Leaflet:information for the user

Oramorph 20 mg/ml oral solution

Morphine, sulfate

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

• Keep this leaflet, as you may need to read it again.
• 1. If you have any doubts, consult yourdoctor or pharmacist.

-This medicine has been prescribedonlyfor you, and you must not give it to others even if they havethe same symptomsas you,as it may harm them.

• If you experience any side effects,consultyour doctor or pharmacist,evenif they are not listed in this leaflet. See section 4.

1.What isOramorphand what it is used for

2.What you need to knowbeforestarting totakeOramorph

3.How to take Oramorph

4.Possible side effects

5Storage ofOramorph

6.Contents of the pack and additional information

Oramorph belongs to a group of medications known as narcotic analgesics.

This medication is used for the prolonged treatment of severe chronic pain and for the relief of post-operative pain.

Do not takeOramorph

• if you are allergic to morphine or any of the other ingredients in this medicine (listed in section 6).
• if you have respiratory depression or are breathing with the help of a machine.
• if you have a severe or acute bronchial obstruction.
• if you have increased intracranial pressure.
• if you have paralytic ileus or acute abdominal pain of unknown cause.
• if you have severe liver disease.
• if you have convulsive disorders.
• if you have a head injury or increased intracranial pressure.
• if you are taking inhibitors of monoamine oxidase (MAO), buprenorphine, nalbuphine, or pentazocine (seeOther medicines and Oramorph).
• if you are under 1 year old.
• if you are pregnant.
• if you are breastfeeding.
• if you have been operated on within the last 24 hours.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Oramorph:

• if you have convulsive disorders.
• if you have increased intracranial hypertension.
• if you have hypotension with hypovolemia.
• in case of opioid dependence.
• if you have acute liver disease.
• in case of acute alcoholism.
• if you have chronic liver or kidney disease.
• if you have hypothyroidism.
• if you have adrenal cortical insufficiency.
• in case of conditions with reduced respiratory reserve, such as kyphoscoliosis, emphysema, and severe obesity.
• if you are at risk of developing paralytic ileus or have chronic constipation.
• if you have biliary, intestinal, or urogenital obstruction.
• in case your ability to maintain blood pressure is compromised due to decreased blood volume or administration of drugs such as phenothiazines or certain anesthetics, as morphine may cause severe hypotension.
• if you are to undergo surgical procedures for pain relief, do not take Oramorph within 24 hours of the operation.

Consult your doctor, pharmacist, or nurse if you experience any of the following symptoms while taking this medicine:

• increased sensitivity to pain despite taking increasing doses (hyperalgesia). Your doctor will decide if you need a dose adjustment or switch to a potent analgesic (see section 2).
• weakness, fatigue, decreased appetite, nausea, vomiting, or low blood pressure. This could indicate that your adrenal glands are producing insufficient amounts of cortisol, and you may need to take hormone supplements.
• loss of libido, impotence, cessation of menstruation. This could be due to reduced production of sex hormones.
• if you have a history of alcoholism or drug addiction. Also inform your doctor if you think you are starting to depend on Oramorph while using it. You may have started thinking too much about when you can take the next dose, even if you don't need it for pain.
• generalized acute pustular exanthema (PEGA) associated with morphine treatment has been reported. Symptoms usually occur within the first 10 days of treatment. Inform your doctor if you have ever suffered from severe skin rash or skin peeling, blisters, and/or mouth sores after taking Oramorph or other opioids. Stop using Oramorph and seek medical attention immediately if you notice any of the following symptoms: blisters, widespread skin peeling, or pus-filled spots (pustules) with fever.
• sleep-related respiratory disorders. Oramorph may cause sleep-related respiratory 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, nocturnal awakenings due to dyspnea, difficulty maintaining sleep, or excessive daytime somnolence. If you or someone else observes these symptoms, contact your doctor. Your doctor may consider reducing the dose.
• contact your doctor if you experience severe upper abdominal pain that may radiate to the back, nausea, vomiting, or fever, as it could be a sign of pancreatitis and biliary tract inflammation.

Tolerance, dependence, and addiction

This medicine contains morphine, an opioid. Repeated use of opioids can lead to reduced effectiveness of the medicine (becoming accustomed to it, known as tolerance). Repeated use of Oramorph can also cause dependence, abuse, and addiction, which could lead to a potentially fatal overdose. The risk of these adverse effects may be higher with a higher dose and longer use.

Dependence or addiction can cause a feeling of lack of control over the amount of medicine you should use or the frequency with which you should use it.

The risk of dependence or addiction varies from person to person. You may have a higher risk of dependence or addiction to Oramorph if:

• You or any family member has abused or had dependence on prescription medications or illegal drugs ("addiction").
• You smoke.
• You have had any problems with your mood (depression, anxiety, or personality disorder) or have been treated by a psychiatrist for other mental illnesses.

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

You need to take the medicine for a longer period than recommended by your doctor.

• You need to take a higher dose than recommended.
• You are using the medicine for reasons other than those prescribed, such as "to stay calm" or "to help you sleep."
• You have made repeated and unsuccessful attempts to stop using the medicine or control its use.
• You feel unwell when you stop using the medicine, and you feel better once you take it again ("withdrawal symptoms").

If you notice any of these symptoms, consult your doctor to determine the best course of treatment for you, including when it is appropriate to stop the medicine and how to do it safely (see section 3 "If you interrupt treatment with Oramorph).

Other medicines and Oramorph

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medicine.

Certain medicines may interact with Oramorph; in these cases, you may need to change the dose or stop taking one of them, as they may put your life at risk and affect the central nervous system, respiratory system, and circulatory function.

It is essential to inform your doctor if you are taking or have taken recently any of the following medicines:

• Anesthetics.
• Hypnotics (sleep-inducing medicines).
• Sedatives and phenothiazines.
• Tricyclic antidepressants.
• Other morphine derivatives (analgesics and cough medicines).
• Antihistamines H1 sedatives (allergic medicines).
• Antihypertensives (blood pressure-lowering medicines).
• Benzodiazepines or other tranquilizers.
• Antipsychotics and related substances.
• MAO inhibitors (monoamine oxidase).
• Muscle relaxants.
• Rifampicin, for example, to treat tuberculosis.
• Some medicines used to treat blood clots (e.g., clopidogrel, prasugrel, ticagrelor) may have a delayed and reduced effect when taken with morphine.
• Gabapentin or pregabalin for the treatment of epilepsy and pain caused by nerve problems (neuropathic pain).
• The concomitant use of this medicine and sedatives such as benzodiazepines or other related medicines increases the risk of somnolence, respiratory depression, coma, and may be potentially fatal. Therefore, concomitant use should only be considered when other treatment options are not possible. However, if your doctor prescribes this medicine along with sedatives, you should limit the dose and duration of concomitant treatment. Inform your doctor of all sedatives you are taking and follow your doctor's recommendations strictly about the dose. It may be helpful to inform friends or family members to recognize the signs and symptoms mentioned above. Contact your doctor if you have these symptoms.

Agonists/antagonists of morphine (buprenorphine, nalbuphine, pentazocine) should not be administered together with morphine, as they reduce its analgesic effect, with a risk of withdrawal syndrome.

Oramorph with food, drinks, and alcohol

The concomitant administration of alcoholic beverages with this medicine may exacerbate the side effects of morphine, particularly increasing central depression with inhibition of respiratory function.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medicine.

This medicine is contraindicated during pregnancy.

If you use this medicine for a prolonged period during pregnancy, there is a risk that the newborn may experience withdrawal symptoms, which should be treated by a doctor.

Morphine is contraindicated during breastfeeding, as it is excreted in milk.

Driving and operating machinery

This medicine may affect your ability to react, so do not drive or use any hazardous tools or machinery while taking it, especially if you take it with alcohol or central nervous system depressants.

Oramorph contains benzoate of sodium (E-211) and sodium

This medicine contains 1 mg of benzoate of sodium (E-211) per ml. Benzoate of sodium may increase the risk of jaundice (yellowing of the skin and eyes) in newborns (up to 4 weeks old).

This medicine contains less than 1 mmol of sodium (23 mg) per ml; it is essentially "sodium-free."

It is reported to athletes that this medicine contains a component that may result in a positive analytical result for doping control.

Follow exactly the administration instructions of this medication as indicated by your doctor.This medication should be taken exactly as directed by your doctor.In case of doubt, consult your doctor or pharmacist again.

Before starting treatment and periodically during treatment, your doctor will explain what you can expect from the use of Oramorph, when and how long you need to take it, when to contact your doctor, and when to interrupt it (see also the section "If you interrupt treatment with Oramorph).

Remember to take your medication.

If you estimate that the action of this medication is too strong or too weak, inform your doctor or pharmacist.

The dose depends on the intensity of the pain and the patient's previous medical history.

It should be administered orally, as indicated by your doctor.

Use in adults and adolescents 13 years and older)

The usual initial dose of morphine sulfate is 10 - 20 mg, corresponding to 8 - 16 dropsor 0.5 - 1 mlof oral solution, administered every 4 - 6 hours.

Use in children

• Children 6 to 13 years old

The maximum dose is 5 - 10 mg of morphine sulfate,corresponding to 4 - 8 drops or 0.25 - 0.5 ml of oral solution,administered every 4 hours.

• Children 1 to 5 years old

This medication will be used forchildrenwho require high doses, also administered at 4-hour intervals.

• It is notrecommendedfor use in children under 1 year old.

Use in patients over 65 years old

It should be administered with caution in patients over 65 years old, as they are especially sensitive to central (confusion) or gastrointestinal side effects and their renal function is physiologically reduced, requiring a reduction in the initial dose.

The dose may be increased under medical supervision depending on the severity of the pain and the patient's previous history of analgesic requirements. An increase in doses to control pain generally does not imply the development of tolerance.

It is recommended to reduce the dose in debilitated patients.

The duration of treatment required by each patient is variable depending on the persistence of pain. Your doctor will indicate the duration of your treatment with this medication. Do not stop treatment before.

Administration form

The solution should be added to a light drink immediately before administration.

• How to measure the dose from the 20 ml bottle: It is recommended to dose the oral solution in drops using the built-in drop counter. For example:

• 4 drops correspond to 5 mg
• 8 drops correspond to 10 mg
• 16 drops correspond to 20 mg

• How to measure the dose from the 100 ml bottle: It is recommended to dose the oral solutionin millilitersusing the graduated syringe. The syringe should not be used to measure drops. For example:

• 0.25 ml corresponds to 5 mg
• 0.5 ml corresponds to 10 mg
• 1 ml corresponds to 20 mg

If you take moreOramorphthan you should

In case of mild or moderate overdose of morphine, symptoms include deep sleep, pinpoint pupils, decreased blood pressure, decreased body temperature, and decreased heart rate. With higher doses, coma is accompanied by respiratory depression and lack of breathing, which can be fatal.

The appearance of drowsiness is an early sign of respiratory depression.

People who have taken an overdose may experience pneumonia from inhaling vomit or foreign particles; symptoms may include shortness of breath, cough, and fever.

People who have taken an overdose may also experience difficulty breathing that causes loss of consciousness or even death.

If you have taken more medicationthan you should, consult your doctor or pharmacist immediately orthe Toxicology Information Service, phone (91) 562 04 20,indicating the medication and the amount used.

If you forget to takeOramorph

Do not take a double dose to compensate for the missed doses.

If you interrupt treatment withOramorph

Do not stop treatment with this medication unless your doctor approves. If you want to stop treatment, ask your doctor how to gradually reduce the dose to avoid withdrawal symptoms.

Withdrawal symptoms begin generally a few hours after treatment interruption, reaching a maximum at 36-72 hours and gradually subsiding thereafter. Symptoms include generalized pain, yawning, dilated pupils (mydriasis), lacrimation, intense nasal secretion (rhinorrhea), sneezing, muscle tremors, headaches, weakness, sweating, anxiety, irritability, sleep disturbances or insomnia, restlessness, orgasm, abdominal pain, anorexia, nausea, vomiting, weight loss, diarrhea, dehydration, bone pain, abdominal and muscle cramps, flu-like symptoms, palpitations, increased heart rate, respiratory rate, blood pressure, and temperature, and vasomotor changes. Psychological symptoms include a deep sense of dissatisfaction, anxiety, and irritability.

Morphine is a narcotic that can be used for unintended purposes (misuse, abuse); in this context, chronic use can lead to physical and mental dependence and tolerance.

If you have any other questions about the use of thismedication, ask your doctor or pharmacist.

Like all medications, this medication may produce adverse effects, although not everyone will experience them.

Adverse effects or important symptoms to be aware of and how to act if they appear:

• Severe allergic reaction that causes difficulty breathing or dizziness.
• Severe skin reaction with blisters, generalized skin peeling, pus-filled spots (pustules) along with fever. It could be a condition called generalized acute pustular psoriasis (GAPP).

If you experience these important adverse effects, consult a doctor immediately.

At normal doses, the most common adverse effects are nausea, vomiting, constipation, and drowsiness. Under chronic treatment, morphine and related opioids may produce a wide range of secondary effects, including: respiratory depression, sleep apnea (pauses in breathing during sleep), symptoms associated with pancreatitis (inflammation of the pancreas) and the biliary system, for example, severe upper abdominal pain that may radiate to the back, nausea, vomiting, or fever, nausea, vomiting, dizziness, mental confusion, dysphoria (depression, anxiety, general discomfort, and low self-esteem), constipation, increased pressure in the bile ducts, urinary retention, hypotension, drowsiness, sedation, euphoria, nightmares (particularly in the elderly) with a possibility of hallucinations, increased intracranial pressure, urticaria, and other types of skin eruptions, increased sensitivity to pain, sweating, dry mouth, symptoms of withdrawal or dependence (see section 3 of this prospectus: If you interrupt treatment with Oramorph).

Reporting Adverse Effects

If you experienceanytype ofadverse effect, consultyour doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

Keepthis medicationout of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Once the bottle is opened, the solutions have a shelf life of 90 days.

Store in the outer packaging to protect it from light.

Medications should not be disposed of through drains or trash. Dispose of packaging and medications you no longer need at the SIGRE drop-off point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition ofOramorph

• The active ingredient is morphine sulfate. Each ml (equivalent to 16 drops) of oral solution contains 20 mg of morphine sulfate.
• The other components (excipients) are: sodium edetate, sodium benzoate (E-211), citric acid and purified water.

Appearance of Oramorph and contents of the container

Almost colourless aqueous solution.

It is presented in amber glass bottles with a safety cap, of 20 and 100 ml oral solution. The 20 ml container includes an incorporated dropper and the 100 ml container a graduated syringe in ml.

Only some container sizes may be commercially available.

Holder of the marketing authorization and responsible for manufacturing

L. MOLTENI & C. DEI F.LLI ALITTI SOCIETÀ DI ESERCIZIO S.p.A.

SS67 Fraz. Granatieri

50018 Scandicci (Florence)

Italy

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Grünenthal Pharma, S.A.

C / Doctor Zamenhof 36

28027 Madrid

Spain

Last review date of thisleaflet:November 2023

Other sources of information

The detailed information about this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/)

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This information is intended solely for healthcare professionals:

Treatment of overdose

Naloxone, a specific opioid antagonist, is the drug of choice: 0.4- 2 mg i.v. is the initial dose that can be repeated every 2-3 minutes if no response is achieved, up to a total of 10- 20 mg.

The duration of naloxone's effect (2- 3 hours) may be shorter than the duration of morphine overdose. Therefore, the patient who has regained consciousness after treatment with naloxone should be kept under surveillance for at least 3- 4 hours after the last dose of naloxone has been administered.

Respiratory tract maintenance should be monitored, as mechanical assisted ventilation may be necessary.

Administration of oxygen, intravenous fluids, vasopressors and other supportive measures may be required.