REMUVA 250 mg PROLONGED-RELEASE TABLETS

2. What you need to know before taking Remuva

Do not take Remuva

• if you are allergic to tapentadol or any of the other ingredients of this medication (listed in section 6),
• if you have asthma or if your breathing is slow or shallow to dangerous levels (respiratory depression, hypercapnia),
• if you have intestinal paralysis,
• if you have consumed alcohol, sleeping pills, analgesics, or other psychotropic medications (medications that affect mood and emotions) (see section "Other medications and Remuva").

Warnings and precautions

Consult your doctor or pharmacist before starting to take this medication:

• if your breathing is slow or shallow,
• if you have increased intracranial pressure or altered consciousness up to coma,
• if you have had a head injury or brain tumors,
• if you have liver or kidney disease (see section "How to take Remuva"),
• if you have a disease of the pancreas or bile ducts, including pancreatitis,
• if you are taking medications called mixed opioid agonist/antagonists (e.g., pentazocine, nalbuphine) or partial agonists of opioid μ receptors (e.g., buprenorphine),
• if you are prone to epilepsy or convulsive seizures, or if you are taking other medications with a known risk of increasing seizures, as the risk of these seizures may increase,
• if you or a family member has a history of substance abuse or dependence on prescription medications or illicit substances ("addiction"),
• if you smoke,
• if you have ever had problems with your mood (depression, anxiety, or personality disorder) or have received psychiatric treatment for other mental illnesses.

This medication contains tapentadol, which is an opioid medication. Repeated use of opioid analgesics can reduce the effectiveness of the medication (you may become accustomed to it). It can also lead to dependence and abuse, which can result in a potentially fatal overdose. It is essential that you inform your doctor if you think you may have developed dependence on tapentadol. Its use (even at therapeutic doses) can cause physical dependence, which may lead to withdrawal symptoms and a recurrence of your problems if you suddenly stop taking this medication.

Tapentadol can cause physical and psychological addiction. If you have a tendency to abuse medications or are dependent on medications, you should only take these tablets for short periods under strict medical supervision.

Respiratory disorders related to sleep

Tapentadol can cause respiratory disorders related to sleep, such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). Symptoms may include pauses in breathing during sleep, nighttime awakenings due to difficulty breathing, difficulty maintaining sleep, or excessive daytime sleepiness. If you or someone else observes these symptoms, consult your doctor. Your doctor may consider reducing the dose.

Other medications and Remuva

Inform your doctor or pharmacist if you are taking, have recently taken, or may need to take any other medication.

• The risk of side effects increases if you are taking medications that can cause seizures (attacks), such as certain antidepressants or antipsychotics. The risk of seizures increases if you take tapentadol simultaneously with these medications. Your doctor will tell you if this medication is suitable for you.
• Concomitant use of tapentadol and sedative medications such as benzodiazepines or related medications (certain sleeping pills or tranquilizers, e.g., barbiturates) or analgesics such as opioids, morphine, and codeine (also as a cough medication), antipsychotics, antihistamines H1, or alcohol increases the risk of drowsiness, respiratory difficulties (respiratory depression), coma, and can be potentially fatal. Due to this, concomitant use should only be considered when other treatment options are not possible. However, if your doctor prescribes tapentadol with sedative medications, you should limit the dose and duration of concomitant treatment.
• Concomitant use of opioids and medications used to treat epilepsy, nerve pain, or anxiety (gabapentin and pregabalin) increases the risk of opioid overdose, respiratory depression, and can be potentially fatal.Inform your doctor if you are taking gabapentin or pregabalin or anyother sedative medication and follow your doctor's dosage recommendations exactly. It may be helpful to inform friends or family members to be aware of the signs and symptoms mentioned above. Contact your doctor when you experience these symptoms.

• If you are taking a type of medication that affects serotonin levels (e.g., certain medications for treating depression), talk to your doctor before taking this medication, as there have been cases of "serotonin syndrome". Serotonin syndrome is a rare but potentially fatal disorder. Symptoms include involuntary rhythmic muscle contractions, including muscles that control eye movement, agitation, excessive sweating, tremors, exaggerated reflexes, increased muscle tension, and body temperature above 38°C. Your doctor can provide additional information.
• The concomitant administration of tapentadol with other types of medications called mixed opioid agonist/antagonists (e.g., pentazocine, nalbuphine) or partial agonists of opioid μ receptors (e.g., buprenorphine) has not been studied. It is possible that Remuva may not have the same efficacy if administered with one of these medications. Inform your doctor if you are currently being treated with one of these medications.
• The administration of tapentadol with potent inhibitors or inducers (e.g., rifampicin, phenobarbital, St. John's Wort) of certain enzymes necessary for the elimination of tapentadol from your body may affect the efficacy of tapentadol or cause side effects, especially when starting or stopping this other type of medication. Keep your doctor informed about all medications you are taking.
• This medication should not be taken with MAO inhibitors (medications for treating depression). Inform your doctor if you are taking MAO inhibitors or if you have taken them in the last 14 days.

Taking Remuva with food, drinks, and alcohol

Do not consume alcohol while taking this medication, as some of its side effects, such as drowsiness, may increase. Food intake does not affect the effect of this medication.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

Do not take this medication:

• if you are pregnant, unless your doctor has indicated it, if used during prolonged periods during pregnancy, tapentadol may cause withdrawal symptoms in the newborn, which can be life-threatening if not detected and treated by a doctor,
• during breastfeeding, as it may be excreted in breast milk.

Tapentadol is not recommended

• during labor, as it may cause slow or shallow breathing to dangerous levels (respiratory depression) in the newborn.

Driving and using machines

This medication can cause drowsiness, dizziness, and blurred vision and may affect your reactions. Be especially careful when starting treatment, after a dose change, and when taking it with alcohol or tranquilizers.

Ask your doctor if you can drive or operate machines.

3. How to take Remuva

Follow your doctor's or pharmacist's instructions for taking this medication exactly. If you are unsure, consult your doctor or pharmacist again.

Your doctor will adjust the dose based on the intensity of your pain and your personal sensitivity to pain. Generally, you should take the minimum effective dose to relieve pain.

Adults

The initial dose is usually 50 mg twice a day, approximately every 12 hours.

Daily doses above 500 mg of tapentadol are not recommended.

Your doctor may prescribe a different dose or dosing regimen, which is more suitable for you. If you think the effect of these tablets is too strong or too weak, consult your doctor or pharmacist.

Elderly patients

In elderly patients (over 65 years of age), the dose does not usually need to be adjusted. However, the elimination of tapentadol may be delayed and slower in some patients in this age group. If this applies to you, your doctor may prescribe a different dosing regimen.

Liver and kidney diseases (hepatic and renal insufficiency)

Patient with severe liver problems should not take this medication. If you have moderate liver problems, your doctor will prescribe a different dosing regimen. In case of mild liver problems, no dose adjustment is necessary.

Patient with severe kidney problems should not take these tablets. In case of mild or moderate kidney problems, no dose adjustment is necessary.

Use in children and adolescents

Tapentadol is not indicated in children and adolescents under 18 years of age.

How and when to take Remuva

Tapentadol should be taken orally.

Always take the tablets whole with a sufficient amount of liquid.

Do not chew or crush them, as this could lead to an overdose because the active ingredient will be released into your body too quickly.

You can take them on an empty stomach (without food) or with meals.

The tablet can be divided into equal doses.

The coating of the tablet may not be completely digested and may appear, apparently unchanged, in the feces. This should not concern you, as the active ingredient of the tablet will have been absorbed by the body, and what you see is only the empty coating.

Instructions for opening the blister pack

This medication is packaged in a child-resistant, perforated unit blister pack. The tablets cannot be pressed through the blister pack. Follow these instructions for opening the blister pack:

1. Cut a single dose along the perforation line of the blister pack.

1. This will allow you to access an unsealed area located at the position where the perforation lines cross.

1. Pull the unsealed part to detach the seal from the lid.

How long to take Remuva

Do not take the tablets for longer than your doctor has indicated.

If you take more Remuva than you should

After taking very high doses, you may experience some of the following effects:

• very small pupils
• vomiting
• decreased blood pressure
• rapid heartbeat
• altered consciousness, fainting, or deep loss of consciousness (coma)
• seizures
• slow or shallow breathing to dangerous levels or respiratory arrest

If this occurs, you should immediately call a doctor.

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested. It is recommended to bring the packaging and package leaflet of the medication to the healthcare professional.

If you forget to take Remuva

If you forget to take a tablet, you will likely feel pain again. Do not take a double dose to make up for forgotten doses, but continue taking the tablets as before.

If you stop taking Remuva

If you stop or discontinue treatment too early, you will likely feel pain again. If you want to stop treatment, consult your doctor before doing so.

Generally, patients do not experience any side effects after stopping treatment, but in rare cases, people who have taken the tablets for a long time may feel unwell if they stop taking them suddenly.

The symptoms may be:

• restlessness, tearful eyes, runny nose, yawning, sweating, chills, muscle pain, and dilated pupils,

• irritability, anxiety, back pain, joint pain, weakness, abdominal cramps, difficulty sleeping, nausea, loss of appetite, vomiting, diarrhea, and increased blood pressure, respiratory rate, or heart rate.

If you experience any of these symptoms after stopping treatment, consult your doctor.

You should not stop taking this medication abruptly, unless your doctor tells you to do so. If your doctor wants you to stop taking these tablets, they will tell you how to do it, which may involve gradually reducing the dose.

If you have any further questions about the use of this medication, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Adverse effects or important symptoms to be aware of and what to do if you are affected by them:

• This medicine may cause allergic reactions. The symptoms may consist of wheezing, difficulty breathing, swelling of the eyelids, face or lips, skin rash or itching, especially if they affect the whole body.
• Another serious adverse effect consists of breathing more slowly or more weakly than normal. It occurs mostly in elderly patients or in debilitated patients.

If you experience any of these important symptoms, consult your doctor immediately.

Other adverse effects that may occur:

Very common(may affect more than 1 in 10 people):

• nausea, constipation,
• dizziness, drowsiness, headache.

Common(may affect up to 1 in 10 people):

• decreased appetite, anxiety, depression, difficulty sleeping, nervousness, restlessness, attention disorders,
• tremors, muscle spasms,
• flushing,
• difficulty breathing,
• vomiting, diarrhea, indigestion,
• itching, increased sweating, rash,
• feeling of weakness, fatigue, feeling of change in body temperature, dryness of the mucous membranes, accumulation of water in the tissues (edema).

Uncommon(may affect up to 1 in 100 people):

• allergic reaction to medicines (including swelling under the skin, hives, and, in severe cases, difficulty breathing, decreased blood pressure, collapse, or shock),
• weight loss,
• disorientation, confusion, excitability (agitation), altered perception, abnormal dreams, euphoric mood, decreased level of consciousness, memory impairment, mental deterioration,
• fainting, sedation, balance disorder, difficulty speaking, numbness, abnormal sensations in the skin (e.g., tingling, pinching)
• abnormal vision,
• accelerated heart rate, decreased heart rate, palpitations, decreased blood pressure,
• abdominal discomfort,
• hives,
• urinary retention, frequent urination,
• sexual dysfunction,
• drug withdrawal syndrome (see "If you stop treatment with Remuva"), feeling of discomfort, irritability.

Rare(may affect up to 1 in 1,000 people):

• drug dependence, altered thinking, epileptic seizures, feeling of being about to faint, altered coordination,
• slow or shallow breathing to dangerous levels (respiratory depression),
• altered gastric emptying,
• feeling of intoxication, feeling of relaxation.

Frequency not known(the frequency cannot be estimated from the available data):

• delirium.

In general, the possibility of having suicidal thoughts and behaviors increases in patients with chronic pain. Additionally, some medications for treating depression (with an impact on the brain's neurotransmitter system) may increase this risk, especially at the start of treatment. Although tapentadol also affects neurotransmitters, experience in patients has not proven that it increases this risk.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Remuva

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date that appears on the packaging and on the blister after CAD. The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE Point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Remuva

The active ingredient is tapentadol.

Remuva 250 mg prolonged-release tablets:

Each prolonged-release tablet contains tapentadol phosphate equivalent to 250 mg of tapentadol.

The other ingredients are:

Tablet core: microcrystalline cellulose (E460), hypromellose (E464), anhydrous colloidal silica (E551), magnesium stearate.

Coating: hypromellose (E464), glycerol (E422), talc (E553b), microcrystalline cellulose (E460), titanium dioxide (E171); red iron oxide (E172), black iron oxide (E172).

Appearance of the Product and Package Contents

Remuva 250 mg prolonged-release tablets are reddish-brown, oblong, biconvex (9 mm x 18 mm) with a break line on both sides.

The tablet can be divided into equal doses.

Remuva 250 mg prolonged-release tablets are packaged in aluminum-PVC/PE/PVDC blisters, with the following package sizes:

20x1, 24x1, 30x1, 50x1, 54x1, 60x1, or 100x1 in child-resistant, perforated unit blisters.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Aristo Pharma GmbH

Wallenroder Straße 8-10

13435 Berlin

Germany

Manufacturer

Develco Pharma GmbH

Grienmatt 27, Farhnau

79650 Schopfheim

Baden-Wuerttemberg

Germany

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Aristo Pharma Iberia, S.L.

C/ Solana, 26

28850, Torrejón de Ardoz

Madrid, Spain

This medicine is authorized in the Member States of the European Economic Area under the following names:

Germany Tapentadol Aristo retard 250 mg Retardtabletten

Italy Tapentadolo Aristo

Denmark Tapentadol Aristo

Norway Tapentadol Aristo

Sweden Tapentadol Depot Aristo

Spain Remuva 250 mg prolonged-release tablets EFG

Date of the last revision of this prospectus:September 2022

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/