Product Information for the User

Duoxona 5 mg/2.5 mg Extended-Release Tablets EFG

Oxycodone Hydrochloride / Naloxone Hydrochloride

Read this entire leaflet carefully before you start 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 questions, ask your doctor or pharmacist.

- This medicine has been prescribed for you only. Do 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 is Duoxona and what it is used for

2. What you need to know before starting Duoxona

3. How to take Duoxona

4. Possible side effects

5. Storage of Duoxona

6. Contents of the pack and additional information

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

These tablets are only for use in adults.

Pain relief

You have been prescribed Duoxona for the treatment of intense pain, which can only be adequately treated with opioid analgesics. Hydrochloride of naloxone is 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 Duoxona; it is a potent analgesic of the opioid group.

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

Do not take Duoxona

- 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 unable to get enough oxygen into your blood or remove 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. (e.g., as a result of COPD, see above),

- if you have severe asthma,

- if you have paralytic ileus (a type of intestinal obstruction) not caused by opioids,

- if you have moderate to severe liver disease.

Consult your doctor if you have severe upper abdominal pain that may radiate to the back, nausea, vomiting, or fever, as these may be symptoms of pancreatitis and biliary tract system inflammation.

Warnings and precautions

Consult your doctor or pharmacist before starting this medicine:

- in the case of elderly or debilitated patients (weak),

- 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 may make you feel very drowsy during the day (sleep apnea),

- if you have mixedema (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 (hypothyroidism),

- if your adrenal glands do not produce enough hormones (adrenal insufficiency or Addison's disease),

- 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 abnormal enlargement of the prostate (prostatic hypertrophy),

- if you have alcoholism or delirium tremens,

- if you have pancreatitis,

- 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 trauma (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, isocarboxazid, moclobemide, and linezolid,

- if you experience drowsiness or sudden episodes of sleep.

• Respiratory disorders related to sleep

Duoxona may 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, 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 oxygen levels in the blood, leading to 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 Duoxona than you should").

Diarrea

If you experience intense diarrhea at the beginning 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, consult your doctor.

Switching to Duoxona

If you have been receiving another opioid, you may experience withdrawal symptoms shortly after starting treatment with oxycodone/naloxone, such as restlessness, sweating, and muscle pain. If you experience any of these symptoms, you may need special monitoring by your doctor. This medicine is not suitable for the treatment of withdrawal syndrome.

Tolerability, dependence, and addiction

This medicine contains oxycodone, which is an opioid. Repeated use of opioid analgesics may make the medicine less effective (you become accustomed to it, known as tolerance). Repeated use of Duoxona may also cause dependence, abuse, and addiction, which may lead to a fatal overdose. 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 medicine you need to take or how often you need to take it. You may feel that you need to continue taking the medicine, even when it no longer helps to relieve your pain.

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

• if you or a family member has a history of alcohol, medication, or substance abuse ("addiction").
• if you smoke.
• if you have ever had problems with your mood (depression, anxiety, or personality disorder) or have received treatment from a psychiatrist for other mental health conditions.

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

• You need to take the medicine for longer than recommended by your doctor.
• You need to take more doses than recommended.
• You are using the medicine 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 medicine.
• You do not feel well when you stop taking the medicine 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 Duoxona.

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

Surgical intervention

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

Like other opioids, oxycodone may affect the normal production of hormones in the body, such as cortisol or sex hormones, especially if you 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 medicine.

You may observe remnants of the prolonged-release tablet in the stool. 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.

How to take Duoxona correctly

These tablets are not suitable for the treatment of withdrawal syndrome.

Abuse

You should never use oxycodone/naloxone if you have a substance abuse problem. If you are addicted to substances such as heroin, morphine, or methadone, you may experience severe withdrawal symptoms if you misuse Duoxona, as it contains naloxone. These symptoms may worsen existing withdrawal symptoms.

Mal use

You should never dissolve Duoxona to inject it (e.g., into a vein). The reason is that it contains talc, which may cause local tissue destruction (necrosis) and pulmonary tissue alterations (pulmonary granuloma). This abuse may also have other serious consequences and may even be fatal.

Long-term treatment

If you are administered for a long time, you may develop tolerance to oxycodone/naloxone. This means that you may need higher doses to relieve pain. Long-term administration of oxycodone/naloxone may cause physical dependence. If you stop treatment abruptly, you may experience withdrawal symptoms (restlessness, sweating, and muscle pain). If you no longer need treatment, it is recommended to gradually reduce the daily dose with the help of your doctor.

Psychological dependence

The abuse profile of oxycodone hydrochloride is similar to that of other potent opioids (strong analgesics). There is a possibility of experiencing psychological dependence. Medicines containing oxycodone hydrochloride should be used with special caution in patients with a history of alcohol, drug, or medication abuse.

Concomitant use of Duoxona with other medicines

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

The risk of adverse effects increases if you use antidepressants (such as citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, or venlafaxine). These medicines may interact with oxycodone and 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/naloxone and sedatives such as benzodiazepines or related medicines, increases the risk of drowsiness, difficulty breathing (respiratory depression), coma, and may be fatal. Therefore, concomitant use should only be considered when other treatment options are not possible.

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

Inform your doctor about all sedatives you are taking and strictly follow your doctor's dosage recommendations. It may be helpful to inform friends or family members to be aware of the mentioned symptoms. Contact your doctor when you experience these symptoms.

Some examples of sedatives or related medicines are:

• other potent analgesics (opioids);
• somnifacients and tranquilizers (sedatives, hypnotics);
• medicines used to treat depression (antidepressants);
• medicines used to treat allergies, dizziness, or nausea (antihistamines or antiemetics);
• medicines used to treat psychiatric or mental disorders (antipsychotics that include phenothiazines and neuroleptics).

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

• medicines that reduce blood clotting (coumarin derivatives), the speed of coagulation 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 medicine known as a protease inhibitor used to treat HIV (for example, ritonavir, indinavir, nelfinavir, or saquinavir);

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

• rifampicin (used to treat tuberculosis);

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

• phenytoin (used to treat seizures or convulsions);

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

• quinidine (a medicine used to treat arrhythmias).

No interactions are expected between oxycodone/naloxone and paracetamol, acetylsalicylic acid, or naltrexone.

Concomitant use of Duoxona with food, drinks, and alcohol

Drinking alcohol while taking this medicine 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 oxycodone/naloxone.

You should avoid drinking grapefruit juice while taking these tablets.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, consult your doctor or pharmacist before using this medicine.

Pregnancy

During pregnancy, these tablets should be avoided as much as 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 will be suspended 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 infant cannot be ruled out, especially if the mother receives several doses of oxycodone/naloxone.

Driving and operating machines

Duoxona may affect your ability to drive and operate machines. This occurs especially at the beginning of treatment with oxycodone/naloxone, after increasing the dose, or after switching from another medicine. However, these adverse effects disappear once the dose of this medicine is established.

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

Ask your doctor if you can drive or operate machines during treatment with Duoxona.

Duoxona contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet, which is essentially "sodium-free".

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

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

The tablet must be swallowed whole and should not be divided, broken, chewed, or crushed.

Not crushing or chewing the tablet may not harm the prolonged-release properties, but it may cause the absorption of a potentially lethal dose of hydrochloride of oxicodone (see "If you take more Duoxona than you should").

Before starting treatment and periodically during treatment, your doctor will discuss with you what you can expect from the use of Duoxona, 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 Duoxona").

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

For pain treatment

Adults

The usual initial dose is 10 mg of hydrochloride of oxicodone / 5 mg of hydrochloride of naloxone 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 dose and the evening dose. Your doctor will also decide if it is necessary to adjust the dose during treatment. Your dose will be adjusted 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 Duoxona may be higher.

The maximum daily dose is 160 mg of hydrochloride of oxicodone and 80 mg of hydrochloride of naloxone. If you need a higher dose, your doctor may prescribe more hydrochloride of oxicodone without hydrochloride of naloxone. However, the maximum daily dose of hydrochloride of oxicodone should not exceed 400 mg. The beneficial effect of hydrochloride of naloxone on intestinal activity may be affected if the dose of hydrochloride of oxicodone 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 Duoxona, you may need a rapid-acting analgesic. Duoxona is not intended as a 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 pain 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 Duoxona" and "Warnings and precautions").

Children and adolescents under 18 years

Duoxona 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 Duoxona in children and adolescents under 18 years is not recommended.

Administration form

Oral.

Take Duoxona every 12 hours, following a fixed schedule (e.g., at 8 am and 8 pm).

Swallow these tablets with sufficient liquid (half a glass of water). The tablet must be swallowed whole and should not be divided, broken, chewed, or crushed. You can take the tablets with or without food.

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 Duoxona than you should

If you have taken more tablets than prescribed, 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)

• A brain disorder (known as toxic leukoencephalopathy)

• drowsiness to loss of consciousness

• low muscle tone (hypotonia)

• reduced heart rate, and

• decreased blood pressure.

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

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

If you forgot to take Duoxona

If you forgot to take Duoxona 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 scheduled dose: Take the missed prolonged-release tablet of Duoxona immediately, and continue with the regular schedule.

• If there areless than 8 hoursbefore the next scheduled dose: Take the missed prolonged-release tablet of Duoxona. 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 Duoxona 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 Duoxona

Do not stop treatment without consulting your doctor. If you no longer need treatment, your doctor should gradually reduce your daily dose after discussing it with you. This will help prevent 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 nearest doctor immediately.

The main danger of opioid overdose is slow and shallow breathing (respiratory depression), which is especially common in elderly and weakened patients. Opioids can also cause a severe drop in blood pressure in susceptible patients.

Side effects are divided into two sections: pain treatment and treatment with the active ingredient hydrochloride oxycodone alone.

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

Frequent (may affect up to 1 in 10 patients)

• Reduced or lost appetite
• Insomnia, fatigue, or exhaustion
• Sensation of dizziness or feeling like everything is spinning
• Drowsiness
• Dizziness
• Headaches
• Abdominal pain, constipation, diarrhea, dry mouth, indigestion, nausea, discomfort, flatulence
• Headache
• Itching, skin reactions, sweating
• Sensation of weakness

Infrequent (may affect up to 1 in 100 patients)

• Allergic reactions
• Anxiety, abnormal thoughts, anxiety, confusion, depression, nervousness
• Seizures (especially in people with epilepsy or predisposition to seizures), difficulty concentrating
• Speech alteration, fainting, tremors
• Vision problems
• Sensation of chest pressure, especially if you already have coronary disease, palpitations
• Low blood pressure, high blood pressure
• Difficulty breathing, runny nose, cough
• Gas
• Increased liver enzymes, biliary colic
• Muscle cramps, muscle contractions, muscle pain
• Urgent need to urinate
• Withdrawal symptoms such as agitation, chest pain, chills, general discomfort, pain, swelling of hands, ankles, and feet
• Weight loss
• Accidents
• Decreased libido
• Lack of energy
• Thirst
• Alteration of taste

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

• Increased heart rate
• Yawns
• Dental alterations
• Weight gain
• Medication dependence

Frequency unknown (cannot be estimated from available data)

• Euphoria, hallucinations, nightmares
• Prickling sensation on the skin, severe sedation
• Respiratory problems during sleep (sleep apnea syndrome), for more information see section 2 "Warnings and precautions".
• Respiratory depression
• Belching
• Difficulty urinating
• Erectile dysfunction

It is known that the active ingredient hydrochloride oxycodone, when not combined with hydrochloride naloxone, has the following side effects, different from those listed:

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

Frequent (may affect up to 1 in 10 patients)

• Mood alteration and changes in personality (e.g., depression, feeling extremely happy), decreased activity, increased activity
• Low blood pressure
• Difficulty urinating

Infrequent (may affect up to 1 in 100 patients)

• Dehydration
• Agitation, perception disorders (e.g., hallucinations, derealization), medication dependence
• Difficulty concentrating, migraines, increased muscle tension, involuntary muscle contractions, reduced sensitivity to pain or touch, coordination anomalies
• Auditory difficulties
• Voice alterations (dysphonia)
• Difficulty swallowing, intestinal dysfunction (ileus), mouth ulcers, gingivitis
• Skin dryness
• Water retention (edema), medication tolerance
• Skin redness
• Increased concentration of sex hormones that can affect sperm production in men or menstrual cycle in women (menstruation)

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

• Infections such as herpes labial or herpes (which can cause blisters around the mouth or genital area)
• Increased appetite
• Black stools (with tar-like appearance), gingival bleeding
• Rash with itching (urticaria)

Frequency unknown (cannot be estimated from available data)

• Acute generalized allergic reactions (anaphylactic reactions)
• Problems with bile flow
• Absence of menstrual periods
• Withdrawal syndrome in newborns
• Dental caries
• Aggression
• Increased sensitivity to pain
• A problem affecting a valve in the intestine, which can cause severe abdominal pain (Oddi sphincter dysfunction).

Reporting 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 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 safe and closed place, where other people cannot access it.

It can cause serious harm and be fatal to people when not prescribed.

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

Blister:

Do not store at a temperature above 25 °C.

Medicines should not be thrown down the drains or in the trash. Dispose of the packaging 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 packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Duoxona

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 2.74 mg of hydrochloride of naloxone dihydrate, equivalent to 2.25 mg of naloxone).

The other components are:

- Tablet core: Povidone K30, polyvinyl acetate, sodium lauryl sulfate, anhydrous colloidal silica, microcrystalline cellulose, magnesium stearate.

- Tablet coating: Polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc.

Appearance of Duoxona and contents of the package

Duoxona 5 mg/2.5 mg are prolonged-release tablets of white color, round, biconvex, with a diameter of 4.7 mm and a height of 4.0 mm.

These tablets are available in child-resistant blisters of 10, 14, 20, 28, 30, 50, 56, 60, 90, 98, and 100 tablets or child-resistant bottles with a screw cap containing 50, 100, or 250 tablets.

Only some package sizes may be marketed.

Marketing authorization holder and manufacturer responsible

Marketing authorization holder

NEURAXPHARM SPAIN, S.L.U.

Avda. Barcelona, 69

08970 Sant Joan Despí

Barcelona - Spain

Manufacturer responsible

Develco Pharma GmbH

Grienmatt 42

79650 Schopfheim

Germany

or

Neuraxpharm Arzneimittel GmbH

Elisabeth-Selbert-Str. 23

40764 Langenfeld

Germany

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

Last review date of this leaflet: April 2025

"Detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/