DUOXONA 40 MG/20 MG PROLONGED-RELEASE TABLETS

Introduction

Package Leaflet: Information for the User

Duoxona 40 mg/20 mg prolonged-release tablets EFG

Oxycodone hydrochloride / Naloxone hydrochloride

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Duoxona and what is it used for

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

These tablets are for use in adults only.

Pain relief

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

How these tablets work for pain relief

These tablets contain oxycodone hydrochloride and naloxone hydrochloride as active substances. Oxycodone hydrochloride is responsible for the analgesic effect of Duoxona; it is a potent analgesic from the opioid group.

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

2. What you need to know before you take Duoxona

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 your breathing is not sufficient to provide enough oxygen to the blood or to remove the carbon dioxide produced by the body (respiratory depression),
• if you have severe lung disease associated with narrowing of the airways (chronic obstructive pulmonary disease or COPD),
• if you have a condition known as cor pulmonale. This condition consists of the right side of the heart becoming enlarged due to increased pressure inside the blood vessels of the lungs, 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

Tell your doctor or pharmacist before you start taking this medicine:

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

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

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

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

Tell 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 medicine contains oxycodone, which is an opioid medicine. Repeated use of opioid analgesics may lead to tolerance (you may need to take more to achieve the same level of pain relief) and physical dependence. The risk of these side effects may increase with higher doses and longer treatment duration.

Dependence or addiction can make you feel that you no longer have control over the amount of medicine you need to take or how often you need to take it. You may feel that you need to keep taking the medicine even when it no longer helps with 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 have a history of abuse or dependence on alcohol, prescription medicines, or illegal substances (“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 diseases.

If you notice any of the following signs while taking Duoxona, it could be a sign thatyou 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, e.g. “to feel calm” or “to help you sleep”.
• You have made repeated 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 discuss the best treatment for you, including when it is appropriate to stop taking it and how to do so safely (see section 3, If you stop taking Duoxona).

Breathing difficulties related to sleep

Duoxona may cause breathing difficulties related to sleep, such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). Symptoms may include pauses in breathing during sleep, nighttime awakenings due to difficulty breathing, difficulty staying asleep, or excessive daytime sleepiness. If you or someone else observes these symptoms, consult your doctor. Your doctor may consider reducing the dose.

Children and adolescents under 18 years

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

How to take Duoxona correctly

Diarrhea

If you experience severe diarrhea at the start of treatment, it may be due to the effect of naloxone. It may be a sign that bowel function is returning to normal. This diarrhea may occur in the first 3 to 5 days of treatment. If it persists beyond this period 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, e.g. 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.

Surgery

If you need to undergo surgery, tell 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 you may need higher doses to achieve pain relief. Long-term administration of oxycodone/naloxone may lead to physical dependence. If treatment is stopped suddenly, withdrawal symptoms (restlessness, sweating, and muscle pain) may occur. 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 oxycodone hydrochloride alone is similar to that of other potent opioids (strong painkillers). There is a possibility of psychological dependence. Medicines containing oxycodone hydrochloride should be used with special caution in patients with a history of alcohol, drug, or medicine abuse.

Incorrect use of Duoxona

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

The tablet can be divided, but it must not be broken, chewed, or crushed.

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

Abuse

Oxycodone/naloxone should never be used if you are addicted to substances such as heroin, morphine, or methadone, as it may cause severe withdrawal symptoms, since it contains naloxone. It may worsen pre-existing withdrawal symptoms.

Abuse

Duoxona should never be dissolved for injection (e.g. into a blood vessel). The reason is that it contains talc, which can cause local tissue destruction (necrosis) and changes in lung tissue (pulmonary granuloma). This abuse can also have other serious consequences and even be fatal.

Doping

Athletes should be aware that the use of this medicine may result in positive doping tests. The use of oxycodone/naloxone as a doping agent can endanger health.

Taking Duoxona with other medicines

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

Concomitant use of oxycodone/naloxone and sedative medicines such as benzodiazepines or related medicines increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and can be life-threatening. Therefore, concomitant use should only be considered when other treatment options are not possible.

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

Tell your doctor about all sedative medicines you are taking and strictly follow your doctor's dosage recommendations. It may be useful to inform friends or family members to be aware of the signs and symptoms mentioned above. Contact your doctor when you experience such symptoms.

Concomitant use of these tablets and other medicines may alter the effect of oxycodone/naloxone and the other medicines. Tell your doctor if you are taking:

• other potent painkillers (opioids);
• sleeping pills and sedatives (sedatives, including benzodiazepines, hypnotics, anxiolytics);
• medicines for treating depression;
• medicines used to treat allergies, nausea, or vomiting (antihistamines or antiemetics);
• medicines used to treat psychiatric or mental disorders (antipsychotics, including phenothiazines and neuroleptics);
• medicines that reduce blood clotting (coumarin derivatives), may increase or decrease blood clotting speed;
• macrolide antibiotics (such as clarithromycin, erythromycin, or telithromycin);
• azole-type antifungal agents (such as ketoconazole, voriconazole, itraconazole, or posaconazole);
• a specific type of medicine known as a protease inhibitor used to treat HIV (e.g. ritonavir, indinavir, nelfinavir, or saquinavir);
• cimetidine (a medicine used to treat stomach ulcers, indigestion, or heartburn);
• rifampicin (used to treat tuberculosis);
• carbamazepine (used to treat seizures or certain painful conditions);
• phenytoin (used to treat seizures);
• a herbal medicine 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.

Taking Duoxona with food, drinks, and alcohol

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

You should avoid drinking grapefruit juice while taking these tablets.

Pregnancy and breastfeeding

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

Pregnancy

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

Breastfeeding

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

Driving and using machines

Duoxona may affect your ability to drive and use machines. This is especially true at the start of treatment with oxycodone/naloxone, after a dose increase, or after switching from another medicine. However, these side effects disappear once the dose of this medicine is established.

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

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

3. How to take Duoxona

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

Duoxona is a prolonged-release tablet, which means 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 oxycodone hydrochloride (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 using 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 stop taking Duoxona").

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

For pain treatment

Adults

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

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

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

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

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

For pain treatment

Elderly patients

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

Liver or kidney disorder

If you have kidney disorder of any degree or mild liver disorder, your doctor will prescribe these tablets with special caution. If you have moderate or severe liver disorder, you should not take these tablets (see also section 2 "Do not take 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. For this reason, the use of Duoxona is not recommended in children and adolescents under 18 years.

Method of administration

Oral route.

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

Swallow these tablets with enough 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

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

If you take more Duoxona than you should

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

An overdose can cause:

• contraction of the pupils
• slow and shallow breathing (respiratory depression)
  • a brain disorder (known as toxic leukoencephalopathy).

• drowsiness up to loss of consciousness
• low muscle tone (hypotonia)
• reduction in heart rate, and
• decrease in blood pressure.

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

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

If you forget to take Duoxona

If you forget to take Duoxona or if you take a lower dose than prescribed, you may not notice the analgesic effect.

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

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

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

If you stop taking 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.

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone experiences them.

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

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

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 significant decrease in blood pressure in susceptible patients.

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

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

Frequent (may affect up to 1 in 10 patients)

• reduced or lost appetite
• insomnia, fatigue, or exhaustion
• feeling of dizziness or "spinning", headache,
• drowsiness
• vertigo
• hot flashes
• abdominal pain, constipation, diarrhea, dry mouth, indigestion, vomiting (nausea), discomfort, flatulence (gas)
• itching, skin reactions/rashes, sweating
• feeling of weakness

Uncommon (may affect up to 1 in 100 patients)

• allergic/hypersensitivity reactions
• restlessness, abnormal thoughts, anxiety, confusion, depression, nervousness.
• seizures (especially in people with seizure disorders or predisposition to convulsions), difficulty concentrating
• speech disorders, fainting, tremors
• vision disorders
• feeling of chest tightness, especially if you already have coronary heart disease, palpitations
• decrease in blood pressure, increase in blood pressure
• breathing difficulties, runny nose, cough.
• bloating
• increased liver enzymes, biliary colic
• muscle cramps, muscle contractions, muscle pain
• increased need to urinate
• withdrawal symptoms such as restlessness, chest pain, chills, feeling of general discomfort, pain, swelling of hands, ankles, and feet
• weight loss
• accidental injuries
• decreased sexual desire
• lack of energy
• thirst
• taste disorders

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

• increased heart rate
• yawning
• dental disorders
• weight gain

Frequency not known (cannot be estimated from available data)

• euphoria
• tingling sensation, severe sedation
• respiratory depression
• belching
• difficulty urinating
• erectile dysfunction

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

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

Frequent (may affect up to 1 in 10 patients)

• mood changes and personality changes (e.g., depression, feeling of extreme happiness), decreased activity, increased activity
• hypo
• difficulty urinating

Uncommon (may affect up to 1 in 100 patients)

• dehydration
• agitation, perception disorders (e.g., hallucinations, derealization), drug dependence
• difficulty concentrating, migraines, increased muscle tension, involuntary muscle contractions, reduced pain or touch sensitivity, coordination disorders
• hearing difficulties
• voice disorders (dysphonia)
• difficulty swallowing, intestinal dysfunction (ileus), mouth ulcers, gingivitis
• dry skin
• water retention (edema), drug tolerance
• skin redness
• increased sex hormone levels, which 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 a tar-like appearance), gum bleeding
• itchy rash (urticaria)

Frequency not known (cannot be estimated from available data)

• acute generalized allergic reactions (anaphylactic reactions)
• bile flow problems
• absence of menstrual periods
• withdrawal syndrome in newborns
• dental caries
• aggression
• increased pain sensitivity
• sleep apnea (interruptions of breathing during sleep)
• a problem affecting a valve in the intestine, which can cause severe abdominal pain (sphincter of Oddi dysfunction).

Reporting side effects

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

5. Storage of Duoxona

Keep this medication out of sight and reach of children.

Store this medication in a safe and closed place, where others cannot access it. It can cause serious harm and be fatal to people who have not been prescribed it.

Do not use this medication after the expiration date shown on the box or blister pack, after "EXP". The expiration date is the last day of the month indicated.

Blister pack:

Do not store above 25°C.

Medications should not be disposed of through wastewater or household waste. Deposit the packaging and medications you no longer need at the SIGRE collection point in the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Package contents and additional information

Duoxona composition

The active ingredients are oxycodone hydrochloride and naloxone hydrochloride.

Each prolonged-release tablet contains 40 mg of oxycodone hydrochloride (equivalent to 36 mg of oxycodone) and 20 mg of naloxone hydrochloride (as 21.8 mg of naloxone hydrochloride dihydrate, equivalent to 18 mg of naloxone).

The other ingredients are:

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

• Tablet coating: Polyvinyl alcohol, titanium dioxide (E171), red iron oxide (E172), macrogol 3350, talc.

Appearance of Duoxona and package contents

Duoxona 40 mg/20 mg are prolonged-release tablets, pink, oblong, and biconvex with break 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 blister packs of 10, 14, 20, 28, 30, 50, 56, 60, 90, 98, and 100 tablets or screw-cap bottles with child-resistant caps containing 50, 100, or 250 tablets.

Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

NEURAXPHARM SPAIN, S.L.U.

Avda. Barcelona, 69

08970 Sant Joan Despí

Barcelona - Spain

Manufacturer

Develco Pharma GmbH

Grienmatt 42

79650 Schopfheim

Germany

or

Neuraxpharm Arzneimittel GmbH

Elisabeth-Selbert-Str. 23

40764 Langenfeld

Germany

or

Saneca Pharmaceuticals A.S.

Nitrianska 100, Slovakia-920 27 Hlohovec

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

Date of last revision of this leaflet: April 2025

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