Leaflet: information for the user

Targin 5 mg/2.5 mg prolonged-release tablets

Oxycodone hydrochloride/naloxone hydrochloride

Read this leaflet carefully before you start taking this medicine, as it contains important information for you.

- Keep this leaflet, as you may need to read it again.

- If you have any questions, consult your doctor or pharmacist.

- This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.

- If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What Targin is and for what it is used

2. What you need to know before starting to take Targin

3. How to take Targin

4. Possible side effects

5. Storage of Targin

6. Contents of the pack and additional informationadditional information

Targin is a prolonged-release tablet, meaning that its active ingredients are released over a prolonged period of time. Its action lasts 12 hours.

These tablets are only for use in adults.

Pain relief

You have been prescribed Targin for the treatment of intense pain, which can only be adequately treated with opioid analgesics. Hydrochloride of naloxone has been added to counteract constipation.

How these tablets work for pain relief

These tablets contain as active ingredients hydrochloride of oxycodone and hydrochloride of naloxone. Hydrochloride of oxycodone is responsible for the analgesic effect of Targin; it is a potent opioid analgesic. The second active ingredient of Targin, hydrochloride of naloxone, has the function of counteracting constipation. Intestinal dysfunction (for example, constipation) is a common adverse effect of treatment with opioid analgesics.

Restless legs syndrome

You have been prescribed Targin for symptomatic treatment of second-line in patients with severe to very severe idiopathic restless legs syndrome, who cannot be treated with dopaminergic drugs. People with restless legs syndrome feel an unpleasant sensation in their limbs. This can start as soon as they sit or lie down and is only relieved by an urgent and irresistible movement of the legs, sometimes the arms and other parts of the body. This makes it very difficult to remain seated and to sleep. Hydrochloride of naloxone has been added to counteract constipation.

How these tablets work in restless legs syndrome

These tablets help to alleviate unpleasant sensations, and therefore, reduce the urgent need to move the limbs.

The second active ingredient of Targin, hydrochloride of naloxone, has the function of counteracting constipation. Intestinal dysfunction (for example, constipation) is a common adverse effect of treatment with opioid analgesics.

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 you have difficulty breathing and are not getting enough oxygen into your blood or removing carbon dioxide from your body (respiratory depression),

- if you have a severe lung disease associated with narrowing of the airways (chronic obstructive pulmonary disease or COPD),

- if you have a condition called cor pulmonale. This condition is characterized by an increase in the size of the right side of the heart due to increased pressure in the blood vessels of the lungs, etc. (for example, as a result of COPD, see above),

- 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.

Additionally 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 disease,

- if you have mild liver disease,

- 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 drowsy during the day (sleep apnea),

- if you have hypothyroidism (a condition where the thyroid gland does not produce enough hormones),

- if you have adrenal insufficiency (a condition where the adrenal glands do not produce enough hormones),

- if you have a mental disorder accompanied by a loss (partial) of reality (psychosis), due to alcoholism or intoxication by other substances (substance-induced psychosis),

- if you have gallstones,

- if you have an enlarged prostate (prostatic hypertrophy),

- if you have 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 a previous cardiovascular disease,

- if you have a head injury (due to the risk of increased intracranial pressure),

- 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 medication in the past two weeks, for example, medications containing tranilcipromina, phenelzine, isocarboxazide, moclobemide, and linezolid,

- if you experience drowsiness or sudden episodes of sleep.

Respiratory disorders related to sleep

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

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

The most severe consequence of opioid overdose is respiratory depression (slow and shallow breathing). This may also cause a decrease in the concentration of oxygen in the blood, which may cause dizziness, etc.

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

If you experience intense diarrhea at the start of treatment, it may be due to the effect of naloxone. It may be a sign that the intestinal function is normalizing. This diarrhea may occur in the first 3 to 5 days of treatment. If it persists after that period of 3 to 5 days, 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, for example, 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 may make the medication less effective (you become accustomed to it, known as tolerance). Repeated use of Targin may also cause dependence, abuse and addiction, which may lead to an overdose that puts your life at risk. The risk of these adverse effects may increase with a higher dose and longer duration of use.

Dependence or addiction may 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 continue taking the medication, even when it no longer helps to relieve your pain or restless legs syndrome.

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

- if you or a family member has a history of abuse or dependence on alcohol, prescription medications or illicit substances ("addiction").

- if you smoke.

- if you have ever had problems with your mood (depression, anxiety or a personality disorder) or have received treatment from a psychiatrist 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 stay calm" or "to help you sleep".

– You have made repeated and 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 analyze the best treatment for you, including when it is appropriate to stop taking it and how to do it safely (see section 3, If you interrupt treatment with Targin).

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

Inform 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, inform the doctors that you are taking Targin.

Like other opioids, oxycodone may affect the normal production of hormones in the body, such as cortisol or sex hormones, especially if you have to take high doses for long periods of time. If you notice persistent symptoms such as discomfort (including vomiting), loss of appetite, fatigue, weakness, dizziness, changes in menstrual cycle, impotence, infertility or decreased libido, consult your doctor to monitor your hormone levels.

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

You may observe remnants of the prolonged-release tablet in the feces. Do not be alarmed, as the active principles (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 a treatment for withdrawal symptoms.

You must never abuse Targin, especially if you have a substance use disorder. 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 may worsen existing withdrawal symptoms.

You must never dissolve these tablets to inject them (for example, into a blood vessel). The reason is that they contain talc, which may cause local tissue destruction (necrosis) and alterations in lung tissue (pulmonary granuloma). This misuse may also have other serious consequences and even cause death.

The use of Targin may result in positive tests in antidoping controls. The use of Targin as a doping agent may put your health at risk.

Taking Targin with other medications

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

The risk of adverse effects increases if you use antidepressants (such as citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine). These medications may interact with oxycodone and you may experience symptoms such as involuntary muscle contractions, agitation, excessive sweating, tremor, 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, with sedatives such as benzodiazepines or related medications increases the risk of drowsiness, difficulty breathing (respiratory depression), coma and may put your life at risk. Therefore, concomitant use should only be considered when other treatment options are not possible.

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

Inform your doctor of all sedatives you are taking and follow the recommended doses closely. 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 sedatives or related medications are:

• other potent analgesics (opioids);

• medications to treat epilepsy, pain and anxiety, such as gabapentin and pregabalin;

• sleep aids and tranquilizers (sedatives, including benzodiazepines, hypnotics, anxiolytics);

• medications to treat depression;

• medications used to treat allergies, dizziness or nausea (antihistamines or antiemetics);

• medications to treat psychiatric or mental disorders (antipsychotics that include phenothiazines and neuroleptics);

• muscle relaxants;

• medications to treat 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. Inform your doctor if you are taking:

• medications that reduce blood clotting (coumarin derivatives), the speed of clotting may increase or decrease;

• macrolide antibiotics (such as clarithromycin, erythromycin or telithromycin);

• azole antifungals (such as ketoconazole, voriconazole, itraconazole or posaconazole);

• a specific type of medication known as a protease inhibitor used to treat HIV (for example, ritonavir, indinavir, nelfinavir or saquinavir);

• cimetidine (a medication to treat stomach ulcers, indigestion or acid reflux);

• rifampicin (used to treat tuberculosis);

• carbamazepine (used to treat seizures or convulsions and certain painful conditions);

• phenytoin (used to treat seizures or convulsions);

• a medicinal plant called St. John's Wort (also known as Hypericum perforatum);

• quinidine (a medication to treat 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 may make you feel more drowsy or increase the risk of severe adverse 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, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

During pregnancy, these tablets should be avoided as much as possible. If they are used for prolonged periods during 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

Stop breastfeeding during treatment with these tablets. Oxycodone hydrochloride passes into breast milk. It is not known if naloxone hydrochloride also passes into breast milk. Therefore, the risk to the infant cannot be ruled out, especially if the mother receives several doses of Targin.

Driving and operating machinery

Targin may affect your ability to drive and operate machinery. This occurs especially at the beginning of treatment with Targin, after increasing the dose or after switching from another medication. However, these adverse effects disappear once the dose of Targin is established.

Targin has been associated with drowsiness and sudden episodes of sleep. If you experience these adverse effects, you should not drive or operate machinery. If this occurs, inform your doctor.

Ask your doctor if you can drive or operate machinery during treatment with Targin.

Targin contains lactose

This medication contains lactose (milk sugar). If your doctor has told you that you have a intolerance to certain sugars, consult with them before taking this medication.

Follow exactly the administration instructions of this medication 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 to stop taking it (see also "If you interrupt treatment with Targin").

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

You must swallow the prolonged-release tablet whole to avoid affecting the slow release of hydrochloride of oxycodone from the tablet.Do not break, crush, or chew the tablets.If you do, your body may absorb a potentially fatal dose of hydrochloride of oxycodone (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 hydrochloride of oxycodone/5 mg of hydrochloride of naloxone in prolonged-release tablets every 12 hours.

Your doctor will decide how much 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 you need to adjust the dose during treatment. Your dose will be adjusted according to your level 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 hydrochloride of oxycodone and 80 mg of hydrochloride of naloxone. If you need a higher dose, your doctor may prescribe more hydrochloride of oxycodone without hydrochloride of naloxone. However, the maximum daily dose of hydrochloride of oxycodone should not exceed 400 mg. The beneficial effect of hydrochloride of naloxone on intestinal activity may be affected if the dose of hydrochloride of oxycodone is increased without increasing the dose of hydrochloride of naloxone.

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

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

For restless legs syndrome treatment

Adults

The usual initial dose is 5 mg of hydrochloride of oxycodone/2.5 mg of hydrochloride of naloxone 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 you need to adjust the dose during treatment. Your dose will be adjusted according to your individual response. The minimum dose necessary to mitigate the symptoms of restless legs syndrome will be chosen.

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

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

For pain or restless legs syndrome treatment

Older adults

Generally, no dose adjustment is necessary in older adults with normal kidney and/or liver function.

Kidney or liver disorder

If you have any degree of kidney disorder 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. Therefore, the use of Targin in children and adolescents under 18 years is not recommended.

Administration form

Oral.

Swallow these tablets whole (without chewing them), 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

Generally, 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 must inform your doctorimmediately. Consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 91 562 04 20 indicating the medication and the amount used. It is recommended to bring the packaging and the medication leaflet to the healthcare professional.

A overdose may cause:

• pupil constriction

• slow and shallow breathing (respiratory depression)

• drowsiness to loss of consciousness

• low muscle tone (hypotonia)

• reduced heart rate

• decreased blood pressure

• a cerebral disorder (known as toxic leukoencephalopathy).

In severe cases, it may cause loss of consciousness (coma), fluid accumulation in the lungs, and circulatory collapse, 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 dose lower than prescribed, you may not notice the analgesic effect.

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

• If there are8 hours or morebefore the next normal dose: Take the forgotten prolonged-release tablet of Targin immediately, and continue with the normal schedule.

• If there areless than 8 hoursbefore the next normal dose: Take the forgotten prolonged-release tablet of Targin. Wait 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 compensate for the missed doses.

If you interrupt treatment with Targin

Do not interrupt treatment without consulting your doctor. If you no longer need 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.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Important side effects to look out for and what to do if you experience them:

If you already experience any of the following important side effects, consult your doctor immediately.

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

The following side effects have been observed in patients receiving pain treatment

Frequent (may affect up to 1 in 10 patients)

Less frequent (may affect up to 1 in 100 patients)

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

Frequency unknown (cannot be estimated from available data)

The active ingredient hydrochloride of oxycodone, if not combined with hydrochloride of naloxone, has the following side effects, different from those listed:

Oxycodone can cause respiratory problems (respiratory depression), pupil constriction, muscle cramps of the bronchial and smooth muscles, and depression of the cough reflex.

Frequent (may affect up to 1 in 10 patients)

Less frequent (may affect up to 1 in 100 patients)

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

Frequency unknown (cannot be estimated from available data)

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

Frequent (may affect up to 1 in 10 patients)

Less frequent (may affect up to 1 in 100 patients)

Frequency unknown (cannot be estimated from available data)

Reporting of side effects

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

Keep this medication out of the sight and reach of children. Store this medication in a secure and closed location where other individuals cannot access it. It can cause severe harm and be fatal to people when not prescribed.

Do not use this medication after the expiration date that appears on the box, label, and blister, after “CAD”. The expiration date is the last day of the month indicated.

Do not store above 25º C.

Store in the original packaging to protect it from light.

Only for bottles

Once opened, use within the next 6 months.

Medications should not be disposed of through drains or trash. Deposit the containers and medications you no longer need at the SIGRE collection point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medications you no longer need. By doing so, you will help protect the environment.

Composition of Targin

The active principles are hydrochloride of oxicodone and hydrochloride of naloxone.

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

The other components are:

- Tablet core: Hydroxypropylcellulose, ethylcellulose, stearic alcohol, lactose monohydrate, talc, magnesium stearate.

- Tablet coating: Partially hydrolyzed polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, aluminum lake FCF blue (E133).

Appearance of Targin and contents of the package

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

These tablets are marketed in blister packs of 10, 14, 20, 28, 30, 50, 56, 60, 98, and 100 or in a child-resistant bottle containing 100 tablets.

Only some sizes and types of packaging may be marketed.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Mundipharma Pharmaceuticals, S.L.

Bahía de Pollensa, 11

28042 Madrid

Spain

Phone: 91 3821870

Responsible for manufacturing

Mundipharma DC B.V.

Leusderend 16

3832 RC Leusden

Netherlands

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

Last review date of this prospectus: April 2025

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) ( http://www.aemps.gob.es/ )