NiaPelf

Package leaflet: Information for the user

Niapelf 25 mg prolonged-release injectable suspension, 50 mg prolonged-release injectable suspension, 75 mg prolonged-release injectable suspension, 100 mg prolonged-release injectable suspension, 150 mg prolonged-release injectable suspension

Niapelf 150 mg prolonged-release injectable suspension
paliperidone

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

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, 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 Niapelf is and what it is used for
2. What you need to know before using Niapelf
3. How to use Niapelf
4. Possible side effects
5. How to store Niapelf
6. Contents of the pack and other information

1. What Niapelf is and what it is used for

Niapelf contains the active substance paliperidone, which belongs to a class of medicines called
antipsychotics. It is used as maintenance treatment for the symptoms of schizophrenia in
adults 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 Niapelf without prior stabilization with
paliperidone or risperidone.
Schizophrenia is a mental disorder characterized by “positive” and “negative” symptoms. “Positive” symptoms refer to an excess of behaviors or experiences that are not normally present. For example, a person with schizophrenia may hear voices or see things that are not actually there (called hallucinations), believe things that are not true (called delusions), or be unusually suspicious of others. “Negative” symptoms refer to a lack or reduction of behaviors or emotions that are normally present. For example, a person with schizophrenia may tend to withdraw socially, may not respond emotionally, or may have difficulty speaking clearly and logically. People with this disorder may also feel depressed, anxious, guilty, or tense.
Paliperidone can help relieve the symptoms of the illness and help prevent their recurrence.

2. What you need to know before using Niapelf

Do not use Niapelf

• 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 another antipsychotic medicine, including risperidone.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Niapelf.
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 any of the following conditions, which 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 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 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 being treated for a heart condition that tends to lower blood pressure
• if you have low blood pressure when standing up or changing suddenly from lying down to sitting
• if you have epilepsy
• if you have kidney problems
• if you have liver problems
• if you have a prolonged and/or painful erection
• if you have difficulty regulating 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 in your family has a history of blood clots (thrombosis), as antipsychotics have been associated with blood clot formation.

If you have any of these conditions, consult your doctor so they can assess whether
dose adjustment or close monitoring for a certain period is necessary.
Since a dangerously low number of a certain type of white blood cells needed to fight infections
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 paliperidone injections. Seek immediate medical attention if you develop a rash, throat swelling, itching, or breathing difficulties, as
these may be signs of a serious allergic reaction.
This medicine may cause weight gain. Significant weight gain can negatively affect 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 monitor for signs of increased blood sugar levels. In patients with pre-existing diabetes mellitus, blood glucose levels should be monitored regularly.
Because this medicine may reduce the vomiting reflex, it may mask the body's normal response to ingesting toxic substances or other medical conditions.
During cataract surgery (removal of clouded lens), the pupil (the black circle in the center of the 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 Niapelf
Tell your doctor if you are taking, have recently taken, or might take any other
medicine.
Taking this medicine with carbamazepine (an antiepileptic and mood stabilizer) may
require dose adjustment 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 sleep medicines—may lead to an exaggeration of 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 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 longer time for an electrical impulse to travel through a specific part of the heart (known as "QT interval prolongation"). Other medicines with 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 with this effect include certain antidepressants and antibiotics, as well as other antipsychotics.
Niapelf should be used with caution together with medicines that increase central nervous system activity (psychostimulants such as methylphenidate).

Niapelf and alcohol
Alcohol should be avoided.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine. You should 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 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
Dizziness, extreme tiredness, and vision problems may occur during treatment with this medicine (see section 4). This should be taken into account in situations requiring full alertness, such as driving a car or operating machinery.

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

3. How to use Niapelf

This medicine is administered by a doctor or other healthcare professional. Your doctor will decide when you will need the next injection. It is important not to miss a 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 once a month (at a dose that may range from 25 mg to 150 mg), either in the upper arm or in the buttock.

If your doctor switches you from long-acting risperidone to this medicine, you will receive the first injection of this medicine (at a dose that may range from 25 mg to 150 mg), either in the upper arm or in the buttock, on the date already scheduled for your next injection. Afterwards, you will receive an injection (at a dose that may range from 25 mg to 150 mg), either 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 the scheduled monthly injection.

Patients with kidney problems
Your doctor may adjust the dose of this medicine according to your 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 take more Niapelf 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 (record of the heart's electrical activity), or slow or abnormal movements of the face, body, arms, or legs.

If you stop using Niapelf
If you stop receiving the 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 how to use this medicine, ask 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 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 or incomprehensible, even briefly. These may be signs of a stroke.
• you develop 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 necessary.
• you experience involuntary rhythmic movements of the tongue, mouth or face. It may be necessary to discontinue paliperidone.
• you develop a severe allergic reaction with fever, swelling of the mouth, face, lips or tongue, shortness of breath, itching, rash and sometimes a sudden drop in blood pressure (consistent with an 'anaphylactic reaction'). Although you may previously have tolerated oral risperidone or oral paliperidone, allergic reactions may rarely occur after receiving paliperidone injections.
• you are planning eye surgery, make sure to inform your ophthalmologist that you are taking this medicine. During cataract surgery, 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 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 common cold, urinary tract infection, feeling as if you have the flu
• paliperidone may increase levels of a hormone called "prolactin" detected in blood tests (which may or may not cause symptoms). When symptoms due to increased prolactin levels occur, they may include (in men) breast enlargement, difficulty achieving or maintaining erections or other sexual dysfunction; (in women) breast discomfort, milk discharge from the breast, 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, feeling of stiffness or muscle tension (resulting in jerky movements), and sometimes a sensation of movement starting and stopping. Other signs of parkinsonism include slow walking with shuffling feet, 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, 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
• 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 of the face, tongue or other body parts that you cannot control). 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, difficulty concentrating, speech problems, loss or altered 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 "slightly reddened" eyes, 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 of the heart, rapid heartbeat when standing up, slow heartbeat, abnormal heart electrical trace (electrocardiogram or ECG), sensation of rapid heartbeat or chest pulsations (palpitations)
• low blood pressure, drop in blood pressure when standing up (as a result, some people taking this medicine may feel faint, dizzy 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
• hives, itching, rash, hair loss, eczema, dry skin, red skin, acne, subcutaneous abscess
• increased CPK (creatine phosphokinase) in the blood, an enzyme that is sometimes released when there is 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 (women), breast development in men, sexual dysfunction, breast pain, milk discharge from the breast
• 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: 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 the urine
• complications leading to life-threatening uncontrolled diabetes
• low blood sugar levels
• excessive water intake
• absence of movement or response when awake (catatonia)
• confusion
• sleepwalking
• lack of emotion
• inability to achieve orgasm
• malignant neuroleptic 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), lack of response 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, rolling of the eyes backward, 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, 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
• pancreatitis, tongue swelling, faecal incontinence, very hard stools
• intestinal blockage
• chapped lips
• drug-related 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 penile erection which may require surgical treatment)
• very low body temperature, chills, feeling of thirst
• 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 characterised by fever, swelling of the mouth, face, lips or tongue, shortness of breath, itching, rash and sometimes sudden drop in blood pressure
• dangerous and excessive water intake
• sleep-related eating disorder
• coma due to uncontrolled diabetes
• reduced oxygen supply to parts of the body (due to reduced blood flow)
• rapid and shallow breathing, infection caused by inhalation of food, voice disorder
• lack of intestinal muscle movement causing 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 / toxic epidermal necrolysis)
• severe allergic reaction with swelling that may affect the throat causing breathing difficulties
• change in skin colour
• abnormal posture
• babies born to mothers who took paliperidone during pregnancy may experience drug-related adverse events 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 get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist or nurse.
You can also report side effects directly via the national reporting system detailed in Annex V.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Niapelf

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard carton. The expiry date refers to the last day of the month.
This medicine does not require any special storage conditions.
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 Niapelf contains
The active substance is paliperidone.
Each pre-filled syringe of Niapelf 25 mg contains 39 mg of paliperidone palmitate.
Each pre-filled syringe of Niapelf 50 mg contains 78 mg of paliperidone.
Each pre-filled syringe of Niapelf 75 mg contains 117 mg of paliperidone palmitate.
Each pre-filled syringe of Niapelf 100 mg contains 156 mg of paliperidone palmitate.
Each pre-filled syringe of Niapelf 150 mg contains 234 mg of paliperidone palmitate.

The other ingredients are:
Polysorbate 20
Macrogol
Monohydrate citric acid (E-330)
Disodium phosphate
Monobasic sodium phosphate monohydrate
Sodium hydroxide (E-524) (for pH adjustment)
Water for injections

Description of the appearance of Niapelf and contents of the pack
Niapelf is a white to off-white prolonged-release injectable suspension in a pre-filled syringe.
Each pack contains 1 pre-filled syringe and 2 needles.

Treatment initiation pack:
Each pack contains 1 pack of Niapelf 150 mg and 1 pack of Niapelf 100 mg.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Neuraxpharm Pharmaceuticals, S.L.
Avda. Barcelona 69
08970 Sant Joan Despí
Barcelona – Spain

Manufacturer
Neuraxpharm Pharmaceuticals, S.L.
Avda. Barcelona 69
08970 Sant Joan Despí
Barcelona – Spain

Neuraxpharm Arzneimittel GmbH
Elisabeth-Selbert-Strasse 23
Richrath, Langenfeld (Rheinland)
40764, Germany

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

More detailed information on this medicine is available on the website of the European Medicines Agency, http://www.ema.europa.eu/
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 confirm the absence 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 2 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. Niapelf is also available in a pack for the initial treatment phase, containing two pre-filled syringes (150 mg + 100 mg) and 2 additional safety needles.

1. 22 G x 1½” (Grey hub)
2. 23 G x 1” (Blue hub)
3. Hub
4. Closure cap
5. Pre-filled syringe

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 Niapelf (150 mg) must be administered on Day 1 into the DELTOID muscle using the needle intended for DELTOID injection. The second initial dose of Niapelf (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 Niapelf, the first Niapelf injection (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 needle (25.4 mm x 0.64 mm) (the needle with the blue-colored hub); if the patient weighs ≥90 kg, use the 1½-inch, 22 G needle (38.1 mm x 0.72 mm) (the needle with the grey-colored hub).
For GLUTEAL injection, use the 1½-inch, 22 G needle (38.1 mm x 0.72 mm) (the needle with the grey-colored hub).

3. Holding the syringe with the closure cap facing upwards, remove the rubber closure cap with a gentle twisting motion.

4. Open the safety needle blister pack halfway. Grasp the needle cap using the open plastic wrapper. Keep the syringe pointing upwards. Attach the safety needle to the syringe using a gentle twisting motion to avoid breakage or damage at the needle hub.

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

6. Hold the syringe with the attached needle in an upright position to expel air. Expel air from the syringe by carefully pushing the plunger forward.

7. Inject the entire contents slowly and deeply by intramuscular route into the patient’s selected DELTOID or GLUTEAL muscle. Do not administer by intravenous or subcutaneous route.
8. After completing the injection, use the thumb or another finger (8a, 8b), or a flat surface (8c) to activate the needle safety device. The device is fully activated when a clicking sound is heard. Dispose of the syringe with the needle properly.

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