MORPHINE SERRA 10 mg/mL INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Morphine SERRA 10 mg/ml Solution for Injection

Morphine Hydrochloride

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet.

Contents of the Package Leaflet:

1. What is Morphine SERRA and what is it used for.
2. What you need to know before you start using Morphine SERRA.
3. How to use Morphine SERRA.
4. Possible side effects.
5. Storage of Morphine SERRA.
6. Package Contents and Further Information.

1. What is Morphine SERRA and what is it used for

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 medicine is indicated in:

• Treatment of severe pain.
• Treatment of pain associated with myocardial infarction.
• Treatment of insomnia produced by severe pain.

2. What you need to know before you start using Morphine SERRA

Do not useMorphine SERRA

• if you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6).
• in patients in a state of shock.
• in patients in states of anoxia (almost total lack of oxygen in a tissue), especially in the presence of cyanosis (bluish discoloration of the skin).
• in patients with excessive bronchial secretion and in bronchial asthma.
• in patients with respiratory depression or severe obstructive respiratory disease.
• in patients treated with monoamine oxidase inhibitors (medicines used for the treatment of depression) or during the 10 days following the suspension of such treatment.
• in case of infection at the injection site and in patients with severe coagulation disorders, administration via the epidural or intrathecal route is contraindicated.

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, known as tolerance). Repeated use of Morphine SERRA can also lead to dependence, abuse, and addiction, which could result in a potentially fatal overdose. The risk of these adverse effects may be greater with a higher dose and longer use.

Dependence or addiction can lead to 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 SERRA 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 SERRA, it could be a sign of dependence or addiction:

If you notice any of the following symptoms while taking Morphine SERRA, 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, unsuccessful attempts to stop using the medicine or control its use.
• You feel unwell when you stop using the medicine, and you feel better once you take 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 so safely (see section 3 "If you stop treatment with Morphine SERRA").

Warnings and Precautions

Consult your doctor, pharmacist, or nurse before starting to use Morphine SERRA.

• if you have prostate adenoma or urethral stenosis (narrowing).
• if you have malfunctioning of the gallbladder.
• if you have severe inflammatory bowel disease.
• if you have hypothyroidism (your thyroid gland does not produce enough thyroid hormones).
• increased intracranial pressure or brain injury.
• if your kidneys do not work properly.
• if your liver does not work properly.
• if you have obstructive respiratory diseases or chronic asthma.
• if you have heart and circulation diseases, hypotension, and tachycardia.
• in patients undergoing treatment with drugs that depress the Central Nervous System (CNS).

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

• Increased sensitivity to pain despite taking increasing 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 your 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 SERRA while using it. You may have started thinking too much about when you can take the next dose, even if you do not need it for pain.
• Withdrawal symptoms or dependence. The most frequent withdrawal symptoms are described in section 3. If they appear, your doctor may change the medicine or modify the interval between doses.

Repeated administration of Morphine SERRA produces tolerance, characterized by the need to progressively increase the dose, with physical and psychological 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 appear after 2 or 3 days.

Sudden interruption of treatment in patients with physical dependence can precipitate a withdrawal syndrome. Withdrawal symptoms may also appear after the administration of a medicine with an effect opposite to that of opioids (Naloxone or Naltrexone) or a medicine with a similar/contrary effect (pentazocine) to patients dependent on opioids. Physiological dependence can occur, which becomes evident due to the withdrawal syndrome that occurs if treatment is abruptly discontinued. Without treatment, most of these symptoms disappear within 5 to 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 increased sensitivity. The elderly are more susceptible to the effects of morphine.

In patients with a history of alcohol or drug dependence: Special care should be taken due to the patient's predisposition to drug addiction.

It should be administered with caution in very young patients as they may be more sensitive to the effects of morphine.

Special precautions should be taken with Morphine SERRA:

Acute generalized exanthematous pustulosis (AGEP) has been reported in association with Morphine SERRA 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 SERRA or other opioids. Stop using Morphine SERRA 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

Morphine SERRA can cause sleep-related respiratory disorders, such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen level in the blood). Symptoms may include pauses in breathing during sleep, nighttime awakenings due to dyspnea, difficulties 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.

Use in athletes

This medicine contains morphine hydrochloride, which may produce a positive result in doping tests.

Morphine SERRA may alter the results of the following laboratory tests:

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

Using Morphine SERRA with other medicines

Tell your doctor or pharmacist that you are using, have recently used, or might use any other medicines, even those obtained without a prescription, homeopathic medicines, herbal remedies, and other health-related products, as it may be necessary to interrupt treatment or adjust the dose of one of them.

There are some medicines with which the use of morphine is not recommended unless strictly necessary:

• Some medicines for the treatment of diarrhea may increase severe constipation and CNS depression.
• Medicines for the treatment of high blood pressure and other medicines that produce hypotension.
• Medicines that, when administered with Morphine SERRA, may increase the risk of severe constipation.
• Monoamine oxidase inhibitors (MAOIs) (medicines for the treatment of depression).
• Naltrexone (used to help people suffering from narcotic or alcohol addiction to stop using these substances).

A large number of drugs can interact with morphine hydrochloride injection, which can significantly alter their effects. These drugs include:

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

Some medicines, when taken at the same time as Morphine SERRA, can affect the mechanism of action of morphine, increasing its effects:

• Medicines that produce CNS depression.
• Neuromuscular blockers (medicines used to produce muscle relaxation during surgical procedures).
• Analgesics with an effect similar to that of opioids (concomitant administration may cause additive effects on CNS depression).
• Opioids (such as pentazocine, nalbuphine, butorphanol).

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

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

This is especially important if you are taking any of the following medicines or medicines for:

• Rifampicin, for example, to treat tuberculosis.
• Some medicines 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.
• Concomitant use of Morphine SERRA and sedatives such as benzodiazepines or other related medicines increases the risk of somnolence, 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 Morphine SERRA along with sedative medicines, you should limit the dose and duration of concomitant treatment. Inform your doctor about all sedative medicines 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.

Using Morphine SERRA with food, drinks, and alcohol

Concomitant administration of Morphine SERRA 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.

This drug crosses the placenta. Regular use during pregnancy can produce physical dependence in the fetus, resulting in withdrawal symptoms in the newborn. The use of this medicine 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, so your doctor must assess the benefit-risk balance.

If Morphine SERRA is used for a prolonged period during pregnancy, there is a risk that the newborn may present with withdrawal symptoms, which must be treated by a doctor.

Driving and Using Machines

Ask your doctor if you can drive or use machines during treatment with Morphine SERRA. It is essential 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 see double, 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 SERRA contains Sodium Chloride

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

3. How to use Morfina Serra

Follow the administration instructions of the medication contained in this prospectus or as indicated by your doctor, pharmacist, or nurse. In case of doubt, ask your doctor, pharmacist, or nurse. Your doctor will indicate the duration of your treatment with Morfina Serra. Do not suspend treatment beforehand, as the expected therapeutic effect may not be achieved.

Before starting treatment and periodically while the treatment lasts, your doctor will explain what you can expect from the use of Morfina Serra, 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 interrupt treatment with Morfina Serra").

If you think the action of Morfina Serra is too strong or 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 infarction: 2-15 mg, which can be administered in increasing doses (1-3 mg) every 5 minutes. In continuous intravenous administration (through continuous perfusion), the initial recommended rate in adults is 0.8-10 mg/h, adjusting later based on response to a maximum of 80 mg/h. In cases of especially intense pain, intravenous infusion rates of up to 440 mg/h have been used.

Epidural administration route:

• Adults: 5 mg. If necessary, administer an additional dose 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.

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

In renal or hepatic insufficiency, the dose should be adjusted according to the degree of functional incapacity of the kidney or liver.

• Dosages and intervals between doses should be individualized according to the severity of the pain, the patient's condition, other medications administered simultaneously, and the patient's response.
• With repeated administration, tolerance may develop.

If you use more Morfina Serra than you should

If you have used more Morfina Serra than 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 prospectus of the medication to the healthcare professional.

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

People who have taken an overdose may suffer from inhalation pneumonia of vomit or foreign particles; symptoms may consist of 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.

The recommended treatment for overdose consists of:

• Maintaining a respiratory route and establishing controlled or assisted breathing.
• 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. Since the duration of the effect of naloxone is considerably shorter than that of morphine via epidural or intrathecal route, repeated administration of the drug may be necessary. It should be kept in mind that naloxone can also inhibit the analgesic actions of morphine and may precipitate withdrawal symptoms in patients with physical dependence.
• Administering fluids intravenously and/or vasopressors (drugs used when a patient's blood pressure drops too low), using other supportive measures as needed.
• Continuing patient monitoring.

If you forget to use Morfina Serra

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

If you interrupt treatment with Morfina Serra

Do not interrupt treatment with Morfina Serra unless your doctor approves it. If you wish to interrupt treatment with Morfina Serra, ask your doctor how to gradually reduce the dose to avoid withdrawal symptoms. Withdrawal symptoms may be generalized pain, tremors, diarrhea, stomach pain, nausea, flu-like symptoms, palpitations, and pupil dilation. Psychological symptoms consist of a deep feeling of dissatisfaction, anxiety, and irritability.

The abrupt interruption of treatment in patients with physical dependence can precipitate a withdrawal syndrome characterized by the following symptoms in varying degrees of intensity for each individual: yawning, tearing, rhinorrhea (nasal secretion), sweating, mydriasis (pupil dilation), tremor, goosebumps, anorexia (loss of appetite), restlessness, vomiting, fever, hyperpnea (increase in respiratory amplitude and frequency), hypertension, and diarrhea.

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

4. Possible adverse effects

Like all medications, Morfina Serra can produce adverse effects, although not all people experience them.

The adverse effects of morphine are, in general, frequent and moderately important. In most cases, the adverse effects are a pharmacological prolongation and mainly affect the central nervous system and the digestive and respiratory systems.

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.

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

The most characteristic adverse reactions are:

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

• Frequent (may 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, cardiac arrest, high blood pressure, low blood pressure, intracranial hypertension, laryngeal spasm, collapse, respiratory depression, apnea (episodes of suspended breathing when the person is sleeping), urinary retention, reduced libido (reduced sexual desire), impotence, blurred vision, nystagmus (jerky eye movement), diplopia (double vision), miosis (excessive pupil constriction), edema, itching, urticaria, skin rashes, contact dermatitis, pain at the injection site.

• Uncommon (may 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.

• Frequency unknown: increased sensitivity to pain, withdrawal symptoms or dependence (to consult the symptoms, see section 3: If you interrupt treatment with Morfina Serra), sleep apnea (pauses in breathing during sleep), symptoms associated with pancreatitis and biliary tract inflammation, for example, severe upper abdominal pain that may radiate to the back, nausea, vomiting, or fever.

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

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

If you consider that any of the adverse effects you suffer is serious or if you notice any adverse effect not mentioned in this prospectus, inform your doctor or pharmacist.

5. Conservation of Morfina Serra

Keep this medication out of sight and reach of children.

Do not store at a temperature above 25°C

It does not contain any type of preservative, so opened and unused ampoules should be rejected.

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.

Medications should not be thrown away through the sewers or in the trash. Deposit the packaging and medications you no longer need at the SIGRE point of 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. Content of the packaging and additional information

Composition of Morfina Serra

• The active principle is morphine hydrochloride. Each ampoule contains 10 mg of morphine hydrochloride (equivalent to 8.9 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 content of the packaging

Morfina Serra is presented in the form of a clear, clean, sterile injectable solution, free of precipitates.

The packaging contains 1 ampoule or 10 ampoules of 1 ml of solution.

Marketing authorization holder and manufacturer

Laboratorios SERRA PAMIES S.A.

Ctra. Castellvell, 24

43206 REUS (Tarragona)

Spain

The last revision of this prospectus was in October 2023

Detailed and updated 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:

The rapid intravenous injection of opioid analgesics can cause anaphylactoid reactions, so it will only be performed by doctors with experience in this administration and they must have available equipment for artificial ventilation and opioid antagonist medications.

When this medication is administered via the epidural and intrathecal routes, patients must be adequately monitored for at least 24 hours, as respiratory depression may occur.

When morphine is administered parenterally, the patient must 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 epidurally or intrathecally during labor, 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 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.

In patients with shock, the alteration of perfusion may prevent complete absorption after intramuscular or subcutaneous administration. Repeated administration may lead to overdose due to the unexpected absorption of an excessive amount when circulation is recovered.

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