Palmeux

Package leaflet: Information for the user

Palmeux® 25 mg prolonged-release injectable suspension in pre-filled syringe
Palmeux® 50 mg prolonged-release injectable suspension in pre-filled syringe
Palmeux® 75 mg prolonged-release injectable suspension in pre-filled syringe
Palmeux® 100 mg prolonged-release injectable suspension in pre-filled syringe
Palmeux® 150 mg prolonged-release injectable suspension in pre-filled syringe
Paliperidone
Equivalent 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 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 Palmeux® is and what it is used for
2. What you need to know before using Palmeux®
3. How to use Palmeux®
4. Possible side effects
5. How to store Palmeux®
6. Contents of the pack and other information

1. What Palmeux® is and what it is used for

Palmeux® 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 who have been 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 Palmeux® 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 are not really there (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 react emotionally, or may have difficulty speaking clearly and logically. People with this condition may also feel depressed, anxious, guilty, or tense.
Palmeux® can help relieve the symptoms of your illness and help prevent them from returning.

2. What you should know before using Palmeux®

Do not use Palmeux®:

• 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 Palmeux®.
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 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 rigidity (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 (hypophysis) in the brain
• if you have heart disease or are being treated for a heart condition that tends to lower your blood pressure
• if you have low blood pressure when standing up or when 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 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 (thrombi), as antipsychotics have been associated with blood clot formation.

If you have any of these conditions, consult your doctor so they can assess whether it is necessary
to adjust your dose or monitor you closely for a period of time.
Because 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 Palmeux® injections. 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. Significant weight gain can 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 vomiting reflex, it may mask the body’s normal response to ingesting toxic substances or other medical conditions.
During eye surgery for cataract (clouding 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 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 individuals under 18 years of age.
Other medicines and Palmeux®
Inform 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 primarily on the brain, interactions with other medicines acting on the brain—such as other psychiatric medicines, opioids, antihistamines, and sleep disorder medications—may lead to an increase in side effects such as drowsiness or other brain-related effects.
Because this medicine may lower blood pressure, caution is advised when used 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), characterized 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 predisposed to developing seizures, this medicine may increase the likelihood of their occurrence. Other medicines with this effect include certain antidepressants, antibiotics, and other antipsychotics.
Palmeux® should be used with caution in combination with medicines that increase central nervous system activity (psychostimulants, such as methylphenidate).
Palmeux® and alcohol
Alcohol should be avoided.
Pregnancy and breastfeeding
If you are pregnant, suspect 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 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
During treatment 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, e.g., when driving vehicles or operating machinery.
Palmeux® contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially ‘sodium-free’.

3. How to use Palmeux®

This medicine will be administered by a doctor or another healthcare professional. 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 one 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 risperidone long-acting injectable to this medicine, you will receive the
first injection of this medicine (ranging from 25 mg to 150 mg) either in the upper arm or in the buttock on
the date already scheduled for your next injection.
Subsequently, you will receive one injection (ranging 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 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 take more Palmeux® 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 (electrical
activity tracing of the heart), or slow or abnormal movements of the face, body, arms, or legs.

If you stop treatment with Palmeux®
If you stop receiving your injections, you will lose the medicine’s effects. Do not stop treatment with this
medicine unless your doctor tells you to do so, 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.
Contact your doctor immediately if:

• you develop blood clots in the 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, 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 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 experience 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. Paliperidone may need to be discontinued

• you develop a severe allergic reaction characterised by fever, swelling of the mouth, face, lips or tongue, shortness of breath, itching, rash and sometimes low 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 (lens opacification), the iris (the coloured part of the eye) may become floppy during the procedure (known as "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 necessary 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 common cold, urinary tract infection, feeling as if you have the flu

• Palmeux® may increase levels of a hormone called "prolactin" detected in blood tests (which may or may not cause symptoms). When symptoms due to high 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 breasts, loss of menstrual periods or other menstrual problems

• high blood sugar levels, weight gain, weight loss, decreased appetite

• irritability, depression, anxiety

• parkinsonism: this condition may include slowness or impaired movement, sensation 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

• milk discharge from the breasts

• fever, weakness, fatigue (tiredness)

• a reaction at the injection site, including itching, pain or swelling.
  Uncommon side effects: may affect up to 1 in 100 people

• pneumonia, chest infection (bronchitis), respiratory tract infection, sinusitis, bladder infection, ear infection, fungal nail infection, tonsillitis, skin infection

• decreased white blood cell count, decreased levels of a certain type of white blood cells in the blood that help protect the body from infections, decreased platelets (blood cells that help stop bleeding), 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 disturbances, 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 "slightly red eye", dry eyes

• sensation of spinning (dizziness), 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, slowed heart rate, abnormal electrical trace 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, respiratory congestion, wheezing, 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

• hives, itching, rash, hair loss, eczema, dry skin, red skin, acne

• increased CPK (creatine phosphokinase) in the blood, an enzyme that is sometimes released when muscle breakdown occurs

• muscle spasms, joint stiffness, muscle weakness, neck pain

• 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

• 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

• skin hardening

• fall.

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

• eye infection
• skin inflammation caused by mites, subcutaneous abscess
• increased eosinophils (a type of white blood cells) in your blood
• inappropriate secretion of a hormone controlling urine volume
• sugar in the urine
• complications of uncontrolled diabetes leading to life-threatening conditions
• 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), brain vascular problems 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 disturbances
• abnormal coordination
• glaucoma (increased pressure within the eyeball)
• eye movement problems, 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 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
• pulmonary crackles (lung sounds)
• pancreatitis, tongue swelling, faecal incontinence, very hard stools
• chapped lips
• drug-related rash, skin thickening, dandruff
• muscle fibre rupture and muscle pain (rhabdomyolysis)
• joint swelling
• inability to urinate
• breast discomfort, enlargement of breast glands, breast enlargement
• vaginal discharge
• very low body temperature, chills, sensation 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 the available data

• dangerous decrease in a certain type of white blood cells in the blood necessary to fight infections
• severe allergic reaction characterised by fever, swelling of the mouth, face, lips or tongue, shortness of breath, itching, rash and sometimes low blood pressure
• dangerous and excessive water consumption
• sleep-related eating disorder
• coma due to uncontrolled diabetes
• head tremor
• blood clots in the lungs which may cause chest pain and difficulty breathing. If you notice such symptoms, contact your doctor immediately
• decreased oxygen supply to parts of your body (due to reduced blood flow)
• rapid and shallow breathing, pneumonia caused by aspiration of food, voice disorder
• intestinal obstruction, lack of intestinal muscle movement causing blockage
• yellowing of the skin and eyes (jaundice)
• a severe or life-threatening skin rash with blisters and skin peeling that may start in the mouth, nose, eyes and genitals or near them 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 colour changes, peeling and itching of the scalp or skin
• abnormal posture
• babies born to mothers who took Palmeux® during pregnancy may have experienced drug-related adverse events or withdrawal symptoms such as irritability, slow or prolonged muscle contractions, tremor, drowsiness, breathing or feeding difficulties
• priapism (a prolonged penile erection that may require surgical treatment)
• reduced 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 http://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 Palmeux®

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the prefilled syringe after EXP. The expiry date refers to the last day of that month.
Do not store above 30°C.
Do not dispose of medicines 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 Palmeux® contains
The active substance is paliperidone.
Each pre-filled syringe of Palmeux® 25 mg contains 25 mg of paliperidone (as paliperidone palmitate).
Each pre-filled syringe of Palmeux® 50 mg contains 50 mg of paliperidone (as paliperidone palmitate).
Each pre-filled syringe of Palmeux® 75 mg contains 75 mg of paliperidone (as paliperidone palmitate).
Each pre-filled syringe of Palmeux® 100 mg contains 100 mg of paliperidone (as paliperidone palmitate).
Each pre-filled syringe of Palmeux® 150 mg contains 150 mg of paliperidone (as paliperidone palmitate).

The other components are:
Polysorbate 20
Macrogol
Citric acid monohydrate
Disodium phosphate
Monosodium phosphate monohydrate
Sodium hydroxide (for pH adjustment)
Water for injections

Description of the appearance of Palmeux® and contents of the pack
Palmeux® 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.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Amdipharm Limited
Unit 17
Northwood House
Northwood Crescent
Northwood
Dublin 9
D09 V504
Ireland

Manufacturer
Pharmathen S.A
Dervenakion 6,
Pallini Attiki, 15351,
Greece
Pharmathen International S.A
Industrial Park Sapes,
Rodopi Prefecture, Block No 5,
Rodopi 69300,
Greece

This medicinal product is authorised in the Member States of the European Economic Area under the following names:

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 should 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 needle and one 1 inch, 23 G needle) for intramuscular injection.

Pre-filled syringe
23 G x 1”
22 G x 1½”
(Blue hub)
(Grey hub)
Closure cap
Hub

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

2. Select the appropriate needle.
The first initiation dose of Palmeux® (150 mg) must be administered on Day 1 into the DELTOID muscle using the needle for injection into the DELTOID. The second initiation dose of Palmeux® (100 mg) must also be administered into the DELTOID muscle one week later (Day 8) using the needle for injection into the DELTOID.
If the patient is switching from long-acting risperidone injection to Palmeux®, the first injection of Palmeux® (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 appropriate needle 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 by twisting it off.

4. Open the safety needle blister halfway. Hold the needle cap using the open plastic wrapper. Attach the safety needle to the luer connection of the syringe with a simple clockwise twisting motion.

5. Remove the needle protective 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. Carefully push the plunger forward to remove air from the syringe.

7. Inject the entire contents slowly and deeply into the selected DELTOID or GLUTEAL muscle by intramuscular route. 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 safety mechanism is fully activated when a "click" sound is heard. Dispose of the syringe with the needle appropriately.

8a
8b

8c