Palexia

Patient Information Leaflet

Palexia, 4 mg/ml, oral solution
Tapentadol
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm someone else even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What Palexia is and what it is used for

Tapentadol, the active substance in Palexia, is an analgesic belonging to the group of strong opioids. Palexia is indicated for the treatment of moderate to severe acute pain in children and adolescents over 2 years of age and in adults, when only an opioid analgesic is expected to provide adequate pain relief.

2. Important information before using Palexia

When not to use Palexia:

• if the patient is allergic to tapentadol or any of the other ingredients of this medicine (listed in section 6),
• in patients with asthma or dangerously slow and shallow breathing (respiratory depression, increased carbon dioxide levels in the blood),
• in patients with intestinal obstruction,
• in cases of acute alcohol intoxication, sedatives, analgesics or other psychotropic medicines (medicines affecting mood and emotions) (see "Palexia with other medicines").

Warnings and precautions
Before starting treatment with Palexia, discuss the following with your doctor, pharmacist or nurse:

• if you have slow or shallow breathing,
• if you have increased intracranial pressure or impaired consciousness up to coma,
• in patients after head injury or with brain tumours,
• in patients with liver or kidney disease (see "How to use Palexia"),
• in patients with diseases of the pancreas or biliary tract, including pancreatitis,
• in patients taking medicines with mixed agonist-antagonist properties at the "mu" opioid receptors (e.g. pentazocine, nalbuphine) or medicines that are partial agonists of the "mu" opioid receptor (e.g. buprenorphine),
• in patients with a tendency to seizures or convulsions, or when taking other medicines that increase the risk of seizures and may increase seizure risk.

Tolerance, dependence and abuse
This medicine contains tapentadol, which is an opioid medicine. Repeated use of opioid-containing medicines may lead to reduced effectiveness of the medicine (the body becomes accustomed to it, known as tolerance). Repeated use of Palexia may lead to dependence, abuse and misuse, which may result in life-threatening overdose. The risk of such adverse effects may increase with higher doses and prolonged duration of use.

Dependence or abuse may lead to loss of control over the amount or frequency of medicine intake.
The risk of developing dependence or abuse varies among individuals. Increased risk of developing abuse or dependence on Palexia may occur in the following situations:

• the patient or any family member has ever abused or been dependent on alcohol, prescription medicines or illicit drugs ("addiction"),
• the patient is a tobacco smoker,
• the patient has ever had mood disorders (depression, anxiety or personality disorders) or has been treated by a psychiatrist for other mental disorders.

If, during treatment with Palexia, the patient notices any of the following symptoms, this may indicate developing dependence or abuse:

• need to take the medicine longer than prescribed by the doctor,
• need to take higher doses than recommended,
• feeling the need to continue taking the medicine, even if it does not help relieve pain,
• using the medicine for reasons other than prescribed, e.g. "to calm down" or "to help fall asleep",
• repeated unsuccessful attempts to stop or control medicine use,
• feeling unwell after stopping the medicine and feeling better after resuming it ("withdrawal effect").

If any of these symptoms are observed, the patient should consult their doctor to discuss the best treatment plan, including the appropriate timing and safe way to discontinue treatment (see section 3 Discontinuation of Palexia).

Children and adolescents
Children and adolescents with obesity should be carefully monitored, and the recommended maximum dose should not be exceeded. Do not give this medicine to children under 2 years of age.

Sleep-related breathing disorders
Palexia may cause breathing disorders during sleep, such as sleep apnoea (pauses in breathing during sleep) and hypoxemia (low blood oxygen levels). Symptoms may include breathing pauses during sleep, nocturnal awakening due to breathlessness, difficulty maintaining sleep or excessive daytime sleepiness. If the patient or another person notices such symptoms, contact a doctor. The doctor may consider reducing the dose.

Palexia with other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.

• The risk of adverse effects increases if the patient takes medicines that may cause seizures (epileptic fits), such as antidepressants or antipsychotics. The risk of seizures may increase if Palexia is taken at the same time. Your doctor will advise whether Palexia is suitable for you.

• Concurrent use of Palexia with sedatives, such as benzodiazepines or benzodiazepine-like medicines [e.g. certain sleeping tablets or tranquilizers (e.g. barbiturates) or analgesics such as opioids, morphine and codeine (also used as cough suppressants), antipsychotics, H1 antihistamines, alcohol], increases the risk of drowsiness, breathing difficulties (respiratory depression), coma and may be life-threatening. Therefore, concomitant use of such medicines should only be considered when no other treatment options are available. If your doctor prescribes Palexia together with sedative medicines, the dose and duration of concurrent treatment should be limited. Concurrent use of opioids and medicines used to treat epilepsy, neuropathic pain or anxiety (gabapentin and pregabalin) increases the risk of opioid overdose, respiratory depression and may be life-threatening. Inform your doctor if you are taking gabapentin or pregabalin or any sedative medicine and strictly follow the doctor's dosing instructions. It may be helpful to inform friends or relatives so they are aware of the above-mentioned subjective and objective symptoms. If such symptoms occur, contact your doctor.

• If the patient is taking medicines that affect serotonin levels (e.g. certain medicines used to treat depression), they should consult their doctor before taking Palexia due to the risk of developing "serotonin syndrome". Serotonin syndrome is rare but may be life-threatening. Symptoms include uncontrolled rhythmic muscle contractions, including eye movement muscles, agitation, excessive sweating, tremor, exaggerated reflexes, increased muscle tone and body temperature above 38°C. If these symptoms occur, seek medical advice.

• The concomitant use of Palexia with opioid medicines that are mixed agonists/antagonists at the "mu" receptor (e.g. pentazocine, nalbuphine) or partial agonists at the "mu" receptor (e.g. buprenorphine) has not been studied. Palexia may not work properly if used simultaneously with the above-mentioned medicines. Inform your doctor immediately if you are currently taking any of the medicines listed above.

• Concurrent use of Palexia with strong inhibitors or inducers (e.g. rifampicin, phenobarbital, St. John's wort) of enzymes responsible for tapentadol elimination from the body may affect tapentadol's action or cause adverse effects, especially when starting or stopping such medicines. Inform your doctor about all medicines currently being taken.

• Palexia must not be used together with MAO inhibitors (medicines used to treat depression). Inform your doctor if these medicines have been taken within the last 14 days.

The risk of adverse effects may increase if the patient takes Palexia together with the following medicines with anticholinergic effects:

• antidepressants,
• medicines used to treat allergies, motion sickness or nausea (antihistamines and antiemetics),
• medicines used to treat mental disorders (antipsychotics or neuroleptics),
• muscle relaxants,
• medicines used to treat Parkinson's disease.

Palexia with food, drink and alcohol
Do not drink alcohol while taking Palexia, as certain adverse effects, such as drowsiness, may be intensified. The medicine can be taken independently of meals.

Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a baby, she should consult her doctor or pharmacist before using this medicine. Do not use Palexia:

• during pregnancy, unless the doctor decides it is necessary. Long-term use of tapentadol during pregnancy may cause withdrawal symptoms in newborns, which may be life-threatening if not recognised and treated by a doctor. Use of Palexia is not recommended:
• during childbirth, as it may cause dangerous slowing or shallowing of the newborn's breathing (respiratory depression),
• during breastfeeding, as tapentadol may be excreted in breast milk.

Driving and using machines
Palexia may cause drowsiness, dizziness, blurred vision and affect reaction ability.
These symptoms may occur especially at the beginning of Palexia treatment, after a dose adjustment recommended by the doctor, or when alcohol or sedative medicines are taken concomitantly. Ask your doctor whether driving and operating machinery are permitted after taking Palexia.

Palexia 4 mg/ml contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per maximum single dose and is therefore considered "sodium-free".

Palexia 4 mg/ml contains sodium benzoate
This medicine contains 59 mg sodium benzoate per volume unit, equivalent to 2.4 mg/ml.
Sodium benzoate may increase jaundice (yellowing of the skin and whites of the eyes) in newborns (up to 4 weeks of age).

Palexia 4 mg/ml contains propylene glycol
This medicine contains 48 mg propylene glycol in 25 ml solution (maximum single dose), equivalent to 2 mg/ml.

3. How to take Palexia

This medicine should always be taken exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Before starting treatment and regularly during treatment, your doctor will discuss with you what you can expect from taking Palexia, when and for how long you should take it, when you should contact your doctor, and when the medicine should be discontinued (see also section "Discontinuation of Palexia").
The dosage should be adjusted according to the intensity of pain and individual patient sensitivity. The lowest effective dose that adequately relieves pain should be used.
Adults
The usual dose is 50 mg tapentadol (12.5 ml oral solution), 75 mg tapentadol (18.75 ml oral solution), or 100 mg tapentadol (25 ml oral solution) every 4 to 6 hours.
Total daily doses exceeding 700 mg tapentadol on the first day of therapy and daily doses exceeding 600 mg tapentadol during subsequent days of therapy are not recommended.
Your doctor may prescribe a different, more appropriate dose or dosing interval if necessary. If you feel the effect of the medicine is too strong or too weak, consult your doctor or pharmacist.
Elderly patients
Dosage adjustment is usually not necessary in elderly patients (over 65 years of age).
Elimination of the medicine may be prolonged in patients in this age group, and therefore your doctor may recommend a different dosing regimen.
Patients with impaired liver or kidney function
Patients with severe liver impairment should not take this medicine.
In cases of moderate liver impairment, your doctor will recommend an adjusted dosing regimen.
Patients with mild liver impairment do not require dose adjustment.
Patients with severe kidney impairment should not take this medicine.
Dose adjustment is not required in patients with mild or moderate kidney impairment.
Use in children and adolescents
Palexia should be administered to children only in a hospital setting.
The dose of Palexia for children over 2 years of age and adolescents under 18 years of age is 1.25 mg/kg every 4 hours.
Always wait 4 hours before administering the next dose. The dose may be reduced as acute pain decreases.
The appropriate dose will be determined by the doctor.
Liver and kidney diseases (impairment)
Children and adolescents with liver or kidney disease should not take this medicine.
Method of administration
Palexia should be taken orally.
The medicine may be taken on an empty stomach or with food.
The package contains a dosing syringe with an adapter, which should be used to draw the correct amount (volume) of solution corresponding to the prescribed tapentadol dose from the bottle.
Instructions for opening the bottle and using the dosing syringe
The bottle has a child-resistant cap. To unscrew the cap,

press down and turn counterclockwise (Figure 1).
Unscrew the cap and remove the protective foil from the top of the bottle. If the safety seal is broken or damaged, do not use the product and contact your pharmacist.
Figure 1
Place the bottle on a hard, flat surface. Open the plastic pouch

containing the dosing syringe with the adapter by tearing along the perforated line and remove the dosing syringe (A) with the attached adapter (B). Screw the adapter with the dosing syringe tightly into the neck of the bottle (Figure 2).
Figure 2

To fill the dosing syringe, turn the bottle upside down. While holding the dosing syringe, gently pull the plunger down (C) to the line indicating the dose prescribed by your doctor (see section "How to take Palexia"). Do not remove the dosing syringe during this procedure! (Figure 3).
Figure 3
Turn the bottle upright and carefully remove the dosing syringe from the bottle. After removal,

check carefully whether the correct amount of solution has been drawn. The adapter (B), which was previously attached to the dosing syringe, should remain in the bottle (Figure 4).
Figure 4
Take the medicine by placing the dosing syringe into the mouth and gently

pushing the plunger. Push the plunger completely down to ensure the entire solution is administered. If preferred, the medicine may be diluted in a glass of water or another non-alcoholic drink before administration. In this case, the entire glass of liquid should be consumed to ensure the full dose of medicine is taken (Figure 5).
Figure 5
Leave the adapter in the bottle, close the bottle tightly, and store it in an upright position.
After each use, wash the dosing syringe with water and allow it to dry.
Before the next dose, insert the dosing syringe into the adapter in the neck of the bottle and follow the instructions described above.
Duration of treatment
Do not use longer than prescribed by your doctor.
Overdose of Palexia
After taking very high doses, the following symptoms may occur:

• pinpoint pupils, vomiting, drop in blood pressure, rapid heartbeat, collapse, disturbances of consciousness or coma (deep unconscious state), seizures, dangerously slow or shallow breathing or respiratory arrest, which may lead to death.
  In such cases, seek immediate medical attention!
  Missed dose of Palexia
  If you forget to take the medicine, your pain symptoms may return.
  Do not take a double dose to make up for a missed dose.
  Resume your regular dosing schedule.
  Discontinuation of Palexia
  If you stop or discontinue Palexia before the end of treatment, your pain symptoms may return. Contact your doctor before stopping the medicine.
  Generally, no withdrawal symptoms are observed upon discontinuation of the medicine; however, in rare cases, patients who have taken the medicine for some time and stop abruptly may experience general malaise.
  The following symptoms may occur:

• restlessness, lacrimation, runny nose, yawning, sweating, chills, muscle aches, and dilated pupils,

• irritability, anxiety, back pain, joint pain, weakness, abdominal cramps, difficulty sleeping, nausea, loss of appetite, vomiting, diarrhea, increased blood pressure, respiratory rate, and heart rate.
  If any of these symptoms occur, consult your doctor immediately. Do not stop taking the medicine suddenly unless instructed by your doctor. Your doctor will advise you on how to discontinue the medicine. Discontinuation may involve gradually reducing the dose.
  If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
Important adverse reactions or symptoms to watch for and what to do if they occur:
This medicine may cause allergic reactions. Symptoms may include wheezing, difficulty breathing, swelling of the eyelids, face or lips, rash or itching, particularly affecting the whole body.
Another serious adverse reaction is excessive drowsiness and markedly slowed or shallow breathing. This occurs most frequently in elderly and debilitated patients.
If any of these serious adverse reactions affect you, contact your doctor immediately.

Other adverse reactions that may occur:

Very common (may occur in more than 1 in 10 people): nausea, vomiting, dizziness, drowsiness, headache.

Common (may occur in less than 1 in 10 people): loss of appetite, anxiety, confusion, hallucinations, sleep disturbances, unusual dreams, tremor, flushing, constipation, diarrhoea, indigestion, dry mouth, itching, excessive sweating, rash, muscle spasms, feeling weak, fatigue, sensation of body temperature changes.

Uncommon (may occur in less than 1 in 100 people): low mood, disorientation, agitation (excitement), nervousness, restlessness, euphoric mood, difficulty concentrating, memory impairment, feeling faint, excessive sedation, balance disorders, speech disorders, tingling sensations, abnormal skin sensations (e.g. numbness, prickling), muscle spasms, visual disturbances, faster heartbeat, palpitations, decreased blood pressure, dangerously slow or shallow breathing (respiratory depression), reduced blood oxygen saturation, shortness of breath, abdominal discomfort, urticaria, heaviness sensation, difficulty urinating, frequent urination, withdrawal syndrome (see "Stopping Palexia medicine"), fluid retention (oedema), feeling of abnormality, alcohol-like intoxication, irritability, feeling of relaxation.

Rare (may occur in less than 1 in 1,000 people): allergic reactions to the medicine (including skin swelling, urticaria, and in severe cases difficulty breathing, low blood pressure, collapse or shock), disturbances in thinking, seizures, reduced level of consciousness, coordination disorders, slower heartbeat, delayed gastric emptying.

Frequency not known: delirium.

Generally, the likelihood of suicidal thoughts and behaviours is higher in patients with chronic pain. Additionally, medicines used in the treatment of depression (which affect the brain's neurotransmitter system) may increase this risk, especially at the beginning of treatment. Although tapentadol also affects neurotransmitters, data obtained from human use of the medicine have not provided evidence of increased risk.

No other adverse reactions have been observed in children and adolescents.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Palexia

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the outer carton and bottle. The expiry date refers to the last day of the stated month.
Unopened: no special storage conditions required.
After first opening of the bottle, the solution should not be used for longer than 6 weeks.
Store in an upright position.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the package and other information

What Palexia contains

• The active substance is tapentadol. 1 ml of Palexia 4 mg/ml oral solution contains 4 mg of tapentadol (as tapentadol hydrochloride).
• The other ingredients are: Sodium benzoate (E 211), Monohydrate citric acid, Sucralose (E 955), Raspberry flavour containing propylene glycol (E 1520), Purified water.

What Palexia looks like and contents of the pack

Palexia is a clear, colourless oral solution. Palexia 4 mg/ml oral solution is supplied in HDPE bottles with an HDPE child-resistant cap, containing 100 ml of solution, together with a 5 ml dosing pipette with 0.1 ml graduations and an LDPE connector for attaching to the dosing pipette, packed in a cardboard carton. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Grünenthal GmbH
Zieglerstrasse 6
52078 Aachen, Germany

For further information on this medicinal product, contact the representative of the Marketing Authorisation Holder:

Stada Pharm Sp. z o.o.
ul. Krakowiaków 44
02-255 Warsaw, Poland
Tel. +48 22 737 79 20

This medicinal product is authorised in the European Economic Area countries and in the United Kingdom (Northern Ireland) under the following names:
Belgium, Croatia, Cyprus, Czech Republic, Netherlands, Germany, Greece, Italy, Luxembourg, Norway, Poland, Portugal, Slovakia, Slovenia, Spain, United Kingdom (Northern Ireland): PALEXIA