Read all of this leaflet carefully before you start

taking this medicine because it contains important

information for you.

•    Keep this leaflet. You may need to read it again.

•    If you have any further questions, ask your doctor or pharmacist.

•    This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of ilhiess 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.

What is in this leaflet:

1.    What Targinact tablets are and what they are used for

2.    What you need to know before you take Targinact tablets

3.    Howto take Targinact tablets

4.    Possible side effects

5.    Howto store Targinact tablets

6.    Contents of the pack and other information

1. What Targinact tablets are and what they are used for

Targinact tablets contain oxycodone hydrochloride and naloxone hydrochloride as active substances. Oxycodone hydrochloride is responsible for the painkilling effect of Targinact tablets, and is a potent analgesic (“painkiller”) of the opioid group. The second active substance of Targinact tablets, naloxone hydrochloride, is intended to counteract constipation. Bowel dysfunction (e.g. constipation) is a typical side effect of treatment with opioid painkillers.

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

Do NOT take Targinact tablets:

•    if you are allergic to oxycodone hydrochloride, naloxone hydrochloride or any of the other ingredients of this medicine (listed in section 6);

•    if your breathing is not able to supply enough oxygen to the blood, and to 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.

Warnings and Precautions

Talk to your doctor or pharmacist before taking

Targinact tablets:

•    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 have myxoedema (a thyroid disorder, with dryness, coldness and swelling [‘pufliness’] 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 ilhiess accompanied by a (partial) loss of reality (psychosis), due to alcohol or intoxication with other substances (substance-induced psychosis);

•    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 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) e.g.

medicines containing tranylcypromine, phenelzine, isocarboxazid, moclobemide and linezolid.

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 Targinact tablets. The most serious result of opioid overdose is respiratory depression (slow and shallow breathing). This may cause blood oxygen levels to fall, resulting in possible fainting, etc.

There is no clinical experience with Targinact tablets in patients with cancer associated to peritoneal metastases or with beginning bowel obstruction in advanced stages of digestive and pelvic cancers. Therefore, the use of Targinact tablets in these patients is not recommended.

How to use Targinact tablets correctly

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

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

If used over the long term, you may become tolerant to Targinact tablets. This means you may need a higher dose to achieve the desired pain relief. Long-term use of Targinact tablets may lead to physical dependence. Withdrawal symptoms may occur if treatment is stopped too suddenly (restlessness, bouts of sweating, muscle pain). If you no longer need treatment, you should reduce your daily dose gradually, in consultation with your doctor.

The active substance oxycodone hydrochloride alone has an abuse profile similar to other strong opioids (strong analgesics). There is potential for development of psychological dependence. Oxycodone hydrochloride containing products should be avoided in patients with a present or past abuse of alcohol, drugs or medicines.

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

Incorrect use of Targinact tablets

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 prolonged-release tablet. Taking broken, chewed or crushed prolonged-release tablets may result in your body absorbing a potentially lethal dose of oxycodone hydrochloride (see under ‘If you take more Targinact tablets than you should’). Targinact tablets are not suitable for withdrawal treatment.

Targinact tablets 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 Targinact tablets because they contain the ingredient naloxone. Pre-existing withdrawal symptoms may be made worse.

You should never misuse Targinact 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 tablets may produce positive results in doping controls.

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

Other medicines and Targinact tablets

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

The risk of side effects is increased if you take Targinact tablets at the same time as medicines which affect brain function. In this case, the side effects of Targinact tablets may be enhanced. For example,

tiredness/drowsiness may occur, or respiratory depression (slow, shallow breathing) may get worse. Examples of medicines which affect brain function include:

•    other potent painkillers (opioids);

•    sleep medication and tranquillisers (sedatives, hypnotics);

•    antidepressants;

•    medicines used to treat allergies, travel sickness or nausea (antihistamines or antiemetics);

•    other medicines which act on the nervous system (phenothiazines, neuroleptics).

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)

•    antifungal medicines of the -azole type(e.g. ketoconazole)

•    ritonavir or other protease inhibitors (used to treat HIV)

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

Targinact tablets with food, drink and alcohol

Drinking alcohol whilst taking Targinact tablets 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 tablets.

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

Pregnancy and breastfeeding

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

Pregnancy

Use of Targinact tablets during pregnancy 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 is given during childbirth, respiratory depression (slow and shallow breathing) may occur in the newborn infant. Breastfeeding

Breastfeeding should be discontinued during treatment with Targinact 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 tablets.

Driving and using machines

This medicine can affect your ability to drive as it may make you sleepy or dizzy. This is most likely at the start of your treatment, after a dose increase or after switching from a different medication. These side effects should disappear once you are on a stable dose.

•    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: o The medicine has been prescribed to treat a

medical or dental problem and o You have taken it according to the instructions given by the prescriber or in the information provided with the medicine and o It was not affecting your ability to drive safely Talk to your doctor or pharmacist if you are not sure whether it is safe for you to drive while taking this medicine.

Targinact tablets contain lactose

If you have been told that you have an intolerance to some sugars, contact your doctor before taking Targinact tablets.

3. How to take Targinact tablets

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

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

Adults

The usual starting dose is 10 mg oxycodone hydrochloride / 5 mg naloxone hydrochloride as prolonged-release tablet(s) every 12 hours.

Your doctor will decide how many Targinact tablets you should take every day and how to divide your total daily dose into morning and evening doses. Your doctor will also decide on any necessary dose adjustments during treatment. Your dose will be adjusted according to your level of pain and individual sensitivity. You should be given the lowest dose needed for pain relief.

If you have already been treated with opioids, Targinact treatment with these tablets can be started at a higher dose.

The maximum daily dose is 160 mg oxycodone hydrochloride and 80 mg naloxone hydrochloride.

If you need a higher dose, your doctor may give you additional oxycodone hydrochloride without naloxone hydrochloride. However, the maximum daily dose of oxycodone should not exceed 400 mg. The beneficial effect of naloxone on bowel activity may be affected if additional oxycodone hydrochloride is given without additional naloxone hydrochloride.

If you are switched from Targinact tablets to another opioid pain medication, your bowel function will probably worsen.

If you experience pain between two doses of Targinact tablets, you may need a rapid-acting painkiller. Targinact tablets are not suitable for this. In this case, please talk to your doctor.

If you have the impression that Targinact tablets are too strong or too weak, please talk to your doctor or pharmacist.

Elderly patients

In general, no dose adjustment is necessary for elderly patients with normal kidney and/or liver function.

Liver or kidney problems

If you have an impairment of your kidney or a mild impairment of your liver function, your attending doctor will prescribe Targinact tablets with special caution.

If you have a moderate or severe impairment of liver function, Targinact tablets should not be used (see also Section 2 ‘Do not take Targinact tablets’ and ‘Warnings and precautions’).

Children and adolescents below 18 years of age Targinact tablets have not yet been studied in children and adolescents under 18 years of age. Its safety and effectiveness have not yet been proven in children and adolescents. For this reason, Targinact use in children and adolescents under 18 years of age is not recommended.

Method of administration

Swallow Targinact tablets whole (without chewing), with sufficient liquid (1/2 glass of water). You can take file prolonged-release tablets with or without food. Take Targinact 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.

Duration of use

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

If you take more Targinact tablets than you should

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

An overdose may result in:

•    narrowed pupils;

•    slow and shallow breathing (respiratory depression);

•    a narcotic-like state (drowsiness to the point of unconsciousness);

•    low muscle tone (hypotonia);

•    reduced pulse rate; and

•    a drop in blood pressure.

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 sihiations which require a high level Y of alertness, e.g. driving.

g If you forget to take Targinact tablets,

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

If you should 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 in less than 8 hours: Take the forgotten dose. Then, wait another 8 horn's 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.

If you stop taking Targinact tablets

Do not stop your treatment with Targinact tablets 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 have any further questions on 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 everybody gets them.

Important side effects or signs to look out for, and what to do if you are affected:

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.

•    rise in blood pressure

•    runny nose

•    cough

•    hypersensitivity/allergic reactions

•    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

•    yawning

•    weight change

Not known (frequency cannot be estimated from available data)

•    euphoric mood

•    severe drowsiness

•    erectile dysfunction

•    nightmares

•    hallucinations

•    shallow breathing

•    difficulties in passing urine

•    tingling in hands or feet

•    belching

The active ingredient oxycodone hydrochloride, if not combined with naloxone hydrochloride, is known to have the following differing side effects:

Breathing problems, such as breathing more slowly or weakly than expected (respiratory depression), reduction in size of the pupils in the eye, muscle cramps and decreased 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

•    taste anomalies

•    increased muscle tension

•    involuntary muscle contractions

•    drug dependence

•    ileus

•    dry skin

•    drug tolerance

•    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)

•    reduced sexual drive

•    flushing of skin

•    dehydration

•    agitation

•    thirst

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

•    itching rash (urticaria)

•    herpes simplex

•    increased appetite

•    black (tarry) stools

•    gingival bleeding

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

•    acute generalized allergic reactions (anaphylactic reactions)

•    absence of menstrual periods

•    problems with bile flow Reporting of side effects

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 (www.mlira.gov.uk/yellowcard). By reporting side effects you can help provide more information on the safety of this medicine.

5.    How to store Targinact tablets

Keep out of the sight and reach of children.

Do not use this medicine after the expiry date wliich is stated on the carton and blister, after “EXP...”

The expiry date refers to the last day of that month.

Do not store above 25°C.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

6.    Contents of the pack and other information

What Targinact tablets contain

The active ingredients are oxycodone hydrochloride and naloxone hydrochloride.

Targinact 2.5 mg/1.25 mg tablets One prolonged-release tablet contains 2.5 mg of oxycodone hydrochloride, equivalent to 2.25 mg oxycodone, and 1.37 mg naloxone hydrochloride dihydrate equivalent to 1.25 mg naloxone hydrochloride and 1.13 mg naloxone.

Targinact 15 mg/7.5 mg tablets One prolonged-release tablet contains 15 mg of oxycodone hydrochloride, equivalent to 13.5 mg oxycodone, and 8.24 mg naloxone hydrochloride dihydrate equivalent to 7.5 mg naloxone hydrochloride and 6.75 mg naloxone.

Targinact 30 mg/15 mg tablets One prolonged-release tablet contains 30 mg of oxycodone hydrochloride, equivalent to 27 mg oxycodone, and 16.48 mg naloxone hydrochloride dihydrate equivalent to 15 mg naloxone hydrochloride or 13.5 mg naloxone.

The other ingredients are:

Targinact 2.5 mg/1.25 mg tablets Tablet core:

Hydroxypropylcellulose, ethylcellulose, stearyl alcohol, lactose monohydrate, talc, magnesium stearate

Tablet coat:

polyvinyl alcohol, partially hydrolysed, titanium dioxide (E171), macrogol 3350, talc, iron oxide red (E172), iron oxide yellow (El72)

Targinact 15 mg/7.5 mg tablets Tablet core:

hydroxypropylcellulose, ethylcellulose, stearyl alcohol, lactose monohydrate, talc, magnesium stearate Tablet coat:

polyvinyl alcohol, partially hydrolysed, titanium dioxide (E171), macrogol 3350, talc, iron oxide black (E172), iron oxide red (El72), iron oxide yellow (El72) Targinact 30 mg/15 mg tablets 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 black (E172), iron oxide red (El72), iron oxide yellow (El72)

What Targinact tablets look like and the contents of the pack

Targinact 2.5 mg/1.25 mg tablets

Light yellow, round tablets, 5 nun in size, with a film

coating.

Targinact 15 mg/7.5 mg tablets Grey, oblong tablets, with a nominal length of 9.5 nun and with a film-coating, embossed ‘OXN’ on one side and ‘ 15’ on the other.

Targinact 30 mg/15 mg tablets

Brown, oblong tablets, with a nominal length of 9.5 mm and with a film-coating, embossed ‘OXN’ on one side and ‘30’ on the other.

In each box there are 14, 28 or 56 tablets.

Marketing Authorisation Holder and Manufacturer Marketing Authorisation Holder:

Napp Pharmaceuticals Limited

Cambridge Science Park, Milton Road, Cambridge

CB4 0GW, UK.

Manufacturers:

Mundiphanna GmbH

Mundiphanna StraBe 2, 65549 Limburg/Lahn, Germany Bard Pharmaceuticals Limited Cambridge Science, Milton Road, Cambridge CB4 0GW, UK.

This leaflet was last revised in May 2015 ® Targinact, NAPP and the NAPP device (logo) are registered trade marks.

© 2009-2014 Napp Pharmaceuticals Limited

02/06/2015 16:00