Prospect: information for the user

ZYPADHERA 210 mg powder and solvent for prolonged-release injectable suspension

ZYPADHERA 300 mg powder and solvent for prolonged-release injectable suspension

ZYPADHERA 405 mg powder and solvent for prolonged-release injectable suspension

Olanzapine

Read this prospect carefully before starting to use this medication, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or nurse.

• If you experience adverse effects, consult your doctor or nurse, even if they are not listed in this prospect. See section 4.

1. What you need to know before starting to use ZYPADHERA
2. How to use ZYPADHERA
3. Possible adverse effects
4. Storage of ZYPADHERA
5. Contents of the package and additional information

ZYPADHERA contains olanzapine as the active substance. ZYPADHERA belongs to a group of medicines called antipsychotics and is used to treat schizophrenia – a condition with symptoms such as hearing, seeing or perceiving things that do not exist, false beliefs, unusual suspicion and withdrawal. People with this condition may also feel depressed, anxious or tense.

ZYPADHERA is indicated for adult patients who have been previously stabilized during treatment with oral olanzapine.

No use ZYPADHERA:

• If you are allergic to olanzapine or any of the other components of this medication (listed in section 6).A severe allergic reactionmay manifest as a skin rash, itching, swelling of the face, lips, or difficulty breathing. If you have experienced any of these symptoms at any time, please inform your doctor or nurse.
• If you have previously been diagnosed with eye problems, such as certain types of glaucoma (increased eye pressure).

Warnings and precautions

Consult your doctor or nurse before starting to use ZYPADHERA.

• A rare but severe reaction may occur after receiving each injection.Attimes, ZYPADHERA may enter the bloodstream too quickly. If this happens to you, you may experience some of the symptoms listed below after each injection. In some cases, these symptoms may cause loss of consciousness.

These symptoms usually disappear within 24 to 72 hours after the injection. After each injection, you should remain under observation in your healthcare center for at least 3 hours if you experience any of the above symptoms.

Although it is unlikely, you may experience these symptoms more than 3 hours after the injection. If this happens, please contact your doctor or nurse immediately. As a result of this risk, you should not drive vehicles or operate machines for the rest of the day after each injection.

• If you feel dizzy or faint after the injection, inform your doctor or nurse. It is likely that you will need to lie down until you feel better. Your doctor or nurse may want to take your blood pressure and check your pulse.
• ZYPADHERA is not recommended for patients over 65 years old with dementia(confusion or memory loss)as it may cause severe side effects.
• In rare cases, medications of this type may cause unusual movements, mainly in the face or tongue or a combination of fever, rapid breathing, sweating, muscle rigidity, and drowsiness or somnolence. If this happens after receiving ZYPADHERA, please inform your doctor or nurse immediately.
• Weight gain has been observed in patients taking ZYPADHERA. You and your doctor should check your weight regularly. If necessary, your doctor may help you plan a diet or consider referring you to a nutritionist.
• High levels of sugar and fats (triglycerides and cholesterol) in the blood have been observed in patients using ZYPADHERA. Your doctor should perform blood tests to monitor your blood sugar and fat levels before starting ZYPADHERA and regularly during treatment.
• Please inform your doctor if you or a family member has a history of blood clots, as medications of this type have been associated with blood clot formation.

Please inform your doctor as soon as possible if you experience any of the following conditions:

• Stroke or "mini" stroke (transient symptoms of cerebral vascular accident)
• Parkinson's disease
• Prostate problems
• Intestinal obstruction (paralytic ileus)
• Liver or kidney disease
• Blood disorders
• Recent myocardial infarction, coronary artery disease, unstable angina, or low blood pressure.
• Diabetes
• Seizures
• If you believe you may be losing electrolytes due to prolonged diarrhea and vomiting or the use of diuretic medications (urine tablets).

As a routine precaution, it is recommended to measure blood pressure periodically in patientsover 65 years old.

ZYPADHERA is not recommended for patients over 75 years old.

Children and adolescents

Patients under 18 years old should not use ZYPADHERA.

Other medications and ZYPADHERA

Please inform your doctor if you are taking, have taken recently, or may need to take any other medication.

Especially, inform your doctor if you are taking:

• medications for Parkinson's disease.
• carbamazepine (an antiepileptic and mood stabilizer), fluvoxamine (an antidepressant), or ciprofloxacin (an antibiotic) – your ZYPADHERA dose may need to be adjusted.

If you are already taking antidepressants, anxiety medications, or sleep aids (tranquilizers), you may feel more drowsy when taking ZYPADHERA.

Use of ZYPADHERA with alcohol

You should avoid all alcohol consumption if you have been administered ZYPADHERA, as it may cause drowsiness when combined with alcohol.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or if you believe you may be pregnant, please consult your doctor before receiving this injection.

You should not receive this injection if you are breastfeeding, as small amounts of olanzapine may pass into breast milk.

The following symptoms may occur in newborn babies whose mothers were treated with ZYPADHERA in the last trimester of pregnancy (last three months of pregnancy): tremors, rigidity, and/or muscle weakness, drowsiness, agitation, breathing difficulties, and feeding difficulties. If your baby develops any of these symptoms, please contact your doctor.

Driving and operating machines

You should not drive or operate machines for the rest of the day after each injection.

ZYPADHERA contains sodium

Once reconstituted, this medication contains less than 1 mmol of sodium (23 mg) per vial; it is essentially "sodium-free".

Your doctor will decide how much ZYPADHERA you need and how often you need to receive an injection. ZYPADHERA is administered in doses of 150 mg to 300 mg every 2 weeks or 300 mg to 405 mg every 4 weeks.

ZYPADHERA is presented as a powder that your doctor or nurse will reconstitute to create a suspension that will then be injected into the muscle of your buttock.

If you use more ZYPADHERA than you should

This medication will be administered under medical supervision. Therefore, it is unlikely that you will receive an excessive amount.

Patients who have received more olanzapine than they should have also experienced the following symptoms:

• rapid heart rate, agitation/aggressiveness, speech problems, unusual movements (especially in the face or tongue) and decreased levels of consciousness.

Other symptoms may include:

• acute confusion, seizures (epilepsy), coma, a combination of fever, rapid breathing, sweating, muscle numbness, and a state of drowsiness or somnolence, slower breathing, aspiration, elevated or low blood pressure, abnormal heart rhythms.

Immediately contact your doctor or hospital if you experience any of the previously described symptoms.

If you forgot to use ZYPADHERA

Do not stop your treatment just because you start feeling better. It is essential that you continue to receive ZYPADHERA for the entire time indicated by your doctor.

If you miss your injection appointment, you must contact your doctor to schedule your next injection as soon as possible.

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.

Immediately contact your doctor if you have:

• excessive drowsiness, dizziness, confusion, disorientation, difficulty speaking, difficulty walking, muscle stiffness or agitation, weakness, irritability, aggression, anxiety, increased blood pressure, or seizures, which may lead to loss of consciousness. These signs and symptoms may be due to ZYPADHERA sometimes entering the bloodstream too quickly (a frequent side effect that can affect up to 1 in 10 people);
• unusual movements (a frequent side effect that can affect up to 1 in 10 people), especially of the face or tongue;
• blood clots in the veins (a rare side effect that can affect up to 1 in 100 people), especially in the legs (symptoms include swelling, pain, and redness in the leg), which can travel through the blood to the lungs, causing chest pain and difficulty breathing. If you experience any of these symptoms, seek medical attention immediately.
• a combination of fever, rapid breathing, sweating, muscle stiffness, and a state of confusion or drowsiness (frequency cannot be estimated from available data)

Other frequent side effects (can affect up to 1 in 10 people) with ZYPADHERA include drowsiness and pain at the injection site.

Among the rare side effects with ZYPADHERA (can affect 1 in 1,000 people) is infection at the injection site.

The side effects listed below have been observed when administering olanzapine orally, but may appear after administration of ZYPADHERA.

Other very frequent side effects (can affect more than 1 in 10 people) include weight gain and increased levels of prolactin in the blood. In the early stages of treatment, some people may feel dizzy or faint (especially with slower heartbeats) when getting up from lying or sitting. This sensation usually disappears spontaneously, but if not, consult your doctor.

Other frequent side effects (can affect up to 1 in 10 people) include changes in levels of some blood cells, fats in the bloodstream, and temporary increases in liver enzymes at the beginning of treatment; increased levels of sugar in the blood and urine; increased levels of uric acid and creatine phosphokinase in the blood; increased appetite; dizziness; agitation; tremor; strange movements (dyskinesias); constipation; dry mouth; skin rash; loss of strength; excessive fatigue; fluid retention causing swelling in the hands, ankles, or feet; fever; joint pain; and sexual dysfunction such as decreased libido in men and women or erectile dysfunction in men.

Other infrequent side effects (can affect up to 1 in 100 people) include hypersensitivity (e.g., inflammation of the mouth and throat, itching; skin rash); diabetes or worsening of diabetes, occasionally related to ketoacidosis (acetone in the blood and urine) or coma; seizures, in most cases related to a history of seizures (epilepsy); muscle stiffness or spasms (including eye movements); restless legs syndrome; speech problems; stuttering; slow heart rate; sensitivity to sunlight; nasal bleeding; abdominal distension; excessive salivation; loss of memory or forgetfulness; urinary incontinence; loss of ability to urinate; hair loss; absence or decrease of menstrual periods; and changes in the breast gland in men and women such as abnormal milk production or abnormal growth.

Rare side effects (can affect up to 1 in 1,000 people) include decreased normal body temperature; abnormal heart rhythms; sudden death of unknown origin; pancreatitis that causes intense stomach pain; fever and vomiting; liver disease that manifests as yellowing of the skin and the white part of the eyes; muscle disease that manifests with unknown joint pain; and prolonged and/or painful erection.

Very rare side effects include severe allergic reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS for its acronym in English). Initially, DRESS manifests with symptoms similar to the flu with a rash on the face and later, with an extensive rash, fever, swollen lymph nodes, elevated liver enzymes observed in blood tests, and increased levels of a type of white blood cell (eosinophilia).

During treatment with olanzapine, elderly patients with dementia may experience stroke, pneumonia, urinary incontinence, falls, excessive fatigue, visual hallucinations, increased body temperature, skin redness, and difficulty walking. Some cases of death have been observed in this particular group of patients.

Olanzapine orally may exacerbate symptoms in patients with Parkinson's disease.

Reporting of side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

Do not administer the injection after the expiration date indicated on the packaging.

Do not refrigerate or freeze.

The chemical and physical stability of the suspension in the vials has been demonstrated for 24 hours at 20 - 25°C. From a microbiological standpoint, the medication should be administered immediately. If not, storage times and usage conditions before use are the responsibility of the healthcare professional and should normally not exceed 24 hours at 20 - 25°C. Do not use this product if you notice discoloration or other visible signs of deterioration.

If the medication is not used immediately, it must be vigorously agitated to achieve resuspension. Once the suspension has been removed from the vial to the syringe, it must be used immediately.

Medications should not be disposed of through drains or trash. Ask your pharmacist how to dispose of the packaging and unused medications. By doing so, you will help protect the environment.

Composition of ZYPADHERA

Theactive principleis olanzapine.

ZYPADHERA 210 mg: Each vial contains pamoate of olanzapine monohydrate, equivalent to 210 mg of olanzapine.

ZYPADHERA 300 mg: Each vial contains pamoate of olanzapine monohydrate, equivalent to 300 mg of olanzapine.

ZYPADHERA 405 mg: Each vial contains pamoate of olanzapine monohydrate, equivalent to 405 mg of olanzapine.

Once reconstituted, each milliliter of the suspension contains 150 mg/ml of olanzapine.

Thecomponents of the solventare sodium carmelose, mannitol, polisorbate 80, water for injection, hydrochloric acid, and sodium hydroxide.

Appearance of the product and contents of the package

ZYPADHERA powder for prolonged-release injectable suspension is presented as a yellow powder in a transparent glass vial. Your doctor or nurse will reconstitute it into a suspension that will be administered as an injection using the contents of the ZYPADHERA solvent vial, which is presented as a transparent, colorless, or pale yellow solution in a transparent glass vial.

ZYPADHERA is a powder and solvent for prolonged-release injectable suspension. Each package contains a vial of powder for prolonged-release injectable suspension, a 3 ml vial of solvent, a hypodermic syringe with a 19-gauge, 38 mm safety needle attached, and three separate safety needles: one 19-gauge, 38 mm, and two 19-gauge, 50 mm.

Marketing authorization holder

CHEPLAPHARM Registration GmbH, Weilerstr. 5e, 79540 Lörrach, Germany.

Responsible for manufacturing

Lilly S.A., Avda. de la Industria 30, 28108 Alcobendas, Madrid, Spain.

Last revision date of this leaflet:

The detailed information on this medicine is available on the website of the European Medicines Agency http://www.ema.europa.eu/.

INSTRUCTIONS FOR HEALTHCARE PROFESSIONALS

INSTRUCTIONS FOR RECONSTITUTION AND ADMINISTRATION

ZYPADHERA olanzapine powder and solvent for prolonged-release injectable suspension

ONLY FOR INTRAMUSCULAR DEEP INJECTION IN THE GLUTEAL REGION.

DO NOT ADMINISTER BY INTRAVENOUS OR SUBCUTANEOUS ROUTE.

Reconstitution

STEP 1: Preparation of materials

The package includes:

• Vial of ZYPADHERA powder for prolonged-release injectable suspension
• Vial of solvent for ZYPADHERA
• Hypodermic syringe and safety needle (hypodermic device)
• Safety needle, 19-gauge, 38 mm
• Two safety needles, 19-gauge, 50 mm
• Leaflet
• Instructions for reconstitution and administration (this document)
• Information on Safety and Instructions for Use of the Hypodermic Device

It is recommended to use gloves as ZYPADHERA may cause skin irritation.

Reconstitute ZYPADHERA powder for prolonged-release injectable suspension exclusively with the solvent provided in the package using standard aseptic techniques for the reconstitution of parenteral products.

STEP 2: Determination of the solvent volume for reconstitution

This table indicates the amount of solvent required to reconstitute ZYPADHERA powder for prolonged-release injectable suspension.

It is essential to note that the vial contains more solvent than necessary for reconstitution of the product.

STEP 3: Reconstitution of ZYPADHERA

1. Gently shake the vial to release the powder.
2. Open the hypodermic syringe and safety needle (hypodermic device). Open the plastic bag and remove the device. Attach the syringe (if not already attached) to the Luer connector of the device with a single turn. Place the needle firmly onto the device, pushing and turning it in a clockwise direction. Then, remove the needle cap directly. If these instructions are not followed, needlestick injury may occur.
3. Remove the predetermined volume of solvent (STEP 2) from the syringe.
4. Inject the required volume of solvent into the powder vial.
5. Remove the air to equalize the pressure in the vial.
6. Remove the needle, with the vial facing upwards to prevent solvent loss.
7. Put the safety needle device on. Place the needle in its holder using a one-handed technique. Perform this maneuver with one hand, applying gentle pressure to the holder against a flat surface. BY APPLYING PRESSURE ON THE HOLDER (Fig. 1), THE NEEDLE IS SECURELY CONNECTED TO IT (Fig. 2)

1. Visually confirm that the needle is completely connected to its protective holder. Remove the device with the needle attached to the syringe, when required, using a specific medical procedure. Remove it by holding the Luer connector of the needle protector with your thumb and index finger, and keeping the other three fingers away from the device where the needle tip is located (Fig. 3).

1. Gently shake the vial repeatedly on a hard surface until no powder is visible. Protect the surface to absorb the impact. (See Figure A)

Figure A: Vigorously shake to mix

1. Visually check the vial to identify undissolved powder. Undissolved powder appears as dry, yellowish clumps attached to the vial. It may be necessary to continue shaking if clumps remain. (See Figure B)

No suspension: visible clumpsSuspended: no clumps

Figure B: Check if there are undissolved powder clumps and continue shaking if necessary.

1. Agitate the vial vigorously until the suspension has a uniform appearance with color and texture.

Figure C: Vigorously agitate the vial

If foam forms, let the vial stand to allow the foam to dissipate. If the product is not used immediately, it must be vigorously agitated to achieve resuspension. ZYPADHERA reconstituted remains stable in the vial for up to 24 hours.

Administration

STEP 1: Inject ZYPADHERA

This table confirms the final volume of ZYPADHERA suspension to be injected. The concentration of the suspension is 150 mg/ml of olanzapine.

1. Determine which needle to use to administer the injection to the patient. For obese patients, 50 mm needles are recommended for injection:
   • If a 50 mm needle is used for injection, place the 38 mm safety needle on the syringe to remove the required volume of suspension.
   • If a 38 mm needle is used for injection, place the 50 mm safety needle to remove the required volume of suspension.
2. Remove the desired amount slowly. Some product will remain in the vial.
3. Put the safety needle device on and remove the needle from the syringe.
4. Put the safety needle, selecting the 50 mm or 38 mm needle, on the syringe before injection. Once the suspension is removed from the vial and passed to the syringe, it must be injected immediately.
5. Choose and prepare the injection site in the gluteal region. DO NOT INJECT BY INTRAVENOUS OR SUBCUTANEOUS ROUTE.
6. After inserting the needle, aspirate for a few seconds to confirm that no blood is drawn. If blood is aspirated into the syringe, discard the syringe and prepare a new suspension. The injection should be administered with firm and continuous pressure.

DO NOT MASSAGE THE INJECTION SITE.

7. Put the safety needle device on. (Fig. 1 and 2)

8. Discard the vials, syringe, used needles, additional needle, and excess solvent according to appropriate clinical procedures. The vial is for single use.