Prescribing Information: Information for the User

Abilify Maintena 720 mg Long-Acting Injectable Suspension in Pre-filled Syringe

Abilify Maintena 960 mg Long-Acting Injectable Suspension in Pre-filled Syringe

aripiprazol (aripiprazole)

Read this entire prescribing information carefully before receiving this medication, as it contains important information for you.

• Keep this prescribing information, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• If you experience any adverse effects, consult your doctor or nurse, even if they are not listed in this prescribing information. See section 4.

Abilify Maintena contains the active ingredient aripiprazol in a pre-filled syringe. Aripiprazol belongs to a group of medicines called antipsychotics. Abilify Maintena is used to treat schizophrenia – a condition with symptoms such as hearing, seeing or feeling things that do not exist, distrust, incorrect beliefs, incoherent language and monotony of emotional and behavioral behavior. People with this condition may also feel depressed, guilty, restless or tense.

Abilify Maintena is indicated for adult patients with schizophrenia who are sufficiently stabilized during treatment with aripiprazol.

If you have responded well to treatment with oral aripiprazol or Abilify Maintena medication, your doctor may initiate treatment with Abilify Maintena. It may help alleviate symptoms of your condition and reduce the risk of them recurring.

Do not use Abilify Maintena

• if you are allergic to aripiprazole or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Speak with your doctor or nurse before they administer Abilify Maintena to you.

Cases of patients experiencing suicidal thoughts and behaviors have been reported during treatment with this medicine. Inform your doctor immediately if you have thoughts or feelings of harming yourself before or after receiving Abilify Maintena.

Tell your doctor if you have:

• an acute agitation state or an intensely psychotic state.
• cardiovascular diseases (heart and circulation diseases), a family history of cardiovascular disease, stroke or mini-stroke, abnormal blood pressure.
• cardiac problems or a history of stroke, especially if you know that other risk factors for stroke are present in you.
• blood clots or a family history of blood clots, as antipsychotics have been associated with the formation of blood clots.
• irregular heartbeats or if someone in your family has a history of irregular heartbeats (including the prolongation of the QT interval observed with ECG monitoring).
• involuntary and irregular muscle movements, especially in the face (tardive dyskinesia).
• present a combination of fever, sweating, rapid breathing, muscle stiffness, and drowsiness or numbness (which may be signs of neuroleptic malignant syndrome).
• seizures, as your doctor may want to monitor you more closely.
• dementia (loss of memory and other mental abilities), especially if you are elderly.
• high blood sugar levels (characterized by excessive thirst, increased urine production, increased appetite, and feeling weak) or a family history of diabetes.
• difficulty swallowing.
• a history of addiction to gambling.

If you notice that you are gaining weight, developing unusual movements, feeling drowsiness that interferes with your normal daily activities, any difficulty swallowing, or experience symptoms of an allergy, speak with your doctor immediately.

Inform your doctor if you, your family, or caregiver notice that you are developing impulses or urges to behave in an unusual way in you and that you cannot resist the impulse, instinct, or temptation to carry out certain activities that may harm you or others. This is known as impulse control disorder and may include behaviors such as addiction to gambling, excessive intake or expenditure, abnormally high sexual appetite, or excessive concern about an increase in sexual thoughts and feelings.

Your doctor may consider adjusting or interrupting the dose.

This medicine may cause drowsiness, a drop in blood pressure when standing up, dizziness, and changes in the ability to move and maintain balance, which could cause falls. Be cautious, especially if you are an elderly patient or have weakness.

Children and adolescents

Do not use this medicine in children and adolescents under 18 years old. The safety and effectiveness of this medicine in these patients are unknown.

Use of Abilify Maintena with other medicines

Inform your doctor or pharmacist if you are taking, have taken recently, or may take any other medicine.

Blood pressure-lowering medicines: Abilify Maintena may increase the effect of medicines used to lower blood pressure. Make sure to inform your doctor if you are taking blood pressure-lowering medicines.

If you are using Abilify Maintena with any other medicine, it may mean that your doctor needs to change your dose of Abilify Maintena or the dose of the other medicines. It is especially important to mention to your doctor if you are taking:

• medicines to correct heart rhythm (such as quinidine, amiodarone, flecainide, diltiazem)
• antidepressants or plant-based medicines used to treat depression and anxiety (such as fluoxetine, paroxetine,escitalopram, St. John's Wort)
• antifungal medicines (such as itraconazole)

• ketoconazole (used to treat Cushing's syndrome when the body produces an excess of cortisol)
• certain medicines to treat HIV infection (such as efavirenz, nevirapine, and protease inhibitors such as, for example, indinavir, ritonavir)
• anticonvulsants used to treat epilepsy (such as carbamazepine, phenytoin, phenobarbital,primidone)
• certain antibiotics used to treat tuberculosis (rifabutin, rifampicin)
• medicines that are known to prolong the QT interval.

These medicines may increase the risk of adverse effects or reduce the effect of Abilify Maintena; if you observe any unusual symptoms when taking any of these medicines at the same time as Abilify Maintena, inform your doctor.

Medicines that increase serotonin levels are generally used in diseases that include depression, generalized anxiety disorder, obsessive-compulsive disorder (OCD), and social phobia as well as migraine and pain:

• triptans, tramadol, and tryptophan used in diseases such as depression, generalized anxiety disorder, OCD, and social phobia as well as migraine and pain
• selective serotonin reuptake inhibitors/inhibitors of serotonin and noradrenaline reuptake (SSRIs/SNRIs) (such as paroxetine and fluoxetine) used in depression, OCD, panic, and anxiety
• other antidepressants (such as venlafaxine and tryptophan) used in severe depression
• tricyclic antidepressants (such as clomipramine and amitriptyline) used in depressive diseases
• St. John's Wort (Hypericum perforatum) used in plant-based medicines for mild depression
• analgesics (such as tramadol and pethidine) used to relieve pain
• triptans (such as sumatriptan and zolmitriptan) used to treat migraine.

These medicines may increase the risk of adverse effects; if you observe any unusual symptoms when taking any of these medicines at the same time as Abilify Maintena, inform your doctor.

Use of Abilify Maintena with alcohol

Alcohol consumption should be avoided.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medicine.

Do not use Abilify Maintena if you are pregnantunless you have discussed this with your doctor. Make sure to inform your doctor immediately if you are pregnant, think you may be pregnant, or are planning to become pregnant.

The following symptoms may occur in newborn babies, from mothers who use this medicine in the last three months of pregnancy (third trimester): tremors, stiffness, and/or muscle weakness, drowsiness, agitation, respiratory problems, and difficulty feeding.

If your baby develops any of these symptoms, contact your doctor.

If you are using Abilify Maintena, your doctor will discuss with you whether you should breastfeed your baby, considering the benefit of your treatment and the benefit of breastfeeding for your baby. If you are being treated with Abilify Maintena, do not breastfeed. Speak with your doctor about the best way to feed your baby if you are using this medicine.

Driving and operating machinery

During treatment with this medicine, dizziness and vision problems (see section 4) may occur. This should be taken into account when maximum attention is required, for example, when driving or operating machinery.

Abilify Maintena contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; it is essentially "sodium-free".

Abilify Maintena is presented as a suspension in a pre-filled syringe that your doctor or nurse will administer to you.

Your doctor will decide on the most suitable dose for you. The recommended initial dose is 960 mg injected once every 2 months (56 days after the previous injection), unless your doctor decides to administer a lower initial or maintenance dose (720 mg) injected once every 2 months (56 days after the previous injection).

There are three ways to start treatment with Abilify Maintena 960 mg, and your doctor will decide which one is suitable for you.

• If you received Abilify Maintena 400 mg 1 or more months before your doctor initiated treatment with Abilify Maintena 960 mg, your next dose may be replaced by an injection of Abilify Maintena 960 mg.
• If you are administered an injection of Abilify Maintena 960 mg on your first day without administration of Abilify Maintena 400 mg 1 month beforehand, oral aripiprazole treatment will continue for 14 days after the first injection.
• If you are administered two injections (one of Abilify Maintena 960 mg and one of Abilify Maintena 400 mg) on your first day, you will also take an oral aripiprazole tablet on this visit. Your doctor will administer the injections in two different sites (arm and buttock).

After that, treatment will be administered with injections of Abilify Maintena 960 mg or 720 mg unless your doctor tells you otherwise.

Your doctor will administer it as a single injection in the buttock (gluteal region) once every 2 months. You may feel a little pain during the injection. Your doctor will alternate the injections between the right and left sides. Injections will not be administered intravenously.

If you are given more Abilify Maintena than you should

This medication will be administered under medical supervision, so it is unlikely that you will be given too much. If you see more than one doctor, make sure to tell them that you are using this medication.

Patients who have been given too much of this medication have experienced the following symptoms:

• rapid heart rate, agitation/aggression, language problems.
• unusual movements (especially of the face or tongue) and decreased level of consciousness.

Other symptoms may include:

• acute confusion, seizures (epilepsy), coma, a combination of fever, rapid breathing, sweating,
• muscle rigidity and drowsiness, slower breathing, choking, high or low blood pressure, abnormal heart rhythms.

Contact your doctor or nearest hospital immediately if you experience any of the above symptoms.

If you did not receive your Abilify Maintena dose

It is essential not to forget your scheduled dose. You should receive an injection once every 2 months. If you forget an injection, you should contact your doctor to schedule the next injection as soon as possible.

If the administration of Abilify Maintena is suspended

Do not stop treatment just because you feel better. It is essential that you continue to receive this medication for the time your doctor has indicated.

If you have any other questions about the use of this medication, ask your doctor or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Severe side effects

Inform your doctor immediately if you experience any of the following severe side effects:

• a combination of any of the following symptoms: excessive sleepiness, dizziness, confusion, disorientation, difficulty speaking, difficulty walking, muscle rigidity, or tremors, fever, weakness, irritability, aggression, anxiety, elevated blood pressure, or seizures that can lead to loss of consciousness.
• unusual movements, mainly of the face or tongue, as your doctor may want to lower the dose.
• if you experience symptoms such as swelling, pain, and redness in the leg, you may have a blood clot, which can travel through the blood vessels to the lungs, causing chest pain and difficulty breathing. If you notice any of these symptoms, seek immediate medical attention.
• a combination of fever, rapid breathing, sweating, muscle rigidity, and somnolence or lethargy, as this may be a sign of a condition called neuroleptic malignant syndrome (NMS).
• increased thirst, frequent urination, excessive appetite, feeling weak or tired, feeling nauseous, feeling confused, or having bad breath, as this may be a sign of diabetes.
• suicidal thoughts, behaviors, or feelings of self-harm.

The following side effects listed below may also occur after administration of Abilify Maintena.

Speak with your doctor or nurse if you experience any of the following side effects:

Frequent side effects (may affect up to 1 in 10 people):

• diabetes mellitus(mellitus)
• restlessness
• anxiety
• inability to remain still, difficulty sitting
• sleep problems (insomnia)
• resistance to passive movements such as tensing and relaxing muscles, abnormal increase in muscle tone, slow body movements
• akathisia (an uncomfortable feeling of internal restlessness and an imperative need to move constantly)
• convulsions or tremors
• incontrollable tics, jerks, or twisting movements
• changes in level of consciousness, drowsiness
• sleepiness
• dizziness
• headache
• dry mouth
• muscle rigidity
• inability to achieve or maintain an erection during sexual intercourse
• pain at the injection site, skin hardening at the injection site
• weakness, extreme loss of strength or fatigue
• during blood tests, your doctor may find elevated or reduced levels of creatine phosphokinase in the blood (an important enzyme for muscle function)
• weight gain
• weight loss

Rare side effects (may affect up to 1 in 100 people):

• low levels of a certain type of white blood cell (neutropenia), low hemoglobin or low red blood cell count, low platelet count in the blood
• allergic reaction (e.g., swelling in the mouth, tongue, face, and throat, itching, urticaria)
• elevated levels of prolactin hormone in the blood
• elevated blood sugar
• elevated levels of cholesterol and triglycerides in the blood
• elevated levels of insulin, a hormone that regulates blood sugar levels
• increased or decreased appetite
• suicidal thoughts
• mental disorder characterized by defective perception or loss of reality
• hallucinations (e.g., seeing and hearing things that are not real)
• delirium (e.g., believing things that are not true)
• increased libido (may lead to behavior that is of significant concern to you or others)
• panic reaction
• depression
• emotional instability
• state of indifference with lack of emotion, feelings of emotional and mental discomfort
• sleep disorder
• grinding teeth or clenching jaw
• decreased libido (libido decreases)
• altered mood
• muscle problems
• uncontrollable muscle movements, such as grimacing, lip smacking, or tongue movements. These usually affect the face and mouth first but can affect other parts of the body. These may be signs of a condition called "tardive dyskinesia."
• parkinsonism: a condition with many and varied symptoms, including slow or decreased movements, slow thinking, joint stiffness (rigidity in ratchet gear), dragging feet, rapid walking, tremors, reduced facial expression, muscle rigidity, drooling
• movement problems
• extreme restlessness and restless legs
• fixation of the eyeballs in a position
• blurred vision
• eye pain
• double vision
• photosensitivity of the eyes
• distortion of taste and smell
• abnormal heart rhythm, rapid or slow heart rate

• high blood pressure
• dizziness when standing up after lying down or sitting due to a drop in blood pressure
• cough
• hoarseness
• gastroesophageal reflux disease. Excessive stomach acid flows back (refluxes) into the esophagus (throat or the tube that goes from the mouth to the stomach through which food passes), causing stomach acid and possibly damaging the esophagus
• heartburn
• vomiting
• diarrhea
• nausea
• stomach pain
• uncomfortable stomach
• constipation
• frequent bowel movements
• excessive salivation
• abnormal hair loss
• acne, skin disease where the nose and cheeks are unusually red, eczema, skin hardening
• muscle rigidity, muscle spasms, muscle tics, muscle tension, muscle pain (myalgia), pain in the limbs
• joint pain (arthralgia), back pain, decreased joint mobility, stiff neck, limited jaw opening
• kidney stones or sugar (glucose) in the urine
• spontaneous milk secretion from the breasts (galactorrhea)
• enlarged breasts in men, painful breasts, vaginal dryness
• fever
• loss of strength
• gait disturbance
• chest discomfort
• reactions at the injection site, such as redness, swelling, discomfort, and itching at the injection site
• thirst
• slowness
• during tests, your doctor may find:

• elevated or reduced levels of glucose in the blood
• elevated levels of hemoglobin A1c
• increased waist circumference
• reduced levels of cholesterol in the blood
• reduced levels of triglycerides in the blood
• reduced levels of white blood cells and neutrophils in the blood
• elevated levels of liver enzymes
• reduced levels of prolactin hormone in the blood
• abnormal ECG reading (e.g., decreased or inverted T wave amplitude)
• elevated levels of alanine aminotransferase
• elevated levels of γ-glutamyl transferase
• elevated levels of bilirubin in the blood
• elevated levels of aspartate aminotransferase

• liver function tests may show abnormal results

The following side effects have been reported since the marketing of medicines containing the same active ingredient and taken orally, but the frequency is unknown (the frequency cannot be estimated from the available data):

• low levels of white blood cells

• decreased appetite
• low sodium levels in the blood
• completed or attempted suicide
• inability to resist the impulse, instinct, or temptation to perform an action that may be harmful to you or others, which may include:

• strong impulse to gamble excessively despite serious personal or family consequences
• uncontrollable excessive buying
• binge eating (ingesting large amounts of food in a short period) or compulsive eating (eating more food than normal and more than needed to satisfy hunger)
• tendency to wander

Inform your doctor if you experience any of these behaviors; they will explain how to manage or reduce symptoms.

• nervousness
• aggression
• neuroleptic malignant syndrome (a syndrome with symptoms such as fever, muscle rigidity, rapid breathing, sweating, decreased consciousness, and sudden changes in blood pressure and heart rate)
• convulsions (seizures)
• serotonin syndrome (a reaction that can cause intense feelings of happiness, drowsiness, clumsiness, feeling drunk, fever, sweating, muscle rigidity)
• speech disorders
• diabetic ketoacidosis (ketones in the blood and urine) or coma
• syncope (fainting)
• cardiac problems, including ventricular tachycardia, cardiac arrest, irregular heart rhythm that may be due to abnormal nerve impulses in the heart
• symptoms related to blood clots in the veins, especially in the legs (symptoms include swelling, pain, and redness in the leg), which can travel through the blood vessels to the lungs, causing chest pain and difficulty breathing
• spasms in the throat that can cause the sensation of having a large object stuck in the throat
• spasm of the muscles around the glottis
• accidental aspiration of food with a risk of pneumonia (lung infection)
• pancreatitis (inflammation of the pancreas)
• difficulty swallowing
• hepatic insufficiency
• jaundice (yellowing of the skin and white part of the eyes)
• hepatitis (inflammation of the liver)
• urticaria
• photosensitivity of the skin
• excessive sweating
• severe allergic reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). DRESS syndrome initially appears as pseudogripal symptoms with facial rash, and later with prolonged skin rash, high temperature, enlarged lymph nodes, elevated liver enzyme levels observed in blood tests, and elevated levels of a type of white blood cell (eosinophilia)
• muscle weakness, sensitivity, or pain, particularly if you also feel unwell, have a high temperature, or have dark urine. These may be caused by abnormal muscle metabolism that is potentially life-threatening and can cause kidney problems (a condition called rhabdomyolysis)
• difficulty urinating
• involuntary loss of urine (incontinence)
• symptoms of withdrawal in newborns

• prolonged and/or painful erection
• sudden and inexplicable death
• difficulty controlling central body temperature or overheating
• chest pain
• swelling of the hands, ankles, or feet
• during tests, your doctor may find:

• fluctuating results during tests to measure blood glucose levels
• prolongation of the QT interval (an abnormal reading during the heart examination [ECG])
• elevated levels of alkaline phosphatase in the blood

Reporting side effects

If you experience side effects, consult your doctor or nurse, even if they are not listed in this prospectus. You can also report them directly through thenational reporting system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the packaging and on the pre-filled syringe. The expiration date is the last day of the month indicated.

Do not freeze.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Composition of Abilify Maintena

• The active ingredient is aripiprazol.

Abilify Maintena 720 mg prolonged-release suspension for injection in pre-filled syringe

Each pre-filled syringe contains 720 mg of aripiprazol.

Abilify Maintena 960 mg prolonged-release suspension for injection in pre-filled syringe

Each pre-filled syringe contains 960 mg of aripiprazol.

• The other components are:

Sodium caramel, macrogol, povidone (E1201), sodium chloride, monohydrated sodium dihydrogen phosphate (E339), sodium hydroxide (E524) (see section 2, Abilify Maintena contains sodium), water for injection.

Appearance of Abilify Maintena and contents of the pack

Abilify Maintena is a prolonged-release suspension for injection in pre-filled syringe.

Abilify Maintena is a prolonged-release suspension for injection in pre-filled syringe of white to off-white colour.

Size of the pack

Each pack of 720 mg contains one pre-filled syringe and two sterile safety needles: one of 38 mm in calibre 22 and one of 51 mm in calibre 21.

Each pack of 960 mg contains one pre-filled syringe and two sterile safety needles: one of 38 mm in calibre 22 and one of 51 mm in calibre 21.

Marketing authorisation holder

Otsuka Pharmaceutical Netherlands B.V.

Herikerbergweg 292

1101 CT, Amsterdam

Netherlands

Responsible person

Elaiapharm

2881 Route des Crêtes Z.I Les Bouillides Sophia Antipolis

06550 Valbonne

France

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder:

Last update of this leaflet:

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agencyhttp://www.ema.europa.eu.

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This information is intended solely for healthcare professionals:

INSTRUCTIONS FOR HEALTHCARE PROFESSIONALS

The disposal of unused medicinal product and of all materials that have been in contact with it shall be in accordance with local guidelines.

Abilify Maintena 720 mg prolonged-release suspension for injection in pre-filled syringe Abilify Maintena 960 mg prolonged-release suspension for injection in pre-filled syringe aripiprazol

• It should be administered by a healthcare professional once every 2 months. Read the instructions carefully before using it.
• The suspension for injection is for single use only.
• For intramuscular use. Only injection in the gluteus. Do notadminister by any other route.
• Before administration, visually inspect the syringe for particles and discoloration.
• The suspension must be uniform and homogeneous, opaque and white milky in colour. Do not use Abilify Maintena if it is discoloured or contains particles.

Contents of the kit

Confirm that the following components are supplied:

• One pre-filled syringe containing Abilify Maintena 960 mg or 720 mg prolonged-release suspension for injection and two safety needles.
• One sterile safety needle of 38 mm in calibre 22 with a black needle cone.
• One sterile safety needle of 51 mm in calibre 21 with a green needle cone.

Preparation of the injection

• Remove the syringe from the pack.
• Hold the syringe with one hand and tap it gently at least 10 times.
• Then, shake the syringe vigorously for at least 10 seconds.

Selection of the appropriate needle

Only for intramuscular use in the gluteus.

The selection of the needle is determined by the patient's body type.

Needle placement

• Twist and remove the syringe's needle cap.
• While holding the syringe's base, ensure the needle is firmly attached to the safety device by applying pressure to it and twisting it gently in a clockwise direction until it is FIRMLY locked in place.

Air expulsion

• When ready to administer the injection, hold the syringe in a vertical position and remove the needle cap by pulling it upwards.Do nottwist the needle cap, as this may loosen the connection between the needle and the syringe.

• Move the plunger slowly upwards to expel the air and until the suspension fills the needle base.
• Inject immediately after expelling the air from the syringe.

Injection of the dose

• Inject the entire contents slowly by intramuscular injection in the patient's gluteus muscle.

Do not administerby any other route.

• Do not massage the injection site.

• Remember to alternate the injection sites between the two gluteus muscles.
• If the administration is started with two injections, inject them in two different gluteus muscles. DO NOT inject both injections in the same gluteus muscle.
• Look for signs or symptoms of accidental intravenous administration.

Disposal procedure

• After the injection, attach the safety device to the needle by pressing the safety cap over a hard surface to cover and block the safety cap over the needle.

• Dispose of the used syringe and any unused needle immediately in a sharps container.
• A used needle should not be stored for future use.