ORAMORPH 20 mg/ml ORAL SOLUTION

2. What you need to know before taking Oramorph

Do not takeOramorph

• if you are allergic to morphine or any of the other components of this medication (listed in section 6).
• if you have respiratory insufficiency or depression without assisted respiration
• if you have acute or severe 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 seizure disorders
• if you have head trauma or increased intracranial pressure
• if you are taking monoamine oxidase inhibitors (MAOIs), buprenorphine, nalbuphine, or pentazocine (see Other medications and Oramorph)
• if you are under 1 year of age
• if you are pregnant
• if you are breastfeeding
• if you are administered within 24 hours after undergoing surgery.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Oramorph:

• If you have seizure disorders.
• If you have increased intracranial pressure.
• 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 kidney or liver disease.
• If you have hypothyroidism.
• If you have adrenocortical insufficiency.
• In case of conditions with reduced respiratory reserve, such as kyphoscoliosis (abnormal curvature of the spine), emphysema, and severe obesity.
• If you are at risk of intestinal paralysis or have chronic constipation.
• If you have biliary, intestinal, or urogenital obstruction.
• In case your ability to maintain hemostatic blood pressure is compromised by decreased blood volume or administration of medications such as phenothiazines or certain anesthetics, as morphine may cause severe hypotension.
• If you need to undergo surgical procedures for pain relief, you should not receive Oramorph during the 24 hours prior to surgery.

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

• Increased sensitivity to pain despite taking higher doses (hyperalgesia). Your doctor will decide if you need a dose adjustment or switch to a more potent analgesic (see section 2).
• Weakness, fatigue, decreased appetite, nausea, vomiting, or low blood pressure. This could indicate that your adrenal glands are not producing enough cortisol hormone, and you may need to take hormonal supplements.
• Loss of libido, impotence, cessation of menstruation. This may be due to decreased production of sex hormones.
• If you have a history of alcoholism or drug addiction. Also, inform your doctor if you think you are becoming dependent 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.
• A generalized acute exanthematous pustulosis (PEGA) has been reported in association with morphine treatment. Symptoms usually occur within the first 10 days of treatment. Inform your doctor if you have ever suffered from a severe skin rash or skin peeling, blisters, and/or ulcers in the mouth after taking Oramorph or other opioids. Stop using Oramorph and seek immediate medical attention if you notice any of the following symptoms: blisters, widespread skin peeling, or pus-filled bumps (pustules) along with fever.
• Respiratory disorders related to sleep. Oramorph may cause sleep-related respiratory disorders, such as sleep apnea and sleep-related hypoxemia. 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, contact your doctor. Your doctor may consider reducing the dose.
• Contact your doctor if you experience severe abdominal pain that may radiate to the back, nausea, vomiting, or fever, as it could be symptoms associated with pancreatitis and bile duct inflammation.

Tolerance, dependence, and addiction

This medication contains morphine, which is an opioid. Repeated use of opioids can lead to decreased effectiveness of the medication (tolerance). Repeated use of Oramorph can also cause dependence, abuse, and addiction, which can lead to potentially fatal overdose.

The risk of these adverse effects may be greater with higher doses and longer use.

Dependence or addiction can cause a feeling of lack of control over the amount of medication you need to use or how often you need to use it.

The risk of dependence or addiction varies from person to person. You may be at greater risk of dependence or addiction to Oramorph if:

• You or a family member have abused or been dependent on alcohol, prescription medications, or illegal drugs ("addiction").
• You smoke.
• You have had 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 medication for a longer period than recommended by your doctor

• You need to take a higher dose than recommended
• You are using the medication for reasons other than those prescribed, for example, "to feel calm" or "to help you sleep"
• You have made repeated attempts to stop using the medication or control its use but have been unsuccessful
• You feel unwell when you stop using the medication, 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 medication and how to do it safely (see section 3 "If you stop treatment with Oramorph").

Other medications andOramorph

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

Certain medications may interact with Oramorph; in these cases, it may be necessary to change the dose or discontinue treatment with one of them, as they can put the patient's 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 recently taken any of the following medications:

• Anesthetics
• Hypnotics (sleep-inducing medications)
• Sedatives and phenothiazines
• Tricyclic antidepressants
• Other morphine derivatives (analgesics and medications used to treat cough)
• Sedating antihistamines (allergy medications)
• Antihypertensives (medications used to lower blood pressure)
• Benzodiazepines or other tranquilizing medications
• Antipsychotics and related substances
• MAO inhibitors (monoamine oxidase inhibitors)
• Muscle relaxants
• Rifampicin, for example, to treat tuberculosis
• Certain medications 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 neuropathic pain
• Concomitant use of this medication and sedatives such as benzodiazepines or other related medications increases the risk of somnolence, respiratory depression, coma, and can be potentially fatal. For this reason, concomitant use should only be considered when other treatment options are not possible. However, if your doctor prescribes this medication with sedatives, you should limit the dose and duration of concomitant treatment. Inform your doctor of all sedatives you are taking and strictly follow your doctor's recommendations regarding dosage. It may be helpful to inform friends or family members so they can recognize the signs and symptoms indicated above. Contact your doctor if you experience these symptoms.

Morphine agonists/antagonists (buprenorphine, nalbuphine, pentazocine) should not be administered concomitantly with morphine, as they reduce its analgesic effect, with the risk of producing withdrawal syndrome.

TakingOramorph withfood,drinks, and alcohol

Concomitant administration of alcoholic beverages with this medication may worsen the side effects of morphine, particularly central depression with inhibition of respiratory function.

Pregnancy,breastfeeding,and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

This medication is contraindicated during pregnancy.

If this medication is used for a prolonged period during pregnancy, there is a risk that the newborn may exhibit withdrawal symptoms, which must be treated by a doctor.

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

Driving and using machines

This medication may affect your reaction ability, so do not drive or use any tool or machinery while taking it, especially if you are also taking alcohol or central nervous system depressants.

Oramorph contains sodium benzoate (E-211) and sodium

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

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

Athletes are informed that this medication contains a component that may result in a positive doping test.

3. How to take Oramorph

Follow your doctor's instructions for administering this medication exactly. If you are unsure, consult your doctor or pharmacist again.

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

Remember to take your medication.

If you think the effect of this medication is too strong or too weak, tell your doctor or pharmacist.

The dose depends on the intensity of the pain and the patient's previous 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 drops or 0.5-1 ml of oral solution, administered every 4-6 hours.

Use in children

• Children 6-13 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 1-5 years old

This medication will be used for children who require higher doses, also administered at 4-hour intervals.

• It is not recommended for use in children under 1 year of age.

Use in patients over 65 years old

It should be administered with caution in patients over 65 years old, as they are particularly sensitive to central or gastrointestinal adverse 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 analgesic requirements. An increase in doses to control pain generally does not imply the development of tolerance.

A dose reduction is recommended 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.

Method of administration

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 incorporated 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 solution in milliliters using 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 morphine overdose, symptoms include deep sleepiness, 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 sleepiness is an early symptom of respiratory depression.

People who have taken an overdose may suffer from inhalation pneumonia; symptoms may include shortness of breath, cough, and fever.

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

If you have taken more medication than you should, consult your doctor or pharmacist immediately or contact the 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 make up for forgotten doses.

If you stop treatment withOramorph

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

Withdrawal syndrome symptoms usually start a few hours after stopping treatment, peak at 36-72 hours, and gradually subside thereafter. Symptoms include generalized pain, yawning, dilated pupils (mydriasis), tearing, intense runny nose (rhinorrhea), sneezing, muscle tremors, headaches, weakness, sweating, anxiety, irritability, sleep disturbances or insomnia, restlessness, orgasm, stomach 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 disturbances. Psychological symptoms consist of a deep feeling 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 this medication, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Important adverse effects or symptoms to which you should pay attention 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 disease called acute generalized exanthematous pustulosis (AGEP).

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

At normal doses, the most frequent adverse effects are nausea, vomiting, constipation, and somnolence. Under chronic treatment, morphine and related opiates can produce a wide range of side effects, including: respiratory depression, sleep apnea (pauses in breathing during sleep), symptoms associated with pancreas inflammation (pancreatitis) 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, restlessness, general discomfort, and low self-esteem), constipation, increased pressure in the bile ducts, urinary retention, hypotension, somnolence, sedation, euphoria, nightmares (especially in the elderly) with the possibility of hallucinations, increased intracranial pressure, urticaria, and other types of skin rashes, increased sensitivity to pain, sweating, dry mouth, withdrawal or dependence symptoms (to consult the symptoms, see section 3 of this prospectus: If you interrupt treatment with Oramorph).

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your 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 Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Oramorph

Keep this medicine out of sight and reach of children.

Do not use this medicine 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 validity period of 90 days.

Store in the outer packaging to protect it from light.

Medicines should not be thrown away through drains or into the trash. Deposit the packaging and medicines you no longer need at the SIGRE Point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

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: disodium edetate, sodium benzoate (E-211), citric acid, and purified water.

Appearance of Oramorph and Package Contents

Almost colorless aqueous solution.

It is presented in topaz glass bottles with a safety cap, of 20 and 100 ml of oral solution. The 20 ml package includes an incorporated drop counter and the 100 ml package a graduated dosing syringe in ml.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

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

SS67 Fraz. Granatieri

50018 Scandicci (Florence)

Italy

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Grünenthal Pharma, S.A.

C / Doctor Zamenhof 36

28027 Madrid

Spain

Date of the last revision of thisprospectus:November 2023

Other Sources of Information

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)

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This information is intended only for healthcare professionals:

Treatment of Overdose

Naloxone, a specific opioid antagonist, is the antidote 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 the effect of naloxone (2-3 hours) may be less than the duration of the effect of the morphine overdose. Therefore, the patient who has regained consciousness after treatment with naloxone should remain under surveillance for at least 3-4 hours more, after the last dose of naloxone has been eliminated.

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

Oxygen, intravenous fluids, vasopressors, and other supportive measures may be necessary.