Package leaflet: Information for the user

Onexila XL 10 mg prolonged-release tablets Onexila XL 20 mg prolonged-release tablets Onexila XL 40 mg prolonged-release tablets Onexila XL 80 mg prolonged-release tablets

Oxycodone hydrochloride

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

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

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

-    This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-    If you get any side effects, talk to your doctor or pharmacist.

This includes any possible side effects not listed in this leaflet.

See section 4.

What is in this leaflet:

1.    What Onexila XL is and what it is used for

2.    What you need to know before you take Onexila XL

3.    How to take Onexila XL

4.    Possible side effects

5.    How to store Onexila XL

6.    Contents of the pack and other information

1.    What Onexila XL is and what it is used for

Onexila XL is a centrally acting, strong painkiller from the group of opioids.

Onexila XL is used to treat severe pain, which can be adequately managed only with opioid analgesics.

Onexila XL is indicated in adults, and adolescents aged 12 years and older.

2.    What you need to know before you take Onexila XL Do not take Onexila XL

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

-    if you suffer from severely depressed breathing (respiratory depression) with too little oxygen in the blood (hypoxia) and/or too much carbon dioxide (hypercapnia) in the blood,

-    if you suffer from severe chronic obstructive lung disease,

-    if you suffer from cor pulmonale (cardiac changes due to chronic overload of lung circulation),

-    if you suffer from acute, severe bronchial asthma,

-    if you suffer from intestinal paralysis (paralytic ileus),

-    if you have an acute abdomen or suffer from a delayed gastric emptying.

Warnings and precautions

Talk to your doctor or pharmacist before taking Onexila XL if any of these conditions apply to you or applied to you in the past:

-    if you are older or debilitated

-    if your lung, liver or kidney function is severely impaired (see also section 3 “Risk patients”),

-    if you suffer from myxoedema (certain illnesses of the thyroid gland), impaired function of the thyroid gland,

-    if you suffer from adrenal insufficiency (Addison’s disease),

-    if you suffer from enlargement of the prostate (prostatic hypertrophy),

-    if you suffer from alcoholism or are undergoing alcohol withdrawal and experience complications (e.g. delirium tremens),

-    if you experience a psychosis that is caused by an intoxication (e.g. alcohol),

-    if you suffer from known opioid-dependence,

-    if you suffer from inflammation of the pancreas (pancreatitis),

-    if you suffer from a disease of the biliary tract,

-    if you suffer from colic of the bile duct and ureter,

-    in conditions with increased brain pressure,

-    if you suffer from disturbances of circulatory regulation,

-    if you suffer from epilepsy or have a seizure (fits) tendency,

-    if you take MAO inhibitors (for the treatment of depression).

Incorrect use of Onexila XL

The prolonged-release tablet must be swallowed whole, not be chewed or crushed as this leads to rapid oxycodone release due to the damage of the prolonged-release properties. The administration of chewed or crushed Onexila XL leads to a rapid release and absorption of a potentially fatal dose of oxycodone (see section 3 “If you take more Onexila XL than you should”).

In case of abusive injection (injection in a vein) the other tablet ingredients may lead to destruction (necrosis) of the local tissue, change of lung tissue (granulomas of the lung) or other serious, potentially lethal events.

Surgery

The administration of Onexila XL before surgery cannot be recommended due to lacking safety data.

Onexila XL should only be administered after bowel surgery when the bowel function has been restored.

Long-term treatment and abuse

Onexila XL has primary dependence potential. When used for a long time tolerance to the effects and progressively higher doses may be required to maintain pain control.

Chronic use of Onexila XL may lead to physical dependence and a withdrawal syndrome may occur upon abrupt cessation. When a patient no longer requires therapy with oxycodone hydrochloride, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.

When used as directed in patients suffering from chronic pain the risk of developing physical or psychological dependence is markedly reduced and needs to be weighed against the potential benefit. Please discuss this with your doctor.

Children

Onexila XL should not be used in children under 12 years of age because of safety and efficacy concerns.

Elderly patients

In elderly patients without impairment of kidney and/or liver function a dose adjustment is usually not necessary.

Anti-doping warning

Athletes should be aware that this medicine may cause a positive reaction to “anti-doping tests”.

Use of Onexila XL as a doping agent may become a health hazard. Other medicines and Onexila XL

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

-    Medicines that dampen the activity of the central nervous system, e.g.

•    sleeping pills or tranquillisers (sedatives, hypnotics)

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

•    medicines used during surgery (anaesthetics)

•    medicines used to treat depressions

•    medicines used for muscle relaxation

•    medicines used to treat allergies or vomiting (antihistamines, antiemetics)

•    other opiods or alcohol can enhance the side effects of oxycodone, in particular depressed breathing (respiratory depression).

-    Medicines with an anticholinergic effect, e.g.

•    other medicines that act against parasympathetic and cholinergic nerve fibres on the central nervous system (psychotropic medicines)

•    medicines used to treat allergies (antihistamines) or vomiting (antiemetics)

•    medicines used to treat Parkinson’s disease can enhance certain side effects of oxycodone (e.g. constipation, dry mouth or urinary disturbances).

-    Cimetidine and inhibitors of cytochrome P450-3A such as ketoconazole, variconazole and erythromycin may inhibit the metabolism of oxycodone. The influence of other medicines that can markedly affect the metabolism of oxycodone has not been investigated.

-    Monoamine oxidase inhibitors (MAOIs) can enhance the side effects of oxycodone (e.g. excitation, decrease or increase in blood pressure).

-    In individuals a clinically relevant increase or decrease of blood clotting have been observed if anticoagulants of the coumarin type (medicinal products against blood clotting) are co-applied with Onexila XL.

Onexila XL with alcohol

Drinking alcohol whilst taking Onexila XL 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 are taking Onexila XL.

Pregnancy and breast-feeding

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

Pregnancy

Onexila XL should not be used in pregnancy unless clearly necessary. There is insufficient experience regarding the use of oxycodone in pregnant women. Oxycodone crosses the placenta into the organism of the child. Prolonged use of oxycodone during pregnancy can cause withdrawal symptoms in newborns. Use of oxycodone during delivery can cause respiratory depression in the newborn.

Breast-feeding

You should not use Onexila XL when you are breast-feeding. Oxycodone passes into breast milk. Therefore, a risk for the sucking infant cannot be excluded in particular following intake of multiple doses of Onexila XL.

Driving and using machines

Oxycodone impairs alertness and reactivity to such an extent that the ability to drive and operate machinery is affected or ceases altogether.

In these circumstances Onexila XL has moderate to major influence on the ability to drive and use machines.

With stable therapy, a general ban on driving a vehicle may be not necessary. In these circumstances Onexila XL has minor influence on the ability to drive and use machines. The treating physician must assess the individual situation. Please discuss with your doctor whether or under what conditions you can drive a vehicle.

To look at the possible side effects affecting the motor skills and concentration see section 4. “Possible side effects”.

Onexila XL contains sucrose

This medicinal product contains sucrose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before you take this medicinal product.

3. How to take Onexila XL

Always take this medicine exactly as your doctor has told you.

Check with your doctor or pharmacist if you are not sure.

The recommended dose is

Adults and adolescents (>12 years of age)

The usual initial dose is 10 mg of oxycodone hydrochloride once daily, preferably taken at the same time each day. Some patients may benefit from a starting dose of 5 mg to minimise the incidence of side effects.

For doses not realisable/practicable with this medicinal product other strengths and medicinal products are available.

Further determination of the daily dose and any dose adjustments during the further course of therapy are performed by the treating physician and depend on the previous dosage. Dose adjustments should be made in steps of approximately one third of the daily dose to reduce the risk of possibly occurring side effects. In general, the lowest effective dose for the relief of pain should be chosen.

Patients who have already taken opioids can start treatment with higher dosages taking into account their experience with opioid treatment.

Some patients who receive Onexila XL need rapidly acting painkillers as rescue medication to control breakthrough pain. Onexila XL is not intended for the treatment of breakthrough pain.

For the treatment of non-cancer pain a daily dose of 40 mg of oxycodone hydrochloride is generally sufficient, but higher dosages may be necessary. Patients with cancer pain usually require dosages from 80 to 120 mg of oxycodone hydrochloride which may be increased up to 400 mg in individual cases.

The treatment needs to be controlled regularly with regard to pain relief and other effects in order to achieve the best pain therapy possible as well as to be able to treat any occurring side effects in good time and to decide whether treatment should be continued.

Your doctor will adjust the dosage depending on the pain intensity and how you respond to the treatment (see also section 2, “Warnings and precautions”).

Risk patients

If you have impaired kidney and/or liver function or if you have a low body weight your doctor may prescribe a lower starting dose.

Use in children under 12 years of age

Onexila XL should not be used in children under 12 years of age because of safety and efficacy concerns.

Method of administration

Onexila XL is for oral use only. Take the tablets once daily as advised by your doctor.

Swallow the prolonged-release tablets whole with a sufficient amount of liquid (‘A glass of water) with or without food, preferably at the same time each day.

The prolonged-release tablets must be swallowed whole, not chewed or crushed (see also section 2, “Warnings and precautions”).

Opening instruction for the blister

This medicinal product is packed in a child-resistant blister. You cannot press out the prolonged-release tablets through the blister.

Please observe the following opening instruction for the blister:

1.    Tear off a single dose along the perforation line of the blister.

2.    Hereby an unsealed area is accessible which is located at the position, where the perforation lines have crossed.

3.    Pull at the unsealed "strap" to peel off the cover seal.

If you take more Onexila XL than you should

If you have taken more Onexila XL as prescribed you should inform your doctor or your local poison control centre immediately. The following symptoms may occur: constricted pupils (miosis), depressed breathing (respiratory depression), sleepiness, skeletal muscle flaccidity and drop in blood pressure. In severe cases circulatory collapse, drowsiness, unconsciousness (coma), slowing of the heart rate (bradycardia) and accumulation of water in the lungs (non-cardiogenic lung oedema) may occur; abuse of high doses of strong opioids such as oxycodone can be fatal. In no case you should expose yourself to situations requiring elevated concentration e.g. driving a car.

If you forget to take Onexila XL

If you miss the intake of Onexila XL, pain relief will consequently be insufficient or cease altogether.

You can make up for a forgotten dose if the next regular intake is not due for at least another 12 hours. You can then continue to take Onexila XL as directed. Do not take a double dose to make up for a forgotten dose.

If you stop taking Onexila XL

Do not stop treatment without informing your doctor.

When a patient no longer requires therapy with Onexila XL, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.

A withdrawal syndrome may occur upon abrupt cessation of therapy. For symptoms of the withdrawal syndrome see section 4 “Possible side effects”.

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.

Significant side effects or signs to consider and measures to be taken when these side effects or signs occur

If you experience any of the following side effects, stop taking Onexila XL and contact your doctor immediately.

Depressed breathing (slowed breathing) is the most significant risk induced by opioids and is most likely to occur in elderly or debilitated patients. As a consequence, in predisposed patients opioids can cause severe drops in blood pressure.

Apart from this oxycodone can cause constricted pupils, bronchial spasms and spasms in smooth muscles and suppress the cough reflex.

Other possible side effects

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

-    sedation (tiredness to drowsiness), dizziness, headache

-    constipation, feeling or being sick

-    itching

Common (may affect up to 1 in 10 people)

-    loss of appetite

-    several psychological side effects such as

•    changes in mood (e.g. anxiety, depression, euphoria)

•    changes in activity (mostly sedation, sometimes accompanied by lethargy, occasionally increase with restlessness, nervousness and sleep disorders)

•    changes in performance (thought process disorder, confusion, amnesia, isolated cases of speech disorders)

-    pins and needles (paraesthesia)

-    lowering of blood pressure, rarely accompanied by symptoms such as pounding or racing heartbeat (palpitations), fainting

-    depressed breathing (dyspnoea), bronchospasm (difficulty in breathing or wheezing)

-    dry mouth, rarely accompanied by thirst and difficulty swallowing,

-    gastrointestinal disorders such as bellyache, diarrhoea, belching, upset stomach (dyspepsia)

-    skin disorders including rash, rarely increased sensitivity to light (photosensitivity), in isolated cases itchy (urticaria) or scaly rash (exfoliative dermatitis)

-    urinary disorders (urinary retention, but also frequent urination)

-    feeling weak (asthenia), sweating, chills

Uncommon (may affect up to 1 in 100 people)

-    allergic reactions

-    syndrome of inappropriate antidiuretic hormone secretion which leads to frequent urination

-    change in perception such as depersonalisation, hallucinations, change in taste

-    both increased and decreased muscle tone, trembling (tremor), tics, reduced sense of touch (hypaesthesia), coordination disturbances, dizziness

-    changes in tear secretion, constriction of the pupil, visual disturbances

-    abnormally acute sense of hearing (hyperacousis)

-    accelerated pulse, widening of the blood vessels (vasodilatation)

-    increased coughing, pharyngitis, runny nose, voice changes

-    oral ulcers, inflammation of the gums, inflamed mouth (stomatitis), flatulence

-    biliary colics, increased liver enzymes

-    disturbances of sexual function (reduced sexual desire and impotence)

-    accidental injuries, pain (e.g. chest pain), feeling unwell, excessive fluid in the tissues (oedema), migraine

-    physical dependence with withdrawal symptoms

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

-    lymph node disease (lymphadenopathy)

-    lack of water in the body (dehydration)

-    fits (seizures), in particular in patients suffering from epilepsy or with a tendency to fits

-    muscle spasms (muscle cramps)

-    gum bleeding, increased appetite, dark-coloured stools, tooth staining and damage, obstruction in the gut (ileus)

-    dry skin, herpes simplex (disorder of the skin and mucosa)

-    blood in urine (haematuria)

-    absence of menstrual bleeding (amenorrhoea)

-    changes in body weight (loss or rise), cellulitis

Very rare (may affect up to 1 in 10,000 people)

-    severe allergic reactions (anaphylactic reactions)

-    speech disorders

Tolerance and dependence may develop with chronic use and a withdrawal syndrome may occur upon abrupt cessation of therapy. The withdrawal syndrome is characterised by some or all of the following: restlessness, increased production of tears, runny nose, yawning, sweating, chills, muscle pain, abnormal dilatation of the pupil and sensation of irregular and forceful heartbeat. Other symptoms may also develop, including: irritability, anxiety, backache, joint pain, weakness, belly cramps, sleeplessness, being sick, lack of appetite, vomiting, diarrhoea, or increased blood pressure, breathing rate or heart rate.

Counteractive measures

If you observe any of the above listed side effects your doctor usually will take appropriate measures. The side effect constipation may be prevented by fibre enriched diet and increased drinking. If you are suffering from sickness or vomiting your doctor will prescribe you an appropriate medicine.

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.

By reporting side effects you can help provide more information on the safety of this medicine.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Rivopharm UK Ltd

30th Floor

40 Bank Street

Canary Wharf

London

E14 5NR

United Kingdom

Manufacturer

Develco Pharma GmbH

Grienmatt 27

Schopfheim

79650

Germany

This leaflet was last revised in 07/2016

5. How to store Onexila XL

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the blister and the carton after “EXP”. The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

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 protect the environment.

6. Contents of the pack and other information

What Onexila XL contains

The active substance is oxycodone hydrochloride.

Onexila XL 10 mg prolonged-release tablets:

Each prolonged-release tablet contains 10 mg oxycodone hydrochloride equivalent to 8.97 mg oxycodone.

Onexila XL 20 mg prolonged-release tablets:

Each prolonged-release tablet contains 20 mg oxycodone hydrochloride equivalent to 17.94 mg oxycodone.

Onexila XL 40 mg prolonged-release tablets:

Each prolonged-release tablet contains 40 mg oxycodone hydrochloride equivalent to 35.87 mg oxycodone.

Onexila XL 80 mg prolonged-release tablets:

Each prolonged-release tablet contains 80 mg oxycodone hydrochloride equivalent to 71.75 mg oxycodone.

The other ingredients are:

Tablet core:

Sugar spheres (sucrose, maize starch), hypromellose, talc, ethylcellulose, hydroxypropylcellulose, propylene glycol, carmellose sodium, cellulose, microcrystalline, magnesium stearate (Ph. Eur.), silica, colloidal anhydrous.

Onexila XL 10 mg prolonged-release tablets:

Tablet coating: Opadry® II White (consisting of polyvinyl alcohol, talc, titanium dioxide (E171), macrogol 3350).

Onexila XL 20 mg prolonged-release tablets:

Tablet coating: Opadry® II White (consisting of polyvinyl alcohol, talc, titanium dioxide (E171), macrogol 3350) and Opadry® II Yellow (consisting of polyvinyl alcohol, talc, macrogol 3350, iron oxide, yellow (E172)).

Onexila XL 40 mg prolonged-release tablets:

Tablet coating: Opadry® II White (consisting of polyvinyl alcohol, talc, titanium dioxide (E171), macrogol 3350) and Opadry® II Red (consisting of polyvinyl alcohol, talc, macrogol 3350 iron oxide, red (E172)).

Onexila XL 80 mg prolonged-release tablets:

Tablet coating: Opadry® II White (consisting of polyvinyl alcohol, talc, titanium dioxide (E171), macrogol 3350).

What Onexila XL looks like and contents of the pack

Onexila XL 10 mg prolonged-release tablets:

White, round, biconvex prolonged-release tablets with a diameter of 6.16 mm.

Onexila XL 20 mg prolonged-release tablets:

Yellowish to yellow, oblonged, biconvex prolonged-release tablets with a diameter of 10.2 mm x 4.7 mm and with a breakline on both sides. The tablet can be divided into equal doses.

Onexila XL 40 mg prolonged-release tablets:

Pink, oblonged, biconvex prolonged-release tablets with a diameter of 12.3 mm x 5.8 mm and with a breakline on both sides.

The tablet can be divided into equal doses.

Onexila XL 80 mg prolonged-release tablets:

White, oblonged, biconvex prolonged-release tablets with a diameter of 16.3 mm x 7.8 mm and with a breakline on both sides.

The tablet can be divided into equal doses.

Pack sizes:

10, 14, 20, 28, 30, 50, 56, 60, 98 and 100 prolonged-release tablets in child-resistant perforated unit dose blister.

Not all pack sizes may be marketed.