ORAMORPH 2 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 medicine (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 a head injury or when intracranial pressure is increased
• if you are taking monoamine oxidase inhibitors (MAOIs), buprenorphine, nalbuphine, or pentazocine (see Other medicines and Oramorph)
• if you are under 1 year old
• if you are pregnant
• if you are breastfeeding
• if you are administered within 24 hours after undergoing surgery.

Warningsand 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 that worsens respiratory function), emphysema, and severe obesity.
• If you are at risk of paralytic ileus 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 drugs 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 medicine:

• 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 producing insufficient cortisol, 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 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 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 severe skin rash or skin peeling, blisters, and/or ulcers in the mouth 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) along with fever.
• Respiratory disorders related to sleep. Oramorph may cause respiratory disorders related to sleep, such as sleep apnea and sleep-related hypoxemia. Symptoms may include pauses in breathing during sleep, nighttime awakenings due to dyspnea, 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 upper 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 medicine contains morphine, which is an opioid. Repeated use of opioids can lead to reduced efficacy of the medicine (getting used to it, also known as tolerance). Repeated use of Oramorph can also cause dependence, abuse, and addiction, which can lead to potentially fatal overdose. The risk of these side 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 medicine you need to take or how often you need to take 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 any member of your family has abused or been dependent on alcohol, prescription medicines, or illegal drugs ("addiction").
• You smoke.
• You have ever 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 medicine for longer 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, for example, "to stay calm" or "to help you sleep"
• You have made repeated attempts to stop using the medicine or control its use, but have been unsuccessful
• 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 stop taking Oramorph").

Other medicines andOramorph

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

Certain medicines may interact with Oramorph; in these cases, it may be necessary to change the dose or interrupt 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 medicines:

• Anesthetics
• Hypnotics (sleep-inducing medicines)
• Sedatives and phenothiazines
• Tricyclic antidepressants
• Other morphine derivatives (analgesics and cough medicines)
• Sedating antihistamines (allergy medicines)
• Antihypertensives (medicines used to lower blood pressure)
• Benzodiazepines or other tranquilizers
• Antipsychotics and related substances
• MAO inhibitors (monoamine oxidase inhibitors)
• 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 neuropathic pain
• Concomitant use of this medicine and sedatives such as benzodiazepines or other related medicines increases the risk of drowsiness, breathing difficulties (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 medicine 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 the dose. 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 a risk of withdrawal syndrome.

TakingOramorph withfood,drinksand alcohol

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

Pregnancy,breastfeedingand 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 medicine.

This medicine is contraindicated during pregnancy.

If this medicine 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 medicine may affect your ability to react, so do not drive or use any tools or machinery while taking it, especially if you are also taking alcohol or central nervous system depressants.

Oramorph contains sucrose, glucose, ethanol, and methyl parahydroxybenzoate (E-218) and propyl parahydroxybenzoate (E-216)

• This medicine contains 300 mg of sucrose and 100 mg of glucose per milliliter, which should be taken into account in patients with diabetes mellitus. If your doctor has indicated that you have an intolerance to certain sugars, consult with them before taking this medicine. It may damage teeth.

• This medicine contains 80 mg of alcohol (ethanol) in each milliliter of oral solution, which is equivalent to 8% w/w. The amount in 5 ml of this medicine is equivalent to less than 10 ml of beer or 4 ml of wine. It is unlikely that the amount of alcohol in this medicine will have a noticeable effect on adults or adolescents. It may have some effects on small children, such as drowsiness. The amount of alcohol in this medicine may alter the effect of other medicines. Consult your doctor or pharmacist if you are taking other medicines. If you are pregnant or breastfeeding, consult your doctor or pharmacist before taking this medicine. If you have a history of alcoholism, consult your doctor or pharmacist before taking this medicine.

• It may cause allergic reactions (possibly delayed) because it contains methyl parahydroxybenzoate (E-218) and propyl parahydroxybenzoate (E-216).

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

3. How to take Oramorph

Follow exactly the administration instructions of this medication indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Before starting treatment and periodically while the treatment lasts, 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 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.

It can be taken directly, without dilution with another liquid.

Use in adults and adolescents (13 years and older)

The usual initial dose of morphine sulfate is 10 - 20 mg, corresponding to 5 - 10 ml of oral solution, administered every 4 - 6 hours.

Use in children

• Children from 6 to 12 years

The maximum dose is 5 - 10 mg of morphine sulfate, corresponding to 2.5 - 5 ml of oral solution, administered every 4 hours.

• Children from 1 to 5 years

The maximum dose is 2.5 - 5 mg of morphine sulfate, corresponding to 1.25 - 2.5 ml of oral solution, administered every 4 hours.

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

Use in patients over 65 years of age

It should be administered with caution in patients over 65 years of age, as they are especially sensitive to central (confusion) or gastrointestinal adverse effects, and their renal function is physiologically reduced, so an initial dose reduction is required.

The dose may be increased under medical control 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.

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 oral solution should be dosed in milliliters.

• How to measure the dose from the 100 ml bottle

It is recommended to dose the oral solution using the 5 ml graduated syringe from 0.25 to 5 ml included in the packaging:

1. Keep the bottle in a vertical position, open it, and firmly insert the syringe that comes with the box into the plastic adapter.
2. Turn the bottle upside down with the syringe and slowly pull the plunger up to the volume you need for your dose.
3. Turn the bottle completely with the syringe upwards and remove the syringe.
4. If you have taken an excessive amount of solution in the pipette, it should be poured back into the bottle, keeping the bottle in a vertical position to avoid spilling liquid.

• How to measure the dose from the 250 ml bottle

It is recommended to dose the oral solution using the graduated measuring cup from 1 to 15 ml included in the packaging.

If you take more Oramorph than you should

In case of a mild or moderate overdose of morphine, the symptoms consist of deep sleepiness, pinpoint pupils, decrease in blood pressure, decrease in body temperature, and decrease in 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 aspiration pneumonia of 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 medication than you should, consult your doctor or pharmacist or the Toxicology Information Service, phone (91) 562 04 20, indicating the medication and the amount used.

If you forget to take Oramorph

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

If you stop treatment with Oramorph

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.

The symptoms of the withdrawal syndrome usually start a few hours after stopping the treatment, reaching a peak at 36-72 hours and gradually subsiding thereafter. The symptoms include generalized pain, yawning, pupil dilation (mydriasis), tearing, intense runny nose (rhinorrhea), sneezing, muscle tremors, headaches, weakness, sweating, anxiety, irritability, sleep disturbance 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. The 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 doubts about the use of this medication, ask your doctor or pharmacist.

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone experiences them.

Important side 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 experience these important side effects, stop using Oramorph and consult a doctor immediately.

At normal doses, the most frequent side effects are nausea, vomiting, constipation, and sleepiness. 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 can radiate to the back, nausea, vomiting, or fever, nausea, vomiting, dizziness, mental confusion, dysphoria (depression, restlessness, discomfort, and low self-esteem), constipation, increased pressure in the biliary tract, urinary retention, hypotension, sleepiness, sedation, euphoria, nightmares (especially in the elderly) with possible hallucinations, increased intracranial pressure, hives, and other types of skin rashes, increased sensitivity to pain, sweating, dry mouth, withdrawal symptoms or dependence (for symptoms, see section 3: if you stop treatment with Oramorph).

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Oramorph

Keep this medication out of 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 validity period of 90 days.

Store in the outer packaging to protect it from light.

Medications should not be thrown down the drain or into the trash. Deposit the packaging and medications 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 medications you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Oramorph

• The active ingredient is morphine sulfate. Each ml of oral solution contains 2 mg of morphine sulfate.
• The other components (excipients) are: sucrose, glucose (in corn syrup), methyl parahydroxybenzoate (E-218), propyl parahydroxybenzoate (E-216), ethanol, and purified water.

Appearance of Oramorph and package contents

Almost colorless aqueous solution.

It is presented in amber glass bottles with a safety cap and a 5 ml graduated syringe from 0.25 to 5 ml for the 100 ml bottle or a measuring cup for the 250 ml bottle.

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 medication 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 this leaflet:November 2023

Detailed information about this medication 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 be kept under surveillance for at least 3-4 hours more, after the last dose of naloxone has been eliminated.

Monitoring of the maintenance of respiratory tract patency is necessary, as mechanical respiratory assistance may be required.

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