Package Insert: Information for the User

Duoxona 40 mg/20 mg Extended-Release Tablets EFG

Oxycodone Hydrochloride / Naloxone Hydrochloride

Read this entire 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 oxycodone, hydrochloride naloxone, or any of the other components of this medication (listed in section 6),

- if you are unable to breathe in enough oxygen or remove carbon dioxide produced in the 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 pulmonary blood vessels, etc. (e.g., 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.

Warnings and precautions

Consult your doctor or pharmacist before starting this medication:

- 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 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 problems,

- if you have an abnormal enlargement of the prostate gland (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 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), for example, medications containing tranilcipromina, phenelzine, isocarboxazide, moclobemide, and linezolid,

- if you experience drowsiness or sudden episodes of sleep.

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 pancreatitis and biliary tract system inflammation.

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

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

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

Tolerance, dependence, and addiction

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

Dependence or addiction can make you feel like 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 like 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 alcohol, prescription medication, or illicit 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 medication for a longer period 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.

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.

Children and adolescents under 18 years

The safety and benefits of oxycodone/naloxone have not been established in children and adolescents under 18 years.

How to take Duoxona correctly

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 intestinal function is normalizing. This diarrhea may occur in the first 3 to 5 days of treatment. If it persists beyond that period of 3 to 5 days, or if you are concerned, contact 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 medication is not suitable for treating withdrawal syndrome.

Surgical intervention

If you need to undergo surgery, inform the doctors that you are taking oxycodone/naloxone.

Long-term treatment

If 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 treatment is suddenly stopped, withdrawal symptoms (restlessness, sweating, and menstrual pain) may appear. If treatment is no longer necessary, it is recommended to gradually reduce the daily dose with the help of your doctor.

Psychological dependence

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

Incorrect use of Duoxona

These tablets are not suitable for treating withdrawal syndrome.

The tablet should not be divided, but it should not be crushed, chewed, or crushed.

To avoid damaging the properties of the prolonged-release tablet, it should not be crushed or chewed, as this may cause the absorption of a potentially lethal dose of hydrochloride oxycodone (see “If you take more Duoxona than you should”).

Abuse

It should never be used 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, as it contains naloxone. These symptoms may worsen existing withdrawal symptoms.

Abuse

Do not dissolve Duoxona at any time, to inject it (e.g., into a blood vessel). 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 even cause death.

Doping

Athletes should know that the use of this medication may result in positive test results in antidoping controls. The use of oxycodone/naloxone as a doping agent may put your health at risk.

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 concomitant use of oxycodone/naloxone and 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 oxycodone/naloxone along 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 signs and symptoms. Contact your doctor when you experience these symptoms.

The effect of oxycodone/naloxone and other medications may be altered by the concomitant use of these tablets and other medications. Inform your doctor if you are taking:

• other potent analgesics (opioids);

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

• medications used to treat depression;

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

• medications used to treat mental or psychiatric disorders (antipsychotics, including phenothiazines and neuroleptics).

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

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

• a specific type of medication known as a protease inhibitor used to treat HIV (e.g., 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 conditions);

• 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 oxycodone/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 oxycodone/naloxone.

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 for prolonged periods during pregnancy, hydrochloride oxycodone may cause withdrawal symptoms in the newborn. If hydrochloride oxycodone is administered during delivery, the newborn may experience respiratory depression (slow and shallow breathing).

Breastfeeding

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

Driving and operating machinery

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

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

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

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 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.

Renal 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). 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)

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

Side effects are subdivided into two sections: pain treatment and treatment with the active ingredient hydrochloride of oxicodone 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", headache,
• Somnolence
• Dizziness
• Headaches
• Abdominal pain, constipation, diarrhea, dry mouth, indigestion, nausea, discomfort, flatulence (gas)
• Itching skin, skin reactions/eruptions, sweating
• Sensation of weakness

Infrequent (may affect up to 1 in 100 patients)

• Allergic reactions/hypersensitivity
• Anxiety, abnormal thoughts, anxiety, confusion, depression, nervousness.
• Seizures (especially in people with epilepsy or predisposition to seizures), difficulty concentrating
• Speech alteration, fainting, tremors
• Vision disorder
• Sensation of chest oppression, especially if you already have coronary disease, palpitations
• Decreased blood pressure, increased blood pressure
• Difficulty breathing, runny nose, cough.
• Flatulence
• Increased liver enzymes, biliary colic
• Muscle cramps, involuntary muscle contractions, muscle pain
• Urgent need to urinate
• Abstinence symptoms such as agitation, chest pain, chills, general feeling of 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

Unknown frequency (cannot be estimated from available data)

• Euphoria
• Prickling sensation on the skin, severe sedation
• Respiratory depression
• Belching
• Difficulty urinating
• Erectile dysfunction

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

Oxicodone can cause respiratory problems (respiratory depression), pupil constriction, muscle cramps of the bronchial muscles 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
• Constipation
• Difficulty urinating

Infrequent (may affect up to 1 in 100 patients)

• Dehydration
• Agitation, perception disorders (e.g. hallucinations, derealization), dependence on the medication
• Difficulty concentrating, migraines, increased muscle tension, involuntary muscle contractions, reduced sensitivity to pain or touch, coordination anomalies
• Auditory difficulties
• Voice alteration (dysphonia)
• Difficulty swallowing, intestinal dysfunction (ileus), oral ulcers, gingivitis
• Skin dryness
• Water retention (edema), tolerance to the medication
• 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)

• Herpes simplex
• Increased appetite
• Black stools (with tar-like appearance), gingival bleeding
• Itching eruption (urticaria)

Unknown frequency (cannot be estimated from available data)

• Generalized anaphylactic reactions
• Problems with bile flow
• Amenorrhea
• Abstinence syndrome in newborns
• Dental caries
• Aggression
• Increased sensitivity to pain
• Sleep apnea (respiratory interruptions during sleep)
• A problem affecting an intestinal valve, 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 prospectus. 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 medication.

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

Store this medication in a safe 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, 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. Deposit containers and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of containers 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 40 mg of hydrochloride of oxicodone (equivalent to 36 mg of oxicodone) and 20 mg of hydrochloride of naloxone (as 21.8 mg of hydrochloride of naloxone dihydrate, equivalent to 18 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), iron oxide red (E172), macrogol 3350, talc.

Appearance of Duoxona and contents of the package

Duoxona 40 mg/20 mg are prolonged-release tablets of pink color, oblong and biconvex with breaking lines on both sides, with a length of 14.2 mm, a width of 6.7 mm and a height of 5.0 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 child-resistant that contain 50, 100 or 250 tablets.

Only some package sizes may be marketed.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

NEURAXPHARM SPAIN, S.L.U.

Avda. Barcelona, 69

08970 sant Joan Despí

Barcelona - Spain

Responsible for manufacturing

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/