MORPHINE B. BRAUN 1 mg/mL INJECTABLE SOLUTION

2. What you need to know before you use Morphine B. Braun

Do not use Morphine B. Braun

• If you are allergic to morphine hydrochloride or any of the other ingredients of this medicine (listed in section 6).
• If you have respiratory diseases (respiratory depression or severe obstructive respiratory disease).
• If you have acute bronchial asthma.
• If you have been treated with antidepressant medicines known as monoamine oxidase inhibitors (MAOIs) or during the 14 days following the end of treatment.
• If you have acute and/or severe liver disease.
• If you have a head injury; increased intracranial pressure.
• If you are in a coma.
• If you have spasms of the renal and biliary tract.
• If you have acute alcoholism.
• If you have a risk of paralytic ileus (reduced intestinal motility).
• If you have ulcerative colitis (inflammatory disease of the colon and rectum that produces diarrhea with or without blood and abdominal pain).
• If you are in shock (a situation in which the body is not receiving enough blood flow and is characterized by low blood pressure, anxiety, confusion, pale skin, dizziness, sweating, chest pain, sometimes loss of consciousness).
• Blood coagulation disorders or infection at the injection site (for epidural and intrathecal administration routes).

Warnings and precautions

Consult your doctor or pharmacist or nurse before starting to use Morphine B. Braun.

• If you have prostate adenoma or urethral stenosis.
• If you have poor gallbladder function.
• If you have severe inflammatory bowel disease.
• If you have hypothyroidism (a condition in which the thyroid gland does not produce enough thyroid hormones).
• Increased intracranial pressure (if you have severe headache or feeling of dizziness) or brain injury.
• If your kidneys do not work well.
• If your liver does not work well.
• If you have obstructive respiratory diseases or chronic asthma.
• If you have heart and circulation diseases, hypotension, and tachycardia.
• In patients who are undergoing treatment with drugs that depress the central nervous system (CNS).

Consult your doctor or pharmacist or nurse if you experience any of the following symptoms:

• Increased sensitivity to pain despite taking increasingly higher doses (hyperalgesia). Your doctor will decide if you need a dose adjustment or a change to a more potent analgesic (see section 2).
• Weakness, fatigue, decreased appetite, nausea, vomiting, or low blood pressure. This could indicate that the adrenal glands are producing insufficient amounts of the hormone 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 Morphine B. Braun while using it. You may have started to think too much about when you can take the next dose, even if you don't need it for pain.
• Withdrawal or dependence symptoms. The most common withdrawal symptoms are described in section 3. If they appear, your doctor may change the medication or modify the dosing interval. If you experience severe abdominal pain that may radiate to the back, nausea, vomiting, or fever, it could be symptoms associated with pancreatitis and biliary tract inflammation.

Your doctor will exercise special caution when administering this medicine to very young patients, elderly patients, severely debilitated patients, or patients with renal or hepatic insufficiency, who may be more sensitive to the effects of morphine.

Special caution is recommended with morphine:

Acute generalized exanthematous pustulosis (AGEP) 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 sores in the mouth after taking morphine or other opioids. Stop using this medicine and seek immediate medical attention if you notice any of the following symptoms: blisters, widespread skin peeling, or pus-filled spots (pustules) along with fever.

Sleep-related respiratory disorders:

This medicine 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, 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.

Tolerance, dependence, and addiction

This medicine contains morphine, which is an opioid. Repeated use of opioids can lead to decreased effectiveness of the medicine (getting used to it, also known as tolerance). Repeated use of this medicine can also cause dependence, abuse, and addiction, which can lead to potentially life-threatening 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 medicine 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 have a greater risk of dependence or addiction to morphine 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 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 morphine, 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 feel 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 start taking it again ("withdrawal effects").

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 treatment with Morphine B. Braun").

Sudden stop of treatment, if you are physically dependent on morphine, can precipitate a withdrawal syndrome.

Withdrawal symptoms can also occur after administration of an opioid antagonist (naloxone or naltrexone) or an agonist/antagonist (pentazocine).

Use in athletes

This medicine contains morphine, which can give a positive result in doping tests.

Other medicines and Morphine B. Braun

Tell your doctor or pharmacist if you are using or have recently used or might use any other medicines.

There are a number of medicines that should not be used with morphine, unless strictly necessary:

• Anti-diarrheal medicines (medicines for the treatment of diarrhea).
• Anti-hypertensive medicines (medicines to lower blood pressure).
• Antimuscarinic medicines (as they may increase the risk of severe constipation).
• Monoamine oxidase inhibitors (MAOIs) (medicines for the treatment of depression) or within 2 weeks after stopping their use.
• Naltrexone (used to help people who suffer from narcotic or alcohol addiction to stop using these substances).
• Rifampicin, for example, to treat tuberculosis.
• Gabapentin and pregabalin for the treatment of epilepsy and pain caused by nerve problems (neuropathic pain).
• Concomitant use of morphine and sedatives such as benzodiazepines or other related medicines increases the risk of drowsiness, difficulty breathing (respiratory depression), coma, and can be potentially life-threatening. For this reason, concomitant use should only be considered when other treatment options are not possible. However, if your doctor prescribes morphine with sedative medicines, you should limit the dose and duration of concomitant treatment. Inform your doctor of all sedative medicines you are taking and strictly follow your doctor's recommendations regarding the dose. It may be useful to inform friends or family members so they can recognize the signs and symptoms indicated above. Contact your doctor if you experience these symptoms.
• Some medicines used to treat blood clots (e.g., clopidogrel, prasugrel, ticagrelor) may have a delayed and reduced effect when taken with morphine.

There is another group of medicines that can increase the effects of morphine. In this case, your doctor will adjust the dose of both medicines:

• Medicines that cause central nervous system depression.
• Neuromuscular blockers (medicines used to produce muscle relaxation during surgical procedures).
• Analgesics (pain medicines) with effects similar to those of opioids.
• Opioids (such as pentazocine, nalbuphine, and butorphanol).

There is a group of medicines that can decrease the effect of morphine, including:

• Buprenorphine.
• Naloxone.

Use of Morphine B. Braun with food, drinks, and alcohol

Concomitant administration of this medicine with alcohol produces mutual potentiation of toxicity, with increased central depression.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Morphine crosses the placenta. Regular use during pregnancy can cause physical dependence in the fetus, resulting in withdrawal symptoms in the newborn (such as convulsions, irritability, excessive crying, tremors, hyperactive reflexes, fever, increased respiratory rate, hyperreflexia, vomiting, increased bowel movements, and diarrhea, sneezing, and yawning), which must be treated by a doctor.

The use of this medicine is only accepted in the absence of safer alternatives.

Morphine is excreted in breast milk. Although no problems have been described in humans, the possible effects on the infant are unknown, so your doctor must weigh the benefits and risks.

Driving and using machines

Ask your doctor if you can drive or use machines while being treated with this medicine. It is important that before driving or using machines, you observe how this medicine affects you. Do not drive or use machines if you feel drowsy, dizzy, have blurred vision, or double vision, or have difficulty concentrating. Be especially careful at the start of treatment, after a dose increase, after a change in formulation, and/or when administering it concomitantly with other medicines.

Morphine B. Braun contains sodium

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

3. How to use Morphine B. Braun

This medicine will be administered only by healthcare personnel.

The dose and duration of treatment will be individualized by your doctor based on the potency and duration of the drug used, the intensity of the pain, other medications administered simultaneously, and the patient's response.

The injection can be administered into a vein (intravenous injection), into a muscle (intramuscular injection), or under the skin (subcutaneous injection). It can be administered intermittently (e.g., every 4 hours) or continuously (e.g., through slow infusion).

Before starting treatment and periodically during treatment, your doctor will explain what you can expect from the use of Morphine B. Braun, 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 Morphine B. Braun").

Use in children and adolescents

This medicine should not be used via the epidural or intrathecal route in children.

If you use more Morphine B. Braun than you should

In case of overdose or accidental ingestion, contact your doctor or the Toxicology Information Service immediately. Telephone (91) 562 04 20, indicating the medicine and the amount used.

Overdose is characterized by respiratory depression with bradypnea (decreased respiratory rate), accompanied or not by central nervous system depression. People who have taken an overdose may also experience difficulty breathing that can lead to loss of consciousness or even death.

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

If you forget to use Morphine B. Braun

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

If you stop treatment with Morphine B. Braun

Do not stop treatment with morphine unless your doctor approves it. If you want to stop treatment with this medicine, ask your doctor how to gradually reduce the dose to avoid withdrawal symptoms. Withdrawal symptoms can be general pain, tremors, diarrhea, stomach pain, nausea, flu-like symptoms, palpitations, and dilated pupils. Psychological symptoms consist of a deep feeling of dissatisfaction, anxiety, and irritability.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

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

Stop using this medicine and seek immediate medical attention if you observe any of the following symptoms:

• 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).

Other possible adverse effects:

Very frequent (may affect more than 1 in 10 patients)

• Nausea.
• Vomiting.
• Constipation.
• Difficulty swallowing.

Frequent (may affect up to 1 in 10 patients)

• Diarrhea.
• Abdominal cramps.
• Drowsiness.
• Disorientation.
• Sweating.
• Euphoria (feeling of extreme happiness).

With prolonged treatments

• Tolerance.
• Dry mouth.
• Taste disturbances.
• Increased or decreased heart rate.
• Cardiac arrest.
• High blood pressure.
• Low blood pressure.
• Increased intracranial pressure.
• Collapse.
• Laryngeal spasm.
• Respiratory depression.
• Urinary retention.
• Reduced libido (reduced sexual desire).
• Impotence.
• Blurred vision.
• Rapid, involuntary eye movement (nystagmus).
• Diplopia (double vision).
• Miosis (excessive pupil contraction).
• Edema (fluid retention).
• Itching.
• Hives.
• Skin eruptions.
• Contact dermatitis.
• Pain at the injection site.

Infrequent (may affect up to 1 in 100 people)

• Headache.
• Agitation.
• Tremor.
• Seizures.
• Mood alteration (anxiety, depression).
• Muscle stiffness.
• Hallucinations.
• Difficulty sleeping.
• Anaphylactic reaction after intravenous injection.

Frequency not known (cannot be estimated from available data):

• Increased sensitivity to pain.
• Withdrawal or dependence symptoms (to consult symptoms, see section 3: If you stop treatment with Morfina B. Braun).
• Sleep apnea (pauses in breathing during sleep).
• Symptoms associated with pancreas inflammation (pancreatitis) and the biliary system, such as severe upper abdominal pain that may radiate to the back, nausea, vomiting, or fever.

This medicine may cause physical dependence when used for a long period. If you suddenly stop treatment with morphine, it may trigger a withdrawal syndrome characterized by the following symptoms: restlessness, anxiety, palpitations, tremors, or sweating.

Reporting of Adverse Effects

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

5. Conservation of Morfina B. Braun

Keep out of sight and reach of children.

This medicine does not require any special storage temperature. Store in the original packaging to protect it from light.

The contents of the ampoules should be used immediately after opening. Once the package is opened, discard the unused portion of the solution.

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

Medicines should not be thrown away through drains or into the trash. Deposit the packaging and medicines you no longer need at the pharmacy's SIGRE point. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Morfina B. Braun

The active ingredient is morphine hydrochloride (as trihydrate). Each ampoule contains 1 mg of morphine hydrochloride trihydrate (equivalent to 0.76 mg of morphine base).

The other components per ampoule are sodium chloride and water for injectable preparations.

Appearance of Morfina B. Braunand Package Contents

Transparent injectable solution presented in 1 ml topaz glass ampoules.

Packages containing 10 ampoules.

Marketing Authorization Holder:

• Braun Medical, S.A.

Ctra. de Terrassa, 121

08191 Rubí (Barcelona),

Spain.

Manufacturer:

• Braun Medical, S.A.

Ronda de los Olivares, Parcela 11,

Polígono Industrial Los Olivares,

23009 Jaén (Jaén),

Spain.

Date of the Last Revision of this Prospectus:October 2024.

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

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This information is intended only for doctors or healthcare professionals:

This medicine should be administered by healthcare personnel and only by subcutaneous, intramuscular, intravenous, intrathecal, and epidural routes.

Morphine hydrochloride trihydrate can be administered intermittently (e.g., every 4 hours) or continuously (e.g., by slow perfusion).

At all times, the necessary equipment for artificial respiration and an opioid antagonist medication should be available.

Instructions for the correct use of Morfina B. Braun

• The patient should remain lying down when administered intravenously to reduce adverse effects.
• For epidural or intrathecal administration, it is preferable to inject in the lumbar region. Before administration, the correct placement of the needle or catheter in the epidural space should be checked. An aspiration can be performed to check for the presence of cerebrospinal fluid or blood, which would indicate subdural or intravascular placement, respectively.

This medicine is incompatible with alkalis, bromides, iodides, potassium permanganate, tannic acid, and vegetable astringents, with iron, lead, magnesium, silver, copper, and zinc salts.

Physical-chemical incompatibility (precipitate formation) has been demonstrated between morphine sulfate solutions and 5-fluorouracil.