TARGIN 5 mg/2.5 mg PROLONGED-RELEASE TABLETS

Introduction

Package Leaflet: Information for the User

Targin 5 mg/2.5 mg prolonged-release tablets

Oxycodone hydrochloride/Naloxone hydrochloride

Read all of this leaflet carefully before you start taking 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 or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What Targin is and what it is used for

Targin is a prolonged-release tablet, which means that the active substances are released over a longer period of time. Its effect lasts 12 hours.

These tablets are for use in adults only.

Pain relief

You have been prescribed Targin for the treatment of severe pain, which can only be adequately managed with opioid analgesics. Naloxone hydrochloride is added to counteract constipation.

How these tablets work for pain relief

These tablets contain oxycodone hydrochloride and naloxone hydrochloride as active substances. Oxycodone hydrochloride is responsible for the analgesic effect of Targin; it is a potent analgesic from the opioid group. The second active substance of Targin, naloxone hydrochloride, has the function of counteracting constipation. Intestinal dysfunction (e.g., constipation) is a common side effect of treatment with opioid analgesics.

Restless Legs Syndrome

You have been prescribed Targin for the symptomatic treatment of moderate to severe idiopathic Restless Legs Syndrome in patients who cannot be treated with dopaminergic medications. People with Restless Legs Syndrome feel an unpleasant sensation in their limbs. This can start as soon as they sit down or lie down and can only be relieved by an urgent and irresistible urge to move their legs, sometimes arms, and other parts of the body. This makes it very difficult to stay seated and to sleep. Naloxone hydrochloride has been added to counteract constipation.

How these tablets work in Restless Legs Syndrome

These tablets help to relieve the unpleasant sensations and thus reduce the urgent need to move the limbs.

The second active substance of Targin, naloxone hydrochloride, has the function of counteracting constipation. Intestinal dysfunction (e.g., constipation) is a common side effect of treatment with opioid analgesics.

2. What you need to know before you take Targin

Do not take Targin

• if you are allergic to oxycodone hydrochloride, naloxone hydrochloride, or any of the other ingredients of this medicine (listed in section 6),
• if your breathing is too weak to take in enough oxygen or remove carbon dioxide from your body (respiratory depression),
• if you have severe lung disease associated with narrowing of the airways (chronic obstructive pulmonary disease or COPD),
• if you have a condition where the right side of the heart is enlarged due to increased pressure in the blood vessels of the lungs (cor pulmonale),
• if you have severe bronchial asthma,
• if you have paralytic ileus (a type of intestinal obstruction) not caused by opioids,
• if you have moderate to severe liver disease.

In addition, for Restless Legs Syndrome

• if you have a history of opioid abuse.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Targin:

• if you are an elderly or debilitated patient,
• if you have paralytic ileus (a type of intestinal obstruction) caused by opioids,
• if you have kidney disorder,
• if you have mild liver disorder,
• if you have severe lung disease (i.e., reduced ability to breathe),
• if you have a condition characterized by frequent pauses in breathing during sleep, which can make you feel very sleepy during the day (sleep apnea),
• if you have myxedema (a thyroid disorder characterized by dryness, coldness, and swelling of the skin, affecting the face and extremities),
• if your thyroid gland does not produce enough hormones (underactive thyroid, or hypothyroidism),
• if your adrenal glands do not produce enough hormones (adrenal insufficiency or Addison's disease),
• if you have a mental illness accompanied by a loss (partial) of contact with reality (psychosis), due to alcoholism or intoxication with other substances (substance-induced psychosis),
• if you have problems with gallstones,
• if you have an enlarged prostate (prostate hypertrophy),
• if you have a history of alcoholism or delirium tremens,
• if you have pancreatitis (inflammation of the pancreas),
• if you have low blood pressure (hypotension),
• if you have high blood pressure (hypertension),
• if you have pre-existing cardiovascular disease,
• if you have had a head injury (due to the risk of increased pressure in the brain),
• if you have epilepsy or are prone to seizures,
• if you are also receiving treatment with MAO inhibitors (used to treat depression or Parkinson's disease), or have taken this type of medicine in the last two weeks, for example, medicines containing tranylcypromine, phenelzine, isocarboxazid, moclobemide, and linezolid,
• if you experience drowsiness or sudden sleep episodes.

Breathing difficulties related to sleep

Targin may cause breathing difficulties 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 staying asleep, or excessive daytime sleepiness. If you or someone else observes these symptoms, consult your doctor. Your doctor may consider reducing the dose.

Tell your doctor if you have had any of these conditions in the past. Also, inform your doctor if you develop any of these conditions during treatment with these tablets.

The most serious consequence of opioid overdose is respiratory depression (slow and shallow breathing). This can also cause a decrease in oxygen concentration in the blood, which can lead to fainting, etc.

Swallow the prolonged-release tablet whole, so that the slow release of oxycodone hydrochloride from the prolonged-release tablet is not affected. Do not break, chew, or crush the tablets. Taking them broken, chewed, or crushed can lead to a potentially fatal overdose of oxycodone hydrochloride (see section 3 "If you take more Targin than you should").

If you experience severe diarrhea at the start of treatment, it may be due to the effect of naloxone. It can be a sign that bowel function is returning to normal. This diarrhea may occur in the first 3 to 5 days of treatment. If it persists beyond this 3 to 5-day period or if you are concerned, contact your doctor.

If you have been receiving another opioid, you may experience withdrawal symptoms shortly after starting treatment with Targin, such as restlessness, sweating, and muscle pain. If you experience any of these symptoms, you may need special monitoring by your doctor.

Tolerance, dependence, and addiction

This medicine contains oxycodone, which is an opioid medication. Repeated use of opioid analgesics can make the medication less effective (you get used to it, which is known as tolerance). Repeated use of Targin can also cause dependence, abuse, and addiction, which can lead to a life-threatening overdose. The risk of these side effects may increase with higher doses and longer treatment duration.

Dependence or addiction can make you feel that you no longer have control over the amount of medication you need to take or how often you need to take it. You may feel that you need to keep taking the medication even when it no longer helps to relieve your pain or Restless Legs Syndrome.

The risk of becoming dependent or addicted varies from person to person. You may have a higher risk of becoming dependent or addicted to Targin:

• if you or a family member have a history of abuse or dependence on alcohol, prescription drugs, or illegal 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 health conditions.

If you notice any of the following signs while taking Targin, it could be a sign that you have become dependent or addicted.

• You need to take the medication for longer than recommended by your doctor.
• You need to take more doses than recommended.
• You are using the medication for reasons other than those prescribed, for example, "to calm down" or "to help you sleep".
• You have made repeated unsuccessful attempts to stop or control the use of the medication.
• You do not feel well when you stop taking the medication and feel better once you take it again ("withdrawal symptoms").

If you notice any of these signs, talk to your doctor to discuss the best treatment for you, including when it is appropriate to stop taking it and how to do so safely (see section 3, "If you stop taking Targin").

Contact your doctor if you have severe abdominal pain that may radiate to the back, nausea, vomiting, or fever, as these may be symptoms associated with pancreatitis or biliary tract disease.

Tell your doctor if you have cancer associated with peritoneal metastasis or initial intestinal obstruction in advanced stages of digestive and pelvic cancers.

If you need to undergo surgery, tell the doctors that you are taking Targin.

Like other opioids, oxycodone can affect the normal production of hormones in the body, such as cortisol or sex hormones, especially if high doses are taken for long periods. If you notice persistent symptoms such as malaise (including vomiting), loss of appetite, fatigue, weakness, dizziness, changes in menstrual cycle, impotence, infertility, or decreased sexual desire, consult your doctor so that they can monitor your hormone levels.

This medicine may increase your sensitivity to pain, especially at high doses. Inform your doctor if this occurs. It may be necessary to reduce the dose or change the medication.

You may notice remains of the prolonged-release tablet in your stool. Do not be alarmed, as the active substances (oxycodone hydrochloride and naloxone hydrochloride) have already been released in the stomach and intestine and have been absorbed by your body.

Incorrect use of Targin

These tablets are not intended for the treatment of withdrawal symptoms.

Never misuse Targin, especially if you have a history of substance abuse. If you are addicted to substances such as heroin, morphine, or methadone, you may experience severe withdrawal symptoms if you misuse these tablets, as they contain naloxone. They can worsen pre-existing withdrawal symptoms.

Also, never dissolve these tablets to inject them (e.g., into a blood vessel). The reason is that they contain talc, which can cause local tissue destruction (necrosis) and changes in lung tissue (pulmonary granuloma). This misuse can also have other serious consequences and even lead to death.

The use of Targin may result in positive findings in doping tests. The use of Targin as a doping agent can endanger health.

Taking Targin with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

The risk of side effects increases if you use antidepressants (such as citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine). These medications can interact with oxycodone and may cause symptoms such as involuntary muscle contractions, agitation, excessive sweating, tremors, exaggerated reflexes, increased muscle tension, and body temperature above 38°C. Contact your doctor if you experience these symptoms.

The concomitant use of opioids, including oxycodone hydrochloride, and sedative medications such as benzodiazepines or related medications, increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and can be life-threatening. Due to this, concomitant use should only be considered when other treatment options are not possible.

However, if your doctor prescribes Targin together with sedative medications, your doctor should limit the dose and duration of concomitant treatment.

Tell your doctor about all sedative medications you are taking and follow the recommended doses carefully. It may be helpful to inform friends or family members who are aware of the signs and symptoms mentioned above. Contact your doctor when you experience these symptoms. Some examples of sedative medications or related medications are:

• other potent analgesics (opioids);
• medications for treating epilepsy, pain, and anxiety, such as gabapentin and pregabalin;
• sleeping pills and tranquilizers (sedatives, including benzodiazepines, hypnotics, anxiolytics);
• medications for treating depression;
• medications used to treat allergies, dizziness, or nausea (antihistamines or antiemetics);
• medications for treating psychiatric or mental disorders (antipsychotics, including phenothiazines and neuroleptics);
• muscle relaxants;
• medications for treating Parkinson's disease.

If you take these tablets at the same time as other medications, the effects of the tablets or the other medications described below may change. Tell your doctor if you are taking:

• medications that reduce blood clotting (coumarin derivatives), the speed of blood clotting may increase or decrease;
• macrolide antibiotics (such as clarithromycin, erythromycin, or telithromycin);
• azole-type antifungal agents (such as ketoconazole, voriconazole, itraconazole, or posaconazole);
• a specific type of medication known as a protease inhibitor used to treat HIV (e.g., ritonavir, indinavir, nelfinavir, or saquinavir);
• cimetidine (a medication for treating stomach ulcers, indigestion, or heartburn);
• rifampicin (used to treat tuberculosis);
• carbamazepine (used to treat seizures or certain painful conditions);
• phenytoin (used to treat seizures);
• a herbal remedy called St. John's Wort (also known as Hypericum perforatum);
• quinidine (a medication for treating arrhythmias).

No interactions are expected between Targin and paracetamol, acetylsalicylic acid, or naltrexone.

Taking Targin with food, drinks, and alcohol

Drinking alcohol while taking Targin can make you feel more drowsy or increase the risk of serious side effects such as shallow breathing with the risk of stopping breathing, and loss of consciousness. It is recommended not to drink alcohol while taking Targin.

You should avoid drinking grapefruit juice while taking these tablets.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

During pregnancy, these tablets should be avoided whenever possible. If used during prolonged periods of pregnancy, oxycodone hydrochloride may cause withdrawal symptoms in the newborn. If oxycodone hydrochloride is administered during delivery, the newborn may experience respiratory depression (slow and shallow breathing).

Breastfeeding

Breastfeeding should be discontinued during treatment with these tablets. Oxycodone hydrochloride passes into breast milk. It is not known whether naloxone hydrochloride also passes into breast milk. Therefore, the risk to the breastfed child cannot be excluded, especially if the mother receives multiple doses of Targin.

Driving and using machines

Targin may affect your ability to drive or use machines. This is especially true at the start of treatment with Targin, after a dose increase, or after switching from another medication. However, these side effects usually disappear once the dose of Targin is established.

Targin has been associated with drowsiness and sudden sleep episodes. If you experience these side effects, do not drive or use machinery. If this happens, inform your doctor.

Ask your doctor if you can drive or use machines during treatment with Targin.

Targin contains lactose

This medicine contains lactose (milk sugar). If your doctor has told you that you have an intolerance to some sugars, consult your doctor before taking this medicine.

3. How to Take Targin

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Before starting treatment and periodically during treatment, your doctor will discuss with you what you can expect from the use of Targin, when and for how long you should take it, when to contact your doctor, and when you should stop taking it (see also "If you stop treatment with Targin").

Targin is a prolonged-release tablet, which means that the active ingredients are released over a prolonged period. Its action lasts 12 hours.

You must swallow the prolonged-release tablet whole to avoid affecting the slow release of oxycodone hydrochloride from the tablet. Do not break, crush, or chew the tablets.If you do, your body may absorb a potentially fatal dose of oxycodone hydrochloride (see section 3 "If you take more Targin than you should").

Unless your doctor tells you otherwise, the usual dose is:

For pain treatment

Adults

The usual initial dose is 10 mg of oxycodone hydrochloride/5 mg of naloxone hydrochloride in prolonged-release tablets every 12 hours.

Your doctor will decide the dose you should take per day and how to divide the total daily dose between the morning and evening doses. Your doctor will also decide if it is necessary to adjust the dose during treatment. Your dose will be adapted to your degree of pain and individual sensitivity. You should receive the minimum dose necessary to relieve pain. If you have already received treatment with opioids, the initial dose of Targin may be higher.

The maximum daily dose is 160 mg of oxycodone hydrochloride and 80 mg of naloxone hydrochloride. If you need a higher dose, your doctor may prescribe more oxycodone hydrochloride without naloxone hydrochloride. However, the maximum daily dose of oxycodone hydrochloride should not exceed 400 mg. The beneficial effect of naloxone hydrochloride on intestinal activity may be affected if the dose of oxycodone hydrochloride is increased without increasing the dose of naloxone hydrochloride.

If you replace these tablets with another opioid analgesic, your intestinal function may worsen. If you experience pain between two doses of Targin, you may need a rapid-acting analgesic. Targin is not suitable for treatment in this case. Discuss this with your doctor.

If you feel that the effect of these tablets is too strong or too weak, consult your doctor or pharmacist.

For the treatment of restless legs syndrome

Adults

The usual initial dose is 5 mg of oxycodone hydrochloride/2.5 mg of naloxone hydrochloride in prolonged-release tablets every 12 hours.

Your doctor will decide how much Targin you should take each day and how to divide the total daily dose between the morning and evening doses. Your doctor will also decide if it is necessary to adjust the dose during treatment. Your dose will be adjusted according to your individual response. The minimum dose will be chosen to mitigate the symptoms of restless legs syndrome.

If you feel that the effect of Targin is too strong or too weak, consult your doctor or pharmacist.

The maximum daily dose is 60 mg of oxycodone hydrochloride and 30 mg of naloxone hydrochloride.

For the treatment of pain or restless legs syndrome

Elderly patients

In general, it is not necessary to adjust the dose in elderly patients with normal kidney and/or liver function.

Liver or kidney disorder

If you have kidney disorder of any degree or mild liver disorder, your doctor will prescribe these tablets with special caution. If you have moderate or severe liver disorder, you should not take these tablets (see also section 2 "Do not take Targin" and "Warnings and precautions").

Children and adolescents under 18 years

Targin has not been studied in children and adolescents under 18 years. Its safety and efficacy have not been demonstrated in these patients. For this reason, the use of Targin is not recommended in children and adolescents under 18 years.

Method of administration

Oral route.

Swallow these tablets whole (without chewing), with sufficient liquid (half a glass of water). You can take the prolonged-release tablets with or without food. Take these tablets every 12 hours, following a fixed schedule (e.g., at 8 am and 8 pm). Do not break, chew, or crush the prolonged-release tablets (see section 2 "Warnings and precautions").

Duration of use

In general, you should not take these tablets for longer than necessary. If you receive these tablets for a long time, your doctor should regularly check that you still need them.

If you take more Targin than you should

If you have taken more tablets than prescribed, you should inform your doctor immediately. Consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount used. It is recommended to take the packaging and the medication leaflet to the healthcare professional.

An overdose can cause:

• pupil constriction
• slow and shallow breathing (respiratory depression)
• drowsiness leading to loss of consciousness
• low muscle tone (hypotonia)
• reduced heart rate
• decreased blood pressure
• a brain disorder (known as toxic leukoencephalopathy)

In severe cases, loss of consciousness (coma), fluid accumulation in the lungs, and circulatory collapse may occur, which can be fatal in some cases.

You should avoid situations that require a high level of alertness, such as driving.

If you forget to take Targin

Or if you take a lower dose than prescribed, you may stop noticing the analgesic effect.

If you forget to take a dose, follow these instructions:

• If there are 8 hours or more left until the next normal dose: Take the forgotten Targin prolonged-release tablet immediately, and continue with the normal schedule.
• If there are less than 8 hours left until the next normal dose: Take the forgotten Targin prolonged-release tablet. Wait another 8 hours before taking the next prolonged-release tablet. Try to recover the original schedule (e.g., 8 am and 8 pm). Do not take Targin more than once in an 8-hour period.

Do not take a double dose to make up for forgotten doses.

If you stop treatment with Targin

Do not stop treatment without consulting your doctor. If you no longer need to continue treatment, you should gradually reduce the daily dose after discussing it with your doctor. This will help you avoid withdrawal symptoms, such as restlessness, sweating, and muscle pain.

If you have any other 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.

Important adverse effects to look for, and what to do if you experience them:

If you are already experiencing any of the following important adverse effects, consult your doctor immediately.

Shallow and slow breathing (respiratory depression) is the main danger of opioid overdose. It occurs mainly in elderly and debilitated patients. Opioids can also cause a significant decrease in blood pressure in susceptible patients.

The following adverse effects have been observed in patients receiving treatment for pain

Frequent (may affect up to 1 in 10 patients)

Uncommon (may affect up to 1 in 100 patients)

Rare (may affect up to 1 in 1,000 patients)

Frequency not known (cannot be estimated from available data)

It is known that the active ingredient oxycodone hydrochloride, if not combined with naloxone hydrochloride, has the following adverse effects, different from those mentioned:

Oxycodone may cause respiratory problems (respiratory depression), decreased pupil size, muscle spasms of the bronchial and smooth muscles, and depression of the cough reflex.

Frequent (may affect up to 1 in 10 patients)

Uncommon (may affect up to 1 in 100 patients)

Rare (may affect up to 1 in 1,000 patients)

Frequency not known (cannot be estimated from available data)

The following adverse effects have been observed in patients receiving treatment for restless legs syndrome

Reporting of adverse effects

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Targin

Keep this medicine out of the sight and reach of children. Store this medicine in a safe and closed place, where others cannot access it. It can cause serious harm and be fatal to people who have not been prescribed it.

Do not use this medicine after the expiration date shown on the box, label, and blister, after "EXP". The expiration date is the last day of the month indicated.

Do not store above 25°C.

Store in the original package to protect it from light.

Only for bottles

Once opened, use within the next 6 months.

Medicines should not be disposed of 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 will help protect the environment.

6. Package contents and additional information

Composition of Targin

The active ingredients are oxycodone hydrochloride and naloxone hydrochloride.

Each prolonged-release tablet contains 5 mg of oxycodone hydrochloride, equivalent to 4.5 mg of oxycodone, and 2.5 mg of naloxone hydrochloride as 2.73 mg of naloxone hydrochloride dihydrate, equivalent to 2.25 mg of naloxone.

The other ingredients are:

• Core of the tablet: Hydroxypropylcellulose, ethylcellulose, stearic alcohol, lactose monohydrate, talc, magnesium stearate.
• Coating of the tablet: Partially hydrolyzed polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, aluminum lake blue brilliant (E133).

Appearance of Targin and package contents

Targin 5 mg/2.5 mg are oblong tablets, blue in color, with a minimum length of 9.5 mm, film-coated, and marked with "OXN" on one side and "5" on the other.

These tablets are marketed in packs with blisters of 10, 14, 20, 28, 30, 50, 56, 60, 98, and 100 or in a clinical pack of 100 (10 x 10) or in a child-resistant bottle containing 100 tablets.

Not all pack sizes and types may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Mundipharma Pharmaceuticals, S.L.

Bahía de Pollensa, 11

28042 Madrid

Spain

Phone: 91 3821870

Manufacturer

Mundipharma DC B.V.

Leusderend 16

3832 RC Leusden

Netherlands

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

Date of last revision of this leaflet:April 2025

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