MEDEPIDOL

Patient Information Leaflet

Medepidol 4 mg prolonged-release tablets, 8 mg prolonged-release tablets, 16 mg prolonged-release tablets, 24 mg prolonged-release tablets

Hydrochloride hydromorphone
Please read this leaflet carefully before taking this medicine because it contains important information for you.

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

Contents of this leaflet:

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

1. What Medepidol is and what it is used for

Medepidol is a strong painkiller that belongs to a group of medicines called opioids.
Medepidol is used to relieve severe pain.

2. What you need to know before taking Medepidol

Do not take Medepidol:

• if you are allergic to hydromorphone or any of the other ingredients of this medicine (listed in section 6)
• if you suffer from severe respiratory centre or breathing function disorders (respiratory depression)
• if you have a severe, chronic airway disease with airway obstruction
• if you have severe bronchial asthma
• if you have sudden abdominal pain (acute abdomen)
• if intestinal motility is impaired (paralytic ileus)
• if you are taking certain medicines for depression or Parkinson’s disease (monoamine oxidase inhibitors [MAOIs]), or if you have taken such medicines within the last 2 weeks

Medepidol must not be used in patients who are comatose.
Warnings and precautions
Talk to your doctor or pharmacist before taking Medepidol.
Special caution is needed while taking Medepidol:

• if you are elderly and in poor general health
• if you suffer from chronic lung disease with airway obstruction or reduced lung function (such as asthma)
• if you have breathing problems during sleep (sleep apnoea)
• if you have a head injury, brain lesion, increased intracranial pressure, or an altered state of consciousness of unknown origin (due to the risk of opioids increasing intracranial pressure)
• if you suffer from seizures, epileptic fits, or epilepsy (seizure disorder)
• if you have low blood pressure (hypotension) with low blood volume (hypovolemia)
• if you suffer from inflammation of the pancreas (pancreatitis)
• if you have an underactive thyroid (hypothyroidism)
• if you have gallbladder, biliary, or kidney problems (colic)
• if you suffer from a mental disorder called toxic psychosis
• if you have an enlarged prostate gland (prostatic hypertrophy)
• if you have intestinal problems such as intestinal inflammation or obstruction
• if you suffer from reduced adrenal gland function (e.g. Addison’s disease)
• if you have severe kidney or liver problems
• if you experience withdrawal symptoms such as restlessness, anxiety, tremors, or sweating after stopping alcohol or drug use
• if you suffer from constipation

If any of the above apply or have applied to you in the past, consult your doctor, as you may require a lower dose of tablets under any of the above conditions.
Tolerance, dependence, and addiction
This medicine contains hydromorphone, which is an opioid substance. It may cause dependence and/or
addiction.
This medicine contains hydromorphone, an opioid. Repeated use of opioid analgesics may make the medicine less effective over time, as your body becomes accustomed to it—a phenomenon known as drug tolerance.
Repeated use of Medepidol may also lead to dependence, abuse, and addiction, which could result in potentially fatal overdose. The risk of these adverse effects may increase with higher doses and prolonged duration of use.
Dependence or addiction may make you feel as though you no longer have control over how much medicine you take or how often you take it.
The risk of developing dependence or addiction varies from person to person. You may have a higher risk of becoming dependent on or addicted to Medepidol if:

• you or a family member have previously suffered from alcohol, prescription medicine, or illegal substance abuse or dependence ("addiction").
• you are a smoker.
• you have previously had mood disorders (depression, anxiety, or a personality disorder) or have been treated by a psychiatrist for other mental illnesses.

If you notice any of the following symptoms while taking Medepidol, it may be a sign of dependence or addiction:

• You feel the need to take the medicine for longer than prescribed by your doctor.
• You feel the need to take a higher dose than recommended.
• You feel compelled to continue taking the medicine even if it does not relieve pain.
• You use the medicine for reasons other than prescribed, e.g., “to stay calm” or “to help sleep”.
• You have repeatedly tried to stop or control your use of this medicine without success.
• When you stop taking the medicine, you feel unwell, and you feel better when you start taking it again (“withdrawal symptoms”).

If you notice any of these symptoms, consult your doctor to discuss the best treatment approach for you, including whether it is appropriate to stop treatment and how to do so safely (see section 3, If you stop taking Medepidol).
Respiratory depression
The most significant risk of opioid overdose is slowed or reduced breathing (respiratory depression).
Sleep-related breathing disorders
Medepidol may cause sleep-related breathing disorders such as sleep apnoea (breathing pauses during sleep) and sleep-related hypoxaemia (low blood oxygen levels). Symptoms may include breathing pauses during sleep, nighttime awakenings due to breathlessness, difficulty maintaining sleep, or excessive daytime sleepiness. If you or someone else observes these symptoms, contact your doctor. Your doctor may consider reducing the dose.
Surgery
Medepidol is not recommended before or within 24 hours after surgery. After this period, Medepidol should be used with caution, especially after abdominal surgery.
Medepidol must not be used in cases of suspected or actual absence of intestinal motility (paralytic ileus).
If paralytic ileus is suspected or occurs during treatment, therapy with hydromorphone must be stopped immediately.
If you are about to receive additional pain therapy (e.g. surgery, plexus block), you must not take hydromorphone 12 hours before the procedure. Afterwards, the dose will be adjusted again. This will be done by your doctor, if necessary.
Despite increasing doses of this medicine, you may experience increased sensitivity to pain (hyperalgesia). Your doctor will decide whether the dose needs to be changed or if a switch to another strong analgesic (“painkiller”) is necessary.
Hormonal changes may occur during treatment with this medicine. Your doctor may wish to monitor these changes.
Children and adolescents
The use of Medepidol is not recommended in children under 12 years of age (see section 3).
Doping
Athletes should be aware that this medicine, due to its active ingredient, may cause a positive result in “anti-doping tests”. The use of Medepidol as a doping agent may pose a health risk.
Other medicines and Medepidol
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
If taken together with other medicines that depress brain function or with alcohol, the side effects of Medepidol or the other medicine may be enhanced, e.g., drowsiness and impaired respiratory function.
Concurrent use of Medepidol with other centrally-acting medicines (which depress brain function) may increase the side effects of both medicines. The risk of drowsiness (sedation), impaired respiratory function (respiratory depression), and coma increases and may be life-threatening. Such depressant medicines include:

• medicines for anxiety (tranquillisers)
• medicines for narcosis (anaesthetics such as barbiturates)
• medicines for psychiatric or mental disorders (neuroleptics)
• medicines that promote sleep (hypnotics or sedatives)
• medicines for depression (antidepressants)
• medicines for allergies or nausea (antihistamines or antiemetics)
• other opioids (strong painkillers).

Concomitant use of Medepidol with sedative medicines such as benzodiazepines (which may help reduce anxiety and seizures, relax muscles, and induce sleep) or similar medicines increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. Therefore, concomitant use should only be considered when no other therapeutic options are available. Concomitant use of opioids and medicines used to treat epilepsy, neuralgia, or anxiety (gabapentin and pregabalin) increases the risk of opioid overdose, respiratory depression, and may be life-threatening.
If your doctor prescribes Medepidol together with sedative medicines, the dose and duration of concomitant treatment must be limited by your doctor.
Inform your doctor about all sedative medicines you are taking and follow the prescribed dose carefully. It may be helpful to inform friends or relatives about the signs and symptoms described above. Contact your doctor if such symptoms occur.
Medepidol must not be taken if you are using medicines for depression called monoamine oxidase inhibitors (MAOIs), or within 2 weeks after stopping such medicines (see section 2 “Do not take Medepidol”).
Concurrent use of Medepidol with certain muscle relaxants may increase breathing difficulties (respiratory depression).
Medepidol and alcohol
Drinking alcohol during treatment with Medepidol may cause drowsiness or increase the risk of serious side effects such as shallow breathing, risk of respiratory arrest, and loss of consciousness. You must not drink alcohol while taking Medepidol.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, plan to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
You must not take Medepidol during pregnancy unless specifically instructed by your doctor.
If Medepidol is administered during pregnancy and labour, uterine contractions may be impaired. In addition, there is a risk of slow and shallow breathing (respiratory depression) in the newborn.
Newborns may experience withdrawal symptoms (such as high-pitched crying, irritability, seizures, poor feeding, and diarrhoea) if their mothers have taken hydromorphone for a prolonged period during pregnancy.
Breastfeeding
Medepidol must not be used if you are breastfeeding, as the active substance may pass into breast milk. If use is necessary, breastfeeding must be discontinued.
Driving and using machines
Medepidol has a mild to moderate influence on the ability to drive and use machines. This is particularly likely at the beginning of hydromorphone treatment, after a dose increase, or when switching medicines. It is also likely if Medepidol is taken together with alcohol or other medicines that depress the central nervous system. If you are stable on a specific dose, your ability may not necessarily be impaired. Therefore, you should consult your doctor to determine whether you can drive or operate machinery.
Medepidol contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially "sodium-free".

3. How to take Medepidol

Take this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Adults and adolescents over 12 years
The dose depends on the severity of pain and previous need for painkillers.
Unless otherwise directed by your doctor, the usual initial dose is 4 mg every 12 hours.
The dose should be gradually increased until optimal pain relief is achieved. In principle, a sufficiently high dose should be administered, while at the same time selecting the lowest effective dose to relieve pain for the individual patient.
For the treatment of chronic pain, Medepidol should be taken at fixed times (e.g., in the morning at 8 a.m. and in the evening at 8 p.m.). The dosing interval should therefore not be less than 12 hours.
You should only take higher doses of Medepidol if you no longer achieve sufficient pain relief.
This does not apply to chronic pain therapy with lower doses of hydromorphone or other analgesics of equivalent potency.
Once an effective dose of Medepidol has been reached, do not switch to other strong painkillers (opioid analgesic preparations). A clinical evaluation and careful dose adjustment by the doctor will be necessary. Otherwise, continuous pain relief cannot be guaranteed.
Use in children
The use of Medepidol is not recommended in children under 12 years of age. Clinical studies on the use of Medepidol in children have not been conducted. Therefore, no dosage recommendations can be provided for this patient group.
Elderly
Elderly patients may require a lower dose to achieve adequate pain relief.
Liver and kidney problems
If you have impaired liver or kidney function, you may need lower doses than other patients to achieve adequate pain relief. Therefore, the dose of Medepidol must be adjusted with particular care.
Contact your doctor if you feel that the effect of Medepidol is too strong or too weak.
Method of administration
Medepidol is for oral use.
The tablets may be divided into equal doses.
Swallow the prolonged-release tablets of Medepidol whole with sufficient liquid (½ glass of water). The prolonged-release tablets must not be chewed or crushed, as this could lead to a rapid release of hydromorphone and cause symptoms of hydromorphone overdose (see below “If you take more Medepidol than you should”).
How to open the child-resistant blister pack

1. Tear off a single dose along the perforation line of the blister.
2. This exposes an unsealed area located where the perforation lines intersect.
3. Pull the unsealed label to remove the covering film.

Duration of treatment
Do not take Medepidol longer than necessary. The treatment should be regularly reassessed regarding pain relief and other effects in order to achieve optimal pain therapy, promptly manage any adverse effects, and consider whether continued treatment is appropriate.
If you take more Medepidol than you should
If you have taken more prolonged-release tablets than prescribed, inform your doctor immediately. The following symptoms may occur: constricted pupils (miosis), slowed heartbeat (bradycardia), reduced breathing (respiratory depression), drop in blood pressure (hypotension), and increased drowsiness (somnolence), progressing to stupor or loss of consciousness (coma). In severe cases, circulatory collapse or deep unconsciousness (coma) may occur, which can be fatal.
Pneumonia may develop (possible symptoms: shortness of breath, cough, and fever), caused by aspiration of vomit or foreign substances.
In the most severe cases, circulatory failure or deep coma may occur, which can be fatal.
Under no circumstances should you expose yourself to situations requiring high concentration, such as driving a vehicle.
In case of overdose, the following measures may be reasonable until the doctor arrives: keep the person awake, give breathing instructions, support respiration.
If you forget to take Medepidol
Do not take a double dose to make up for a missed tablet.
If you take a lower dose than indicated or skip taking the prolonged-release tablets, pain relief will be correspondingly insufficient or cease completely.
If you have forgotten to take a tablet, you may take the missed dose. In principle, you should not take Medepidol more than once every 12 hours.
If you stop taking Medepidol
Do not stop taking Medepidol without consulting your doctor.
If you stop taking Medepidol after prolonged use, withdrawal symptoms may occur (e.g., restlessness, anxiety, nervousness, inability to sleep, involuntary movements, tremors, and stomach/intestinal disturbances). If treatment is no longer necessary, it should be discontinued by gradually reducing the dose.
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 experiences them.
This medicine may cause allergic reactions (hypersensitivity), which can be severe (anaphylactic reactions). The frequency of these reactions is unknown. Contact your doctor immediately if
you experience sudden shortness of breath, breathing difficulties, swelling of the eyelids, face, lips, mouth or throat, or skin rashes or itching, particularly if widespread over the body.
The most serious risk of opioid overdose is a condition in which your breathing becomes slower or more shallow (respiratory depression); see section 3 "If you take more Medepidol than you should".
Most people will experience constipation while taking this medicine. Increasing dietary fibre (fruit, vegetables, wholemeal bread, pasta, brown rice) and fluid intake may help reduce this problem, but if needed, your doctor may prescribe a laxative. If you already have constipation problems before starting treatment, you should begin taking laxatives from the outset. Consult your doctor.
You may feel nauseous or vomit during treatment with this medicine. This usually improves after a few days, but your doctor may prescribe an anti-emetic medicine if the problem persists.

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

• dizziness, drowsiness
• constipation, feeling unwell

Common (may affect up to 1 in 10 people)

• loss of appetite
• anxiety, confusion, difficulty sleeping
• headache
• low blood pressure
• abdominal pain, dry mouth, vomiting
• itching, sweating
• sudden need to urinate
• feeling weak

Uncommon (may affect up to 1 in 100 people)

• restlessness, depression, euphoria, hallucinations, nightmares
• tremors or uncontrolled muscle movements (myoclonus), abnormal skin sensations (pins and needles)
• blurred vision
• shortness of breath
• indigestion, diarrhoea, altered taste
• changes in liver function blood tests (increased liver enzymes)
• skin rash
• difficulty urinating
• erectile dysfunction, decreased sex drive
• withdrawal symptoms such as: restlessness, anxiety, nervousness, difficulty sleeping, tremors or stomach/intestinal disturbances, tiredness, swelling of the feet, ankles or hands, general feeling of being unwell

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

• sedation, lethargy
• fast heartbeat, slow heartbeat, palpitations
• difficulty breathing (respiratory depression), uncontrolled tightening of the muscles around the airways (bronchospasm)
• changes in blood tests related to pancreatic function
• flushing of the face

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

• seizures, uncontrolled movements (dyskinesia), increased sensitivity to pain (hyperalgesia)
• biliary colic

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

• hypersensitivity, anaphylactic reactions
• medicine dependence, dysphoria
• sleep apnoea (breathing pauses during sleep)
• pinpoint pupils
• hot flushes
• condition in which the bowel does not work properly (paralytic ileus)
• urticaria
• tolerance to the medicine, withdrawal symptoms in babies born to mothers who used hydromorphone (see section 2 "Pregnancy and breastfeeding").

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

5. How to store Medepidol

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and 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 any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Medepidol contains

• The active substance is hydromorphone hydrochloride. Each prolonged-release tablet contains 4 mg of hydromorphone hydrochloride (equivalent to 3.55 mg of hydromorphone). Each prolonged-release tablet contains 8 mg of hydromorphone hydrochloride (equivalent to 7.09 mg of hydromorphone). Each prolonged-release tablet contains 16 mg of hydromorphone hydrochloride (equivalent to 14.19 mg of hydromorphone). Each prolonged-release tablet contains 24 mg of hydromorphone hydrochloride (equivalent to 21.28 mg of hydromorphone).
• The other components are: Tablet core: microcrystalline cellulose, hypromellose, ethylcellulose, hydroxypropylcellulose, propylene glycol, talc, sodium carmellose, magnesium stearate, anhydrous colloidal silica. Tablet coating: hypromellose, macrogol 6000, talc, titanium dioxide (E171). Medepidol 8 mg also contains: iron oxide red (E172). Medepidol 16 mg also contains: iron oxide yellow (E172).

Description of the appearance of Medepidol and the contents of the pack
Medepidol 4 mg are film-coated tablets, white to off-white in colour, round, biconvex, with score lines on both sides.
The tablet can be divided into equal doses.
Medepidol 8 mg are film-coated tablets, pink in colour, oblong, biconvex, with score lines on both sides.
The tablet can be divided into equal doses.
Medepidol 16 mg are film-coated tablets, light yellow in colour, oblong, biconvex, with score lines on both sides.
The tablet can be divided into equal doses.
Medepidol 24 mg are film-coated tablets, white to off-white in colour, oblong, biconvex, with score lines on both sides.
The tablet can be divided into equal doses.
The prolonged-release tablets are available in child-resistant Alu/PVC-PE-PVDC blisters.
Packs:
10, 30, 60 prolonged-release tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
G.L. Pharma GmbH, Schlossplatz 1, 8502 Lannach, Austria

Manufacturer
G.L. Pharma GmbH
Industriestrasse 1,
8502 Lannach
Austria
Develco Pharma GmbH
Grienmatt 27
79650 Schopfheim
Germany

This medicinal product is authorised in the European Economic Area Member States under the following names:
Germany Hydagelan 4 mg, 8 mg, 16 mg, 24 mg Retardtabletten
France Hydagelan LP 4 mg, 8 mg, 16 mg, 24 mg, comprimé sécable à libération prolongée
Italy Medepidol