Palifren long

Patient Information Leaflet

Palifren Long, 25 mg, prolonged-release suspension for injection
in pre-filled syringe
Palifren Long, 50 mg, prolonged-release suspension for injection
in pre-filled syringe
Palifren Long, 75 mg, prolonged-release suspension for injection
in pre-filled syringe
Palifren Long, 100 mg, prolonged-release suspension for injection
in pre-filled syringe
Palifren Long, 150 mg, prolonged-release suspension for injection
in pre-filled syringe
Palifren Long, 100 mg / 150 mg, prolonged-release suspension for injection
in pre-filled syringe: initiation pack
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 further questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of the leaflet

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

1. What Palifren Long is and what it is used for

Palifren Long contains the active substance paliperidone, which belongs to a group of medicines called antipsychotics. It is used for the maintenance treatment of symptoms of schizophrenia in stable adult patients previously treated with paliperidone or risperidone.
For patients who have previously responded to oral paliperidone or risperidone and whose psychotic symptoms are mild to moderate, your doctor may initiate treatment with Palifren Long without prior stabilisation with paliperidone or risperidone.
Schizophrenia is a disorder with "positive" and "negative" symptoms. Positive symptoms mean the presence of symptoms that normally do not occur. For example, a person with schizophrenia may hear voices or see things that are not there (hallucinations), believe things that are not true (delusions), or be excessively suspicious of others. Negative symptoms mean the absence of usual behaviours or emotions. For example, a person with schizophrenia may seem withdrawn, emotionally flat or unresponsive, or may have difficulty speaking clearly and logically. People affected by this disorder may also experience depression, anxiety, feelings of guilt or tension.
Palifren Long helps to reduce the symptoms of the illness and helps prevent their recurrence.

2. Important information before using Palifren Long

When not to use Palifren Long

• If the patient is allergic to paliperidone or any of the other ingredients of this medicine (listed in section 6).
• If the patient is allergic to another antipsychotic medicine, including the substance risperidone.

Warnings and precautions
Before starting treatment with Palifren Long, discuss this with your doctor, pharmacist, or nurse.
The use of this medicine in elderly patients with dementia has not been studied. However, in such patients treated with other similar types of medicines, there may be an increased risk of stroke or death (see section 4 "Possible side effects").

All medicines have side effects. Some of the side effects of this medicine may worsen symptoms of other medical conditions. Therefore, during treatment with this medicine, discuss with your doctor any of the following conditions:

• if the patient has Parkinson's disease
• if the patient has ever been diagnosed with a condition characterised by high fever and muscle stiffness (also known as neuroleptic malignant syndrome)
• if the patient has ever experienced abnormal movements of the tongue or facial muscles (tardive dyskinesia)
• if the patient has previously had a low white blood cell count (which may or may not have been caused by other medicines)
• if the patient has diabetes or is predisposed to developing diabetes
• if the patient has breast cancer or a pituitary gland tumour
• if the patient has heart disease or is being treated for heart conditions that predispose to hypotension
• if the patient has low blood pressure upon sudden change to standing or sitting position
• if the patient has epilepsy
• if the patient has been diagnosed with impaired kidney function
• if the patient has been diagnosed with impaired liver function
• if the patient experiences prolonged and (or) painful erection
• if the patient has problems with body temperature regulation or overheating
• if the patient has abnormally increased levels of the hormone prolactin in the blood or suspicion of a prolactin-dependent tumour
• if the patient or a family member has had blood clots in blood vessels, as antipsychotic medicines are associated with their development.

If the patient meets any of the above criteria, they should consult their doctor, who may adjust the dose or monitor the patient periodically.
The treating doctor may order a white blood cell count test, as in rare cases, patients taking this medicine have been found to have dangerously low levels of certain types of white blood cells essential for fighting infections.
Even if the patient previously tolerated orally administered paliperidone or risperidone, allergic reactions may rarely occur after injections of Palifren Long. Immediate medical help should be sought if the patient develops rash, throat swelling, itching, or difficulty breathing, as these may be symptoms of a severe allergic reaction.
This medicine may cause weight gain. Significant weight gain may adversely affect the patient's health. The treating doctor will regularly monitor the patient's body weight.
The treating doctor will check for symptoms of elevated blood sugar levels, as new-onset diabetes or worsening of pre-existing diabetes has been observed in patients taking this medicine. In patients with pre-existing diabetes, blood glucose levels should be monitored regularly.
Because this medicine may suppress vomiting, it may mask the body's normal response to ingesting toxic substances or other medical conditions.
During cataract surgery, the pupil may not dilate sufficiently.
Also, the iris of the eye may be flaccid during surgery, which may result in eye damage.
If the patient has planned eye surgery, they should inform the ophthalmologist that they are taking this medicine.

Children and adolescents
This medicine is not intended for use in individuals under 18 years of age.

Palifren Long and other medicines
Tell your doctor about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Taking this medicine together with carbamazepine (an anticonvulsant and mood-stabilizing medicine) may require adjustment of the dose of this medicine.
Because this medicine acts primarily in the brain, combining it with other medicines such as other psychotropic medicines, opioids, antihistamines, and sedatives that act on the brain may increase side effects such as drowsiness or other effects on the brain.
This medicine may lower blood pressure; therefore, caution is advised when using this medicine together with other medicines that lower blood pressure.
This medicine may reduce the effectiveness of medicines used in Parkinson's disease and restless legs syndrome (e.g. levodopa).
This medicine may cause abnormalities in the electrocardiogram (ECG), manifesting as prolongation of the electrical impulse through a specific part of the heart (known as "QT interval prolongation"). Other medicines with this effect include certain medicines used to regulate heart rhythm or treat infections, as well as other antipsychotic medicines.
If the patient is prone to seizures, this medicine may increase the risk of their occurrence. Other medicines with this effect include certain antidepressants or medicines used to treat infections, as well as other antipsychotics.
Caution is advised when using Palifren Long together with medicines that increase central nervous system activity (psychostimulants such as methylphenidate).

Palifren Long and alcohol
Alcohol consumption should be avoided.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
This medicine should not be used during pregnancy unless discussed with the doctor.
Newborns whose mothers used paliperidone during the third trimester (last three months of pregnancy) may experience the following symptoms: tremors, muscle stiffness and (or) weakness, drowsiness, agitation, breathing difficulties, and feeding problems. If such symptoms are observed in the child, contact a doctor immediately.
This medicine may pass from the mother's body into breast milk and harm the child. Therefore, breastfeeding should not be performed during treatment with this medicine.

Driving and operating machinery
During treatment with this medicine, dizziness, extreme tiredness, and vision disturbances may occur (see section 4). These effects should be taken into account in situations requiring full alertness, such as driving a vehicle or operating machinery.

Palifren Long contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, meaning the medicine is considered "sodium-free".

3. How to use Palifren Long

Palifren Long will be administered by a doctor or other healthcare professional. Your doctor will inform you when the next injection is due. It is important not to miss a scheduled dose. If you are unable to keep the scheduled appointment, you should contact your doctor immediately to arrange a new appointment as soon as possible.

The first (150 mg) and second (100 mg) injections of this medicine will be given into the upper arm, approximately one week apart. After that, an injection (at a dose ranging from 25 mg to 150 mg) will be administered once a month into the upper arm or buttock.

If your doctor decides to switch you from long-acting risperidone injections to this medicine, the first injection of this medicine (at a dose ranging from 25 mg to 150 mg) will be given into the upper arm or buttock on the day the next scheduled injection is due. After that, an injection (at a dose ranging from 25 mg to 150 mg) will be administered once a month into the upper arm or buttock.

Depending on your symptoms, your doctor may increase or decrease the dose by one level during the scheduled monthly injection.

Patients with kidney function disorders

Your doctor will adjust the dose of the medicine based on kidney function. If you have mild kidney impairment, your doctor may reduce the dose. This medicine should not be used in patients with moderate or severe kidney impairment.

Elderly patients

Your doctor may reduce the dose if you have impaired kidney function.

Use of a higher than recommended dose of Palifren Long

This medicine will be administered under medical supervision, so overdose is unlikely.

In patients who have received too high a dose of paliperidone, the following symptoms may occur:
drowsiness and sedation, increased heart rate, low blood pressure, abnormal ECG (electrocardiogram) findings, or slowed or abnormal movements of the face, body, arms, or legs.

Stopping Palifren Long

If you stop receiving the injections, the medicine will stop working. Do not discontinue treatment unless instructed by your doctor, as symptoms of the illness may return.

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

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
You should immediately inform your doctor if:

• the patient develops blood clots in the veins, especially in the legs (symptoms include swelling, pain and redness of the leg), which may travel through blood vessels to the lungs, causing chest pain and difficulty breathing. If such symptoms occur, seek immediate medical help.
• the patient with dementia experiences a sudden change in mental state or sudden weakness or numbness of the face, arms or legs, particularly on one side, or speech disturbances, even if brief. These symptoms may indicate a stroke.
• fever, muscle stiffness, sweating or reduced level of consciousness occurs (a condition called neuroleptic malignant syndrome). Immediate treatment may be required.
• the male patient experiences prolonged or painful erection. This condition is known as "priapism". Immediate treatment may be necessary.
• involuntary rhythmic movements of the tongue, lips or face occur. Discontinuation of paliperidone treatment may be necessary.
• a severe allergic reaction occurs, characterised by: fever, swelling of the lips, face, tongue or mouth, shortness of breath, itching, skin rash, and sometimes low blood pressure (known as "anaphylactic reaction"). Even if the patient previously tolerated risperidone or oral paliperidone, allergic reactions may rarely occur after paliperidone injections.
• the patient is scheduled for eye surgery, the ophthalmologist should be informed about taking this medicine. During cataract removal, floppy iris syndrome may occur, which may lead to eye damage.
• the patient has a dangerously low number of certain white blood cells essential for fighting infections. The following adverse reactions may occur:

Very common adverse reactions (may occur in more than 1 in 10 patients)

• difficulty falling asleep or waking up

Common adverse reactions (may occur in less than 1 in 10 patients)

• cold-like symptoms, urinary tract infection, flu-like symptoms
• Palifren Long may increase blood levels of the hormone prolactin (which may, but does not necessarily, cause symptoms). If symptoms of elevated prolactin occur, they may include in men: breast swelling, difficulty achieving or maintaining erection or other sexual disturbances. In women, they may include breast discomfort, milk discharge from the breasts, absence of menstrual bleeding or other menstrual cycle disturbances
• high blood sugar levels, weight gain, weight loss, decreased appetite
• irritability, depression, anxiety
• parkinsonism: this condition may include slow or abnormal movements, feelings of stiffness or muscle tension (causing uneven, jerky movements), and sometimes even a sensation of "freezing" of movements followed by sudden release. Other symptoms of parkinsonism include: slow shuffling gait, resting tremor, increased salivation and/or drooling, and expressionless face
• psychomotor restlessness, feeling of drowsiness or reduced alertness
• dystonia: this condition involves slow or sustained involuntary muscle contractions. Although it may affect any part of the body (possibly resulting in abnormal posture), dystonia most commonly affects facial muscles, including abnormal eye, mouth, tongue or jaw movements
• dizziness
• dyskinesia: this condition involves involuntary muscle movements and may manifest as repetitive, spasmodic or twisting movements or jerks
• tremor
• headache
• rapid heartbeat
• high blood pressure
• cough, nasal congestion
• abdominal pain, vomiting, nausea, constipation, diarrhoea, indigestion, toothache
• increased liver enzyme activity in blood
• bone or muscle pain, back pain, joint pain
• absence of menstruation
• galactorrhea
• fever, weakness, fatigue
• injection site reaction, including itching, pain or swelling

Uncommon adverse reactions (may occur in less than 1 in 100 patients)

• pneumonia, bronchitis, respiratory tract infections, sinus infection, bladder infection, ear infection, fungal nail infection, tonsillitis, skin infection
• decreased number of white blood cells, decreased number of certain white blood cells protecting against infections, decreased platelet count (blood cells responsible for stopping bleeding), anaemia
• allergic reaction
• development of diabetes and worsening of pre-existing diabetes, increased blood insulin levels (hormone regulating blood sugar levels)
• increased appetite
• loss of appetite leading to malnutrition and low body weight
• high blood triglyceride (fats) levels, increased blood cholesterol levels
• sleep disturbances, elevated mood (mania), reduced libido, nervousness, nightmares
• tardive dyskinesia (involuntary, jerky movements of the face, tongue or other body parts). Inform your doctor immediately if rhythmic involuntary movements of the tongue, lips or face occur. Discontinuation of this medicine may be necessary
• fainting, need to move body parts, dizziness upon standing, concentration difficulties, speech difficulties, loss or altered sense of taste, reduced sensitivity to pain and touch on the skin, tingling, pricking or numbness of the skin
• blurred vision, eye infection or conjunctivitis, dry eyes
• sensation of dizziness, ringing in the ears, ear pain
• conduction block between heart chambers, abnormal electrical impulse conduction in the heart, QT interval prolongation in the heart, rapid heartbeat upon standing, slow heart rate, abnormal electrocardiogram (ECG), sensation of heart palpitations
• low blood pressure, low blood pressure upon standing
• (as a result, some patients taking this medicine may faint, feel dizzy or lose consciousness when standing up suddenly or rising)
• shallow breathing, congestion of respiratory tract, wheezing, sore throat, nosebleed
• abdominal discomfort, stomach or intestinal infection, difficulty swallowing, dry mouth
• excessive passing of gas
• increased GGTP enzyme activity (liver enzyme - gamma-glutamyl transferase) in blood, increased liver enzyme activity in blood
• hives, itching, rash, hair loss, skin rash, dry skin, redness of the skin, acne
• increased CPK (creatine phosphokinase) activity in blood – an enzyme sometimes released from damaged muscles
• muscle cramps, joint stiffness, muscle weakness, neck pain
• urinary incontinence, frequent urination, painful urination
• erectile dysfunction, ejaculation disorders, absence of menstrual bleeding and other menstrual cycle disturbances (in women), breast enlargement in men, sexual disturbances, breast pain
• swelling of face, lips, eyes or mouth, body swelling, swelling of upper or lower limbs
• increased body temperature
• change in gait
• chest pain, chest discomfort, malaise
• skin hardening
• fall

Rare adverse reactions (may occur in less than 1 in 1,000 patients)

• eye infection
• skin inflammation caused by mites, subcutaneous abscess
• increased number of eosinophils (a type of white blood cells) in blood
• abnormal secretion of the hormone regulating urine volume
• glucose in urine
• life-threatening complications of untreated diabetes
• low blood sugar levels
• excessive water drinking
• lack of movement and response to stimuli in a patient who is not asleep (catatonia)
• disorientation
• sleepwalking (somnambulism)
• lack of emotions
• inability to achieve orgasm
• neuroleptic malignant syndrome (disorientation, reduced or lost consciousness, high fever and severe muscle rigidity), cerebral vascular disorders including sudden interruption of blood flow to the brain (stroke or "mini" stroke), lack of response to stimuli, loss of consciousness, low level of consciousness, seizures, balance disturbances
• abnormal motor coordination
• glaucoma (increased intraocular pressure)
• eye movement disorders, rotary eye movements, light sensitivity of the eyes, increased tearing, redness of the eyes
• atrial fibrillation (irregular heartbeat), irregular heart rhythm
• blood clots in veins, particularly in the lower limbs (symptoms include swelling, pain and redness of the lower limbs). If such symptoms occur, seek immediate medical help
• flushing attacks
• breathing disturbances during sleep (sleep apnoea)
• blood congestion in the lungs
• crackling sounds in the lungs
• pancreatitis, tongue swelling, faecal incontinence, very hard stool
• chapped lips
• drug-related skin rash, skin thickening, dandruff
• breakdown of muscle fibres and muscle pain (rhabdomyolysis)
• joint swelling
• inability to urinate
• breast discomfort, enlargement of mammary glands, breast enlargement
• vaginal discharge
• very low body temperature, chills, sensation of thirst
• withdrawal symptoms
• abscess due to infection at injection site, deep skin infection, cyst at injection site, bruising at injection site

Adverse reactions with unknown frequency (frequency cannot be determined from available data)

• dangerously low number of certain white blood cells responsible for fighting infections;
• severe allergic reaction characterised by fever, swelling of lips, face, mouth or tongue, shallow breathing, itching, skin rash, and sometimes low blood pressure
• dangerously excessive water drinking – water intoxication
• sleep-related eating disorders
• coma due to uncontrolled diabetes
• head tremors
• pulmonary embolism causing chest pain and breathing difficulties. If such symptoms occur, seek immediate medical help
• reduced oxygenation of various body parts (due to reduced blood flow)
• rapid, shallow breathing, aspiration pneumonia, voice disturbances
• intestinal obstruction, lack of intestinal peristalsis leading to obstruction
• yellowing of the skin and eyes (jaundice)
• severe or life-threatening blistering rash with skin peeling, which may appear in the mouth, nose, eyes and genital areas and around these sites and may also spread to other body parts (Stevens-Johnson syndrome or toxic epidermal necrolysis)
• severe allergic reaction with swelling which may involve the throat and lead to breathing difficulties
• skin depigmentation, peeling and itching of the scalp or body skin
• abnormal body posture
• in newborns whose mothers used Palifren Long during pregnancy, adverse drug reactions and (or) withdrawal symptoms may occur, such as: irritability, slow or sustained muscle contractions, tremor, drowsiness, breathing difficulties and feeding problems
• priapism (prolonged erection which may require surgical intervention)
• decreased body temperature
• necrosis at injection site and ulcer at injection site

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel.: +48 22 4921301, Fax: +48 22 4921309, Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder. By reporting adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store Palifren Long

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton. The expiry date refers to the last day of the specified month.
Do not store above 30°C.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

What Palifren Long contains
The active substance is paliperidone.
Each vial-syringe of Palifren Long 25 mg contains 39 mg of paliperidone palmitate, equivalent to
25 mg of paliperidone.
Each vial-syringe of Palifren Long 50 mg contains 78 mg of paliperidone palmitate, equivalent to
50 mg of paliperidone.
Each vial-syringe of Palifren Long 75 mg contains 117 mg of paliperidone palmitate, equivalent to
75 mg of paliperidone.
Each vial-syringe of Palifren Long 100 mg contains 156 mg of paliperidone palmitate, equivalent to
100 mg of paliperidone.
Each vial-syringe of Palifren Long 150 mg contains 234 mg of paliperidone palmitate, equivalent to
150 mg of paliperidone.
The other ingredients are: polysorbate 20, macrogol 4000, citric acid monohydrate, disodium phosphate,
sodium dihydrogen phosphate monohydrate, sodium hydroxide (for pH adjustment), water for injections.

What Palifren Long looks like and contents of the pack
Palifren Long is a white or off-white (broken white colour) injectable suspension for prolonged release,
supplied in a vial-syringe.
Each pack contains: 1 vial-syringe and 2 needles.
Starting dose pack:
Each pack contains 1 vial-syringe containing 150 mg of paliperidone and 2 needles, and
1 vial-syringe containing 100 mg of paliperidone and 2 needles.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
tel.: +48 22 732 77 00

Manufacturer
Adamed Pharma S.A.
ul. Marszałka Józefa Piłsudskiego 5
95-200 Pabianice
Pharmathen International S.A.
Industrial Park Sapes
Rodopi Prefecture, Block No 5
69300 Rodopi
Greece
Pharmathen S.A.
Dervenakion 6
15351 Pallini Attiki
Greece

This medicinal product is authorised in the European Economic Area countries under the following names:
Austria: Palibon
Croatia: Arion
Cyprus: Psokardon
Denmark: Psokardon
Greece: Psokardon
Luxembourg: Psokardon
Portugal: Psokardon

Information intended exclusively for medical personnel or healthcare professionals and must be read together with the complete product information (Summary of Product Characteristics).

The injection suspension is for single use only. Before administration, inspect the suspension for the presence of particulate matter. If foreign particles are visible in the prefilled syringe, do not use the medicinal product.

The package contains a prefilled syringe and 2 safety needles [22G 1.5 inch (38.1 mm x 0.72 mm) and 23G 1 inch (25.4 mm x 0.64 mm)] for intramuscular administration. The medicinal product Palifren Long is also available in a starter pack containing two prefilled syringes (150 mg + 100 mg) and 2 additional safety needles.

(A) 22 G x 1.5 inch (gray hub)
(B) 23 G x 1 inch (blue hub)
(C) Prefilled syringe
(D) Hub
(E) Tip cap

1. Shake the prefilled syringe vigorously for at least 10 seconds to ensure homogeneity of the suspension.

2. Select the appropriate needle.

The first initiating dose of the medicinal product Palifren Long (150 mg) should be administered on day 1 of treatment into the DELTOID MUSCLE using the needle for the DELTOID MUSCLE. The second initiating dose of the medicinal product Palifren Long (100 mg) should be administered one week later (day 8), also into the DELTOID MUSCLE using the needle for the DELTOID MUSCLE.

When switching from long-acting risperidone injections to the medicinal product Palifren Long, the first injection of Palifren Long (at a dose ranging from 25 mg to 150 mg) may be administered on the next scheduled injection day into either the DELTOID MUSCLE or the GLUTEAL MUSCLE, using the appropriate needle. Subsequently, monthly maintenance doses may be administered into either the DELTOID MUSCLE or the GLUTEAL MUSCLE, using the appropriate needle.

For intramuscular injections into the DELTOID MUSCLE in patients with body weight <90 kg, use a 1-inch, 23G needle (25.4 mm x 0.64 mm) (blue hub). If the patient's body weight is ≥90 kg, use a 1.5-inch, 22G needle (38.1 mm x 0.72 mm) (gray hub).

For intramuscular injections into the GLUTEAL MUSCLE, use a 1.5-inch, 22G needle (38.1 mm x 0.72 mm) (gray hub).

3. Holding the prefilled syringe vertically upright, remove the rubber tip cap with a twisting motion.

4. Partially peel off the outer part of the safety needle blister packaging. Hold the needle shield through the plastic packaging. Attach the Luer tip of the safety needle to the prefilled syringe with a gentle clockwise twisting motion.

5. Remove the needle shield with a straight pull. Do not twist the shield, as this may loosen the needle from the prefilled syringe.

6. Expel air from the prefilled syringe by gently pressing the plunger while holding the syringe in an upright position.

7. Administer the entire contents of the prefilled syringe intramuscularly, slowly and deeply, into the selected patient muscle—deltoid or gluteal. Do not administer the medicinal product intravenously or subcutaneously.

8. After completing the injection, activate the needle safety mechanism by pressing the thumb or finger of one hand against the shield (8a, 8b) or against a flat surface (8c). A clicking sound indicates successful activation of the needle safety. Dispose of the prefilled syringe with the attached needle appropriately.

8a

8b

8c