Targinact 10 mg/5 mg prolonged-release tablets

• 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.

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

• if you are allergic to oxycodone hydrochloride, naloxone hydrorochloride or any of the other ingredients of this medicine (listed in section 6),
• if your breathing is not able to supply enough oxygen to the blood, and get rid of carbon dioxide produced in the body (respiratory depression),
• if you suffer from a severe lung disease associated with narrowing of the airways (chronic obstructive pulmonary disease or COPD),
• if you suffer from a condition known as cor pulmonale. In this condition the right side of the heart becomes enlarged, due to increased pressure inside blood vessels in the lung etc (e.g. as a result of COPD – see above),
• if you suffer from severe bronchial asthma,
• if you have paralytic ileus (a type of bowel obstruction) not caused by opioids,
• if you have moderate to severe liver dysfunction.

Additionally for restless legs syndrome

• if you have a history of opioid abuse

Talk to your doctor or pharmacist before taking Targinact

• if you are or anyone in your family have ever abused or been dependent on opioids, alcohol, prescription medicines, or illegal drugs ("addiction"),
• in the case of elderly patients or debilitated (weak) patients,
• if you have paralytic ileus (a type of bowel obstruction) caused by opioids,
• if you have kidney impairment,
• if you have mild liver impairment,
• if you have severe lung impairment (i.e. reduced breathing capacity),
• if you suffer with a condition characterised by frequent breathing stops during the night which may make you feel very sleepy during the daytime (sleep apnoea),
• if you have myxoedema (a thyroid disorder, with dryness, coldness and swelling ['puffiness'] of the skin, affecting the face and limbs),
• if your thyroid gland is not producing enough hormones (underactive thyroid, or hypothyroidism),
• if your adrenal glands are not producing enough hormones (adrenal insufficiency, or Addison's disease),
• if you have a mental illness accompanied by a (partial) loss of reality (psychosis), due to alcohol or intoxication with other substances (substance-induced psychosis),
• if you have ever had problems with your mood (depression, anxiety or a personality disorder) or have been treated by a psychiatrist for other mental illnesses.
• if you suffer from gallstone problems,
• if your prostate gland is abnormally enlarged (prostate 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 disease,
• if you are a smoker
• if you have a head injury (due to the risk of increased brain pressure),
• if you suffer from epilepsy or are prone to seizures,
• if you are also taking MAO inhibitors (used to treat depression or Parkinson's disease), or you have taken this type of medicine in the last two weeks, e.g. medicines containing tranylcypromine, phenelzine, isocarboxazid, moclobemide and linezolid,
• if sleepiness or episodes of suddenly falling asleep occur,
• if you have any biliary tract disorder (diseases affecting the bile ducts, gallbladder etc).

Repeated use of Targinact may lead to dependence and abuse which may result in life threatening overdose. If you have concern that you may become dependent on Targinact, it is important that you consult your doctor.

Sleep-related breathing disorders

Targinact can cause sleep-related breathing disorders such as sleep apnoea (breathing pauses during sleep) and sleep related hypoxemia (low oxygen level in the blood). The symptoms can include breathing pauses during sleep, night awakening due to shortness of breath, difficulties to maintain sleep or excessive drowsiness during the day. If you or another person observe these symptoms contact your doctor. A dose reduction may be considered by your doctor.

Tell your doctor if any of the above has ever applied to you in the past. Also, please tell your doctor if you develop any of the above disorders while you are taking these tablets. The most serious result of opioid overdose is respiratory depression (slow and shallow breathing). This may also cause blood oxygen levels to fall, resulting in possible fainting, etc.

You must swallow the prolonged-release tablet whole, so as not to affect the slow release of oxycodone hydrochloride from the prolonged-release tablet. Do not break, chew or crush the tablets. Taking broken, chewed or crushed tablets may lead to the absorption of a potentially lethal dose of oxycodone hydrochloride (see section 3 "If you take more Targinact than you should").

If you experience severe diarrhoea at the start of treatment, this may be due to the effect of naloxone. It may be a sign that bowel function is returning to normal. Such diarrhoea can occur within the first 3-5 days of treatment. If diarrhoea should persist after 3-5 days, or give you cause for concern, please contact your doctor.

If you have been using another opioid, withdrawal symptoms may occur when you initially switch to Targinact treatment, e.g. restlessness, bouts of sweating and muscle pain. If you experience such symptoms, you may need to be specially monitored by your doctor.

Tolerance, dependence and addiction

This medicine contains oxycodone which is an opioid medicine. Repeated use of opioid painkillers can result in the drug being less effective (you become accustomed to it, known as tolerance). Repeated use of Targinact can also lead to dependence, abuse and addiction, which may result in life-threatening overdose. The risk of these side effects can increase with a higher dose and longer duration of use. Your prescriber should have explained how long you will be taking it for and when it is appropriate to stop, how to do this safely.

Dependence or addiction can make you feel that you are no longer in control of how much medicine you need to take or how often you need to take it. You might feel that you need to carry on taking your medicine, even when it doesn't help to relieve your pain or severe restless legs syndrome.

The risk of becoming dependent or addicted varies from person to person. You may have a greater risk of becoming dependent or addicted on Targinact if:

• You or anyone in your family have ever abused or been dependent on alcohol, prescription medicines or illegal drugs ("addiction").
• You are a smoker.
• You have ever had problems with your mood (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 whilst taking Targinact, it could be a sign that you have become dependent or addicted.

• You need to take the medicine for longer than advised by your doctor
• You need to take more than the recommended dose
• You are using the medicine for reasons other than prescribed, for instance, 'to stay calm' of 'help you sleep'
• You have made repeated, unsuccessful attempts to quit or control the use of the medicine
• When you stop taking the medicine you feel unwell, and you feel better once taking the medicine again ('withdrawal effects').

If you notice any of these signs, speak to your doctor to discuss the best treatment pathway for you, including when it is appropriate to stop and how to stop safely (See section 3, If you stop taking Targinact).

Tell your doctor in case you have cancer associated to peritoneal metastases or beginning bowel obstruction in advanced stages of digestive and pelvic cancers.

If you need to undergo surgery, please tell your doctors that you are taking Targinact.

Similar to 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 of time. If you experience symptoms which persist, such as feeling or being sick (including vomiting), loss of appetite, tiredness, weakness, dizziness, changes in menstrual cycle, impotence, infertility or decreased sex drive, talk to your doctor as he/she may want to monitor your hormone levels.

This medicine may increase your sensitivity to pain particularly at high doses. Tell your doctor if this happens. A reduction in your dose or a change in your medicine may be necessary.

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

These tablets are not suitable for withdrawal treatment.

Targinact should never be abused, particularly if you have a drug addiction. If you are addicted to substances such as heroin, morphine or methadone, severe withdrawal symptoms are likely if you abuse these tablets because they contain the ingredient naloxone. Pre-existing withdrawal symptoms may be made worse.

You should never misuse these tablets by dissolving and injecting them (e.g. into a blood vessel). In particular, they contain talc, which can cause destruction of local tissue (necrosis) and changes in lung tissue (lung granuloma). Such abuse can also have other serious consequences and may even be fatal.

The use of Targinact may produce positive results in doping controls.

The use of Targinact as a doping agent may become a health hazard.

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 you may experience symptoms such as involuntary, rhythmic contractions of muscles, including the muscles that control movement of the eye, agitation, excessive sweating, tremor, exaggeration of reflexes, increased muscle tension, body temperature above 38°C. Contact your doctor when experiencing such symptoms.

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

However, if your doctor does prescribe Targinact together with sedative medicines the dose and duration of concomitant treatment should be limited by your doctor.

Please tell your doctor about all sedative medicines you are taking and follow your doctor's dose recommendation closely. It could be helpful to inform friends or relatives to be aware of the signs and symptoms stated above. Contact your doctor when experiencing such symptoms. Examples of these sedatives or related medicines include:

• other potent painkillers (opioids);
• medicines to treat epilepsy, pain, and anxiety such as gabapentin and pregabalin;
• sleep medication and tranquilisers (sedatives including benzodiazepines, hypnotics, anxiolytics);
• medicines to treat depression;
• medicines used to treat allergies, travel sickness or nausea (antihistamines or antiemetics);
• medicines to treat psychiatric or mental disorders (antipsychotics which includes phenothiazines and neuroleptics).

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

• medicines that decrease the blood's clotting ability (coumarin derivatives), this clotting time may be speeded up or slowed down;
• antibiotics of the macrolide type (such as clarithromycin, erythromycin or telithromycin);
• antifungal medicines of the -azole type (such as ketoconazole, voriconazole, itraconizole or posaconizole);
• a specific type of medicine known as a protease inhibitor used to treat HIV (examples include ritonavir, indinavir, nelfinavir or saquinavir);
• cimetidine (a medicine for stomach ulcers, indigestion or heartburn);
• rifampicin (used to treat tuberculosis);
• carbamazepine (used to treat seizures, fits or convulsions and certain pain conditions);
• phenytoin (used to treat seizures, fits or convulsions);
• a herbal remedy called St John's Wort (also known as Hypericum perforatum);
• quinidine (a medicine to treat an irregular heartbeat).

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

Drinking alcohol whilst taking Targinact may make you feel more sleepy 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 you're taking Targinact.

You should avoid drinking grapefruit juice while you are taking these tablets.

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

Use of these tablets should be avoided to the extent possible during pregnancy. If used over prolonged periods during pregnancy, oxycodone hydrochloride may lead to withdrawal symptoms in newborn infants. If oxycodone hydrochloride is given during childbirth, respiratory depression (slow and shallow breathing) may occur in the newborn infant.

Breastfeeding

Breastfeeding should be discontinued during treatment with these tablets. Oxycodone hydrochloride passes into breast milk. It is not known whether naloxone hydrochloride also passes into breast milk. Therefore, a risk for the suckling infant cannot be excluded in particular following intake of multiple doses of Targinact.

Targinact may affect your ability to drive or operate machines. In particular, this is likely at the start of Targinact therapy, after a dose increase or after switching from a different medication. However, these side effects disappear once you are on a stable Targinact dose.

Targinact has been associated with sleepiness and episodes of suddenly falling asleep. If you experience these side effects, you must not drive or operate machinery. You should tell your doctor if this occurs.

• Do not drive while taking this medicine until you know how it affects you.
• It is an offence to drive if this medicine affects your ability to drive.
• However you would not be committing an offence if:
  • The medicine has been prescribed to treat a medical or dental problem and
  • You have taken it according to the instructions given by the prescriber or in the information provided with the medicine and
  • It was not affecting your ability to drive safely.

Ask your doctor whether you may drive or operate machines.

This medicine contains lactose (milk sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking these tablets.

Oral use

Swallow these tablets whole (without chewing), with sufficient liquid (½ glass of water). You can take the prolonged-release tablets with or without food. Take the tablets every 12 hours, according to a fixed time schedule (e.g. at 8 o'clock in the morning and 8 o'clock in the evening). Do not break, chew or crush the prolonged-release tablets (see section 2 "Warnings and precautions").

In general, you should not take these tablets for any longer than you need to. If you are on long-term treatment, your doctor should regularly check whether you still need these tablets.

If you have taken more than the prescribed dose of these tablets you must inform your doctor immediately.

An overdose may result in:

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

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

You should avoid situations which require a high level of alertness, e.g. driving.

Or if you take a dose lower than the one prescribed, you may not feel any effect.

If you forget to take your dose, please follow the instructions below:

• If your next usual dose is due in 8 hours or more: Take the forgotten dose immediately and continue with your normal dosing schedule.
• If your next usual dose is due within less than 8 hours: Take the forgotten dose. Then, wait another 8 hours before taking your next dose. Try to get back on track with your original dosing schedule (e.g. 8 o'clock in the morning and 8 o'clock in the evening). Do not take more than one dose within any 8-hour period.

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

Do not stop your treatment without consulting your doctor.

If you do not require any further treatment, you must reduce the daily dose gradually after talking to your doctor. In this way, you will avoid withdrawal symptoms, such as restlessness, bouts of sweating and muscle pain.

If you are affected by any of the following important side effects, consult your nearest doctor immediately. Slow and shallow breathing (respiratory depression) is the main danger of an opioid overdose. It mostly occurs in elderly and debilitated (weak) patients. Opioids can also cause a severe drop in blood pressure in susceptible patients.

Common (may affect up to 1 in 10 people)

• abdominal pain
• constipation
• diarrhoea
• dry mouth
• indigestion
• vomit (be sick)
• feel sick
• flatulence (wind)
• decreased appetite up to loss of appetite
• a feeling of dizziness or 'spinning'
• headache
• hot flushes
• a feeling of unusual weakness
• tiredness or exhaustion
• itchy skin
• skin reactions/rash
• sweating
• vertigo
• difficulty in sleeping
• drowsiness

Uncommon (may affect up to 1 in 100 people)

• abdominal bloating
• abnormal thoughts
• anxiety
• confusion
• depression
• nervousness
• chest tightness especially if you already have coronary heart disease
• drop in blood pressure
• fainting
• lack of energy
• thirst
• altered taste
• palpitations
• biliary colic
• chest pain
• generally feeling unwell
• pain
• swelling of hands, ankles or feet
• difficulties to concentrate
• impaired speaking
• shaking
• difficulties breathing
• restlessness
• chills
• hepatic enzymes increased
• rise in blood pressure
• reduced sexual drive
• runny nose
• cough
• hypersensitivity/allergic reactions
• weight loss
• injuries from accidents
• increased urge to urinate
• muscle cramps
• muscle twitches
• muscle pain
• vision impairment
• epileptic seizures (especially in persons with epileptic disorder or predisposition to seizures)

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

• increase in pulse rate
• dental changes
• weight gain
• yawning

Not known (frequency cannot be estimated from the available data)

• euphoric mood
• severe drowsiness
• erectile dysfunction
• nightmares
• drug dependence
• hallucinations
• shallow breathing
• difficulties in passing urine
• aggression
• withdrawal symptoms such as agitation
• tingling skin (pins and needles)
• belching
• sleep apnoea (breathing pauses during sleep)

Oxycodone can cause breathing problems (respiratory depression), reduction in size of the pupil in the eye, cramping of the bronchial muscles and cramping of the smooth muscles, as well as depression of the cough reflex.

Common (may affect up to 1 in 10 people)

• altered mood and personality changes (e.g. depression, feeling of extreme happiness)
• decreased activity
• increased activity
• difficulties in passing urine
• hiccups

Uncommon (may affect up to 1 in 100 people)

• impaired concentration
• migraines
• increased muscle tension
• involuntary muscle contractions
• a condition where the bowel stops working properly (ileus)
• dry skin
• reduced sensitivity to pain or touch
• abnormal coordination
• vocal changes (dysphonia)
• water retention
• difficulties in hearing
• mouth ulcers
• difficulties in swallowing
• sore gums
• perception disturbances (e.g. hallucination, derealisation)
• flushing of skin
• dehydration
• agitation
• a decrease in sex hormone levels which may affect sperm production in men or the menstrual cycle in females

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

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

Not known (frequency cannot be estimated from the available data)

• acute generalized allergic reactions (anaphylactic reactions)
• an increase in sensitivity to pain
• absence of menstrual periods
• withdrawal symptoms in the newborn
• increase in the severity of symptoms associated with inflammation of the pancreas (e.g. worsening of pain in the abdomen) or colicky abdominal pain or discomfort
• problems with bile flow
• tooth decay
• drug tolerance

Very common (may affect 1 in 10 people or more)

• headache
• drowsiness
• constipation
• feel sick
• sweating
• tiredness or exhaustion

Common (may affect up to 1 in 10 people)

• decreased appetite up to loss of appetite
• difficulty in sleeping
• depression
• a feeling of dizziness or 'spinning'
• difficulties to concentrate
• shaking
• tingling in hands or feet
• vision impairment
• vertigo
• hot flushes
• drop in blood pressure
• rise in blood pressure
• abdominal pain
• dry mouth
• vomit (be sick)
• hepatic enzymes increased (alanine aminotransferase increased, gamma-glutamyltransferase increased)
• itchy skin
• skin reactions/rash
• chest pain
• chills
• pain
• thirst

Uncommon (may affect up to 1 in 100 people)

• reduced sexual drive
• episodes of suddenly falling asleep
• altered taste
• difficulties breathing
• wind
• erectile dysfunction
• withdrawal symptoms such as agitation
• swelling of hands, ankles or feet
• injuries from accidents

Not known (frequency cannot be estimated from the available data)

• hypersensitivity/allergic reactions
• abnormal thoughts
• anxiety
• confusion
• nervousness
• restlessness
• euphoric mood
• hallucinations
• nightmares
• epileptic seizures (especially in persons with epileptic disorder or predisposition to seizures)
• drug dependence
• severe drowsiness
• impaired speaking
• fainting
• chest tightness especially if you already have coronary heart disease
• palpitations
• increase in pulse rate
• shallow breathing
• cough
• runny nose
• shallow breathing
• yawning
• abdominal bloating
• diarrhoea
• aggression
• indigestion
• belching
• dental changes
• biliary colic
• muscle cramps
• muscle twitches
• muscle pain
• difficulties in passing urine
• increased urge to urinate
• generally feeling unwell
• weight loss
• weight increase
• a feeling of unusual weakness
• lack of energy

Drug Withdrawal

When you stop taking Targinact, you may experience drug withdrawal symptoms, which include restlessness, difficulty sleeping, irritability, agitation, anxiety, feeling your heartbeat (palpitations), increased blood pressure, feeling or being sick, diarrhoea, shaking, shivering or sweating.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

The active substances are oxycodone hydrochloride and naloxone hydrochloride.

Targinact 5 mg/2.5 mg

Each prolonged-release tablet contains 5 mg oxycodone hydrochloride, equivalent to 4.5 mg oxycodone and 2.5 mg naloxone hydrochloride as 2.73 mg naloxone hydrochloride dihydrate, equivalent to 2.25 mg naloxone.

Targinact 10 mg/5 mg

Each prolonged-release tablet contains 10 mg oxycodone hydrochloride, equivalent to 9 mg oxycodone and 5 mg naloxone hydrochloride as 5.45 mg naloxone hydrochloride dihydrate, equivalent to 4.5 mg naloxone.

Targinact 20 mg/10 mg

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

Targinact 40 mg/20 mg

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

The other ingredients are:

Targinact 5 mg/2.5 mg

Tablet core:

Ethyl cellulose, stearyl alcohol, lactose monohydrate, talc, magnesium stearate, hydroxypropylcellulose

Tablet coat:

Polyvinyl alcohol, partially hydrolysed, titanium dioxide (E171), macrogol 3350, talc, brilliant blue FCF aluminium lake (E133)

Targinact 10 mg/5 mg

Tablet core:

Povidone K30, ethyl cellulose, stearyl alcohol, lactose monohydrate, talc, magnesium stearate

Tablet coat:

Polyvinyl alcohol, partially hydrolysed, titanium dioxide (E171), macrogol 3350, talc

Targinact 20 mg/10 mg

Tablet core:

Povidone K30, ethylcellulose, stearyl alcohol, lactose monohydrate, talc, magnesium stearate

Tablet coat:

Polyvinyl alcohol, partially hydrolysed, titanium dioxide (E171), macrogol 3350, talc, iron oxide red (E172)

Targinact 40 mg/20 mg

Tablet core:

Povidone K30, ethylcellulose, stearyl alcohol, lactose monohydrate, talc, magnesium stearate

Tablet coat:

Polyvinyl alcohol, partially hydrolysed), titanium dioxide (E171), macrogol 3350, talc, iron oxide yellow (E172)

Targinact 5 mg/2.5 mg

Blue, oblong tablets, with a nominal length of 9.5 mm and with a film coating, embossed "OXN" on one side and "5" on the other side

Targinact 10 mg/5 mg

White, oblong tablets, with a nominal length of 9.5 mm and with a film coating, embossed "OXN" on one side and "10" on the other side.

Targinact 20 mg/10 mg

Pink, oblong tablets, with a nominal length of 9.5 mm and with a film coating, embossed "OXN" on one side and "20" on the other side.

Targinact 40 mg/20 mg

Yellow, oblong tablets, with a nominal length of 14 mm and with a film coating, embossed "OXN" on one side and "40" on the other side.

These tablets are available in blister packs of 10, 14, 20, 28, 30, 50, 56, 60, 98 and 100 or in a bottle with child-resistant closure containing 100 tablets.

Not all pack sizes and container types may be marketed.

This leaflet is also available in large print, Braille or as an audio CD. To request a copy, please call the RNIB Medicine Information line (free of charge) on:

0800 198 5000

You will need to give details of the product name and reference number.

These are as follows:

Product name: Targinact

Reference number: 16950/0162