MORPHINE B. BRAUN 10 mg/ml INJECTABLE SOLUTION

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

Do not use Morfina B. Braun

• If you have had an allergic reaction to morphine hydrochloride or any other opioid analgesic.
• If you have any of the following diseases:
• respiratory diseases (respiratory depression or severe obstructive respiratory disease),
• 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 Morfina B. Braun.

If you have any of the following diseases, your doctor will perform special clinical monitoring:

• increased intracranial pressure,
• brain injury,
• chronic asthma,
• low blood pressure (hypotension),
• deficient thyroid secretion (hypothyroidism),
• rapid heart rate (supraventricular tachycardia),
• prostate hypertrophy or urethral stricture (urethral stenosis),
• gallbladder dysfunction,
• intestinal disorders such as severe intestinal inflammation,
• history of drug dependence.

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

• Increased sensitivity to pain despite taking increasingly larger 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 the adrenal glands are producing an insufficient amount 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 become dependent on Morfina 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, as it could be symptoms associated with pancreatitis and bile duct inflammation.

Your doctor will have special precautions when administering it 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 precautions 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, skin peeling, blisters, and/or sores in the mouth after taking morphine or other opioids. Stop using this medication 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 medication 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 medication contains morphine, which is an opioid. Repeated use of opioids can lead to decreased effectiveness of the medication (getting used to it, also known as tolerance). Repeated use of this medication can also cause dependence, abuse, and addiction, which could lead to a potentially fatal overdose. The risk of these adverse effects may be greater with higher doses and longer use.

Dependence or addiction can cause a 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 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 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 morphine, it could be a sign of dependence or addiction:

• You need to take the medication for longer 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 start taking 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 Morfina B. Braun").

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

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

This medication should only be used by expert medical professionals, and the necessary equipment for artificial respiration and an opioid antagonist should always be available.

Your doctor will take into account:

• When using the intravenous route, that you remain lying down to reduce adverse effects.
• When using the epidural and intrathecal routes, using a needle of appropriate size and correct placement of the needle and catheter in the epidural space.

Your doctor will inject slowly in the lumbar region, performing an aspiration to reduce the risk of accidental intravascular administration.

Use in athletes

It is reported that this medication contains a component that can give a positive result in doping control tests.

Other medications and Morfina B. Braun

Tell your doctor or pharmacist that you are using, have recently used, or may need to use any other medication.

Administration of morphine with the following medications may require modification of the dose of one of them.

It is important that you inform your doctor if you are using any of the following medications:

• anti-diarrheal medications,
• medications to lower blood pressure (antihypertensives),
• antimuscarinics (as they may increase the risk of severe constipation),
• antidepressants of the monoamine oxidase inhibitor (MAOI) group,
• naltrexone,
• 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 medications increases the risk of drowsiness, difficulty breathing (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 morphine with sedative medications, you should limit the dose and duration of concomitant treatment. Inform your doctor of all sedative medications 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,
• certain medications 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 medications that can increase the effects of morphine. In this case, your doctor will adjust the dose of both medications:

• medications that cause central nervous system depression, as they can potentiate the effects of respiratory depression and hypotension,
• neuromuscular blockers as they can prolong the effects of respiratory difficulty,
• analgesic medications (for pain) opioid agonists, as they can cause additive effects on respiratory depression and decreased blood pressure,
• pentazocine, nalbuphine, and butorphanol.

In case you are receiving treatment with medications such as buprenorphine and naloxone, they may decrease the effects of morphine.

In case of doubt, consult your doctor or pharmacist.

Pregnancy and breastfeeding

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.

Your doctor will assess the risk-benefit ratio since morphine crosses the placenta. Regular use during pregnancy can cause physical dependence in the fetus, leading to withdrawal symptoms in the newborn, such as convulsions, irritability, excessive crying, tremors, hyperactive reflexes, fever, vomiting, diarrhea, sneezing, and yawning, which must be treated by a doctor.

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 will assess whether to discontinue or continue breastfeeding.

Driving and using machines

Do not drive or operate tools or machines because this medication can cause drowsiness.

Morfina B. Braun contains sodium

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

3. How to use Morfina B. Braun

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

Your doctor will determine the most suitable dose for you.

The dosage varies depending on the route of administration, the intensity of the pain, and other medications that are administered concomitantly.

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

As a general rule, in adults, the usual doses are as follows:

• Subcutaneous or intramuscular:

5-20 mg/4 hours; 10 mg initially.

Pain relief during labor: 10 mg.

• Intravenous:

2.5 - 15 mg diluted in 4-5 ml of sterile water for injection or with a 0.9% sodium chloride solution and administered slowly by intravenous route over 4-5 minutes.

• Patients with acute myocardial infarction:

2 - 15 mg of morphine hydrochloride, which can be administered in increasing doses (1 - 3 mg) every 5 minutes.

• Continuous intravenous infusion:

Initial dose: 0.8-10 mg/h, subsequently increased according to the patient's response.

Maintenance dose: 0.8-80 mg/h, although sometimes higher doses have been necessary (150 mg/h). Very high doses may be needed for several hours or days (275-440 mg/h) to provide relief in cases of severe pain.

• Epidural (lumbar region):

5 mg. If necessary, additional doses of 1 or 2 mg can be administered after one hour, without exceeding a total dose of 10 mg in 24 hours.

• Intrathecal (lumbar region):

0.2 - 1 mg / 24 hours.

The administration of morphine hydrochloride by the epidural or intrathecal route during labor may cause adverse effects in the newborn, especially if premature. The intrathecal administration of up to 1 mg of morphine hydrochloride has little effect on the first phase of labor, although it may prolong the second phase.

Elderly and debilitated patients may require lower doses.

Use in children and adolescents:

In children, the usual doses are as follows:

• Subcutaneous or intramuscular:

0.1 - 0.2 mg/kg/4 hours as needed, without exceeding 15 mg in 24 hours.

• Intravenous:

0.05 - 0.1 mg/kg administered very slowly, without exceeding 15 mg in 24 hours.

• In children with severe chronic pain:

Continuous intravenous infusion:

0.04- 0.07 mg/kg/h.

Maintenance dose:

0.025-1.79 mg/kg/h.

• For postoperative pain relief, maintenance doses of 0.01-0.04 mg/kg/h by continuous intravenous infusion are required.

In neonates, the elimination of the medication is slower, and they are more susceptible to effects on the central nervous system; it is recommended not to exceed the dose of 0.015 - 0.02 mg/kg/h by continuous intravenous infusion.

This medication should not be used by the epidural and intrathecal routes in children.

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

If you use more Morfina B. Braun than you should

Overdose is characterized by respiratory depression with bradypnea (slow breathing) 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 aspiration pneumonia or inhalation of foreign particles; symptoms may include shortness of breath, cough, and fever.

The recommended treatment for overdose consists of:

• Maintaining a respiratory tract and ensuring adequate breathing with oxygen, if necessary by assisted respiration.
• Administering naloxone (0.4 to 2 mg) in a single dose, preferably intravenously. The injection of naloxone can be repeated at intervals of two to three minutes.
• Administering intravenous fluids and/or vasopressors.
• Continuing to monitor the patient.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service phone: 91.562 04 20, indicating the medication and the amount used. Bring this leaflet with you.

If you stop treatment with Morfina B. Braun

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

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

. Severe allergic reaction that causes difficulty breathing or dizziness.

. Severe skin reaction with blisters, generalized peeling of the skin, pus-filled spots (pustules) along with fever. It could be a disease called acute generalized exanthematous pustulosis (AGEP).

Other possible adverse effects:

• Very frequent (>1/10):

. Gastrointestinal disorders: nausea, vomiting, constipation.

. Nervous system disorders:drowsiness, disorientation, sweating, euphoria, and in prolonged treatments, tolerance.

• Infrequent (>1/1000, <1>

. Nervous system disorders: headache, agitation, tremor, convulsions, anxiety, depression, muscle stiffness, hallucinations, difficulty sleeping.

. Gastrointestinal disorders: dry mouth, laryngeal spasm, diarrhea, abdominal cramps, taste alterations.

. Cardiac disorders: cardiac arrest, tachycardia and bradycardia, increased blood pressure (hypertension), decreased blood pressure (hypotension), intracranial hypertension, collapse.

. Respiratory disorders: respiratory depression, difficulty breathing (apnea).

. Renal and urinary disorders; reduced libido, impotence.

. Ocular disorders: blurred vision, nystagmus, diplopia, miosis.

. Skin disorders: edema, itching, urticaria, eruptions, contact dermatitis, pain at the injection site.

• Very rare (<1>

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

. Increased sensitivity to pain.

. Symptoms of withdrawal or dependence (for 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.

The epidural or intrathecal administration does not eliminate the risk of serious adverse effects. Respiratory depression may occur shortly after administration due to direct venous redistribution to the central nervous system's respiratory centers.

Additionally, delayed respiratory depression may occur up to 24 hours after administration, possibly as a result of rostral spread. After epidural or intrathecal administration of morphine, urinary retention frequently occurs, especially in males, which may persist for 10 to 20 hours after injection, and catheterization may be necessary.

Additionally, generalized pruritus often occurs, which is dose-dependent.

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: 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 below 25°C and in the original packaging.

Keep this medicine out of sight and reach of children.

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

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

Medicines should not be thrown away through the sewers or in 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. Packaging Content and Additional Information

Composition of Morfina B. Braun

The active principle is morphine hydrochloride (as trihydrate). Each ampoule contains 10 mg of morphine hydrochloride trihydrate (equivalent to 7.6 mg of morphine base).

The other components (excipients) are sodium chloride and water for injectable preparations.

Appearance of Morfina B. Braun and Packaging Content

Transparent injectable solution presented in 1 ml capacity topaz glass ampoules.

Packaging containing 1 and 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 is incompatible with bases, bromides, iodides, potassium permanganate, and tannic acid. It is also incompatible with iron, lead, magnesium, silver, copper, and zinc salts.

Handle under usual asepsis conditions for the use of injectable solutions.

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