Prospect: information for the user

Morfina SERRA 20 mg/ml injectable solution

Morphine hydrochloride

Read this prospect carefully before starting to use this medication, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only to you, and you should not give it to other people, even if they present the same symptoms of illness as you, as it may harm them.
• If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they do not appear in this prospect.

Content of the prospect:

1.What is Morfina Serra and for what it is used.

2.What you need to know before starting to use Morfina Serra.

3.How to use Morfina Serra.

4.Possible adverse effects.

5.Storage of Morfina Serra.

6.Contents of the package and additional information.

Morphine is an opioid analgesic that acts directly on the pain center. In humans, its action is translated into analgesia and often into narcosis.

This medication is indicated for:

- Intense pain treatment

- Treatment of pain associated with myocardial infarction

- Treatment of insomnia caused by intense pain

No useMorphine Sulfate

-if you are allergic to the active ingredient or any of the other components of this medication (listed in section 6).

- in patients in shock.

- in patients with anoxia (almost total lack of oxygen in a tissue), especially with cyanosis (blue discoloration of the skin).

- in patients with excessive bronchial secretion and asthma.

- in patients with respiratory depression or severe respiratory disease.

- in patients treated with monoamine oxidase inhibitors (medication used for the treatment of depression) or within 10 days of discontinuing such treatment.

- in case of infection at the injection site and in patients with severe coagulation disorders, epidural or intrathecal administration is contraindicated.

Tolerance, dependence, and addiction

This medication contains morphine, which is an opioid. Repeated use of opioids can lead to a decrease in the effectiveness of the medication (becoming accustomed to it, known as tolerance). Repeated use of Morphine Sulfate 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 medication to be used or the frequency with which it is used.

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

- You or any member of your family 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 Morphine Sulfate, it could be a sign of dependence or addiction:

If you notice any of the following symptoms while taking Morphine Sulfate, 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 keep calm" or "to help you sleep".
• You have made repeated and unsuccessful attempts to stop using the medication or control its use.
• 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 discontinue the medication and how to do it safely (see section 3 "If you interrupt treatment with Morphine Sulfate").

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Morphine Sulfate.,especially if:

- You have an adenoma of the prostate or urethral stenosis.

- You have impaired liver function.

- You have severe inflammatory bowel disease.

- You have hypothyroidism (produces insufficient thyroid hormones).

- You have elevated intracranial pressure or brain injury.

- Your kidneys do not function properly.

- Your liver does not function properly.

- You have obstructive respiratory diseases or chronic asthma.

- You have heart and circulation diseases, hypotension, and tachycardia.

- In patients undergoing treatment with central nervous system depressants (CNS).

Consult your doctor or pharmacist if you experience any of the following symptoms while using Morphine Sulfate:

- 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 the adrenal glands produce insufficient cortisol hormone, 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 Morphine Sulfate 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.

- Withdrawal or addiction symptoms. The most common withdrawal symptoms are described in section 3. If they appear, your doctor may change medication or modify the interval between doses.

Repeated administration of Morphine Sulfate produces tolerance, characterized by the need to progressively increase the dose, with psychological and physical dependence. There is cross-tolerance and cross-dependence between opioids that act on the same pain receptors. Dependence usually occurs after 1-2 weeks of administering therapeutic doses, although some dependence may occur within 2 or 3 days.

Abrupt discontinuation of treatment in patients with physical dependence can precipitate withdrawal syndrome. Withdrawal symptoms may also occur after administration of a medication with an opposite effect to opioids (Naloxone or Naltrexone) or a medication with a similar/ opposite effect (pentazocine) to patients with opioid dependence. Physiological dependence may occur, which becomes evident by the withdrawal syndrome that occurs if treatment is discontinued abruptly. Without treatment, most of these symptoms disappear within 5-14 days, although a secondary withdrawal syndrome with irritability, insomnia, and muscle pain can persist for several months.

Use in elderly patients: Special care should be taken in the elderly due to their exaggerated sensitivity. The elderly are more susceptible to the effects of morphine.

Use in patients with a history of alcoholism or drug addiction:Special care should be taken due to the patient's predisposition to drug addiction.

It should be administered with caution invery young patientsas they may be more sensitive to the effects of morphine.

Special precautions with Morphine Sulfate:

A generalized acute pustular exanthema (PEGA) has been reported in association with treatment with Morphine Sulfate. Symptoms usually occur within the first 10 days of treatment. Inform your doctor if you have ever had a severe skin rash or skin peeling, blisters, and/or mouth sores after taking Morphine Sulfate or other opioids. Stop using Morphine Sulfate and seek medical attention immediately if you notice any of the following symptoms: blisters, widespread skin peeling, or pus-filled points (pustules) along with fever.

Respiratory disorders related to sleep

Morphine Sulfate may cause respiratory disorders related to sleep, such as sleep apnea (pauses in breathing during sleep) and hypoxemia related to sleep (low oxygen level in the blood). Symptoms may include pauses in breathing during sleep, nocturnal awakening 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 bile duct inflammation.

Use in athletesThis medication contains hydrochloride of morphine, which can produce a positive result in doping control tests.

Morphine Sulfate may alter the following laboratory determinations:

• Blood: increased (biological) creatine kinase and prolactin.
• Reduced (biological) testosterone.

Use of Morphine Sulfate with other medications

Inform your doctor or pharmacist that you are using, have used recently, or may need to use any other medication. Even those acquired without a prescription, homeopathic, herbal, or other health-related products, as it may be necessary to interrupt treatment or adjust the dose of one of them.

There are some medications with which morphine should not be used unless strictly necessary:

• Some medications for the treatment of diarrhea may increase severe constipation and central nervous system depression.
• Medications for the treatment of high blood pressure and other medications that produce hypotension.
• Medications that, when administered with Morphine Sulfate, may increase the risk of severe constipation.
• Monamine oxidase inhibitors (MAOIs) (medications used for the treatment of depression).
• Naltrexone (used to help people who suffer from addiction to narcotics or alcohol to stop using these substances).

A large number of medications can interact with the injection of hydrochloride of morphine, significantly altering its effects. These medications include:

• Gabapentin or pregabalin for the treatment of epilepsy and pain caused by nerve problems (neuropathic pain).

Some medications, when taken at the same time as Morphine Sulfate, may affect the mechanism of action of morphine, increasing its effects:

Medications that produce central nervous system depression

Bloqueantes neuromusculares (medications used to produce muscle relaxation before surgical procedures).

Analgesics with a similar effect to opioids (concomitant administration may cause additive effects on central nervous system depression).

Opioids (such as: pentazocine, nalbuphine, butorphanol)

There is a group of medications that reduce the effect of morphine, including:

• Buprenorphine (medication for the treatment of opioid dependence).
• Naloxone (medication for the treatment of respiratory depression).

This is especially important if you are taking any of the medications mentioned below or medications for:

• Rifampicin, for example, to treat tuberculosis.
• Some medications used in the treatment of blood clots (e.g., clopidogrel, prasugrel, ticagrelor) may have a delayed and reduced effect when taken with morphine.
• Cimetidine may increase the effect of morphine.

The concomitant use of Morphine Sulfate and sedatives such as benzodiazepines or other related medications increases the risk of somnolence, difficulty breathing (respiratory depression), coma, and may 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 Sulfate 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 indicated above. Contact your doctor if you experience these symptoms.

Use of Morphine Sulfate with food, drinks, and alcohol

The concomitant administration of Morphine Sulfate with alcohol produces mutual potentiation of toxicity, with increased central depression.

Pregnancy, lactation, and fertility

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

This medication crosses the placenta. Regular use during pregnancy may cause physical dependence in the fetus, leading to withdrawal symptoms in the newborn. The use of this medication is only accepted in the absence of safer alternatives.

Morphine passes into breast milk.

Although no problems have been described in humans, the possible adverse effects on the infant are unknown, and your doctor should evaluate the benefit-risk balance.

If Morphine Sulfate is used for a prolonged period during pregnancy, there is a risk that the newborn may experience withdrawal symptoms, which should be treated by a doctor.

Driving and operating machinery

Ask your doctor if you can drive or operate machinery during treatment with Morphine Sulfate. It is essential to observe how this medication affects you before driving or operating machinery. Do not drive or operate machinery if you feel drowsy, dizzy, have blurred vision, or double vision, or have difficulty concentrating. Be especially careful at the start of treatment, after increasing the dose, after changing the formulation, and/or when administering it concomitantly with other medications.

Morphine Sulfate contains sodium chloride

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

Follow exactly the medication administration instructions contained in this leaflet or those indicated by your doctor, pharmacist or nurse. In case of doubt, ask your doctor, pharmacist or nurse. Your doctor will inform you of the duration of your treatment withMorphineSerra. Do not discontinue treatment beforehand, as the desired therapeutic effect may not be achieved.

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

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

Subcutaneous or intramuscular administration route:

• Adults:Pain: 5-20 mg every 4 hours

Intravenous administration route:

• Adults:Pain associated with myocardial infarction: 2-15 mg, with the possibility of administering increasing doses (1-3 mg) every 5 minutes. In continuous intravenous administration (via continuous infusion), the initial recommended rate in adults is 0.8-10 mg/h, adjusting it subsequently based on the response to a maximum of 80 mg/h. In cases of intense pain, intravenous infusion rates up to 440 mg/h have been used.

Epidural administration route:

• Adults:5 mg. If necessary, administer additional doses of 1 or 2 mg after one hour, without exceeding a total dose of 10 mg/24 hours.

Intrathecal administration route:

• Adults: 0.2-1 mg/24 h.

Older adults and debilitated patients may require lower doses than those corresponding to adults.

In renal or hepatic insufficiencythe dose should be adjusted according to the degree of renal or hepatic functional impairment.

- Dosages and intervals between doses should be individualized according to the severity of pain, the patient's condition, other medications administered simultaneously, and the patient's response.

- Tolerance may develop with repeated administration.

If you use more Morphine Serra than you should

If you have used moreMorphineSerrathan you should, consult your doctor or pharmacist immediately or call the toxicology information service, phone: 91 562 04 20, indicating the medication and the amount used. It is recommended to bring the packaging and the leaflet of the medication to the healthcare professional.

Accidental overdose intoxication manifests with: respiratory depression with bradypnea (decreased respiratory frequency), accompanied or not by central nervous system depression.

People who have taken an overdose may experience pneumonia due to inhalation 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 may cause loss of consciousness or even death.

The recommended treatment for overdose consists of:

-Maintaining a respiratory tract and establishing controlled or assisted ventilation.

-Administering naloxone (from0.4 to2 mg) in a single dose, preferably intravenously. The naloxone injection can be repeated at intervals of two to three minutes. Since the duration of the effect of naloxone is significantly shorter than that of morphine by epidural or intrathecal route, repeated administration of the drug may be necessary. It should be noted that naloxone can also inhibit the analgesic actions of morphine and may precipitate withdrawal symptoms in physically dependent patients.

-Administering intravenous fluids and/or vasopressors (drugs used when a patient's blood pressure is too low), using other supportive measures as needed.

-Continuing patient monitoring.

If you forget to use Morphine Serra

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

If you interrupt treatment with Morphine Serra

Do not discontinue treatment with Morphine Serra unless your doctor approves it. If you want to discontinue treatment with Morphine Serra, ask your doctor how to gradually reduce the dose to avoid withdrawal symptoms. Withdrawal symptoms may include generalized pain, tremors, diarrhea, stomach pain, nausea, flu-like symptoms, palpitations, and dilated pupils. Psychological symptoms include a deep sense of dissatisfaction, anxiety, and irritability.

Abrupt discontinuation of treatment in physically dependent patients may precipitate a withdrawal syndrome characterized by the following symptoms in varying degrees of intensity for each individual: yawning, lacrimation, rhinorrhea (nasal secretion), sweating, mydriasis (pupil dilation), tremors, goosebumps, anorexia (loss of appetite), restlessness, vomiting, fever, hyperventilation (increased amplitude and frequency of breathing), hypertension, and diarrhea.

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

Like all medications,MorphineSerracan cause side effects, although not everyone will experience them.

The side effects of morphine are generally frequent and moderately serious. In most cases, side effects are a pharmacological prolongation and affect mainly the central nervous system and the digestive and respiratory systems.

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

Severe allergic reaction that causes difficulty breathing or dizziness.

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

The most characteristic adverse reactions are:

- Very frequent (can affect more than 1 in 10 people): nausea, vomiting, difficulty swallowing, constipation.

- Frequent (can affect up to 1 in 10 people): diarrhea, abdominal cramps,somnolence, disorientation, sweating, euphoria; with prolonged treatments: tolerance, dry mouth, taste alterations, increased or decreased heart rate, heart stoppage, high blood pressure, low blood pressure, intracranial hypertension, laryngeal spasm, collapse, respiratory depression, apnea (episodes of suspension of breathing when the person is sleeping), urinary retention, reduced libido (reduced sexual desire), impotence, blurred vision, eye twitching, diplopia (double vision), miosis (excessive contraction of the pupil), edema, pruritus, urticaria, skin eruptions, contact dermatitis, pain at the injection site.

- Infrequent (can affect up to 1 in 100 people): headache, agitation, tremor, convulsions, mood alterations (anxiety, depression), muscle rigidity, hallucinations, insomnia, generalized allergic reaction after intravenous injection.

- Unknown frequency: increased sensitivity to pain, symptoms of withdrawal or dependence (to consult symptoms, see section 3: If it interrupts treatment with Morphine Serra),sleep apnea (pauses in breathing during sleep), symptoms associated with pancreatitis and biliary system inflammation, for example, severe upper abdominal pain that may radiate to the back, nausea, vomiting, or fever.

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

Severe skin reaction with blisters, generalized skin peeling, pus-filled points (pustules) along with fever. It could be a disease called generalized acute pustular exanthema (PEGA).

If you consider that any of the side effects you are experiencing is severe or if you notice any side effect not mentioned in this prospectus, inform your doctor or pharmacist.

Keep this medication out of the sight and reach of children.

Do not store at a temperature above25ºC

This product does not contain any type of preservative, so opened ampoules that have not been used immediately should be discarded.

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

Medications should not be disposed of through drains or inthe trash. Depositunwanted packaging and medications at the SIGREcollection pointat the pharmacy. If in doubt, ask your pharmacist how to dispose of unwanted packaging and medications. By doing so, you will help protect the environment.

Composition ofMorphine Serra

• The active principle is hydrochloride of morphine. Each ampoule contains 20 mg of hydrochloride of morphine(equivalent to 17.8 mg of morphine base).
• The other components(excipients)are:sodium chloride, hydrochloric acid (for pH adjustment) and water for injectable preparations.

Appearance of the product and contents of the package

Morphine Serrais presented in the form ofa transparent, clear, sterile, and precipitate-free injectable solution.

The packages contain 1 ampoule of 1 ml of solution.

Holder of the marketing authorization and responsible for manufacturing

Serra Pamies Laboratories S.A.

Ctra. Castellvell, 24

43206 REUS (Tarragona)

Spain

Last review of this leaflet was in October 2023

Detailed and updated information on this medication 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:

The rapid intravenous injection of opioid analgesics can cause anaphylactic reactions, so it will only be performed by experienced doctors and a ventilation equipment and opioid antagonists must be available.

When administering this medication via epidural and intrathecal routes, patients must be adequately monitored for at least 24 hours as it may cause respiratory depression.

When administering morphine parenterally, the patient should be lying down and should remain recumbent to minimize adverse reactions such as hypotension, dizziness, drowsiness, nausea, and vomiting.

For epidural or intrathecal administration, it is preferable to inject in the lumbar region due to the increased risk of respiratory depression when administered in the thoracic region.

If morphine is administered via epidural or intrathecal during delivery, it can easily enter the fetal circulation, potentially causing respiratory depression in the newborn, especially if premature.

Before epidural administration, the correct placement of the needle or catheter in the epidural space must be checked. Aspiration can be performed to check for the presence of cerebrospinal fluid or blood, indicating subdural or intravascular placement, respectively.

In patients with shock, altered perfusion may prevent complete absorption after intramuscular or subcutaneous administration. Repeated administration may lead to overdose due to unexpectedly high absorption when circulation is restored.

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