Paliperidone Zentiva

Package leaflet: Information for the user

Paliperidone Zentiva 50 mg prolonged-release injectable suspension in pre-filled syringe
Paliperidone Zentiva 75 mg prolonged-release injectable suspension in pre-filled syringe
Paliperidone Zentiva 100 mg prolonged-release injectable suspension in pre-filled syringe
Paliperidone Zentiva 150 mg prolonged-release injectable suspension in pre-filled syringe
Generic medicine
Please read all of this leaflet carefully before you start using this medicine, as it contains important
information for you.

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

Contents of this leaflet:

1. What Paliperidone Zentiva is and what it is used for
2. What you need to know before you use Paliperidone Zentiva
3. How to use Paliperidone Zentiva
4. Possible side effects
5. How to store Paliperidone Zentiva
6. Contents of the pack and other information

1. What Paliperidone Zentiva is and what it is used for

Paliperidone Zentiva contains the active substance paliperidone, which belongs to a class of medicines called antipsychotics. It is used as a maintenance treatment for the symptoms of schizophrenia in adult patients stabilized on paliperidone or risperidone.
If you have previously responded to paliperidone or risperidone and have mild to moderate symptoms, your doctor may initiate treatment with Paliperidone Zentiva without prior stabilization with paliperidone or risperidone.
Schizophrenia is a condition characterized by "positive" and "negative" symptoms. "Positive" symptoms refer to an excess of symptoms that are normally not present. For example, a person with schizophrenia may hear voices or see things that do not actually exist (called hallucinations), believe things that are not true (called delusions), or be unusually suspicious of others. "Negative" symptoms refer to a lack of behaviours or feelings that are normally present. For example, a person with schizophrenia may tend to isolate themselves and may not respond emotionally, or may have difficulty speaking clearly and logically. People with this condition may also feel depressed, anxious, guilty, or tense.
Paliperidone Zentiva can help relieve the symptoms of your illness and help prevent them from returning.

2. What you need to know before using Paliperidone Zentiva

Do not use Paliperidone Zentiva

• if you are allergic to paliperidone or to any of the other excipients of this medicine (listed in section 6).
• if you are allergic to any other antipsychotic medicine, including risperidone.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Paliperidone Zentiva.
This medicine has not been studied in elderly patients with dementia. However, elderly patients with dementia treated with similar medicines may have an increased risk of stroke or death (see section 4, possible side effects).
All medicines have side effects, and some of the side effects of this medicine may worsen symptoms of other medical conditions. Therefore, it is important that you discuss with your doctor if you have any of the following conditions, as they could potentially worsen during treatment with this medicine:

• if you have Parkinson’s disease
• if you have ever been diagnosed with a condition whose symptoms include high body temperature and muscle stiffness (also known as Neuroleptic Malignant Syndrome)
• if you have ever had abnormal movements of the tongue or face (Tardive Dyskinesia)
• if you know you have previously had low levels of white blood cells in your blood (whether or not caused by other medicines)
• if you have diabetes or are predisposed to diabetes
• if you have been diagnosed with breast cancer or a tumour of the pituitary gland in the brain
• if you have heart disease or are taking treatment for heart disease that tends to lower your blood pressure
• if you have low blood pressure when standing up or changing suddenly from lying down to sitting
• if you suffer from epilepsy
• if you have kidney problems
• if you have liver problems
• if you have a prolonged and/or painful erection
• if you have difficulty controlling your internal body temperature or conditions involving excessive heat
• if you have abnormally high levels of the hormone prolactin in your blood or if you may have a prolactin-dependent tumour
• if you or someone else in your family has a history of blood clots, as antipsychotics have been associated with blood clot formation.

If you have any of these conditions, talk to your doctor so they can assess whether your dose needs adjusting or whether you need to be closely monitored for a period of time.
Because a dangerously low number of a certain type of white blood cells needed to fight infections in the blood has been observed very rarely in patients taking this medicine, your doctor may monitor your white blood cell count.
Even if you previously tolerated oral paliperidone or oral risperidone, allergic reactions may rarely occur after receiving injections of Paliperidone Zentiva. Contact your doctor immediately if you develop a skin rash, throat swelling, itching, or breathing difficulties, as these may be signs of a serious allergic reaction.
This medicine may cause weight gain. A significant weight gain may negatively affect your health. Your doctor should weigh you regularly.
Since diabetes mellitus or worsening of pre-existing diabetes mellitus has been observed in patients taking this medicine, your doctor should check for high blood sugar levels. In patients with pre-existing diabetes mellitus, blood glucose levels should be monitored regularly.
Because this medicine may reduce the urge to vomit, it may mask the body’s normal response to ingesting toxic substances or other medical conditions.
During cataract surgery (an operation to remove cloudiness of the lens), the pupil (the black circle in the center of your eye) may not dilate as required. In addition, the iris (the coloured part of the eye) may become floppy during surgery, which could lead to eye damage. If you are planning eye surgery, make sure to inform your ophthalmologist that you are taking this medicine.

Children and adolescents
This medicine must not be used in children and adolescents under 18 years of age.

Other medicines and Paliperidone Zentiva
Tell your doctor if you are taking, have recently taken, or might take any other medicines.
Taking this medicine with carbamazepine (an antiepileptic and mood stabiliser) may require adjustment of the dose of this medicine.
Since this medicine acts mainly on the brain, interactions with other medicines that act on the brain—such as other psychiatric medicines, opioids, antihistamines, and sleep medicines—may increase side effects such as drowsiness or other brain-related effects.
Because this medicine may lower blood pressure, caution is advised when using it together with other medicines that lower blood pressure.
This medicine may reduce the effect of medicines used to treat Parkinson’s disease and restless legs syndrome (e.g., levodopa).
This medicine may cause an abnormality in the electrocardiogram (ECG), characterised by a longer time for an electrical impulse to travel through a certain part of the heart (known as “QT interval prolongation”). Other medicines that have this effect include certain medicines used to treat heart rhythm disorders or infections, and other antipsychotics.
If you are prone to seizures, this medicine may increase the likelihood of having them. Other medicines with this effect include certain medicines used to treat depression or infections, and other antipsychotics.
Paliperidone Zentiva should be used with caution together with medicines that increase central nervous system activity (psychostimulants such as methylphenidate).

Paliperidone Zentiva and alcohol
Alcohol should be avoided.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine. Do not use this medicine during pregnancy unless you have discussed it with your doctor. The following symptoms may occur in newborns of mothers who used paliperidone during the third trimester (last three months of pregnancy): tremors, muscle stiffness and/or weakness, drowsiness, agitation, breathing difficulties, and feeding problems. If your baby shows any of these symptoms, you may need to contact your doctor.
This medicine can pass from mother to child through breast milk and may harm the baby. Therefore, do not breastfeed while using this medicine.

Driving and using machines
While being treated with this medicine, you may experience dizziness, extreme tiredness, and vision problems (see section 4). This should be taken into account when full alertness is required, for example when driving a car or operating machinery.

Paliperidone Zentiva contains sodium and polysorbate
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially ‘sodium-free’.
This medicine contains 12 mg of polysorbate per mL, equivalent to 12 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to use Paliperidone Zentiva

This medicine will be administered by a doctor or another healthcare professional. It will be injected into the muscle. Your doctor will determine when you will need the next injection. It is important not to miss your scheduled dose. If you think you will not be able to attend your appointment, contact your doctor immediately to arrange a new appointment as soon as possible.

You will receive a first injection (150 mg) and a second injection (100 mg) of this medicine in the upper arm, approximately one week apart. Afterwards, you will receive an injection (ranging from 25 mg to 150 mg) once a month, either in the upper arm or in the buttock.

If your doctor is switching you from long-acting injectable risperidone to this medicine, you will receive the first injection of this medicine (ranging from 25 mg to 150 mg) in the upper arm or in the buttock on the date already scheduled for your next injection. Afterwards, you will receive an injection (ranging from 25 mg to 150 mg) in the upper arm or in the buttock once a month.

Depending on your symptoms, your doctor may increase or decrease the dose level of the medicine you receive at your scheduled monthly injection.

Patients with kidney problems
Your doctor may adjust the dose of this medicine based on kidney function. If you have mild kidney problems, your doctor may prescribe a lower dose. If you have moderate to severe kidney problems, this medicine must not be used.

Elderly patients
Your doctor may reduce the dose of this medicine if kidney function is reduced.

If you receive more Paliperidone Zentiva than you should
This medicine will be administered under medical supervision; therefore, it is unlikely that you will receive an overdose.
In patients who have received an excessive dose of paliperidone, the following symptoms may occur: drowsiness or sedation, increased heart rate, low blood pressure, abnormal electrocardiogram (ECG, recording of the heart's electrical activity), or slow or abnormal movements of the face, body, arms, or legs.

If you stop treatment with Paliperidone Zentiva
If you stop receiving your injections, you will lose the medicine's effects. You must not stop using this medicine unless instructed by your doctor, as your symptoms may return.

If you have any further questions about the use of this medicine, please consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor immediately if:

• you think you have blood clots in your veins, particularly in your legs (symptoms include swelling, pain and redness in the legs), which may travel through the blood vessels to the lungs, causing chest pain and difficulty breathing. If you notice any of these symptoms, consult your doctor immediately.
• you have dementia and notice a sudden change in your mental state or sudden weakness or numbness of the face, arms or legs, especially on one side, or if your speech becomes slurred, even briefly. These may be signs of a stroke.
• you have fever, muscle stiffness, sweating or reduced level of consciousness (a condition called "Neuroleptic Malignant Syndrome"). Immediate medical treatment may be required.
• you are male and have a prolonged or painful erection. This condition is called priapism. Immediate medical treatment may be required.
• you experience involuntary rhythmic movements of the tongue, mouth or face. Discontinuation of paliperidone may be necessary.
• you develop a severe allergic reaction characterized by fever, swelling of the mouth, face, lips or tongue, shortness of breath, itching, skin rash and sometimes a drop in blood pressure (corresponding to an 'anaphylactic reaction'). Although you may have previously tolerated oral risperidone or oral paliperidone, allergic reactions may rarely occur after receiving paliperidone injections.
• you are planning to undergo eye surgery, make sure to inform your ophthalmologist that you are taking this medicine. During cataract surgery (removal of a cloudy lens), the iris (the coloured part of the eye) may become floppy during the procedure (known as "intraoperative floppy iris syndrome"), which may lead to eye damage.
• you know you have a dangerously low number of a certain type of white blood cells in your blood that are needed to fight infections.

The following side effects may occur:
Very common: may affect more than 1 in 10 people

• difficulty falling asleep or staying asleep.

Common: may affect up to 1 in 10 people

• symptoms of the common cold, urinary tract infection, feeling as if you have the flu
• Paliperidone Zentiva may increase levels of a hormone called "prolactin" found in a blood test (which may or may not cause symptoms). When symptoms due to high prolactin levels occur, these may include (in men) breast enlargement, difficulty in achieving or maintaining erections or other sexual dysfunction; (in women) breast tenderness, milk discharge from the breasts, loss of menstrual periods or other menstrual problems
• high blood sugar levels, weight gain, weight loss, decreased appetite
• agitation, depression, anxiety
• parkinsonism: this condition may include slow or abnormal movements, a feeling of stiffness or tension in the muscles (making movements jerky), and sometimes a sensation of movement starting and stopping. Other signs of parkinsonism include slow shuffling gait, resting tremor, increased or decreased saliva, and loss of facial expression
• restlessness, drowsiness or reduced alertness
• dystonia: this is a condition involving slow or prolonged involuntary muscle contractions. While it may affect any part of the body (resulting in abnormal posture), dystonia often involves the facial muscles, including abnormal eye, mouth, tongue or jaw movements
• dizziness
• dyskinesia: this is a condition involving involuntary muscle movements and may include repetitive, jerky or twisting movements, or spasms
• tremor
• headache
• rapid heartbeat
• high blood pressure
• cough, stuffy nose
• abdominal pain, vomiting, nausea, constipation, diarrhoea, indigestion, toothache
• increased liver transaminases in the blood
• bone or muscle pain, back pain, joint pain
• loss of menstrual periods
• fever, weakness, fatigue (tiredness)
• a reaction at the injection site, including itching, pain or swelling.

Uncommon: may affect up to 1 in 100 people

• lung infection, chest infection (bronchitis), respiratory tract infection, sinusitis, bladder infection, ear infection, fungal nail infection, tonsillitis, skin infection
• decreased white blood cell count, decrease in a certain type of white blood cells in the blood that help protect the body from infections, anaemia
• allergic reaction
• diabetes or worsening of diabetes, increased insulin in the blood (a hormone that controls blood sugar levels)
• increased appetite
• loss of appetite leading to malnutrition and low body weight
• increased triglycerides (a fat) in the blood, increased cholesterol in the blood
• sleep disorders, elevated mood (mania), reduced sexual drive, nervousness, nightmares
• tardive dyskinesia (spasms or jerky movements that you cannot control in the face, tongue or other parts of the body). Contact your doctor immediately if you experience involuntary rhythmic movements of the tongue, mouth and face. Discontinuation of this medicine may be necessary.
• fainting, an urgent need to move a part of the body, dizziness when standing up, attention disturbances, speech problems, loss or abnormal sense of taste, reduced skin sensitivity to pain and touch, a sensation of tingling, prickling or numbness of the skin
• blurred vision, eye infection or "conjunctivitis", dry eyes
• sensation of spinning (vertigo), ringing in the ears, ear pain
• interruption of conduction between the upper and lower parts of the heart, abnormal electrical conduction of the heart, QT interval prolongation of the heart, rapid heartbeat when standing up, slow heartbeat, abnormal heart electrical tracing (electrocardiogram or ECG), a sensation of rapid heartbeat or pounding in the chest (palpitations)
• low blood pressure, drop in blood pressure when standing up (as a result, some people taking this medicine may feel faint, lightheaded or may faint when standing up or sitting down suddenly)
• shortness of breath, sore throat, nosebleed
• abdominal discomfort, stomach or intestinal infection, difficulty swallowing, dry mouth
• excessive passing of gas or air
• increased GGT in the blood (a liver enzyme called gamma-glutamyltransferase), increased liver enzymes in the blood
• skin rash (or hives), itching, skin rash, hair loss, eczema, dry skin, red skin, acne, subcutaneous abscess
• increased CPK (creatine phosphokinase) in the blood, an enzyme that is sometimes released in case of muscle damage, muscle spasms, joint stiffness, muscle weakness
• urinary incontinence (lack of control), frequent urination, pain during urination
• erectile dysfunction, ejaculation disorders, absence of menstruation or other menstrual problems (females), breast development in males, sexual dysfunction, breast pain, milk discharge from the breasts
• swelling of the face, mouth, eyes or lips, body swelling, swelling of arms or legs
• increased body temperature
• change in the way of walking
• chest pain, chest discomfort, feeling of uneasiness
• hardening of the skin
• fall.

Rare: may affect up to 1 in 1,000 people

• eye infection
• skin inflammation caused by mites, scalp or skin flaking and itching
• increased eosinophils (a type of white blood cells) in the blood
• decreased platelets (blood cells that help stop bleeding)
• head tremor
• inappropriate secretion of a hormone controlling urine volume
• sugar in the urine
• complications leading to life-threatening conditions due to uncontrolled diabetes
• low blood sugar
• excessive water intake
• absence of movements or responses when awake (catatonia)
• confusion
• sleepwalking
• lack of emotion
• inability to reach orgasm
• neuroleptic malignant syndrome (confusion, reduced or loss of consciousness, high fever and severe muscle rigidity), vascular problems in the brain including sudden loss of blood supply to the brain (stroke or "mini" stroke), unresponsiveness to stimuli, loss of consciousness, low level of consciousness, seizures (fits), balance disorders
• abnormal coordination
• glaucoma (increased pressure inside the eyeball)
• problems with eye movements, eye rolling, light sensitivity of the eyes, increased tearing, redness of the eyes
• atrial fibrillation (abnormal heart rhythm), irregular heartbeat
• blood clots in the lungs which may cause chest pain and difficulty breathing. If you notice any of these symptoms, contact your doctor immediately
• blood clots in the veins, particularly in the legs (symptoms include swelling, pain and redness in the legs). If you notice any of these symptoms, consult your doctor immediately.
• hot flushes
• breathing problems during sleep (sleep apnoea), lung congestion, respiratory congestion
• lung crackles, wheezing
• inflammation of the pancreas, tongue swelling, faecal incontinence, very hard stools
• intestinal blockage
• chapped lips
• drug-related skin rash, skin thickening, dandruff
• muscle fibre breakdown and muscle pain (rhabdomyolysis)
• joint swelling
• inability to urinate
• breast discomfort, enlargement of mammary glands, breast enlargement
• vaginal discharge
• priapism (a prolonged penile erection which may require surgical treatment)
• very low body temperature, chills, feeling thirsty
• drug withdrawal symptoms
• pus accumulation due to infection at the injection site, deep skin infection, cyst at the injection site, bruising at the injection site.

Not known: frequency cannot be estimated from available data

• dangerous decrease in a certain type of white blood cells in the blood that helps protect the body from infections
• severe allergic reaction characterized by fever, swelling of the mouth, face, lips or tongue, shortness of breath, itching, skin rash and sometimes a drop in blood pressure
• dangerous and excessive water consumption
• sleep-related eating disorder
• coma due to uncontrolled diabetes
• reduced oxygen supply to parts of your body (due to reduced blood flow)
• rapid and shallow breathing, lung infection caused by inhalation of food, voice disorder
• lack of intestinal muscle movement causing a blockage
• yellowing of the skin and eyes (jaundice)
• severe or life-threatening skin rash with blisters and skin peeling that may start inside and around the mouth, nose, eyes and genitals and spread to other areas of the body (Stevens-Johnson syndrome or toxic epidermal necrolysis)
• severe allergic reaction with swelling that may affect the throat causing breathing difficulties
• skin discolouration
• abnormal posture
• babies born to mothers who took Paliperidone Zentiva during pregnancy may have experienced drug-related adverse events and/or withdrawal symptoms such as irritability, slow or prolonged muscle contractions, tremor, drowsiness, breathing or feeding problems
• a reduction in body temperature
• death of skin cells at the injection site and ulceration at the injection site.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Paliperidone Zentiva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pre-filled syringe and
on the outer carton. The expiry date refers to the last day of that month.
Do not freeze.
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 Paliperidone Zentiva contains
The active substance is paliperidone.
Each 50 mg pre-filled syringe contains paliperidone palmitate equivalent to 50 mg of
paliperidone.
Each 75 mg pre-filled syringe contains paliperidone palmitate equivalent to 75 mg of
paliperidone.
Each 100 mg pre-filled syringe contains paliperidone palmitate equivalent to 100 mg of
paliperidone.
Each 150 mg pre-filled syringe contains paliperidone palmitate equivalent to 150 mg of
paliperidone.
The other components are:
Polysorbate 20
Macrogol
Monohydrate citric acid
Disodium phosphate
Monohydrate sodium dihydrogen phosphate
Sodium hydroxide (for pH adjustment)
Water for injections

Description of the appearance of Paliperidone Zentiva and contents of the pack
Paliperidone Zentiva is a white to off-white suspension for injection in a pre-filled syringe (suspension for injection).
Each single pack contains:
1 pre-filled syringe (clear glass, type I) with plunger, safety device and protective cap, together with one 22G 1½" safety needle and one 23G 1" safety needle.
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder:
Zentiva Italia S.r.l.
Via P. Paleocapa, 7
20121 Milan
Italy

Manufacturer:
Pharmascience International Limited
1st Floor Iacovides Tower
81-83 Griva Digeni Avenue
1090 Nicosia - Cyprus
Universal Farma, S.L
Polígono Industrial Miralcampo
C/ El Tejido 2
19200 Azuqueca de Henares – Guadalajara, Spain

The following information is intended exclusively for physicians or healthcare professionals and must be read by physicians or healthcare professionals together with the complete prescribing information (Summary of Product Characteristics):
The injectable suspension is for single use only. A visual inspection must be performed to exclude the presence of particulate matter prior to administration. Do not use if the syringe is not visually free of particulate matter.
The pack contains one pre-filled syringe and two safety needles (one 1½ inch, 22 G [38.1 mm x 0.72 mm] and one 1 inch, 23 G [25.4 mm x 0.64 mm]) for intramuscular injection.
The pack for the initial treatment phase contains two pre-filled syringes (150 mg + 100 mg) and a total of four needles.

1. Shake the syringe vigorously for at least 10 seconds to ensure a homogeneous suspension.

2. Select the appropriate needle.

The first initial dose of Paliperidone Zentiva (150 mg) must be administered on Day 1 into the DELTOID muscle using the needle intended for DELTOID injection. The second initial dose of Paliperidone Zentiva (100 mg) must also be administered into the DELTOID muscle one week later (Day 8) using the needle intended for DELTOID injection.
If the patient is switching from long-acting risperidone injection to Paliperidone Zentiva, the first injection of Paliperidone Zentiva (which may range from 25 mg to 150 mg) may be administered either into the DELTOID or the GLUTEAL muscle at the time of the next scheduled injection, using the appropriate needle for the injection site.
Subsequently, monthly maintenance injections may be administered either into the DELTOID or the GLUTEAL muscle, using the appropriate needle for the injection site.
For DELTOID injection: if the patient weighs < 90 kg, use the 1 inch, 23 G (25.4 mm x 0.64 mm) needle (the needle with the blue hub); if the patient weighs ≥ 90 kg, use the 1½ inch, 22 G (38.1 mm x 0.72 mm) needle (the needle with the grey hub).
For GLUTEAL injection, use the 1½ inch, 22 G (38.1 mm x 0.72 mm) needle (the needle with the grey hub).

3. Holding the syringe in an upright position, remove the rubber closure cap by twisting.

4. Open the safety needle blister. Hold the base of the needle, not the safety cap. Attach the safety needle to the Luer connection of the syringe by pushing and turning with a single clockwise rotation.

5. Remove the safety needle cap by pulling it off at the angle shown, moving it toward the syringe body.

6. Remove the needle protective cap with a straight motion. Do not rotate the cap, as the needle may loosen from the syringe.

7. Hold the syringe with attached needle in an upright position to remove air. Remove air from the syringe by gently pushing the plunger forward.

8. Inject the entire content slowly and deeply into the selected deltoid or gluteal muscle of the patient by intramuscular route. Do not administer intravenously or subcutaneously.
9. After completing the injection, use the fingers of one hand (9a) or a flat surface (9b) to activate the needle safety device. The safety system is fully activated when a "click" sound is heard. Dispose of the syringe with the needle appropriately.

9a

9b

Any unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.