadol, mefloquine)
• medicines used to treat Parkinson's disease
• lorazepam or other centrally-acting medicines (for treating anxiety, depression, pain, or to help you sleep), or any other medicine that causes drowsiness
• recreational (illegal) drugs
• medicines such as fluvoxamine, propranolol, and enoxacin, and other medicines that inhibit a liver enzyme called "CYP450 1A2"
• medicines used to treat schizophrenia, depression, or pain, as you may be at increased risk of seizures. The use of ADASUVE together with adrenaline may cause a drop in blood pressure.

ADASUVE and alcohol
Since ADASUVE affects the central nervous system, alcohol should be avoided when using
ADASUVE.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding,
ask your doctor for advice before using this medicine. You must not breastfeed for a period of 48 hours after receiving ADASUVE and must discard any milk produced during this time.
In newborns whose mothers have used antipsychotic medicines repeatedly during the last three months of pregnancy, the following symptoms may occur: tremors, muscle stiffness and/or weakness, drowsiness, agitation, breathing difficulties, and feeding problems. If your baby develops any of these symptoms, contact your doctor.
Driving and using machines
Do not drive or operate tools or machinery after using ADASUVE until you know how ADASUVE affects you, as symptoms such as dizziness, sedation, and drowsiness have been reported as potential side effects of ADASUVE.

3. How to use ADASUVE

Use this medicine exactly as instructed by your doctor or nurse. If you
have any doubts, consult your doctor or nurse.
The recommended initial dose is 9.1 mg. After carefully assessing your
condition, your doctor may prescribe a second dose after 2 hours, and the dose
may be reduced to 4.5 mg if the doctor considers this a more appropriate dose for treating 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,
you will be asked to take the device in hand, exhale (breathe out air from the lungs), then place
the mouthpiece in your mouth, inhale the medicine through the device, and then briefly hold your
breath.
If you use more ADASUVE than you should
If you are concerned that you have been given more ADASUVE than you think necessary, inform your doctor
or nurse about your concern. Patients who have been given more ADASUVE than required
may experience the following symptoms: severe tiredness or drowsiness, difficulty breathing, low
blood pressure, throat irritation or bad taste in the mouth, uncontrollable muscle or eye movements.
If you have any questions about how to use this medicine, consult your doctor or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
If you experience any of the following adverse reactions, inform your doctor immediately and stop taking the medicine:

• any respiratory symptoms such as wheezing, cough, shortness of breath, or chest tightness, as this may mean that the medicine is irritating your airways (uncommon event if you do not have asthma or COPD);
• mental confusion or fainting, as these may indicate that the medicine is lowering your blood pressure (uncommon event);
• worsening of agitation or confusion, especially together with fever or muscle rigidity (rare event). These effects may be associated with a serious condition called neuroleptic malignant syndrome (NMS).

Also inform your doctor if you experience any of the following adverse reactions that may occur with other pharmaceutical forms containing loxapine:
Very common (may affect more than 1 in 10 people): unpleasant taste in the mouth or drowsiness.
Common (may affect up to 1 in 10 people): dizziness, throat irritation, dry mouth, or fatigue.
Uncommon (may affect up to 1 in 100 people): uncontrolled muscle or eye movements, lack of coordination, prolonged muscle contraction, or feeling restless or unable to remain still.
Additional adverse reactions associated with long-term oral use of loxapine and which may be relevant for ADASUVE include feeling unwell when standing up, increased heart rate, increased blood pressure, blurred vision, dry eyes, and reduced urination (urinary retention).

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, consult your doctor or nurse. You may also report adverse reactions directly via the national reporting system listed in Annex V.
By reporting adverse reactions, 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 stated on the inhaler label. The expiry date refers to the last day of that month.
Store in the original packaging until use to protect the medicine from light and moisture.
Do not use ADASUVE if you notice that the packaging is open or torn, or if there are any signs of physical damage to the medicine.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What ADASUVE contains
The active substance is loxapine. Each single-dose inhaler contains 5 mg of loxapine and delivers 4.5 mg
of loxapine.
Description of the appearance of ADASUVE and contents of the pack
ADASUVE 4.5 mg inhalation powder in a single-dose container consists of a disposable, single-dose, white plastic inhaler containing loxapine. Each inhaler is packaged in a sealed aluminium foil pouch. ADASUVE 4.5 mg is available in a cardboard box containing 1 or 5 single-dose inhalers.
Marketing Authorisation Holder
Ferrer Internacional, S.A.
Gran Vía Carlos III, 94
08028- Barcelona
Spain
Manufacturer
Ferrer Internacional, S.A.
Joan Buscalla, 1-9, 08173 Sant Cugat del Vallès
Barcelona, Spain
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
Ferrer Internacional, S.A. AOP Orphan Pharmaceuticals GmbH
Tél/Tel: +34 93 600 37 00 Tel +370 672 12222
България Luxembourg/Luxemburg
AOP Orphan Pharmaceuticals GmbH Ferrer Internacional, S.A.
Teл.: +35 988 6666096 Tél/Tel: +34 93 600 37 00
Česká republika Magyarország
AOP Orphan Pharmaceuticals GmbH AOP Orphan Pharmaceuticals GmbH
Tel: +420 251 512 947 Tel.: +36 1 3192633
Danmark Malta
Ferrer Internacional, S.A. Ferrer Internacional, S.A.
Tlf: +34 93 600 37 00 Tel.: +34 93 600 37 00
Deutschland Nederland
Ferrer Deutschland GmbH Ferrer Internacional, S.A.
Tel: +49 (0) 2407 502311 0 Tel.: +34 93 600 37 00
Eesti Norge
AOP Orphan Pharmaceuticals GmbH Ferrer Internacional, S.A.
Tel: +370 672 12222 Tlf: +34 93 600 37 00
Ελλάδα Österreich
Ferrer Galenica S.A. AOP Orphan Pharmaceuticals GmbH
Τηλ: +30 210 52 81 700 Tel: +43 1 5037244-0
España Polska
Ferrer Farma, S.A. AOP Orphan Poland Sp. z o. o.
Tel.: +34 93 600 37 00 Tel: +48 22 5428180
France Portugal
Ferrer Internacional, S.A. Ferrer Portugal, S.A.
Tél: +34 93 600 37 00 Tel: +351 214449600
Hrvatska România
AOP Orphan Pharmaceuticals GmbH Galenica S.A.
Tel: +43 1 5037244-0 Tel: +30 210 52 81 700
Ireland Slovenija
Ferrer Internacional, S.A. AOP Orphan Pharmaceuticals GmbH
Tel.: +34 93 600 37 00 Tel: +43 1 5037244-0
Ísland Slovenská republika
Ferrer Internacional, S.A. AOP Orphan Pharmaceuticals GmbH
Sími: +34 93 600 37 00 Tel: +421 902 566333
Italia Suomi/Finland
Angelini S.p.A. Ferrer Internacional, S.A.
Tel: +39 06 780531 Puh/Tel: +34 93 600 37 00
Κύπρος Sverige
Thesbis Pharmaceutical Ltd Ferrer Internacional, S.A.
Tηλ: +357 22 67 77 10 Tel: +34 93 600 37 00
Latvija
AOP Orphan Pharmaceuticals GmbH
Tel +370 672 12222
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu
The following information is intended for healthcare professionals only:
Read all instructions before use. See the Summary of Product Characteristics.
Familiarise yourself with ADASUVE: the figures below illustrate important features of ADASUVE.

• ADASUVE is supplied in a sealed container.
• When ADASUVE is removed from the container, the indicator light is off.
• The indicator light turns on (green) when the tab is pulled. The inhaler is then ready for use.
• The indicator light turns off automatically after the medicine is inhaled. Read the following 5 points before administering ADASUVE to a patient.

1. Open the package

Do not open the package until ready to use. Tear the aluminum package and remove the inhaler from the package.

2. Pull the tab

Firmly pull the plastic tab from the back of the inhaler.
The green light indicating that the inhaler is ready for use will turn on.
Use within 15 minutes of removing the tab (or before the green light turns off)
to prevent automatic deactivation of the inhaler.
Instruct the patient to:

3. Breathe out

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

4. Inhale

Inhale through the mouthpiece with a steady and
deep breath.
IMPORTANT: Check that the green light turns off
after the patient has inhaled.

5. Hold your breath

Remove the mouthpiece and hold your breath briefly.
NOTE: If the green light remains on after the patient has inhaled, instruct the patient to repeat steps
3 through 5.

Package leaflet: Information for the user

ADASUVE 9.1 mg inhalation powder, in single-dose container

loxapine
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or nurse.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor or nurse. See section 4.

Contents of this leaflet

1. What ADASUVE is and what it is used for
2. What you need to know before using 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, thereby producing calming effects and reducing aggressive behaviour.

ADASUVE is used to treat acute symptoms of mild to moderate agitation occurring in adult patients with schizophrenia or bipolar disorder. These are conditions characterized by symptoms such as:

• (Schizophrenia) Hearing, seeing or sensing things that are not there, suspiciousness, false beliefs, incoherent speech and behaviour, and emotional blunting. People affected by this condition may also feel depressed, guilty, anxious or tense.
• (Bipolar disorder) Feeling overly elated, having excessive amounts of energy, needing less sleep than usual, speaking very rapidly with racing thoughts, and sometimes being highly irritable.

2. What you should know before using ADASUVE

Do not use ADASUVE

• if you are allergic to loxapine or amoxapine;
• if you experience symptoms such as wheezing or shortness of breath;
• if you have lung problems such as asthma or chronic obstructive pulmonary disease (which your doctor may call COPD).

Warnings and precautions
Your doctor or nurse will speak with you before you use ADASUVE and determine whether this
medicinal product is suitable for you.

• ADASUVE may cause narrowing of the airways (bronchospasm) and wheezing, coughing, chest tightness, or shortness of breath. This usually occurs within 25 minutes after use.

• Neuroleptic Malignant Syndrome (NMS) is a group of symptoms that may occur when taking antipsychotic medicines, including ADASUVE. These symptoms may include
  high fever, muscle stiffness, irregular or rapid heartbeat or pulse. NMS can lead to death. Do not use ADASUVE again if NMS occurs.

• Antipsychotic medicines such as ADASUVE may cause movements that you cannot control, including grimacing, sticking out your tongue, lip smacking or puckering, rapid blinking, or fast movements of legs, arms, or fingers. If this occurs, treatment with ADASUVE may need to be stopped.

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

• Serious skin reactions have been reported with loxapine treatment, including drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). Seek immediate medical attention if, after using ADASUVE, you notice any of the following symptoms: widespread rash, high body temperature, or swollen lymph nodes.

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

• have or have had breathing problems, such as asthma or other chronic lung diseases such as bronchitis or emphysema
• have or have had heart problems or stroke
• have or have had low or high blood pressure
• have or have had seizures
• have or have had glaucoma (increased pressure in the eye)
• have or have had urinary retention (incomplete emptying of the bladder)
• have previously used ADASUVE and developed symptoms such as wheezing or shortness of breath
• have experienced uncontrolled muscle or eye movements, lack of coordination, prolonged muscle contractions, or feelings of restlessness or inability to stay still
• are an elderly patient with dementia (loss of memory and other mental abilities)
• have had a severe widespread rash, high body temperature, and swollen lymph nodes after taking loxapine

Children and adolescents
ADASUVE must not be used in children and adolescents under 18 years of age.
Other medicines and ADASUVE
Inform your doctor if you are currently using, have recently used, or might use any other medicines, including:

• adrenaline
• medicines for breathing problems
• medicines that may increase your risk of seizures (e.g., clozapine, tricyclic antidepressants, or selective serotonin reuptake inhibitors (SSRIs), tramadol, mefloquine)
• medicines for the treatment of Parkinson's disease
• lorazepam or other centrally-acting medicines (for the treatment of anxiety, depression, pain, or to help you sleep), or any other medicine causing drowsiness
• recreational (illegal) drugs
• medicines such as fluvoxamine, propranolol, and enoxacin, and other medicines that inhibit a liver enzyme called "CYP450 1A2"
• medicines for treating schizophrenia, depression, or pain, as you may be at increased risk of seizures. Concomitant use of ADASUVE and adrenaline may cause a drop in blood pressure.

ADASUVE and alcohol
Since ADASUVE affects the central nervous system, alcohol should be avoided when using
ADASUVE.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before using this medicinal product. You must not breastfeed for a period of 48 hours after receiving ADASUVE, and you must discard any milk produced during this time.
In newborns of mothers who have repeatedly used antipsychotic medicines during the last three months of pregnancy, the following symptoms may occur: tremors, muscle stiffness and/or weakness, drowsiness, agitation, breathing difficulties, and feeding problems. If your baby develops any of these symptoms, contact your doctor immediately.
Driving and using machines
Do not drive or operate tools or machinery after using ADASUVE until you know how ADASUVE affects you, as symptoms such as dizziness, sedation, and drowsiness have been reported as potential side effects of ADASUVE.

3. How to use ADASUVE

Use this medicine exactly as instructed by your doctor or nurse. If you have
any doubts, consult your doctor or nurse.
The recommended initial dose is 9.1 mg. After carefully assessing your condition, your doctor may
prescribe a second dose after 2 hours, which may be reduced to 4.5 mg if the doctor considers this a
more appropriate dose for treating 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, you will be
asked to take the device in your hand, exhale (breathe out fully), then place 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 have been given more ADASUVE than you think necessary, inform your
doctor or nurse about your concern. Patients who have received more ADASUVE than required may
experience the following symptoms: severe tiredness or drowsiness, difficulty breathing, low blood
pressure, throat irritation, bad taste in the mouth, or uncontrollable muscle or eye movements.
If you have any questions about how to use this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody experiences them.
If you experience any of the following side effects, inform your doctor immediately and stop taking
the medicine:

• any respiratory symptoms such as wheezing, cough, shortness of breath, or chest tightness, as these may mean that the medicine is irritating your airways (uncommon event if you do not have asthma or COPD);
• mental confusion or fainting, as these may indicate that the medicine is lowering your blood pressure (uncommon event);
• worsening of agitation or confusion, especially together with fever or muscle stiffness (rare event). These effects may be associated with a serious condition called neuroleptic malignant syndrome (NMS).

Also inform your doctor if you experience any of the following side effects that may occur with other
pharmaceutical forms containing loxapine:
Very common (may affect more than 1 in 10 people): unpleasant taste in the mouth or drowsiness.
Common (may affect up to 1 in 10 people): dizziness, throat irritation, dry mouth or fatigue.
Uncommon (may affect up to 1 in 100 people): uncontrolled muscle or eye movements, lack of coordination, sustained muscle contraction, or feeling restless or unable to stay still.

Additional side effects that have been associated with long-term oral use of loxapine and that may be relevant for ADASUVE include feeling unwell when standing up, increased heart rate, increased blood pressure, blurred vision, dry eyes, and reduced urination (urinary retention).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system listed in Annex 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 stated on the inhaler label. The expiry date refers to the last day of that month.
Store in the original packaging until the time of use to protect the medicine from light and moisture.
Do not use ADASUVE if you notice that the packaging is open or torn, or any sign of physical damage to the medicine.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What ADASUVE contains
The active substance is loxapine. Each single-dose inhaler contains 10 mg of loxapine and delivers 9.1
mg of loxapine.
Description of the appearance of ADASUVE and contents of the pack
ADASUVE 9.1 mg inhalation powder in a single-dose container consists of a disposable white plastic inhaler containing loxapine. Each inhaler is packaged in a sealed aluminium foil pouch. ADASUVE 9.1 mg is available in cardboard boxes containing 1 or 5 single-dose inhalers.
Marketing Authorisation Holder
Ferrer Internacional, S.A.
Gran Vía Carlos III, 94
08028- Barcelona
Spain
Manufacturer
Ferrer Internacional, S.A.
Joan Buscalla, 1-9, 08173 Sant Cugat del Vallès
Barcelona, Spain
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
Ferrer Internacional, S.A. AOP Orphan Pharmaceuticals GmbH
Tél/Tel: +34 93 600 37 00 Tel +370 672 12222
България Luxembourg/Luxemburg
AOP Orphan Pharmaceuticals GmbH Ferrer Internacional, S.A.
Teл.: +35 988 6666096 Tél/Tel: +34 93 600 37 00
Česká republika Magyarország
AOP Orphan Pharmaceuticals GmbH AOP Orphan Pharmaceuticals GmbH
Tel: +420 251 512 947 Tel.: +36 1 3192633
Danmark Malta
Ferrer Internacional, S.A. Ferrer Internacional, S.A.
Tlf: +34 93 600 37 00 Tel.: +34 93 600 37 00
Deutschland Nederland
Ferrer Deutschland GmbH Ferrer Internacional, S.A.
Tel: +49 (0) 2407 502311 0 Tel.: +34 93 600 37 00
Eesti Norge
AOP Orphan Pharmaceuticals GmbH Ferrer Internacional, S.A.
Tel: +370 672 12222 Tlf: +34 93 600 37 00
Ελλάδα Österreich
Ferrer Galenica S.A. AOP Orphan Pharmaceuticals GmbH
Τηλ: +30 210 52 81 700 Tel: +43 1 5037244-0
España Polska
Ferrer Farma, S.A. AOP Orphan Poland Sp. z o. o.
Tel.: +34 93 600 37 00 Tel: +48 22 5428180
France Portugal
Ferrer Internacional, S.A.
Ferrer Portugal, S.A.
Tél: +34 93 600 37 00 Tel: +351 214449600
Hrvatska România
AOP Orphan Pharmaceuticals GmbH Galenica S.A.
Tel: +43 1 5037244-0 Tel: +30 210 52 81 700
Ireland Slovenija
Ferrer Internacional, S.A. AOP Orphan Pharmaceuticals GmbH
Tel.: +34 93 600 37 00 Tel: +43 1 5037244-0
Ísland Slovenská republika
Ferrer Internacional, S.A. AOP Orphan Pharmaceuticals GmbH
Sími: +34 93 600 37 00 Tel: +421 902 566333
Italia Suomi/Finland
Angelini S.p.A. Ferrer Internacional, S.A.
Tel: +39 06 780531 Puh/Tel: +34 93 600 37 00
Κύπρος Sverige
Thesbis Pharmaceutical Ltd Ferrer Internacional, S.A.
Tηλ: +357 22 67 77 10 Tel: +34 93 600 37 00
Latvija
AOP Orphan Pharmaceuticals GmbH
Tel +370 672 12222
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu
The following information is intended for healthcare professionals only:
Read all instructions before use. See the product characteristics summary.
Familiarise yourself with ADASUVE: the figures below illustrate important features of ADASUVE.

• ADASUVE is supplied in a sealed container.
• When ADASUVE is removed from the container, the indicator light is off.
• The indicator light turns on (green) when the tab is pulled. The inhaler is then ready for use.
• The indicator light turns off automatically after the medicine has been inhaled. Read the following 5 points before administering ADASUVE to a patient.

1. Open the package

Do not open the package until ready to use. Tear open the
aluminum package and remove the inhaler from the package.

2. Pull the tab

Firmly pull the plastic tab from the back of the inhaler.
The green light indicating that the inhaler is ready for use will turn on.
Use within 15 minutes of removing the tab (or before the green light turns off) to avoid automatic deactivation of the inhaler.
Instruct the patient to:

3. Breathe out

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

4. Inhale

Inhale through the mouthpiece with a steady and deep breath.
IMPORTANT: Check that the green light turns off
after the patient has inhaled.

5. Hold your breath

Remove the mouthpiece and hold your breath briefly.
NOTE: If the green light remains on after the patient has inhaled, instruct the patient to repeat steps
3 to 5.
Annex IV
Scientific conclusions and grounds for the variation to the terms of the marketing authorisation
Scientific conclusions
Taking into account the assessment of the Pharmacovigilance and Risk Assessment Committee (PRAC) and the Periodic Safety Update Report (PSUR) for loxapine (powder for inhalation in single-dose containers), the PRAC's scientific conclusions are as follows:
In light of the available literature data on drug rash with eosinophilia and systemic symptoms (DRESS syndrome), including one clinical case with very strong evidence (DRESS diagnosis confirmed by RegiSCAR 6 and positive skin test for loxapine), the PRAC considers that a causal relationship between loxapine (powder for inhalation in single-dose containers) and DRESS syndrome is at least a reasonable possibility. The PRAC concluded that the product information for medicinal products containing loxapine (powder for inhalation in single-dose containers) should therefore be amended accordingly.
Having reviewed the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the overall conclusions and the rationale of the recommendation.
Grounds for the variation to the terms of the marketing authorisation
Based on the scientific conclusions for loxapine (powder for inhalation in single-dose containers), the CHMP considers that the risk-benefit balance of the medicinal product containing loxapine (powder for inhalation in single-dose containers) remains unchanged, subject to the proposed amendments to the product information.
The CHMP recommends a variation to the terms of the marketing authorisation.