Palbran

Patient Information Leaflet

Palbran 25 mg prolonged-release injectable suspension in pre-filled syringe, 50 mg prolonged-release injectable suspension in pre-filled syringe, 75 mg prolonged-release injectable suspension in pre-filled syringe, 100 mg prolonged-release injectable suspension in pre-filled syringe, 150 mg prolonged-release injectable suspension in pre-filled syringe

Palbran 100 mg + 150 mg prolonged-release injectable suspension in pre-filled syringe
paliperidone
Generic medicine
Please read all of 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 further questions, ask your doctor, pharmacist, or nurse.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

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

1. What Palbran is and what it is used for

Palbran contains the active substance paliperidone, which belongs to the class of antipsychotic medicines, and is used as maintenance treatment for the symptoms of schizophrenia in adult patients who have been previously stabilized on paliperidone or risperidone.
If you have previously responded to paliperidone or risperidone and have mild to moderate symptoms, your doctor may start treatment with Palbran without prior stabilization with paliperidone or risperidone.
Schizophrenia is a disorder characterized by "positive" and "negative" symptoms. "Positive" symptoms refer to an excess of symptoms that are not normally present. For example, a person with schizophrenia may hear voices or see things that do not actually exist (known as hallucinations), believe things that are not true (known as 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, may not react emotionally, or may have difficulty speaking clearly and logically. People with this disorder may also feel depressed, anxious, guilty, or tense.
Palbran may help relieve the symptoms of your illness and help prevent them from returning.

2. What you need to know before using Palbran

Do not use Palbran

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

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Palbran.
This medicine has not been studied in elderly patients with dementia. However, elderly patients with dementia, treated with similar types of 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. For this reason, it is important that you discuss with your doctor any of the following conditions, which may potentially worsen during treatment with this medicine:

• if you have Parkinson’s disease
• if you have ever been diagnosed with an illness whose symptoms include high body temperature and muscle stiffness (also known as Neuroleptic Malignant Syndrome)
• if you have ever experienced abnormal movements of the tongue or face (Tardive Dyskinesia)
• if you know you have previously had low levels of white blood cells in the 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 a lying to a sitting position
• 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 are exposed to excessive heat
• if you have abnormally high levels of the hormone prolactin in your blood or if you have a possible 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 it is necessary to adjust your dose or monitor you closely for a period of time.
Since 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 Palbran injections. Seek immediate medical attention if you develop a skin rash, swelling of the throat, itching, or breathing difficulties, as these may be signs of a serious allergic reaction.
This medicine may cause weight gain. A significant increase in weight may negatively affect your health. Your doctor should weigh you regularly.
Since diabetes mellitus has been observed or worsening of pre-existing diabetes mellitus has occurred 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.
As this medicine may reduce the vomiting reflex, it may mask the body’s normal response to ingestion of toxic substances or other medical conditions.
During cataract surgery (an operation to remove cloudiness of the lens), the pupil (the black circle in the centre 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 to undergo eye surgery, make sure to inform your ophthalmologist that you are taking this medicine.

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

Other medicines and Palbran
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 stabilizer) may require adjustment of the dose of this medicine.
Since this medicine acts mainly on the brain, interactions with other medicines acting on the brain—such as other psychiatric medicines, opioids, antihistamines, and medicines for sleep disorders—may lead to an increased risk of side effects such as drowsiness or other brain-related effects.
As this medicine may lower blood pressure, caution is advised when used together with other medicines that lower blood pressure.
This medicine may reduce the effectiveness 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), characterized by a prolonged time for an electrical impulse to travel through a specific 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 predisposed to seizures, this medicine may increase the likelihood of having them. Other medicines that have this effect include certain medicines used to treat depression or infections, and other antipsychotics.
Palbran should be used with caution with medicines that increase central nervous system activity (psychostimulants such as methylphenidate).

Palbran and alcohol
Alcohol should be avoided.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine. You must not use this medicine during pregnancy unless you have discussed it with your doctor. The following symptoms may occur in newborns of mothers who have 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 may 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, dizziness, extreme tiredness, and vision problems may occur (see section 4). This should be taken into account when full alertness is required, for example when driving a car or operating machinery.

Palbran 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 Palbran

This medicine is administered by a doctor or other healthcare professional. It will be injected into the muscle. Your doctor will determine when you will need your next injection. It is important not to miss your scheduled dose. If you think you will be unable 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) either in the upper arm or in the buttock once a month.

If your doctor switches you from long-acting injectable risperidone to this medicine, you will receive your 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 by one dose level the amount of 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 you 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 take more Palbran 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 (recording of the heart's electrical activity), or slow or abnormal movements of the face, body, arms, or legs.

If you stop using Palbran

If you stop receiving your injections, you will lose the medicine's effects. You must not stop using this medicine unless your doctor decides otherwise, as your symptoms may return.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

• you think you may have blood clots in your veins, particularly in the 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 if only 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 needed.
• you experience involuntary rhythmic movements of the tongue, mouth or face. Discontinuation of paliperidone may be necessary.
• you develop a severe allergic reaction with symptoms such as fever, swelling of the mouth, face, lips or tongue, shortness of breath, itching, skin rash and sometimes a drop in blood pressure (consistent with 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 (clouding of the 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 side effects: may affect more than 1 in 10 people

• difficulty falling asleep or staying asleep.

Common side effects: may affect up to 1 in 10 people

• symptoms of the common cold, urinary tract infection, feeling as if you have the flu
• Palbran may increase levels of a hormone called "prolactin" found in blood tests (which may or may not cause symptoms). When symptoms due to high prolactin levels occur, they may include (in men) breast swelling, difficulty achieving or maintaining erections or other sexual dysfunction; (in women) breast discomfort, milk leakage 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, feelings of stiffness or muscle tension (resulting in jerky movements), and sometimes a sensation of movement starting and stopping. Other signs of parkinsonism include slow shuffling gait, resting tremor, increased saliva and/or drooling, 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 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 heart rate
• high blood pressure
• cough, nasal congestion
• 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)
• injection site reaction, including itching, pain or swelling.

Uncommon side effects: 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
• decrease in 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 body part, dizziness when standing up, attention disturbances, speech problems, loss or altered sense of taste, reduced skin sensitivity to pain and touch, tingling, prickling or numbness of the skin
• blurred vision, eye infection or "slightly red eye", dry eyes
• sensation of spinning (vertigo), ringing in the ears, ear pain
• interruption of conduction between upper and lower parts of the heart, abnormal electrical conduction of the heart, QT interval prolongation, rapid heartbeat when standing up, slow heartbeat, abnormal electrical tracing of the heart (electrocardiogram or ECG), 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, nosebleeds
• 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, rash, hair loss, eczema, dry skin, red skin, acne, subcutaneous abscess
• increased CPK (creatine phosphokinase) in the blood, an enzyme 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 leakage from the breasts
• swelling of the face, mouth, eyes or lips, body swelling, swelling of arms or legs
• increased body temperature
• change in walking pattern
• chest pain, chest discomfort, feeling of uneasiness
• skin hardening
• fall.

Rare side effects: 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
• decrease in platelets (blood cells that help stop bleeding)
• head tremor
• inappropriate secretion of a hormone controlling urine volume
• sugar in urine
• complications leading to life-threatening 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, reduced level of consciousness, seizures (fits), balance disturbances
• abnormal coordination
• glaucoma (increased pressure within the eyeball)
• problems with eye movements, eye rolling, light sensitivity of the eyes, increased tearing, eye redness
• 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, consult 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 obstruction
• 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 breast glands, breast enlargement
• vaginal discharge
• priapism (a prolonged erection of the penis which may require surgical treatment)
• very low body temperature, chills, feeling thirsty
• drug withdrawal symptoms
• pus accumulation due to infection at injection site, deep skin infection, cyst at injection site, bruising at 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 characterised 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
• decrease in oxygen in 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 Palbran during pregnancy may experience adverse drug reactions and/or withdrawal symptoms such as irritability, slow or prolonged muscle contractions, tremor, drowsiness, breathing or feeding difficulties
• 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, tell 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.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Palbran

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 store above 30°C. Do not freeze.
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 Palbran contains
The active substance is paliperidone.
Each 25 mg pre-filled syringe contains paliperidone palmitate equivalent to 25 mg of 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.

Initiation treatment pack
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 Palbran and package contents
Palbran is a white to off-white injectable suspension in a pre-filled syringe (injectable suspension).
Each single pack contains:
1 pre-filled syringe (transparent type I glass) with plunger stopper, safety device and protective cap, with one 22G 1½" safety needle and one 23G 1" safety needle.

Each multiple initiation treatment pack contains:
1 carton of Palbran 150 mg, 1 pre-filled syringe and 2 needles (to be used on day 1 of treatment)
1 carton of Palbran 100 mg, 1 pre-filled syringe and 2 needles (to be used on day 8 of treatment)
Not all pack sizes may be marketed.

Marketing Authorization Holder
Medical Valley Invest AB
Brädgårdsvägen 28 2 Tr,
23632 Höllviken
Sweden

Manufacturer
Universal Farma, S.L
Calle El Tejido 2
Poligono Industrial Miralcampo
19200 Azuqueca de Henares – Guadalajara
Spain

Pharmascience International Limited
1st Floor Jacovides Tower
81-83 Griva Digeni Avenue
1095 Nicosia
Cyprus

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 from 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 initiation treatment pack contains two pre-filled syringes (150 mg + 100 mg) and four needles in total.

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 Palbran (150 mg) must be administered on Day 1 into the DELTOID muscle using the needle intended for DELTOID injection. The second initial dose of Palbran (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 Palbran, the first Palbran injection (which may range from 25 mg to 150 mg) can be administered either into the DELTOID or GLUTEAL muscle at the time of the next scheduled injection, using the needle appropriate for the injection site.
Subsequently, monthly maintenance injections may be administered either into the DELTOID or 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 with a twisting motion.

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 simple clockwise rotation.

5. Remove the safety needle cap by pulling it toward the syringe body until the angle shown is reached.

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

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

8. Inject the entire contents slowly and deeply by intramuscular route into the selected deltoid or gluteal muscle of the patient. Do not administer by intravenous or subcutaneous route.

9. After completing the injection, use either one hand’s fingers (9a) or a flat surface (9b) to activate the needle safety device. The safety mechanism is fully activated when a clicking sound (“click”) 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.