OXYCODONE/NALOXONE KRKA 20 mg/10 mg PROLONGED-RELEASE TABLETS

2. What you need to know before you take Oxicodona/Naloxona Krka

Do not take Oxicodona/Naloxona Krka

• 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 too weak to take in enough oxygen or remove carbon dioxide from your 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 bowel 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 Oxicodona/Naloxona Krka:

• if you are elderly or debilitated (weak);
• if you have paralytic ileus (a type of bowel obstruction) caused by opioids;
• if you have kidney disease;
• if you have mild liver disease;
• if you have severe lung disease (i.e. reduced breathing capacity);
• if you have a disease characterized by frequent pauses in breathing during sleep, which can make you feel very sleepy during the day (sleep apnea);
• if you have myxedema (a thyroid disorder characterized by dryness, cooling, and swelling of the skin, affecting the face and extremities);
• 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 illness accompanied by a loss (partial) of contact with reality (psychosis), due to alcoholism or intoxication with other substances (substance-induced psychosis);
• if you have gallstones, or if you have any other biliary tract disorder (disease affecting the bile ducts, gallbladder, etc.);
• if you have an abnormal increase in the size of the prostate (prostate hyperplasia);
• 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 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 taking MAO inhibitors (used to treat depression or Parkinson's disease), or have taken this type of medicine in the last two weeks, e.g. medicines containing tranylcypromine, phenelzine, isocarboxazid, moclobemide, and linezolid);
• if you feel drowsy or if you sometimes fall asleep suddenly.

Breathing-related sleep disorders

Oxicodona/naloxona may cause breathing-related sleep disorders 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 sleepiness during the day. If you or someone else notices 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, tell your doctor if you develop any of the disorders described above during treatment with this medicine.

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

Swallow the prolonged-release tablet whole, so that the slow release of oxycodone hydrochloride from the prolonged-release tablet is not affected. Do not divide, chew, or crush the tablets. Taking them divided, chewed, or crushed can lead to a potentially fatal absorption of oxycodone hydrochloride (see section 3 “If you take more Oxicodona/Naloxona Krka than you should”).

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 after this 3 to 5-day period, or if you are concerned, contact your doctor.

If you have been receiving another opioid, you may experience withdrawal symptoms shortly after starting treatment with oxicodona/naloxona, e.g. restlessness, sweating, and muscle pain. If you experience any of these symptoms, you may need special monitoring by your doctor.

Tolerance, dependence, and addiction

This medicine contains oxycodone, which is an opioid medicine. Repeated use of opioid analgesics may make the medicine less effective (you get used to it, which is known as tolerance). Repeated use of oxicodona/naloxona can also lead to dependence, abuse, and addiction, which can lead to a life-threatening overdose.

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 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 oxicodona/naloxona if:

• you or a family member have a history of abuse or dependence on alcohol, prescription medicines, or illegal drugs (“addiction”).
• you are a smoker.
• you have ever had problems with your mood (depression, anxiety, or personality disorder) or have received psychiatric treatment for other mental health diseases.

If you notice any of the following signs while taking oxicodona/naloxona, 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, e.g. “to calm down” 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 the medicine 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 Oxicodona/Naloxona Krka”).

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 or biliary tract disease.

Tell your doctor if you have cancer associated with peritoneal metastases or the onset of bowel obstruction in advanced digestive or pelvic cancer.

If you need to undergo surgery, inform your doctor that you are taking oxicodona/naloxona.

Like other opioids, oxycodone can affect the normal production of hormones in the body, such as cortisol or sex hormones, especially if you have taken high doses for a long time. If you experience persistent symptoms such as feeling or being sick (including vomiting), loss of appetite, tiredness, weakness, dizziness, changes in menstrual cycle, impotence, infertility, or decreased sexual desire, talk to your doctor as they should check your hormone levels.

This medicine may increase your sensitivity to pain, especially at high doses. Tell your doctor if this happens. It may be necessary to reduce the dose or change the medicine.

You may notice remains of the prolonged-release tablet in your stools. Do not be alarmed, as the active substances (oxycodone hydrochloride and naloxone hydrochloride) will have already been released earlier in your stomach and intestine and absorbed by your body.

Incorrect use of Oxicodona/Naloxona Krka

This medicine is not suitable for withdrawal treatment.

Never misuse this medicine, especially if you have a history of drug addiction. If you are addicted to substances such as heroin, morphine, or methadone, you may experience severe withdrawal symptoms if you misuse this medicine due to its naloxone content. It may worsen pre-existing withdrawal symptoms.

Never misuse this medicine by dissolving it to inject it (e.g. into a blood vessel). The reason is that it contains talc, which can cause local tissue destruction (necrosis) and lung tissue changes (pulmonary granuloma). This misuse can also have other serious consequences that can be fatal.

The use of oxicodona/naloxona may result in positive doping tests.

The use of oxicodona/naloxona as a doping agent can endanger health.

Other medicines and Oxicodona/Naloxona Krka

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

The risk of side effects increases if you use antidepressants (such as citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine). These medicines may interact with oxycodone and symptoms such as involuntary muscle contractions, agitation, excessive sweating, tremors, exaggerated reflexes, increased muscle tension, and body temperature above 38 °C may occur. Contact your doctor if you experience these symptoms.

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

However, if your doctor prescribes oxicodona/naloxona 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 follow the recommended doses carefully. It may be useful to inform friends or family members who are aware of the signs and symptoms mentioned above. Contact your doctor when you experience these symptoms. Some examples of sedative medicines or related medicines are:

• other potent analgesics (opioids);
• medicines for treating epilepsy, pain, and anxiety such as gabapentin and pregabalin;
• sleeping pills and tranquilizers (sedatives, including benzodiazepines, hypnotics, anxiolytics);
• medicines for treating depression;
• medicines used to treat allergies, dizziness, or nausea (antihistamines or antiemetics);
• medicines for treating psychiatric or mental disorders (antipsychotics including phenothiazines and neuroleptics);
• muscle relaxants;
• medicines for treating Parkinson's disease.

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

• medicines that reduce blood clotting (coumarin derivatives), the blood clotting speed may increase or decrease;
• 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 for treating stomach ulcers, indigestion, or heartburn);
• rifampicin (used to treat tuberculosis);
• carbamazepine (used to treat seizures or certain painful diseases);
• phenytoin (used to treat seizures or certain painful diseases);
• a herbal medicine called St. John's Wort (also known as Hypericum perforatum);
• quinidine (a medicine for treating arrhythmias).

No interactions are expected between oxicodona/naloxona and paracetamol, acetylsalicylic acid, or naltrexone.

Taking Oxicodona/Naloxona Krka with food, drinks, and alcohol

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

Avoid drinking grapefruit juice while taking this medicine.

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

This medicine should be avoided during pregnancy if 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 should be discontinued during treatment with this medicine. Oxycodone hydrochloride passes into breast milk. It is not known if naloxone hydrochloride also passes into breast milk. Therefore, the risk to the breastfed child cannot be excluded, especially if the mother receives multiple doses of oxicodona/naloxona.

Driving and using machines

Oxicodona/naloxona may affect your ability to drive or use machines. This occurs more frequently at the start of treatment with oxicodona/naloxona, after a dose increase, or when switching from another treatment. However, these side effects should disappear once the dose of oxicodona/naloxona is established.

This medicine has been associated with drowsiness and sudden sleep episodes. If you experience this side effect, do not drive or operate machinery. Tell your doctor if this happens to you.

Ask your doctor if you can drive or use machines.

Oxicodona/Naloxona Krka contains lactose

This medicine contains lactose (milk sugar). If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Oxicodona/Naloxona Krka

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

Before starting treatment and periodically during treatment, your doctor will discuss with you what you can expect from the use of Oxicodona/Naloxona Krka, when and for how long you should take it, when to contact your doctor, and when you should stop taking it (see also "If you stop treatment with Oxicodona/Naloxona Krka").

Oxicodona/Naloxona Krka is a prolonged-release tablet, which means that the active ingredients are released over a prolonged period of time. Its action lasts 12 hours.

You must swallow the prolonged-release tablet whole to avoid affecting the slow release of oxicodone hydrochloride from the prolonged-release tablet. Do not break, crush, or chew the tablets. If you take it broken, crushed, or chewed, your body may absorb a potentially fatal dose of oxicodone hydrochloride (see section 3 "If you take more Oxicodona/Naloxona Krka than you should").

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

Pain treatment

Adults

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

Your doctor will decide the amount you should take per day and how to divide it between the morning and evening/night 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 Oxicodona/Naloxona Krka may be higher.

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

If you replace this medication with another opioid analgesic, it is likely that your intestinal function will worsen.

If you experience pain between two doses of oxicodona/naloxona, you may need a fast-acting analgesic. Oxicodona/naloxona is not suitable for treatment in this case. Consult your doctor or pharmacist.

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

Elderly patients

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

Liver or kidney disorders

If you have kidney disorder of any degree or mild liver disorder, your doctor will prescribe this medication with special caution. If you have moderate or severe liver disorder, you should not take this medication (see also section 2 "Do not take Oxicodona/Naloxona Krka" and "Warnings and precautions").

Children and adolescents under 18 years

Oxicodona/naloxona has not been studied in children and adolescents under 18 years. Its safety and efficacy have not been established in these patients. For this reason, the use of oxicodona/naloxona is not recommended in children and adolescents under 18 years.

Method of administration

Oxicodona/Naloxona Krka is for oral use.

Swallow these tablets whole (without chewing), with sufficient liquid (half a glass of water). You can take these prolonged-release tablets with or without food. Take these tablets every 12 hours, following a fixed schedule (e.g., at 8 am and 8 pm). Do not break, chew, or crush the prolonged-release tablets (see section 2 "Warnings and precautions").

Only for single-dose blister pack, pre-cut, child-resistant:

Oxicodona/Naloxona Krka is provided in a single-dose blister pack, pre-cut, child-resistant. Remove a prolonged-release tablet from the package as follows:

1. Hold the blister by the sides and separate an individual wrapper from the rest along the perforations.
2. Pull the aluminum edge and pull it out completely.
3. Drop the tablet into your hand.
4. Swallow the prolonged-release tablet whole with sufficient liquid, with or without food.

Duration of use

In general, you should not take this medication for longer than necessary. If it is administered for a long time, your doctor should regularly check that you still need this medication.

If you take more Oxicodona/Naloxona Krka than you should

If you have taken more oxicodona/naloxona than prescribed, you should inform your doctor immediately. You can also contact the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount used.

An overdose can cause:

• constricted pupils;
• slow and shallow breathing (respiratory depression);
• drowsiness leading to loss of consciousness;
• low muscle tone (hypotonia);
• reduced heart rate;
• decreased blood pressure;
• a brain disorder (known as toxic leukoencephalopathy).

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 Oxicodona/Naloxona Krka

Or if you take a lower dose than prescribed, you may not notice any effect.

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

• If there are 8 hours or more left before the next scheduled dose: take the missed dose immediately, and continue with the scheduled plan.
• If you forgot to take your dose and there are less than 8 hours left before the next scheduled dose: take the missed dose and wait another 8 hours before taking the next dose. Try to recover the original plan (e.g., 8 am and 8 pm).

Do not take more than once in an 8-hour period.

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

If you stop treatment with Oxicodona/Naloxona Krka

Do not stop treatment without consulting your doctor.

If you no longer need to continue treatment, you should gradually reduce the daily dose after consulting 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 will experience them.

Important side effects to which you should pay attention, and what to do if you experience them:

If you experience 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.

The following side effects were observed in patients treated for pain

Frequent(may affect up to 1 in 10 people)

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

Uncommon(may affect up to 1 in 100 people)

• meteorism
• anomalous thoughts
• anxiety
• confusion
• depression
• nervousness
• feeling of chest pressure, especially if you already have coronary heart disease
• decreased blood pressure
• withdrawal symptoms, such as agitation
• fainting
• lack of energy
• thirst
• taste alteration
• palpitations
• biliary colic
• chest pain
• feeling of general malaise
• pain
• swelling of hands, ankles, or feet
• difficulty concentrating
• speech alteration
• tremor
• breathing difficulties
• restlessness
• chills
• increased liver enzymes
• increased blood pressure
• reduced sexual desire
• rhinorrhea
• cough
• hypersensitivity/allergic reactions
• weight loss
• accidental injuries
• increased urination urgency
• muscle cramps
• muscle contractions
• muscle pain
• vision disorders
• seizures (especially in people with seizure disorders or predisposition to convulsions)

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

• increased heart rate
• drug dependence
• dental alterations
• weight gain
• yawning

Frequency not known(frequency cannot be estimated from available data)

• aggression
• euphoric mood
• severe sedation
• erectile dysfunction
• nightmares
• hallucinations
• respiratory depression
• difficulty urinating
• tingling sensation on the skin (tingling)
• belching
• sleep apnea (interruptions of breathing during sleep)

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

Oxicodone 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 people)

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

Uncommon(may affect up to 1 in 100 people)

• difficulty concentrating
• migraines
• increased muscle tension
• involuntary muscle contractions
• a condition in which the intestine stops functioning properly (ileus)
• dry skin
• drug tolerance
• reduced sensitivity to pain or touch
• coordination disorders
• voice alterations (dysphonia)
• fluid retention
• hearing difficulties
• mouth ulcers
• difficulty swallowing
• gum pain
• perception disorders (e.g., hallucinations, derealization)
• skin redness
• dehydration
• agitation
• a decrease in sex hormone levels that can affect sperm production in men or the menstrual cycle in women

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

• urticaria (hives)
• infections such as herpes labialis or herpes (which can cause blisters around the mouth or genital area)
• increased appetite
• black stools (with a tar-like appearance)
• gum bleeding

Frequency not known(frequency cannot be estimated from available data)

• acute generalized allergic reactions (anaphylactic reactions)
• increased sensitivity to pain
• absence of menstrual periods
• withdrawal symptoms in the newborn
• biliary flow problems: a problem that affects a valve in the intestine, which can cause severe abdominal pain (sphincter of Oddi dysfunction)
• dental caries

Reporting of side effects

If you experience any side effects, 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 Medicines Surveillance System for Human Use: https://www.notificaram.es/. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Oxicodona/Naloxona Krka

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date stated on the package after CAD. The expiration date is the last day of the month indicated.

Do not store above 30°C.

Keep in the original packaging to protect it from moisture.

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. 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

Composition of Oxicodona/Naloxona Krka

• The active ingredients are oxicodone hydrochloride and naloxone hydrochloride.

Each prolonged-release tablet contains 20 mg of oxicodone hydrochloride (equivalent to 18 mg of oxicodone) and 10 mg of naloxone hydrochloride (as 10.9 mg of naloxone hydrochloride dihydrate, equivalent to 9 mg of naloxone).

• The other ingredients are hydroxypropylcellulose, ethylcellulose, glycerol distearate, lactose monohydrate, talc (E553b), and magnesium stearate (E470b) in the core; and polyvinyl alcohol, titanium dioxide (E171), macrogol 4450, talc (E553b), and red iron oxide (E172) in the coating. See section 2 "Oxicodona/Naloxona Krka contains lactose".

Appearance of the product and package contents

Prolonged-release tablets are light pink, oval, and slightly biconvex, engraved with a "20" on one face. Dimensions: 9.5 mm × 4.5 mm.

Oxicodona/Naloxona Krka 20 mg/10 mg is available in child-resistant blister packs of 28 or 56 prolonged-release tablets; or single-dose blister packs, pre-cut, child-resistant, of 28 or 56 prolonged-release tablets.

Only some package sizes may be marketed.

Marketing authorization holder and manufacturer

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

or

TAD Pharma GmbH,

Heinz-Lohmann-Straße 5,

27472 Cuxhaven,

Germany

You can request more information about this medication from the local representative of the marketing authorization holder:

KRKA Farmacéutica, S.L. Calle Anabel Segura 10, 28108 Alcobendas, Madrid, Spain

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

Date of the last revision of this leaflet:09/2024

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