Dolstip

Patient Information Leaflet: Information for the Patient

Dolstip 5 mg/2.5 mg prolonged-release tablets, 10 mg/5 mg prolonged-release tablets, 20 mg/10 mg prolonged-release tablets, 30 mg/15 mg prolonged-release tablets, 40 mg/20 mg prolonged-release tablets

oxycodone/naloxone
Equivalent medicinal product
Please read all of this leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Dolstip is and what it is used for

Dolstip is a prolonged-release tablet, which means that the active substances it contains
are released over an extended period of time. Their effect lasts for 12 hours.
These tablets are intended for use in adults only.
Pain relief
You have been prescribed Dolstip for the treatment of severe pain that can be adequately managed
only with opioid analgesics. Naloxone hydrochloride is added to counteract constipation.
How these tablets work for pain relief
Dolstip contains the active substances oxycodone hydrochloride and naloxone hydrochloride. Oxycodone hydrochloride is responsible for the analgesic effect of Dolstip and is a potent analgesic (painkiller) belonging to the group of opioids.
Naloxone hydrochloride, the second active substance in Dolstip, counteracts constipation. Gastrointestinal dysfunction (constipation) is a typical adverse effect of treatment with opioid analgesics.

2. What you need to know before taking Dolstip

Do not take Dolstip

• 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 unable to provide enough oxygen to the blood and remove the carbon dioxide produced (respiratory depression);
• if you suffer from severe chronic lung disease associated with narrowing of the airways (chronic obstructive pulmonary disease or COPD);
• if you have a condition known as "pulmonary heart disease". In this condition, the right side of the heart enlarges due to increased pressure in the blood vessels of the lung, etc. (for example, as a consequence 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 dysfunction.

Warnings and precautions
Talk to your doctor or pharmacist before taking Dolstip:

• if you are elderly or debilitated (weak);
• if you suffer from paralytic ileus (a type of intestinal obstruction) caused by opioids;
• if you have impaired kidney function;
• if you have mild impairment of liver function;
• if you have severe lung impairment (for example, reduced respiratory capacity);
• if you suffer from a condition characterized by recurrent breathing interruptions during sleep that may cause extreme daytime sleepiness (sleep apnoea syndrome);
• if you have myxoedema (a thyroid disorder, with dry, cold, and swollen skin [oedema] in facial and limb areas);
• if your thyroid gland does not produce enough hormones (hypothyroidism or thyroid insufficiency);
• if your adrenal glands do not produce enough hormones (adrenal insufficiency, or Addison's disease);
• if you have mental disorders accompanied by a (partial) loss of sense of reality (psychosis) due to alcohol or intoxication with other substances (substance-induced psychosis);
• if you have gallstones or any other disorder of the biliary tract (disease affecting the bile ducts, gallbladder, etc.);
• if your prostate gland is abnormally enlarged (prostatic hypertrophy);
• if you suffer from alcoholism or delirium tremens;
• if your pancreas is inflamed (pancreatitis);
• if you have low blood pressure (hypotension);
• if you have high blood pressure (hypertension);
• if you have pre-existing cardiovascular diseases;
• if you have suffered a head injury (due to the risk of increased intracranial pressure);
• if you suffer from epilepsy or are prone to seizures;
• if you are also taking MAO inhibitors (used to treat depression, Parkinson's disease), or if you have taken such medicines within the last two weeks, for example medicines containing tranylcypromine, phenelzine, isocarboxazid, moclobemide, or linezolid;
• if you feel drowsy or have suddenly fallen asleep without warning.

Sleep-related breathing disorders
This medicine may cause breathing problems during sleep, such as sleep apnoea (breathing pauses during sleep) and sleep-related hypoxaemia (low oxygen levels in the blood). These problems may include breathing pauses during sleep, being awakened by breathlessness, difficulty staying asleep, or excessive daytime sleepiness. If you or someone else notices these symptoms, contact your doctor. Your doctor may wish to reduce your dose.
Inform your doctor if any of the above conditions have occurred in the past. Also, inform your doctor if you develop any of these conditions while taking Dolstip.
The most serious effect of an opioid overdose is respiratory depression (slow and shallow breathing). This also causes a drop in blood oxygen levels, potentially leading to fainting, etc.
Contact your doctor if you experience severe pain in the upper abdomen that may radiate to the back, nausea, vomiting, or fever, as these may be symptoms associated with inflammation of the pancreas (pancreatitis) or biliary tract.
If severe diarrhoea occurs at the beginning of treatment, this may be due to the effect of naloxone. It may be a sign that intestinal function is returning to normal. Diarrhoea may occur during the first 3–5 days of treatment. If diarrhoea persists beyond 3–5 days, or causes concern, contact your doctor.
When switching to treatment with Dolstip, if you are using high doses of another opioid, withdrawal symptoms may initially occur, such as agitation, sweating episodes, and muscle aches. If such symptoms occur, careful monitoring by your doctor may be necessary.

Tolerance, dependence, and abuse
This medicine contains oxycodone, which is an opioid. It may cause dependence and/or tolerance.
This medicine contains oxycodone, an opioid substance. Repeated use of opioid painkillers may make the medicine less effective (you become accustomed to it, through a mechanism known as tolerance). Repeated use of Dolstip may also lead to physical dependence, abuse, and psychological dependence, which may result in a potentially fatal overdose. The risk of these adverse effects may increase with higher doses and longer duration of use.
Physical or psychological dependence may cause you to lose control over the amount of medicine you take or how often you take it. You may feel the need to continue taking the medicine, even when it no longer helps relieve your pain or severe restless legs syndrome.
The risk of developing physical or psychological dependence varies from person to person. You may have a higher risk of developing dependence on Dolstip if:

• you or someone in your family has ever abused or been dependent on alcohol, medicines, or illegal drugs ("psychological dependence");
• you are a smoker;
• you have ever had mood-related disorders (depression, anxiety, or a personality disorder) or have been treated by a psychiatrist for other mental illnesses.

If you notice any of the following signs while taking Dolstip, it could be a sign that you have developed physical or psychological dependence:

• you need to take the medicine for longer than prescribed by your doctor;
• you need to take more than the recommended dose;
• you are using the medicine for reasons other than prescribed, for example, to "stay calm" or "help you sleep";
• you have made repeated unsuccessful attempts to stop or control your use of the medicine;
• you feel unwell when stopping the medicine and feel better once you restart it ("withdrawal effects").

If you notice any of these signs, talk to your doctor to discuss the best treatment approach for you, including when and how to stop safely (see section 3, “If you stop taking Dolstip”).
Inform your doctor if you have cancer with peritoneal metastases or if you have the onset of intestinal obstruction in advanced-stage digestive or pelvic tumours.
Like other opioids, oxycodone may affect the normal production of hormones in the body, such as cortisol or sex hormones, particularly if high doses are taken for long periods. If persistent symptoms occur, such as feeling unwell (including vomiting), loss of appetite, fatigue, weakness, dizziness, changes in menstrual cycle, impotence, infertility, or reduced sexual desire, consult your doctor, who may monitor your hormone levels.
This medicine may increase your sensitivity to pain, especially at high doses. Inform your doctor if this occurs. It may be necessary to reduce the dose or change the medicine.

Surgery
Inform your doctor that you are taking Dolstip if you are scheduled for surgery.

Misuse of Dolstip
These tablets are not suitable for the treatment of withdrawal.
5 mg/2.5 mg:
The tablet must be swallowed whole and must not be divided, split, chewed, or crushed. Taking divided, split, chewed, or crushed tablets may result in the absorption of a potentially fatal dose of oxycodone hydrochloride (see section 3 below, “If you take more Dolstip than you should”).
10 mg/5 mg; 20 mg/10 mg; 30 mg/15 mg; 40 mg/20 mg:
The tablet must not be split, chewed, or crushed. However, the tablets may be divided into two equal halves (see section 3, “How to take Dolstip”).
Taking split, chewed, or crushed tablets may result in the absorption of a potentially fatal dose of oxycodone hydrochloride (see section 3 below, “If you take more Dolstip than you should”).
You must never misuse Dolstip, especially if you are drug-dependent. If you are dependent on substances such as heroin, morphine, or methadone, severe withdrawal symptoms are similar if you misuse Dolstip, as it contains the active ingredient naloxone. Pre-existing withdrawal symptoms may worsen.
You must not misuse these tablets by dissolving and injecting them (e.g., into a blood vessel). In particular, they contain talc, which may cause local tissue destruction (necrosis) and changes in lung tissue (pulmonary granuloma). Such misuse may have other serious consequences and may even be fatal.
You may notice tablet residues in your faeces. Do not be alarmed, as the active ingredients (oxycodone hydrochloride and naloxone hydrochloride) have already been released in the stomach and intestine and absorbed into your body.

For athletes:
Using this medicine without a medical need constitutes doping and may lead to a positive result in anti-doping tests.

Children and adolescents
Dolstip has not yet been studied in children and adolescents under 18 years of age. Its safety and efficacy have not been established in children and adolescents. Therefore, the use of Dolstip in children and adolescents under 18 years of age is not recommended.

Other medicines and Dolstip
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The concomitant use of opioids, including oxycodone hydrochloride, and sedative medicines such as benzodiazepines or related medicines (medicines affecting brain function – see below) increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be fatal. Therefore, concomitant use should only be considered when no other treatment options are possible.
However, if your doctor prescribes Dolstip together with sedative medicines, the dose and duration of concomitant treatment must be limited by your doctor. Inform your doctor about all sedative medicines you are taking and follow your doctor’s dose recommendations carefully. It may be helpful to inform friends or family members to be aware of the signs and symptoms listed above. Contact your doctor if such symptoms occur.
Medicines that affect brain function include, for example:

• other strong painkillers (opioids);
• medicines for epilepsy, pain, and anxiety, such as gabapentin and pregabalin;
• sleeping pills and tranquillisers (sedative medicines, including benzodiazepines, hypnotics, anxiolytics);
• medicines for depression;
• medicines used to treat allergies, motion sickness, or nausea (antihistamines or antiemetics);
• medicines for mental or psychiatric disorders (phenothiazines, neuroleptics, antipsychotics);
• muscle relaxants;
• medicines for Parkinson’s disease.

The risk of adverse effects increases when taking antidepressants (such as citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine). These medicines may interact with oxycodone, and you may experience symptoms such as involuntary rhythmic muscle contractions, including muscles controlling 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.
If you take Dolstip together with other medicines, the effects of Dolstip or the other medicines may be altered. Inform your doctor if you are taking:

• medicines that reduce blood clotting ability (coumarin derivatives), as clotting time may be accelerated or slowed;
• macrolide antibiotics (e.g., clarithromycin, erythromycin, or telithromycin);
• azole antifungals (e.g., ketoconazole, voriconazole, itraconazole, or posaconazole);
• certain medicines used to treat HIV infections (protease inhibitors such as ritonavir, indinavir, nelfinavir, or saquinavir);
• cimetidine (used to treat stomach ulcers, indigestion, or heartburn);
• rifampicin (used to treat tuberculosis);
• carbamazepine (used to treat epileptic seizures, fits, or convulsions and in some pain conditions);
• phenytoin (used to treat epileptic seizures, fits, or convulsions);
• St. John’s wort (a herbal remedy for depression, also known as Hypericum perforatum);
• quinidine (a medicine used to treat irregular heartbeat).

No interactions are expected between Dolstip and paracetamol, acetylsalicylic acid, or naltrexone.

Dolstip with food, drinks, and alcohol
Drinking alcohol while taking Dolstip may increase drowsiness or the risk of serious adverse effects such as shallow breathing, breathing cessation, and loss of consciousness. It is recommended not to drink alcohol while taking Dolstip.
You should avoid drinking grapefruit juice while taking Dolstip.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
The use of Dolstip should be avoided as much as possible during pregnancy. If used for prolonged periods during pregnancy, oxycodone hydrochloride may cause withdrawal symptoms in the newborn.
If oxycodone hydrochloride is administered during labour, the newborn may experience breathing problems (respiratory depression).

Breastfeeding
Breastfeeding must be discontinued during treatment with Dolstip. Oxycodone hydrochloride passes into breast milk. It is not known whether naloxone hydrochloride also passes into breast milk. Therefore, a risk to the infant cannot be excluded, particularly after taking multiple doses of Dolstip.

Driving and using machines
Dolstip may affect your ability to drive or operate machinery. This is more likely at the beginning of Dolstip therapy, after a dose increase, or when switching from another medicine. However, these adverse effects should disappear once your Dolstip dose has stabilised.
Dolstip has been associated with drowsiness and episodes of sudden onset of sleep. If you experience this adverse effect, you must not drive or operate machinery. Consult your doctor if you experience these adverse effects.
Ask your doctor whether you can drive or use machines.

Dolstip contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per prolonged-release tablet, i.e., it is essentially "sodium-free".

3. How to take Dolstip

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Before starting treatment and regularly during treatment, your doctor will discuss with you what to expect from using Dolstip, 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 taking Dolstip”).

Dolstip tablets are prolonged-release, meaning that the active ingredient is released over an extended period. Its effect lasts for 12 hours.

Unless otherwise prescribed by your doctor, the recommended dose is:

Pain treatment
Adults
The recommended starting dose is 10 mg of oxycodone hydrochloride / 5 mg of naloxone hydrochloride as prolonged-release tablets every 12 hours.

Your doctor will decide how much Dolstip you should take each day and how to divide the total daily dose between morning and evening. Your doctor will also determine any necessary dose adjustments during treatment. The dose will be adjusted according to the level of pain and individual sensitivity. You should receive the lowest dose necessary to achieve pain relief. If you have previously been treated with opioids, treatment with Dolstip may be initiated at a higher dose.

The maximum daily dose is 160 mg of oxycodone hydrochloride and 80 mg of nalnoxone hydrochloride. If you require a higher dose, your doctor may prescribe additional doses of oxycodone hydrochloride without naloxone hydrochloride. However, the maximum daily dose of oxycodone hydrochloride must not exceed 400 mg. The beneficial effect of naloxone hydrochloride on intestinal activity may diminish if higher doses of oxycodone hydrochloride are administered without additional doses of naloxone hydrochloride.

If you switch from Dolstip to another strong opioid medicine for pain treatment, intestinal function may likely worsen.

If you experience pain between two doses of Dolstip, you may need a fast-acting painkiller. Dolstip is not suitable for this purpose. In such cases, consult your doctor.

If you feel that the effect of Dolstip is too strong or too weak, speak with your doctor or pharmacist.

Other strengths of this medicine are available for doses that cannot be achieved or are impractical with this formulation.

Elderly patients
In general, dose adjustment is not necessary in elderly patients with normal kidney and/or liver function.

Liver or kidney problems
If you have impaired renal function or mild hepatic impairment, your doctor will prescribe Dolstip with particular caution. If you have moderate or severe hepatic impairment, Dolstip must not be used (see also section 2 “Do not take Dolstip” and “Warnings and precautions”).

Method of administration
Oral use.

• Take Dolstip with a glass of water.
• 5 mg/2.5 mg: The tablet must be swallowed whole and must not be divided, broken, chewed, or crushed.
• 10 mg/5 mg; 20 mg/10 mg; 30 mg/15 mg; 40 mg/20 mg: The tablet may be split into equal doses. The tablet must not be broken, chewed, or crushed.
• Prolonged-release tablets may be taken with or without food.

Take Dolstip every 12 hours according to a fixed schedule (e.g., 8 a.m. and 8 p.m.).

Blister with push-through opening
How to remove tablets from the child-resistant blister
The tablets are packaged in single-dose perforated blisters with child-resistant packaging.
Do not push the tablets through the blister foil.
Remove the tablets as follows:

1. Bend the blister back and forth along the perforation line.

2. Separate one blister cavity from the strip using the perforation lines.

3. To open the cavity, slowly peel back the foil starting from the corner marked.

Remove the tablet.

Push-through blister
How to remove tablets from the child-resistant blister
The tablets are packaged in single-dose perforated blisters with child-resistant packaging.
To remove the tablet, push the tablet through the reinforced blister foil.

Duration of use
In general, you should not take Dolstip for longer than necessary. If you have been taking Dolstip for a long time, your doctor should regularly assess whether you still need treatment with Dolstip.

If you take more Dolstip than you should
If you have taken more than the prescribed dose of Dolstip, inform your doctor immediately.
An overdose may cause:

• constricted pupils,
• slow and shallow breathing (respiratory depression),
• drowsiness (up to loss of consciousness),
• reduced muscle tone (hypotonia),
• reduced pulse rate,
• drop in blood pressure,
• brain disorder (known as leukoencephalopathy).

In severe cases, unconsciousness (coma), fluid accumulation in the lungs, and circulatory collapse may occur, which in some cases can be fatal.
You should avoid situations requiring a high level of alertness, such as driving.

If you forget to take Dolstip
If you forget to take Dolstip or take a lower dose than prescribed, you may not experience any analgesic effect.
If you forget to take a dose, follow the instructions below:

• if your next regular dose is due in 8 hours or more: take the missed tablet immediately, then continue with your usual dosing schedule.
• if your next regular dose is due in less than 8 hours: take the missed tablet. Then wait at least 8 hours before taking the next tablet. Try to return to your original dosing schedule (e.g., 8 a.m. and 8 p.m.). Do not take more than one dose within an 8-hour period.

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

If you stop taking Dolstip
Do not stop taking Dolstip without consulting your doctor.
If further treatment is no longer needed, you must gradually reduce the daily dose after speaking with your doctor. This will help you avoid withdrawal symptoms such as restlessness, sweating episodes, and muscle pain.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Important side effects to be aware of, and what to do if they occur:
If you experience any of the following serious side effects, contact your doctor immediately.
Slow and shallow breathing (respiratory depression) is the main danger of an opioid overdose. This occurs particularly in elderly and debilitated (weak) patients. Opioids may also cause a severe drop in blood pressure in predisposed patients.
The following side effects have been observed in patients being treated for pain:
Common (may affect up to 1 in 10 people)

• reduced appetite up to complete loss of appetite
• difficulty sleeping, tiredness or weakness
• dizziness or "lightheadedness", headache, drowsiness
• hot flushes
• abdominal pain, constipation, diarrhoea, dry mouth, indigestion, feeling unwell, malaise, flatulence
• itching, skin reactions, increased sweating
• feeling of unusual weakness
• dizziness

Uncommon (may affect up to 1 in 100 people)

• hypersensitivity/allergic reactions
• agitation, abnormal thoughts, anxiety, confusion, depression, nervousness
• reduced sexual drive
• seizures (especially in people with epilepsy or a predisposition to seizures), difficulty concentrating, taste disturbances, speech disorders, fainting, tremors, loss of energy
• changes in vision
• chest tightness, especially if you already suffer from coronary heart disease, palpitations
• low blood pressure, high blood pressure
• breathing difficulties, runny nose, cough
• abdominal distension
• increased liver enzymes, biliary colic
• muscle cramps, muscle spasms, muscle pain
• increased urge to urinate
• withdrawal symptoms such as agitation
• chest pain
• tremors, general malaise, pain, thirst
• swelling of the hands, ankles or feet
• weight loss
• injury-related lesions

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

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

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

• euphoria, hallucinations, nightmares, aggression
• tingling (pins and needles), severe drowsiness
• shallow breathing
• belching
• difficulty urinating
• erectile dysfunction
• breathing problems during sleep (sleep apnoea syndrome)

It is known that the active substance oxycodone hydrochloride, when not combined with naloxone
hydrochloride, causes the following side effects:
Oxycodone may cause breathing problems (respiratory depression), reduced pupil size, bronchial muscle spasms and spasms of smooth muscles, and suppression of the cough reflex.
Common (may affect up to 1 in 10 people)

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

Uncommon (may affect up to 1 in 100 people)

• dehydration
• agitation, perceptual disturbances (e.g. hallucinations, derealization)
• impaired concentration, migraine, increased muscle tension, involuntary muscle contractions, reduced sensitivity to pain or touch, abnormal coordination
• hearing difficulties
• dilation of blood vessels
• voice changes (dysphonia)
• difficulty swallowing
• a condition in which the bowel stops functioning properly (ileus)
• mouth ulcers, inflamed gums
• dry skin
• a reduction in sex hormone levels, which may affect sperm production in men or the menstrual cycle in women
• swelling due to fluid retention, tolerance to the medicine

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

• infections such as cold sores or herpes (which may cause blisters around the mouth or genital area)
• increased appetite
• black stools (tarry stools), bleeding gums
• itchy rash (urticaria)

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

• severe generalized allergic reactions (anaphylactic reactions)
• increased sensitivity to pain
• dental caries
• bile flow problems, a condition affecting a valve in the intestine that may cause severe upper abdominal pain (Oddi sphincter dysfunction)
• absence of menstruation
• withdrawal symptoms in newborns

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at: www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Dolstip

Keep this medicine out of the sight and reach of children.
Store this medicine in a locked, secure and protected place, where other people cannot access it. It may cause serious harm or be fatal to individuals for whom it has not been prescribed.
Do not use this medicine after the expiry date stated on the carton, bottle or blister after “Exp”. The expiry date refers to the last day of that month.
Blister:
Do not store above 25°C.
Bottle:
Do not store above 30°C.
Period of validity after first opening: 3 months.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Dolstip contains
The active substances are oxycodone hydrochloride and naloxone hydrochloride.
5 mg/2.5 mg:
Each prolonged-release tablet contains 5 mg of oxycodone hydrochloride (equivalent to 4.5 mg of
oxycodone) and 2.5 mg of naloxone hydrochloride (as 2.74 mg of naloxone hydrochloride dihydrate, equivalent
to 2.25 mg of naloxone).
The other components are:
Tablet core
Polyvinyl acetate
Povidone K30
Sodium lauryl sulfate
Anhydrous colloidal silica
Microcrystalline cellulose
Magnesium stearate
Tablet coating
Polyvinyl alcohol
Titanium dioxide (E171)
Macrogol 3350
Talc
10 mg/5 mg:
Each prolonged-release tablet contains 10 mg of oxycodone hydrochloride (equivalent to 9 mg of
oxycodone) and 5 mg of naloxone hydrochloride (as 5.45 mg of naloxone hydrochloride dihydrate, equivalent
to 4.5 mg of naloxone).
The other components are:
Tablet core
Polyvinyl acetate
Povidone K30
Sodium lauryl sulfate
Anhydrous colloidal silica
Microcrystalline cellulose
Magnesium stearate
Tablet coating
Polyvinyl alcohol
Titanium dioxide (E171)
Macrogol 3350
Talc
Iron oxide red (E172)
20 mg/10 mg:
Each prolonged-release tablet contains 20 mg of oxycodone hydrochloride (equivalent to 18 mg of
oxycodone) and 10 mg of naloxone hydrochloride (as 10.9 mg of naloxone hydrochloride dihydrate, equivalent
to 9 mg of naloxone).
The other components are:
Tablet core
Polyvinyl acetate
Povidone K30
Sodium lauryl sulfate
Anhydrous colloidal silica
Microcrystalline cellulose
Magnesium stearate
Tablet coating
Polyvinyl alcohol
Titanium dioxide (E171)
Macrogol 3350
Talc
30 mg/15 mg:
Each prolonged-release tablet contains 30 mg of oxycodone hydrochloride (equivalent to 27 mg of
oxycodone) and 15 mg of naloxone hydrochloride (as 16.35 mg of naloxone hydrochloride dihydrate,
equivalent to 13.5 mg of naloxone).
The other components are:
Tablet core
Polyvinyl acetate
Povidone K30
Sodium lauryl sulfate
Anhydrous colloidal silica
Microcrystalline cellulose
Magnesium stearate
Tablet coating
Polyvinyl alcohol
Titanium dioxide (E171)
Macrogol 3350
Talc
Iron oxide yellow (E172)
40 mg/20 mg:
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 components are:
Tablet core
Polyvinyl acetate
Povidone K30
Sodium lauryl sulfate
Anhydrous colloidal silica
Microcrystalline cellulose
Magnesium stearate
Tablet coating
Polyvinyl alcohol
Titanium dioxide (E171)
Macrogol 3350
Talc
Iron oxide red (E172)

Description of the appearance of Dolstip and contents of the pack
5 mg/2.5 mg:
White, round, biconvex prolonged-release tablet with a diameter of 4.7 mm and a height of 2.9 - 3.9 mm.
10 mg/5 mg:
Pink, oblong, biconvex prolonged-release tablet with a breakline on both sides, with a length of 10.2 mm, a width of 4.7 mm and a height of 3.0 - 4.0 mm. The tablet can be divided into equal doses.
20 mg/10 mg:
White, oblong, biconvex prolonged-release tablet with a breakline on both sides, with a length of 11.2 mm, a width of 5.2 mm and a height of 3.3 - 4.3 mm. The tablet can be divided into equal doses.
30 mg/15 mg:
Yellow, oblong, biconvex prolonged-release tablet with a breakline on both sides, with a length of 12.2 mm, a width of 5.7 mm and a height of 3.3 - 4.3 mm. The tablet can be divided into equal doses.
40 mg/20 mg:
Pink, oblong, biconvex prolonged-release tablet with a breakline on both sides, with a length of 14.2 mm, a width of 6.7 mm and a height of 3.6 - 4.6 mm. The tablet can be divided into equal doses.

Dolstip is available in single-dose perforated blisters made of aluminum/PVC/PE/PVDC with child-resistant closure, either lift-off or push-through, in packs of 10x1 (hospital pack), 14x1, 20x1, 28x1, 30x1, 50x1, 56x1, 60x1, 98x1 and 100x1 prolonged-release tablets, or in aluminum/PVC/PE/PVDC blisters with child-resistant closure containing 28, 56 and 84 prolonged-release tablets, or in HDPE bottles with child-resistant screw caps containing 50 and 100 prolonged-release tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Sandoz S.p.A.
Viale Luigi Sturzo 43
20154 Milan
Italy

Manufacturers
Develco Pharma GmbH
Grienmatt 27, Baden-Wuerttemberg 79650 Schopfheim, Germany
Salutas Pharma GmbH
Barleben, Otto-von-Guericke-Allee 1, Saxony-Anhalt, 39179 Barleben, Germany

This medicinal product is authorised in the European Economic Area Member States and in the United Kingdom (Northern Ireland) under the following names:
Germany Oxycodon comp - HEXAL 5 mg/2.5 mg Retardtabletten
Oxycodon comp - HEXAL 10 mg/5 mg Retardtabletten
Oxycodon comp - HEXAL 20 mg/10 mg Retardtabletten
Oxycodon comp - HEXAL 30 mg/15 mg Retardtabletten
Oxycodon comp - HEXAL 40 mg/20 mg Retardtabletten
Spain Oxicodona/Naloxona Sandoz 5 mg/2.5 mg comprimidos de liberación prolongada EFG
Oxicodona/Naloxona Sandoz 10 mg/5 mg comprimidos de liberación prolongada EFG
Oxicodona/Naloxona Sandoz 20 mg/10 mg comprimidos de liberación prolongada EFG
Oxicodona/Naloxona Sandoz 40 mg/20 mg comprimidos de liberación prolongada EFG
Finland Tanonalla 5 mg/2.5 mg depottabletti
Tanonalla 10 mg/5 mg depottabletti
Tanonalla 20 mg/10 mg depottabletti
Tanonalla 30 mg/15 mg depottabletti
Tanonalla 40 mg/20 mg depottabletti
Iceland Tanonalla 5 mg/2.5 mg forðatafla
Tanonalla 10 mg/5 mg forðatafla
Tanonalla 20 mg/10 mg forðatafla
Tanonalla 40 mg/20 mg forðatafla
Ireland Dancex SR Plus 5 mg/2.5 mg Prolonged-release tablets
Dancex SR Plus 10 mg/5 mg Prolonged-release tablets
Dancex SR Plus 20 mg/10 mg Prolonged-release tablets
Dancex SR Plus 40 mg/20 mg Prolonged-release tablets
Italy Dolstip
Norway Tanonalla 5 mg/2.5 mg depottablett
Tanonalla 10 mg/5 mg depottablett
Tanonalla 20 mg/10 mg depottablett
Tanonalla 30 mg/15 mg depottablett
Tanonalla 40 mg/20 mg depottablett
Sweden Oxycodone/Naloxone Sandoz 5 mg/2.5 mg depottabletter
Oxycodone/Naloxone Sandoz 10 mg/5 mg depottabletter
Oxycodone/Naloxone Sandoz 20 mg/10 mg depottabletter
Oxycodone/Naloxone Sandoz 30 mg/15 mg depottabletter
Oxycodone/Naloxone Sandoz 40 mg/20 mg depottabletter
Slovenia Codilek Combo 5 mg/2.5 mg tablete s podaljšanim sproščanjem
Codilek Combo 10 mg/5 mg tablete s podaljšanim sproščanjem
Codilek Combo 20 mg/10 mg tablete s podaljšanim sproščanjem
Codilek Combo 30 mg/15 mg tablete s podaljšanim sproščanjem
Codilek Combo 40 mg/20 mg tablete s podaljšanim sproščanjem

Patient information leaflet

Dolstip 60 mg/30 mg prolonged-release tablets, 80 mg/40 mg prolonged-release tablets

oxycodone hydrochloride/naloxone hydrochloride
Equivalent medicinal product
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Dolstip is and what it is used for

Pain relief
You have been prescribed Dolstip for the treatment of severe pain, which can be adequately managed
only with opioid analgesics.
How Dolstip works
Dolstip contains the active substances hydrochloride oxycodone and hydrochloride naloxone. Hydrochloride oxycodone is
responsible for the analgesic effect of Dolstip and is a potent analgesic (painkiller) belonging to the
opioid group.
The second active substance in Dolstip, hydrochloride naloxone, counteracts constipation. Gastrointestinal dysfunction (constipation) is a typical adverse effect of treatment with opioid analgesics.
Dolstip is for use in adults only.

2. What you should know before taking Dolstip

Do not take Dolstip

• 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 unable to supply enough oxygen to the blood and remove the carbon dioxide produced (respiratory depression)
• if you suffer from severe chronic lung disease associated with narrowing of the airways (chronic obstructive pulmonary disease or COPD)
• if you have a condition known as “pulmonary heart disease”. In this condition, the right side of the heart enlarges due to increased pressure in the blood vessels of the lung, etc. (for example, as a consequence of COPD – see above)
• if you suffer from severe bronchial asthma
• if you have paralytic ileus (a type of intestinal obstruction) not caused by opioids
• if you have moderate to severe liver dysfunction.

Warnings and precautions
Talk to your doctor or pharmacist before taking Dolstip:

• if you are elderly or debilitated (weak)
• if you suffer from paralytic ileus (a type of intestinal obstruction) caused by opioids
• if you have impaired kidney function
• if you have mild impairment of liver function
• if you have severe lung impairment (for example, reduced respiratory capacity)
• if you have myxedema (a thyroid disorder, with dry, cold, and swollen skin in the face and limbs)
• if your thyroid gland does not produce enough hormones (hypothyroidism or underactive thyroid)
• if your adrenal glands do not produce enough hormones (adrenal insufficiency, or Addison’s disease)
• if you have mental disorders accompanied by (partial) loss of perception of reality (psychosis) due to alcohol or intoxication with other substances (substance-induced psychosis)
• if you have gallstones, or if you suffer from any other disorder of the biliary tract (disease affecting the bile ducts, gallbladder, etc.)
• if your prostate gland is abnormally enlarged (prostatic hypertrophy)
• if you suffer from alcoholism or delirium tremens
• if your pancreas is inflamed (pancreatitis)
• if you have low blood pressure (hypotension)
• if you have high blood pressure (hypertension)
• if you have pre-existing cardiovascular diseases
• if you have had a head injury (due to the risk of increased intracranial pressure)
• if you suffer from epilepsy or are prone to seizures
• if you are also taking MAO inhibitors (used to treat depression, Parkinson’s disease, or bacterial infections), or if you have taken such medicines within the last two weeks, for example medicines containing tranylcypromine, phenelzine, isocarboxazid, moclobemide, or linezolid.

Sleep-related breathing disorders
Dolstip can cause breathing problems during sleep such as nocturnal apnea (breathing pauses during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). Symptoms may include breathing pauses during sleep, nighttime awakenings due to breathlessness, difficulty staying asleep, or excessive daytime sleepiness. If you or someone else observes these symptoms, contact your doctor. Opioids may also worsen pre-existing sleep apnea (see section 4). Your doctor may consider reducing the dose. Inform your doctor if any of these conditions occurred previously. Also, inform your doctor if you develop any of these disorders while taking Dolstip.
The most serious effect of opioid overdose is respiratory depression (slow and shallow breathing). This also causes reduced oxygen levels in the blood, potentially leading to fainting, etc.
Inform your doctor if you have cancer with peritoneal metastases or if there is a beginning of intestinal obstruction in advanced-stage digestive or pelvic tumors.
Contact your doctor if you experience severe pain in the upper abdomen that may radiate to the back, nausea, vomiting, or fever, as these may be symptoms associated with inflammation of the pancreas (pancreatitis) or the biliary tract.
If severe diarrhea occurs at the beginning of treatment, this may be due to the effect of naloxone. It may be a sign that intestinal function is returning to normal. Diarrhea may occur during the first 3–5 days of treatment. If diarrhea persists beyond 3–5 days, or if it causes concern, contact your doctor.
If you are using another opioid, withdrawal symptoms may initially occur when switching to treatment with Dolstip, such as restlessness, sweating episodes, and muscle aches. If you experience such symptoms, careful monitoring by your doctor may be necessary.
Like other opioids, oxycodone may affect the normal production of hormones in the body, such as cortisol or sex hormones, particularly if you have taken high doses for long periods. If you experience persistent symptoms such as vomiting, loss of appetite, fatigue, weakness, dizziness, changes in menstrual cycle, impotence, infertility, or reduced sexual desire, consult your doctor, as they may monitor your hormone levels.
This medicine may increase your sensitivity to pain, especially at high doses. Inform your doctor if this occurs. The dose may need to be reduced or the medicine changed.

Surgery
Inform your doctor that you are taking Dolstip if you are scheduled for surgery.

Tolerance, physical dependence, and psychological dependence
This medicine contains oxycodone, which is an opioid. It may cause dependence and/or tolerance.
This medicine contains oxycodone, an opioid substance. Repeated use of opioid painkillers may make the medicine less effective (you become accustomed to it, through a mechanism known as tolerance). Repeated use of Dolstip may also lead to dependence, abuse, and psychological dependence, which could result in a potentially fatal overdose. The risk of these adverse effects may increase with higher doses and longer duration of use.
Dependence or psychological dependence may cause you to lose control over the amount of medicine you take or how often you take it. You may feel the need to continue taking the medicine, even when it no longer helps relieve your pain.
The risk of becoming dependent or psychologically dependent varies from person to person. You may have a higher risk of developing dependence on Dolstip if:

• you or a family member have ever abused or been dependent on alcohol, medicines, or illegal drugs ("psychological dependence").
• you are a smoker.
• you have ever had mood-related disorders (depression, anxiety, or a personality disorder) or have been treated by a psychiatrist for other mental illnesses.

If you notice any of the following signs while taking Dolstip, it may indicate that you have developed dependence or psychological dependence:

• you need to take the medicine longer than prescribed by your doctor
• you need to take more than the recommended dose
• you are using the medicine for reasons other than prescribed, for example, to “stay calm” or “help you sleep”
• you have made repeated unsuccessful attempts to stop or control the use of the medicine
• when you stop taking the medicine, you feel unwell and feel better once you restart it ("withdrawal effects")

If you notice any of these signs, talk to your doctor to discuss the best treatment approach for you, including when and how to stop safely (see section 3, "If you stop taking Dolstip").

Misuse of Dolstip
The tablet must not be broken, chewed, or crushed. However, the tablets may be divided into equal parts (see section 3, "How to take Dolstip").
Taking broken, chewed, or crushed tablets may lead to the absorption of a potentially fatal dose of oxycodone hydrochloride (see section 3, "If you take more Dolstip than you should").
These tablets are not suitable for the treatment of withdrawal.
You must never abuse Dolstip, especially if you are substance-dependent. If you are dependent on substances such as heroin, morphine, or methadone, abusing Dolstip may cause severe withdrawal symptoms similar to those of the substances you are dependent on, because it contains the active ingredient naloxone. Pre-existing withdrawal symptoms may worsen.
You must not misuse these tablets by dissolving and injecting them (e.g., into a blood vessel). In particular, they contain talc, which may cause local tissue destruction (necrosis) and changes in lung tissue (pulmonary granuloma). Such abuse may also have other serious consequences and be fatal.
You may notice tablet residue in your stools. Do not be alarmed, as the active ingredients (oxycodone hydrochloride and naloxone hydrochloride) have already been released in the stomach and intestine and absorbed into your body.

For athletes: using this medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.

Children and adolescents
Dolstip has not yet been studied in children and adolescents under 18 years of age. Safety and efficacy have not been established in children and adolescents. Therefore, the use of Dolstip in children and adolescents under 18 years of age is not recommended.

Other medicines and Dolstip
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The concomitant use of opioids, including oxycodone hydrochloride, and sedative medicines such as benzodiazepines or related drugs increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be fatal. For this reason, concomitant use should only be considered when no other therapeutic alternatives are possible.
However, if your doctor prescribes Dolstip together with sedative medicines, the dose and duration of concomitant treatment must be limited by your doctor. Inform your doctor about all sedative medicines you are taking and follow your doctor’s dose recommendations carefully. It may be helpful to inform friends or family members to be aware of the signs and symptoms listed above. Contact your doctor if such symptoms occur.
Sedative medicines or similar include:

• other strong painkillers (opioids)
• medicines for epilepsy, pain, and anxiety, such as gabapentin and pregabalin
• sleeping pills and tranquilizers (sedative medicines including benzodiazepines, hypnotics, anxiolytics)
• medicines for depression
• medicines used to treat allergies, motion sickness, or nausea (antihistamines or antiemetics)
• medicines for mental or psychiatric disorders (called neuroleptics or antipsychotics such as phenothiazines)
• muscle relaxants
• medicines for Parkinson’s disease.

The risk of adverse effects increases when taking antidepressants (such as citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine). These medicines may interact with oxycodone, and you may experience symptoms such as involuntary and rhythmic muscle contractions, including muscles controlling 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.
If you take Dolstip together with other medicines, the effects of Dolstip or the other medicines may change. Inform your doctor if you are taking:

• medicines that reduce blood clotting ability (coumarin derivatives), which may accelerate or slow down clotting time
• macrolide antibiotics (e.g., clarithromycin, erythromycin, or telithromycin)
• azole antifungals (e.g., ketoconazole, voriconazole, itraconazole, or posaconazole)
• certain medicines used to treat HIV infections (protease inhibitors such as ritonavir, indinavir, nelfinavir, or saquinavir)
• cimetidine (used to treat stomach ulcers, indigestion, or heartburn)
• rifampicin (used to treat tuberculosis)
• carbamazepine (used to treat epileptic seizures, fits, or convulsions and in some pain conditions)
• phenytoin (used to treat epileptic seizures, fits, or convulsions)
• St. John’s wort (a herbal remedy for depression, also known as Hypericum perforatum)
• quinidine (a medicine used to treat irregular heartbeat).

No interactions are expected between Dolstip and paracetamol, acetylsalicylic acid, or naltrexone.

Dolstip with food, drinks, and alcohol
Drinking alcohol while taking Dolstip may increase drowsiness or the risk of serious adverse effects such as shallow breathing, risk of respiratory arrest, and loss of consciousness. It is recommended not to drink alcohol while taking Dolstip.
You should avoid drinking grapefruit juice when taking Dolstip.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
The use of Dolstip should be avoided as much as possible during pregnancy. If used for prolonged periods during pregnancy, oxycodone hydrochloride may cause withdrawal symptoms in the newborn.
If oxycodone hydrochloride is administered during childbirth, the newborn may experience slow and shallow breathing (respiratory depression).

Breastfeeding
Breastfeeding must be discontinued during treatment with Dolstip. Oxycodone hydrochloride passes into breast milk. It is not known whether naloxone hydrochloride also passes into breast milk. Therefore, the risk to the infant cannot be excluded, particularly after taking multiple doses of Dolstip.

Driving and using machines
Dolstip may affect your ability to drive or operate machinery. This is more likely at the beginning of Dolstip therapy, after a dose increase, or after switching from another medicine. However, these side effects should disappear once your Dolstip dose has stabilized.
Ask your doctor whether you can drive or operate machinery.

Dolstip contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per prolonged-release tablet, i.e., essentially “sodium-free”.

3. How to take Dolstip

Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Before starting treatment and regularly during treatment, your doctor will discuss with you what to expect from using Dolstip, 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 taking Dolstip”).
Unless otherwise prescribed by your doctor, the recommended dose is:
Adults
The recommended starting dose is 10 mg of oxycodone hydrochloride / 5 mg of naloxone hydrochloride as prolonged-release tablets every 12 hours.
Your doctor will decide how much Dolstip you should take each day and how to divide the total daily dose between morning and evening. Your doctor will also determine any necessary dose adjustments during treatment. Dose adjustments will be based on the level of pain and individual sensitivity. You should be given the lowest dose necessary to relieve your pain. If you have previously been treated with opioids, treatment with Dolstip may be started at a higher dose.
The maximum daily dose is 160 mg of oxycodone hydrochloride and 80 mg of naloxone hydrochloride. If a higher dose is required, your doctor may give you additional doses of oxycodone hydrochloride without naloxone hydrochloride. However, the maximum daily dose of oxycodone hydrochloride must not exceed 400 mg. The beneficial effect of naloxone hydrochloride on intestinal activity may diminish if higher doses of oxycodone hydrochloride are administered without additional doses of naloxone hydrochloride.
If you switch from Dolstip to another strong opioid medicine for pain treatment, your bowel function will likely worsen.
If you experience pain between doses of Dolstip, you may need a fast-acting painkiller.
Dolstip is not suitable for this purpose. In such a case, consult your doctor.
If you feel that the effect of Dolstip is too strong or too weak, talk to your doctor or pharmacist.
Other strengths of this medicine are available for doses that cannot be achieved or are impractical with this formulation.
Elderly patients
In general, dose adjustment is not necessary in elderly patients with normal kidney and/or liver function.
Liver or kidney problems
If you have impaired renal function or mild impairment of liver function, your doctor will prescribe Dolstip with particular caution. If you have moderate or severe impairment of liver function, Dolstip must not be used (see also section 2 “Do not take Dolstip” and “Warnings and precautions”).
Method of administration
Dolstip is for oral use.
Dolstip tablets are prolonged-release, meaning that the active ingredient is released over an extended period. The effect lasts for 12 hours.

• Take Dolstip every 12 hours, following a fixed dosing schedule (e.g., 8 a.m. and 8 p.m.).
• Take Dolstip with a sufficient amount of liquid (e.g., a glass of water).
• The tablet may be split into equal doses. The tablet must not be broken, chewed, or crushed. Taking broken, chewed, or crushed tablets may result in the absorption of a potentially lethal dose of oxycodone hydrochloride (see section 3. "If you take more Dolstip than you should").
• Prolonged-release tablets may be taken with or without food.

[Blister with push-through child-resistant packaging]
How to remove tablets from the child-resistant blister
The tablets are packaged in a unit-dose divisible child-resistant blister.
Do not push the tablets through the blister foil.
Remove the tablets as follows:

1. Bend the blister forward and backward along the perforated line.

2. Separate one blister cavity from the strip using the perforated lines.

3. To open the cavity, slowly peel back the foil starting from the marked corner.

Remove the tablet.
[Blister with push-through packaging]
How to remove tablets from the child-resistant blister
The tablets are packaged in a unit-dose divisible child-resistant blister.
To remove the tablet, push the tablet through the reinforced backing of the blister.
Duration of treatment
In general, you should not take Dolstip for longer than necessary. If you have been taking Dolstip for a long time, your doctor should regularly assess whether you still need treatment with Dolstip.
If you take more Dolstip than you should
If you have taken more than the prescribed dose of Dolstip, inform your doctor immediately.
An overdose may cause:

• brain disorder (known as leukoencephalopathy),
• constricted pupils,
• slow and shallow breathing (respiratory depression),
• drowsiness (up to loss of consciousness),
• low muscle tone (hypotonia),
• reduced pulse rate, and
• low blood pressure.

In severe cases, loss of consciousness (coma), fluid accumulation in the lungs, and circulatory collapse may occur, which in some cases can be fatal.
Situations requiring high levels of alertness, such as driving, should be avoided.
If you forget to take Dolstip
If you forget to take Dolstip or take a lower dose than prescribed, you may not experience any analgesic effect.
If you forget to take your dose, follow these instructions:

• if your next regular dose is due in 8 hours or more: take the missed tablet immediately, then continue with your usual dosing schedule.
• if your next regular dose is due in less than 8 hours: take the missed tablet, then wait at least 8 hours before taking the next tablet. Try to return to your original dosing schedule (e.g., 8 a.m. and 8 p.m.). Do not take more than one dose within an 8-hour period.

Do not take a double dose to make up for a forgotten dose.
If you stop taking Dolstip
Do not stop taking Dolstip without consulting your doctor.
If further treatment is no longer needed, you must gradually reduce the daily dose after speaking with your doctor. This will help you avoid withdrawal symptoms such as restlessness, sweating episodes, and muscle pain.
If you have any questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Relevant side effects to which you should pay attention, and what to do if they occur:
If you experience any of the following relevant side effects, consult your doctor immediately.
Slow and shallow breathing (respiratory depression) is the main danger of an opioid overdose. This occurs especially in elderly and debilitated patients (weak patients). Opioids may also cause a severe drop in blood pressure in predisposed patients.
The following side effects have been observed in patients being treated for pain:

Common (may affect up to 1 in 10 people)

• reduced appetite up to loss of appetite
• difficulty sleeping, tiredness or weakness
• dizziness or spinning sensation, headache, drowsiness
• hot flushes
• abdominal pain, constipation, diarrhoea, dry mouth, indigestion, malaise, feeling unwell, flatulence
• itchy skin, skin reactions, increased sweating
• feeling of unusual weakness
• vertigo

Uncommon (may affect up to 1 in 100 people)

• hypersensitivity/allergic reactions
• restlessness, abnormal thoughts, anxiety, confusion, depression, nervousness
• reduced sex drive
• epileptic seizures (especially in people with epilepsy or predisposition to seizures), difficulty concentrating, altered taste, speech disorders, fainting, tremor, lack of energy
• impaired vision
• chest tightness, especially if you already suffer from coronary heart disease, palpitations
• reduced blood pressure, increased blood pressure
• breathing difficulties, runny nose, cough
• abdominal distension
• increased liver enzymes, biliary colic
• muscle cramps, muscle spasms, muscle pain
• increased urge to urinate
• withdrawal symptoms such as agitation
• chest pain
• chills, general feeling of being unwell, pain, thirst
• swelling of hands, ankles or feet
• weight loss
• injuries due to accidents

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

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

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

• euphoric mood, hallucinations, nightmares, aggression
• tingling (pins and needles), severe drowsiness
• shallow breathing
• belching
• difficulty urinating
• erectile dysfunction
• sleep apnoea (pauses in breathing during sleep)

It is known that the active substance oxycodone hydrochloride, when not in combination with naloxone
hydrochloride, has the following side effects:
Oxycodone may cause respiratory problems (respiratory depression), reduction in pupil size, bronchial muscle cramps and cramps of smooth muscles, and suppression of the cough reflex.

Common (may affect up to 1 in 10 people)

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

Uncommon (may affect up to 1 in 100 people)

• dehydration
• agitation, perceptual disturbances (e.g. hallucinations, derealisation)
• impaired concentration, migraine, increased muscle tension, involuntary muscle contractions, reduced sensitivity to pain or touch, abnormal coordination
• hearing difficulties
• skin redness
• voice changes (dysphonia)
• difficulty swallowing
• a condition in which the intestine stops functioning properly (ileus)
• mouth ulcers, gum pain
• dry skin
• a reduction in sex hormone levels, which may alter sperm production in men or the menstrual cycle in women
• swelling due to fluid retention, drug tolerance

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

• infections such as cold sores or herpes (which may cause blisters around the mouth or genital area)
• increased appetite
• black (tarry) stools, bleeding gums
• itchy skin rash (urticaria)

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

• severe generalized allergic reactions (anaphylactic reactions)
• increased sensitivity to pain
• dental caries
• bile flow problems, a condition affecting a valve in the intestine that may cause severe upper abdominal pain (Oddi sphincter dysfunction)
• absence of menstruation
• withdrawal symptoms in newborns
• sleep apnoea (pauses in breathing during sleep)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Dolstip

Keep this medicine out of the sight and reach of children.
Store this medicine in a locked, safe and secure place, inaccessible to other people.
It may cause serious harm or be fatal to individuals for whom it has not been prescribed.
Do not use this medicine after the expiry date stated on the carton or blister after "Exp.". The expiry date refers to the last day of that month.
Do not store above 25 °C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Dolstip contains
The active substances are oxycodone hydrochloride and naloxone hydrochloride.
Dolstip 60 mg/30 mg prolonged-release tablets
Each prolonged-release tablet contains 60 mg of oxycodone hydrochloride (equivalent to 54 mg of
oxycodone) and 30 mg of naloxone hydrochloride (as 32.7 mg of naloxone hydrochloride dihydrate, equivalent
to 27 mg of naloxone).
The other components are:
Tablet core
Polyvinyl acetate
Povidone
Sodium lauryl sulfate
Anhydrous colloidal silica
Microcrystalline cellulose
Magnesium stearate
Tablet coating
Polyvinyl alcohol
Titanium dioxide (E171)
Macrogol 3350
Talc
Yellow iron oxide (E172)
Red iron oxide (E172)
Dolstip 80 mg/40 mg prolonged-release tablets
Each prolonged-release tablet contains 80 mg of oxycodone hydrochloride (equivalent to 72 mg of
oxycodone) and 40 mg of naloxone hydrochloride (as 43.6 mg of naloxone hydrochloride dihydrate, equivalent
to 36 mg of naloxone).
The other components are:
Tablet core
Polyvinyl acetate
Povidone
Sodium lauryl sulfate
Anhydrous colloidal silica
Microcrystalline cellulose
Magnesium stearate
Tablet coating
Polyvinyl alcohol
Titanium dioxide (E171)
Macrogol 3350
Talc
Red iron oxide (E172)

Description of the appearance of Dolstip and package contents
Dolstip 60 mg/30 mg prolonged-release tablets
Orange film-coated, oblong, biconvex tablets with a breakline on both sides, measuring 15 mm in length, 7 mm in width, and 3.8 – 4.8 mm in height. The tablet can be divided into equal doses.
Dolstip 80 mg/40 mg prolonged-release tablets
Red film-coated, oblong, biconvex tablets with a breakline on both sides, measuring 16 mm in length, 7.5 mm in width, and 4.5 – 5.6 mm in height. The tablet can be divided into equal doses.
Dolstip is available in child-resistant unit-dose divisible blisters with push-through opening or removable foil in packs of 28x1, 50x1 and 60x1 prolonged-release tablets, or in child-resistant blisters containing 60 prolonged-release tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Sandoz S.p.A.
Viale Luigi Sturzo 43
20154 Milan
Italy

Manufacturer
Develco Pharma GmbH
Grienmatt 27,
79650 Schopfheim,
Germany
Salutas Pharma GmbH
Otto-von-Guericke-Allee 1,
39179 Barleben,
Germany

This medicinal product is authorized in the European Economic Area countries under the following names:
Germany: Oxycodon comp - HEXAL 60 mg/30 mg Retardtabletten
Oxycodon comp - HEXAL 80 mg/40 mg Retardtabletten
Czech Republic: Oxycodon/Naloxon Sandoz
Italy: Dolstip