Patient Information Leaflet: Information for the User

ELIPSODOX, 5 mg/2.5 mg prolonged-release tablets

ELIPSODOX, 10 mg/5 mg prolonged-release tablets
ELIPSODOX, 20 mg/10 mg prolonged-release tablets
ELIPSODOX, 40 mg/20 mg prolonged-release tablets
Oxycodone hydrochloride/naloxone hydrochloride
Generic medicine
Please read 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 others, even if they have the same symptoms as yours, as it could be harmful.
If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

What ELIPSODOX is and what it is used for
What you need to know before taking ELIPSODOX
How to take ELIPSODOX
Possible side effects
How to store ELIPSODOX
Contents of the pack and other information

1. What ELIPSODOX is and what it is used for

ELIPSODOX 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 should only be used by adults.
Pain relief
You have been prescribed ELIPSODOX for the treatment of severe pain, which can only be adequately managed with opioid analgesics. Naloxone hydrochloride is added to counteract constipation.
How these tablets relieve pain
These tablets contain the active substances oxycodone hydrochloride and naloxone hydrochloride.
Oxycodone hydrochloride is responsible for the pain-relieving effect of ELIPSODOX and is a potent analgesic (painkiller) belonging to the opioid group. The second active substance in ELIPSODOX, naloxone hydrochloride, acts against constipation. Bowel dysfunction (constipation) is a typical side effect of treatment with opioid painkillers.

2. What you should know before taking ELIPSODOX

Do not use ELIPSODOX

if you are allergic (hypersensitive) to oxycodone hydrochloride, naloxone hydrochloride, or to any of the other ingredients of this medicine (listed in section 6),
if your breathing is unable to provide adequate amounts of oxygen to the blood and to eliminate carbon dioxide produced in the body (respiratory depression),
if you suffer from severe lung disease associated with narrowing of the airways (chronic obstructive pulmonary disease or COPD),
if you have a condition known as cor pulmonale. In this condition, the right side of the heart becomes enlarged due to increased pressure in the pulmonary blood vessels, etc. (e.g., 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 or severe liver dysfunction.

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

in elderly or debilitated patients
if you suffer from paralytic ileus (a type of intestinal obstruction) caused by opioids
if you have kidney impairment
if liver function is mildly impaired
if you have severe lung disease (e.g., reduced respiratory capacity)
if you suffer from myxedema (a thyroid disorder, with dry, cold, and swollen skin – edema – in the face and limbs)
if your thyroid gland does not produce sufficient hormones (thyroid insufficiency or hypothyroidism)
if your adrenal glands do not produce sufficient hormones (adrenal insufficiency, or Addison's disease)
if you have mental disorders accompanied by (partial) loss of sense of reality (psychosis) due to alcohol or intoxication with other substances (substance-induced psychosis)
if you suffer from gallstones
if your prostate gland is abnormally enlarged (prostatic hypertrophy)
if you or a family member has ever abused or been dependent on alcohol, prescription medicines, or illegal drugs (“dependence”)
if you are a smoker
if you have had mood disorders (depression, anxiety, or a personality disorder) or have been treated by a psychiatrist for other mental illnesses
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 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 or Parkinson’s disease), e.g., medicines containing tranylcypromine, phenelzine, isocarboxazid, moclobemide, linezolid.

Inform your doctor if you have previously experienced any of the conditions listed above. Also, inform your doctor if, while taking these tablets, you develop any of the conditions listed above.
The most serious effect of an opioid overdose is respiratory depression (slow and shallow breathing). This may also cause reduced oxygen levels in the blood, leading to fainting, etc.
Sleep-related breathing disorders
ELIPSODOX may cause sleep-related breathing disorders, such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). Symptoms may include pauses in breathing during sleep, nighttime awakenings due to shortness of breath, difficulty maintaining sleep, or excessive daytime sleepiness. If you or someone else observes these symptoms, consult your doctor. The doctor may consider reducing the dose.
The prolonged-release tablet must be swallowed whole to ensure the slow release of oxycodone hydrochloride from the tablet. The tablets must not be broken, chewed, or crushed. Swallowing 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 ELIPSODOX than you should).
If severe diarrhoea occurs at the beginning of treatment, this may be due to the effect of naloxone. It may indicate 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.
If you have previously used another opioid medicine, withdrawal symptoms such as restlessness, excessive sweating, and muscle pain may occur when switching to ELIPSODOX. If such symptoms occur, close medical supervision may be required.
You may become tolerant to these tablets if used for a long time. This means that a higher dose may be needed to achieve the desired effect. In addition, long-term use of these tablets may lead to physical dependence. Withdrawal symptoms such as agitation, excessive sweating, and muscle pain may occur if treatment is stopped abruptly. If you no longer need treatment, the daily dose should be gradually reduced under medical supervision.
The active ingredient oxycodone hydrochloride alone has an abuse profile similar to other strong opioids (strong analgesics). There is a possibility of developing psychological dependence. Medicines containing oxycodone hydrochloride should be avoided in patients with a history of alcohol, drug, or medicine abuse.

Repeated use of ELIPSODOX may lead to dependence and abuse, which may result in a potentially fatal overdose.

Consult your doctor if you are concerned about developing dependence on ELIPSODOX.
Inform your doctor if you have cancer associated with peritoneal metastases or are in the early stages of intestinal obstruction in advanced tumours of the digestive tract and pelvis.
If surgery is required, inform your doctor that you are taking ELIPSODOX.
Like other opioids, oxycodone may impair the normal production of hormones such as cortisol or sex hormones, particularly if taken at high doses for a prolonged period. If you experience persistent symptoms such as malaise or feeling unwell (including vomiting), loss of appetite, fatigue, weakness, dizziness, changes in menstrual cycle, impotence, infertility, or reduced sexual drive, inform your doctor, as they may wish to monitor your hormone levels.
Residual tablet shells from the prolonged-release formulation may be found in the 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 by your body.
Misuse of ELIPSODOX
These tablets are not suitable for the treatment of opioid withdrawal.
You must never abuse ELIPSODOX, especially if you are dependent on substances such as heroin, morphine, or methadone. Severe withdrawal symptoms may occur if you abuse these tablets, as they contain naloxone. Pre-existing withdrawal symptoms may worsen.
You must never misuse these tablets by dissolving and injecting them (e.g., into a blood vessel). In particular, they contain talc, which may locally cause tissue destruction (necrosis) and changes in lung tissue (pulmonary granuloma). Such abuse may have other serious consequences and may be fatal.
For athletes: the use of ELIPSODOX without therapeutic need constitutes doping and may lead to a positive result in anti-doping tests. The use of ELIPSODOX as a doping agent may pose a health risk.
Other medicines and ELIPSODOX
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 medicines increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. For this reason, concomitant use should only be considered when other treatment options are not possible.
However, if your doctor prescribes ELIPSODOX together with sedative medicines, the dose and duration of concomitant treatment must be limited by the doctor.
Inform your doctor about all sedative medicines you are taking and carefully follow the doctor's dosage recommendations. It may be helpful to inform friends or family members to watch for the signs and symptoms listed above. Consult your doctor if you experience such symptoms.
Examples of these sedative medicines or related medicines include:

other strong painkillers (opioids);
medicines for sleep and tranquillisers (sedatives including benzodiazepines, hypnotics, anxiolytics);
medicines used to treat depression;
medicines used to treat allergies, motion sickness, or nausea (antiemetics or antihistamines);
medicines used to treat psychiatric or mental disorders (antipsychotics including phenothiazines and neuroleptics);
if you are taking these tablets together with other medicines, the effect of these tablets on the other medicines, as described below, may change. Inform your doctor if you are taking:
medicines that reduce blood clotting ability (coumarin derivatives), which may increase or decrease clotting time;
macrolide antibiotics (e.g., clarithromycin, erythromycin, telithromycin);
azole antifungals (e.g., ketoconazole, voriconazole, itraconazole, or posaconazole);
a specific type of medicine known as protease inhibitors (used to treat HIV, e.g., ritonavir, indinavir, nelfinavir, or saquinavir);
cimetidine (a medicine for stomach ulcers, indigestion, or heartburn);
rifampicin (used to treat tuberculosis);
carbamazepine (used to treat seizures, epileptic fits, or convulsions and for certain types of pain);
phenytoin (used to treat seizures, epileptic fits, or convulsions);
a herbal remedy called St. John's Wort (also known as Hypericum perforatum);
quinidine (a medicine used to treat irregular heartbeat).

No interactions between ELIPSODOX and paracetamol, acetylsalicylic acid, or naltrexone are expected.
ELIPSODOX with food, drinks, and alcohol
Drinking alcohol while taking ELIPSODOX may increase drowsiness or increase the risk of serious adverse effects such as shallow breathing, risk of respiratory arrest, and loss of consciousness. Alcohol must not be consumed while taking ELIPSODOX.
Do not drink grapefruit juice while taking these tablets.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
During pregnancy, the use of these tablets should be avoided as much as possible. If used for prolonged periods during pregnancy, oxycodone hydrochloride may cause withdrawal symptoms in newborns. If oxycodone hydrochloride is administered during childbirth, respiratory depression (slow and shallow breathing) may occur in the newborn.
Breastfeeding
Breastfeeding must be discontinued during treatment with these tablets. Oxycodone hydrochloride passes into breast milk. It is not known whether naloxone hydrochloride passes into breast milk. Therefore, a risk to the breastfed infant cannot be excluded, particularly after multiple doses of ELIPSODOX.
Driving and using machines
ELIPSODOX may affect your ability to drive or operate machinery. This is particularly likely at the beginning of ELIPSODOX therapy, after a dose increase, or after switching from treatment with another medicine. However, these adverse effects disappear once the ELIPSODOX dose has been stabilised.
Ask your doctor whether you can drive or operate machinery.

3. How to take ELIPSODOX

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

ELIPSODOX is a prolonged-release tablet, which means that the active substances it contains are released slowly over an extended period of time. The effect lasts for 12 hours.

The prolonged-release tablet must be swallowed whole to ensure the slow release of hydrochloride oxycodone from the tablet. The tablets must not be broken, chewed, or crushed. Swallowing broken, chewed, or crushed tablets may result in the absorption of a potentially lethal dose of hydrochloride oxycodone (see section 3: "If you take more ELIPSODOX than you should").

In the absence of any other medical prescription, the recommended dose is:

For the treatment of pain

Adults

The recommended starting dose of ELIPSODOX is one prolonged-release tablet containing 10 mg of hydrochloride oxycodone/5 mg of hydrochloride naloxone, every 12 hours.

Your doctor will decide how much you should take each day and how to distribute the 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 will be given the lowest dose necessary to relieve your pain. If you have previously been treated with opioids, treatment with ELIPSODOX may be initiated at a higher dose.

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

If you switch from these tablets to another opioid medicine for pain treatment, your intestinal function may worsen.

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

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

Elderly

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

Hepatic or renal impairment

If you have impaired renal function or mild hepatic impairment, your doctor will prescribe these tablets with particular caution. If you have moderate or severe hepatic impairment, these tablets must not be used (see also section 2 "Do not take ELIPSODOX..." and "Warnings and precautions").

Children and adolescents under 18 years of age

ELIPSODOX has not yet been studied in children and adolescents under 18 years of age. Its safety and efficacy have not been established in this population. Therefore, the use of these tablets in children and adolescents under 18 years of age should be avoided.

Method of administration

Oral use

Swallow these tablets whole, without chewing, with an adequate amount of liquid (½ glass of water). You may take the prolonged-release tablets with or without food. Take these tablets every 12 hours according to a fixed schedule (e.g., 8 a.m. and 8 p.m.). The prolonged-release tablets must not be broken, chewed, or crushed (see section 2 "Warnings and precautions").

Instructions for opening

This medicine is contained in a blister pack with single doses protected by a foil, perforated lines, and child-resistant closure.

Three line illustrations show how to separate a blister pack, open the individual wrapper, and handle the medical device

Detach a single dose by tearing along the perforated line of the blister and lift the protective foil from the blister to remove the tablet.

Duration of use

In general, you should not take these tablets for longer than necessary. If you have been on long-term treatment with ELIPSODOX, your doctor should regularly assess whether continued use of these tablets is still necessary.

If you take more ELIPSODOX than you should

If you have taken a dose of these tablets higher than prescribed, you must inform your doctor immediately.

An overdose may cause:

constricted pupils
slow and shallow breathing (respiratory depression)
drowsiness progressing to unconsciousness
low muscle tone (hypotonia)
reduced pulse rate
drop in blood pressure.

In severe cases, unconsciousness (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 vehicles, should be avoided.

If you forget to take ELIPSODOX

If you miss a dose or take a lower dose than prescribed, you may not experience any analgesic effect.

If you forget to take your 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 your next tablet, trying to return to your original dosing schedule (e.g., 8 a.m. and 8 p.m.). Do not take more than one tablet within an 8-hour period.

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

If you stop taking ELIPSODOX

Do not stop treatment without consulting your doctor.

If further treatment is not required, you must gradually reduce the daily dose after discussing it with your doctor. This will help you avoid withdrawal symptoms such as restlessness, excessive sweating, 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 everyone gets them.

Important side effects or signs to watch for, and what to do if they occur:
If you notice any of the following important side effects, consult your doctor immediately.
Slow and shallow breathing (respiratory depression) is the main danger in opioid overdose. This occurs especially in elderly and debilitated (weak) patients. Opioids may also cause a severe drop in blood pressure in predisposed patients.

Common (may occur in up to 1 in 10 patients)

abdominal pain – feeling unwell – unusual sensation
constipation – flatulence (gas) – weakness
diarrhoea – reduced appetite up to loss of appetite – fatigue and exhaustion
dry mouth – itchy skin
indigestion – dizziness or “dizzy spells” – skin reactions/irritation
vomiting (feeling sick) – sweating
headache – hot flushes
dizziness – difficulty sleeping
drowsiness

Uncommon (may occur in up to 1 in 100 patients)

abdominal swelling
abnormal thoughts
anxiety
confusion
depression
nervousness
chest tightness
palpitations – runny nose
biliary colic – cough
chest pain – hypersensitivity/allergic reactions
general malaise – weight loss
pain – injuries
swelling of hands, ankles or feet – increased urge to urinate, especially if you already have coronary heart disease
difficulty concentrating – muscle cramps
low blood pressure – impaired speech – muscle contractions
muscle pain – withdrawal symptoms – tremors
breathing difficulty – vision impairment
fainting – agitation – seizures
lack of energy – chills (particularly in people with epilepsy or predisposition to convulsions)
thirst – increased liver enzymes
altered taste – increased blood pressure
reduced sexual drive

Rare (may occur in up to 1 in 1,000 patients)

increased pulse rate – dental abnormalities – weight gain
yawning
drug dependence

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

euphoric mood – hallucinations – tingling of the skin
severe drowsiness – shallow breathing – apnoea during sleep (pauses in breathing during sleep)
nightmares – difficulty urinating
aggression – eructation (belching)

The active substance oxycodone hydrochloride, when not in combination with naloxone hydrochloride, has the following side effects:

Oxycodone may cause breathing problems (respiratory depression), reduced pupil size (miosis), bronchial muscle spasms, and spasms of smooth muscles, as well as suppression of the cough reflex.

Common (may occur in up to 1 in 10 patients)

mood changes – reduced activity – difficulty urinating
changes in personality (e.g., depression, feeling of extreme happiness) – increased activity – hiccups

Uncommon (may occur in up to 1 in 100 patients)

impaired concentration – reduced sensitivity to pain or touch – gum pain
disturbances in perception (e.g., hallucinations, derealization)
migraine – abnormal coordination
increased muscle tension – voice changes (dysphonia) – skin flushing
involuntary muscle contractions – fluid retention – dehydration
hearing difficulty – agitation
intestinal dysfunction (ileus) – mouth ulcers – difficulty swallowing
dry skin
reduced levels of sex hormones that may impair sperm production in men or the menstrual cycle in women
drug tolerance

Rare (may occur in up to 1 in 1,000 patients)

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

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

acute generalized allergic reactions (anaphylactic reactions) – absence of menstruation – impaired bile flow
neonatal withdrawal symptoms – increased sensitivity to pain
dental caries

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor or pharmacist. You can 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 ELIPSODOX

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the outer label and on the blister, after "Exp.". The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines 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 ELIPSODOX contains
The active substances are: oxycodone hydrochloride and naloxone hydrochloride.
ELIPSODOX 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 2.75 mg of naloxone hydrochloride
dihydrate, equivalent to 2.25 mg of naloxone.
ELIPSODOX 10 mg/5 mg
Each prolonged-release tablet contains 10 mg of oxycodone hydrochloride, equivalent to
9.0 mg of oxycodone, and 5 mg of naloxone hydrochloride as 5.5 mg of naloxone hydrochloride
dihydrate, equivalent to 4.5 mg of naloxone.
ELIPSODOX 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 11 mg of naloxone hydrochloride
dihydrate, equivalent to 9.01 mg of naloxone.
ELIPSODOX 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 22 mg of naloxone hydrochloride
dihydrate, equivalent to 18.02 mg of naloxone.

The other components are:
Tablet core: Hypromellose 603, Polyvinyl acetate dispersion 30%, Povidone K30,
Sodium lauryl sulfate, Microcrystalline cellulose PH 102, Silica, Magnesium stearate.

ELIPSODOX 5 mg/2.5 mg
Tablet coating: Polyvinyl alcohol, Titanium dioxide (E171), Macrogol 3350,
Talc, Brilliant Blue FCF-aluminum lake (E133).

ELIPSODOX 10 mg/5 mg
Tablet coating: Polyvinyl alcohol, Titanium dioxide (E171), Macrogol 3350,
Talc.

ELIPSODOX 20 mg/10 mg
Tablet coating: Polyvinyl alcohol, Titanium dioxide (E171), Macrogol 3350,
Talc, Iron oxide red (E172), Iron oxide yellow (E172).

ELIPSODOX 40 mg/20 mg
Tablet coating: Polyvinyl alcohol, Titanium dioxide (E171), Macrogol 3350,
Talc, Iron oxide red (E172), Iron oxide yellow (E172), Iron oxide black (E172).

Description of the appearance of ELIPSODOX and contents of the pack
Prolonged-release tablet
ELIPSODOX 5 mg/2.5 mg
Blue, 9.6x4.8 mm, elliptical, biconvex coated tablet, engraved with "5" on one side.
ELIPSODOX 10 mg/5 mg
White to off-white, 9.6x4.8 mm, elliptical, biconvex coated tablet, engraved with "10"
on one side.
ELIPSODOX 20 mg/10 mg
Pink, 9.6x4.8 mm, elliptical, biconvex coated tablet, engraved with "20" on one side.
ELIPSODOX 40 mg/20 mg
Yellow, 11x5.5 mm, elliptical, biconvex coated tablet, engraved with "40" on one side.

ELIPSODOX prolonged-release tablets are available in packages containing 28 x 1 tablets.

Marketing Authorization Holder
L. Molteni & C. dei F.lli Alitti Società di Esercizio SpA
Strada Statale 67, Loc. Granatieri
50018 Scandicci (Florence) – Italy

Manufacturer:
ETHYPHARM
Chemin de la Poudrière
76120 Grand Quevilly
France
L. Molteni & C. dei F.lli Alitti Società di Esercizio SpA
Strada Statale 67, Loc. Granatieri
50018 Scandicci (Florence) – Italy

This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Germany: Oxycodon-HCl/Naloxon-HCl Ethypharm 5 mg/2.5 mg, 10/5 mg, 20/10 mg, 40 mg/20 mg Retardtabletten
Italy: ELIPSODOX 5 mg/2.5 mg, 10/5 mg, 20/10 mg, 40 mg/20 mg prolonged-release tablets

Elipsodox