Package Insert: Information for the User

Duoxona 30 mg/15 mg Extended-Release Tablets EFG

Oxycodone Hydrochloride / Naloxone Hydrochloride

Read this package insert carefully before starting to take this medication, as it contains important information for you.

- Keep this package insert, as you may need to refer to it again.

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

- This medication has been prescribed only for you, and you should not give it to others who may have the same symptoms as you, as it may harm them.

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

1. What is Duoxona and how is it used

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

3. How to take Duoxona

4. Possible adverse effects

5. Storage of Duoxona

6. Contents of the package 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 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 hydrochloride of oxicodone, hydrochloride of naloxone or any of the other components of this medication (listed in section 6),

- if you are unable to breathe in enough oxygen into your blood or remove the carbon dioxide produced in 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 consists of the right side of the heart increasing in size due to the increase in pressure inside the blood vessels of the lung, etc. (for example, 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 extend to the back, nausea, vomiting or fever, as these may be symptoms associated with inflammation of the pancreas (pancreatitis) and the biliary tract system.

Warnings and precautions

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

- 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 disease 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 any mental illness accompanied by a loss (partial) of reality (psychosis), due to alcoholism or intoxication by other substances (substance-induced psychosis),

- if you have gallstones problems,

- 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 any 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 last 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

Duoxona may cause respiratory disorders related to sleep such as sleep apnea (pause 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.

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

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

Do not break, chew or crush the tablets. Taking them broken, chewed or crushed may lead to potentially fatal absorption of hydrochloride of oxicodone (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 oxicodone/naloxone, for example, restlessness, sweating and muscle pain. If you experience any of these symptoms, you may need special monitoring by your doctor. This medication is not suitable for the treatment of withdrawal syndrome.

Tolerance, dependence and addiction

This medication contains oxicodone, 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 Duoxona may also cause dependence, abuse and addiction, which may lead to a overdose that puts your life at risk. The risk of these adverse effects may increase with a higher dose and a 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.

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

• 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 illnesses.

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 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 Duoxona.

Tell 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, oxicodone 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 medication may increase your sensitivity to pain, especially at high doses. Tell 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 (hydrochloride of oxicodone and hydrochloride of naloxone) 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 must never use oxicodone/naloxone if you have any addiction. If you are addicted to substances such as heroin, morphine or methadone, you may experience severe withdrawal symptoms if you misuse Duoxona, because it contains naloxone. These symptoms may worsen existing withdrawal symptoms.

Mal use

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

Long-term treatment

If you are administered for a long time, you may develop tolerance to oxicodone/naloxone. This means that you may need higher doses to relieve pain. Long-term administration of oxicodone/naloxone may cause physical dependence. If you suddenly stop treatment, 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 profile of abuse of hydrochloride of oxicodone is similar to that of other potent opioids (strong analgesics). There is a possibility of experiencing psychological dependence. Medications containing hydrochloride of oxicodone should be used with special care in patients with a history of abuse of alcohol, drugs or medications.

Taking Duoxona 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 oxicodone and you may experience symptoms such as involuntary and rhythmic muscle contractions, including those that control eye movements, 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 oxicodone/naloxone and sedative medications such as benzodiazepines or related medications, increases the risk of drowsiness, difficulty breathing (respiratory depression), coma and may put your life at risk. Due to this, concomitant use should only be considered when other treatment options are not possible.

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

Inform your doctor about all sedative medications 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 sedative medications or related medications are:

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

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 the ability of the blood to coagulate (cumarinic derivatives), the speed of coagulation may increase or decrease;

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

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

• cimetidine (a medication 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 medication used to treat arrhythmias).

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

Taking Duoxona with food, drinks and alcohol

Drinking alcohol while taking this medication 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 oxicodone/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 medication.

Pregnancy

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

Breastfeeding

Breastfeeding will be suspended during treatment with these tablets. Hydrochloride of oxicodone passes into breast milk. It is not known if hydrochloride of naloxone also passes into breast milk. Therefore, the risk to the infant cannot be ruled out, especially if the mother receives several doses of oxicodone/naloxone.

Driving and operating machinery

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

Oxicodone/naloxone 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, you should inform your doctor.

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

Duoxona contains sodium

This medication 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 can be divided, but it should not be broken, chewed, or crushed.

To avoid damaging the prolonged-release properties of the tablet, it should not be crushed or chewed, as this 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 and evening doses. Your doctor will also decide if the dose needs to be adjusted 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 suitable for this purpose. Discuss this with your doctor.

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

For pain treatment

Older patients

Generally, no dose adjustment is necessary in older patients 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 can be divided into equal doses. Do not break, crush, or chew the tablets. 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 normal dose: Take the forgotten prolonged-release tablet of Duoxona immediately, and continue with the normal schedule.

• If there areless than 8 hoursbefore the next normal dose: Take the forgotten 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 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.

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

Important side effects you should 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). This is especially common in elderly and weakened patients. Opioids can also cause a severe drop in blood pressure in susceptible patients.

Side effects are subdivided 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

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

• Allergic reactions
• Anxiety, abnormal thoughts, anxiety, confusion, depression, nervousness
• Seizures (especially in people with epilepsy or a predisposition to seizures), difficulty concentrating
• Speech alteration, fainting, tremors
• Vision problems
• Sensation of chest pressure, especially if you already have coronary disease, palpitations
• Drop in blood pressure, increase in 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

Unknown frequency (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 of the bronchial and smooth muscles, 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
• Hypo
• Difficulty urinating

Less frequent (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 labialis 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)

Unknown frequency (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
• Sleep apnea (interrupted breathing during sleep)
• 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 not listed 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 location, where other people cannot access it. It may cause severe harm and be fatal to individuals 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.

Medications should not be disposed of through drains or trash. Dispose of packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If unsure, ask your pharmacist how to dispose of packaging and medications you no longer need. This will help protect the environment.

Composition of Duoxona

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

Each prolonged-release tablet contains 30 mg of hydrochloride of oxicodone (equivalent to 27 mg of oxicodone) and 15 mg of hydrochloride of naloxone (as 16.35 mg of hydrochloride of naloxone dihydrate, equivalent to 13.5 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), yellow iron oxide (E172), macrogol 3350, talc.

Appearance of Duoxona and contents of the package

Duoxona 30 mg/15 mg are prolonged-release tablets of yellow color, oblong and biconvex with breaking lines on both sides, with a length of 12.2 mm, a width of 5.7 mm and a height of 4.0 mm. The tablet can be divided into equal doses.

These tablets are available in child-resistant blisters of 10, 14, 20, 28, 30, 50, 56, 60, 90, 98 and 100 tablets or bottles with screw cap and child-resistant closure 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 medicine 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 medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/