Morphine hydrochloride S.A.L.F.: detailed information

Package leaflet: Information for the user

MORPHINE HYDROCHLORIDE S.A.L.F. 10 mg/ml Injection solution, 20 mg/ml Injection solution

Morphine hydrochloride
Equivalent medicine
Please read all of this leaflet carefully before you start using this medicine as it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist or nurse.
If you get any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

What MORPHINE HYDROCHLORIDE S.A.L.F. is and what it is used for
What you need to know before using MORPHINE HYDROCHLORIDE S.A.L.F.
How to use MORPHINE HYDROCHLORIDE S.A.L.F.
Possible side effects
How to store MORPHINE HYDROCHLORIDE S.A.L.F.
Contents of the pack and other information

1. What MORFINA CLORIDRATO S.A.L.F. is and what it is used for

MORFINA CLORIDRATO S.A.L.F. contains the active substance morfina cloridrato (morphine chloride), which belongs to a group of medicines called opioid analgesics (derived from opium processing), that act by reducing pain at the brain level.
This medicine is indicated for the treatment of moderate to severe pain:

when other pain-relief treatments have not been effective;
due to tumors (neoplasia);
due to heart problems (myocardial infarction);
after surgical procedures;
due to lung problems (acute pulmonary edema).

Morphine is also indicated to induce anesthesia during childbirth (obstetric analgesia-epidural) and during surgical procedures (general and loco-regional anesthesia).

2. What you need to know before using MORPHINE HYDROCHLORIDE S.A.L.F.

Do not use MORPHINE HYDROCHLORIDE S.A.L.F.

if you are allergic to morphine hydrochloride, to other medicines of the same class as MORPHINE HYDROCHLORIDE S.A.L.F., or to any of the other ingredients of this medicine (listed in section 6). If you are allergic, you may experience facial flushing, itching, difficulty breathing due to bronchial narrowing (bronchospasm), or more severe allergic reactions (anaphylactic reactions);
if you suffer from stomach or intestinal problems (acute abdomen, paralytic ileus);
if you suffer from breathing difficulties (respiratory depression);
if you suffer from severe liver problems (severe hepatocellular insufficiency);
if you suffer from heart problems associated with other respiratory disorders (heart failure secondary to chronic lung disease);
if you have sustained head trauma or have increased pressure inside the head (trauma, intracranial hypertension);
if you have undergone surgery on the liver or biliary tract (biliary pathways);
during a respiratory crisis (asthma due to bronchitis);
if you suffer from seizures;
if you suffer from uncontrolled epilepsy;
if you suffer from alcohol dependence (acute alcoholism, delirium tremens);
if you suffer from depression, particularly due to other medicines (hypnotics, sedatives, tranquillisers);
if you are being treated with medicines for depression (monoamine oxidase inhibitors, furazolidone) or if you have stopped treatment with these medicines less than 2–3 weeks ago;
if you are being treated with naltrexone for opioid or morphine dependence;
if you are pregnant or breastfeeding (see section “Pregnancy and breastfeeding”).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using MORPHINE HYDROCHLORIDE S.A.L.F.
Use this medicine with caution if:

you are elderly, very elderly, or debilitated; in these cases, a dose reduction may be necessary;
you suffer from heart disorders due to lung diseases;
you suffer from brain disorders (organic cerebral conditions);
you have breathing problems (respiratory insufficiency and chronic lung diseases, particularly if accompanied by increased bronchial secretions, airway obstruction, and reduced ventilatory reserve, as in kyphoscoliosis and obesity);
you suffer from kidney or gallbladder problems (renal and biliary colic);
you have prostate problems (prostatic hypertrophy);
you have altered thyroid hormone levels (myxoedema, hypothyroidism);
you suffer from liver problems (hepatitis and acute hepatopathies);
your liver or kidneys are not functioning properly;
you suffer from hormonal disorders (adrenocortical insufficiency);
you have severe low blood pressure (severe hypotensive states) and loss of consciousness (shock);
you suffer from digestive problems (slowed or blocked gastrointestinal motility, intestinal disorders due to inflammation or obstruction);
you suffer from muscle disorders (severe myasthenia gravis);
you suffer from dependence on opioid painkillers such as morphine (habituation);
you suffer from disturbances in heart rhythm and circulation (cardiovascular disorders, cardiac arrhythmias), or if you suffer from heart valve problems (aortic valve dysfunction) and coronary circulation disorders.

Talk to your doctor, pharmacist, or nurse if you notice any of the following symptoms during use of MORPHINE HYDROCHLORIDE S.A.L.F.:

Increased sensitivity to pain despite increasing doses (hyperalgesia). Your doctor will decide whether a dose adjustment or a change in the strong analgesic (“painkiller”) is needed (see section 2).
Weakness, fatigue, loss of appetite, nausea, vomiting, or low blood pressure. This may indicate that your adrenal glands are producing insufficient cortisol, and you may need hormonal supplementation.
Loss of libido, impotence, cessation of menstruation. This may be due to reduced production of sex hormones.
If you have previously been dependent on drugs or alcohol. Also inform your doctor if you feel you are becoming dependent on MORPHINE HYDROCHLORIDE S.A.L.F. while using it. You may find yourself thinking frequently about when you can take the next dose, even if you do not need it for pain.
Symptoms of withdrawal or dependence. The most common withdrawal symptoms are listed in section 3. If this occurs, your doctor may change the type of medicine or the dosing schedule.

Morphine, due to its pain-relieving (analgesic) effect, its action on consciousness, pupil size, and respiration, may mask certain symptoms and make clinical assessment difficult.
Administration of morphine, especially if prolonged, may lead to the development of tolerance and dependence.
Therefore, morphine should only be used under medical supervision and when other pain-relieving medicines have not been effective.

Tolerance to morphine is characterised by reduced effectiveness and shorter duration of analgesic effect. If you develop dependence on this medicine, your dose will be increased. The dose increase does not pose risks to respiration (respiratory depression). Tolerance to this medicine ceases within a few days after discontinuation of treatment.
Morphine dependence develops concurrently with tolerance, especially as morphine administration approaches discontinuation. Dependence is characterised by a series of symptoms (collectively known as withdrawal syndrome) such as widespread pain, diarrhoea, increased blood pressure (hypertension), chills (withdrawal syndrome), which appear within a few hours after the last dose. Withdrawal symptoms peak within 36–72 hours, then gradually subside. The most frequent symptoms within the first 24 hours are restlessness, yawning, pupil dilation (mydriasis), tearing, runny nose (rhinorrhoea), increased sweating, and goosebumps (piloerection). After 24 hours, involuntary muscle contractions (fasciculations and muscle spasms), abdominal and leg pain, back pain (lumbago), headache (cephalalgia), sneezing, weakness, anxiety, irritability, sleep disturbances or loss (insomnia), agitation, loss of appetite (anorexia), nausea, vomiting, diarrhoea, fluid loss (dehydration), weight loss, increased heart rate (tachycardia), increased respiratory rate (tachypnea), increased blood pressure (hypertension), increased body temperature (fever), and vascular (vasomotor) disturbances may occur. If untreated, these symptoms may resolve within 5–14 days.

Dependence and tolerance develop slowly when morphine is administered clinically to prevent pain, rather than on an as-needed basis. MORPHINE HYDROCHLORIDE S.A.L.F. will be administered in a clinical or hospital setting by trained personnel, so the development of severe dependence and tolerance is rare.
However, it is essential that you remain under close medical supervision during treatment with this medicine. Discontinuation of treatment must be gradual and always occur under strict medical supervision. In cases of high-grade tolerance, specialist intervention may be required.
Morphine should not be used for painful conditions that respond to less potent analgesics, in order to eliminate even the slightest risk of developing dependence (see section “If you stop using MORPHINE HYDROCHLORIDE S.A.L.F.”).
For athletes: using the medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.

Children
Morphine should only be administered to children when strictly necessary, particularly in newborns.

Other medicines and MORPHINE HYDROCHLORIDE S.A.L.F.
Inform your doctor or pharmacist if you are using, have recently used, or might use any other medicine.
This is particularly important if you are taking any of the medicines listed below or medicines for:
Rifampicin, used to treat, for example, tuberculosis.
The combination of MORPHINE HYDROCHLORIDE S.A.L.F. with antidepressants (tricyclic antidepressants) and medicines acting on inflammation (aspirin, non-steroidal anti-inflammatory drugs) is effective in enhancing analgesic effects, allowing for a reduction in morphine dose.
If you have pain (with a neurological component), the combination of MORPHINE HYDROCHLORIDE S.A.L.F. with medicines for epilepsy (carbamazepine, anticonvulsants) may increase the analgesic and sedative effects.
If you have pain due to brain nerve inflammation (neuralgias), thalamic lesions (thalamic syndrome), or spinal cord injuries, MORPHINE HYDROCHLORIDE S.A.L.F. may not be effective. In such cases, other medicines (anticonvulsants, antidepressants, and long-acting phenothiazines) may be required.
Concomitant use of MORPHINE HYDROCHLORIDE S.A.L.F. and sedative medicines such as benzodiazepines or related drugs increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. Therefore, concomitant use should only be considered when no other treatments are possible.
However, if your doctor prescribes MORPHINE HYDROCHLORIDE S.A.L.F. together with sedative medicines, the dose and duration of concomitant treatment must be limited by the doctor.
Inform your doctor about all sedative medicines you are taking and strictly follow the recommended dose.
It may be helpful to inform friends or relatives to watch for the signs and symptoms listed above. Contact your doctor if such symptoms occur.

Do not use MORPHINE HYDROCHLORIDE S.A.L.F. if you are taking:

medicines for depression (monoamine oxidase inhibitors and furazolidone), because the combination may cause low blood pressure (hypotension) and breathing difficulties (respiratory depression, see section “Warnings and precautions”);
naltrexone and similar medicines used to treat morphine dependence (see section “Warnings and precautions”), because they may mask the analgesic effect of morphine;
other medicines containing alcohol or alcoholic beverages (MORPHINE HYDROCHLORIDE S.A.L.F. with alcohol), because they increase the sedative effect of morphine, alter wakefulness, and make driving dangerous (see section “Driving and use of machinery”).

Use MORPHINE HYDROCHLORIDE S.A.L.F. with caution if you are taking:

rifampicin, a medicine used to treat infections caused by viruses. Concurrent use may reduce the effect of morphine. During and after rifampicin therapy, your doctor will monitor you and adjust the morphine dose if necessary;
cimetidine and other medicines used to lower blood lipid levels. The combination of morphine and cimetidine may cause confusion and breathing problems if you are undergoing mechanical blood filtration (haemodialysis). These medicines increase the effect and duration of morphine;
barbiturates, used to treat seizures and to induce anaesthesia;
benzodiazepines and other medicines for anxiety, which may increase the risk of respiratory problems, including severe and fatal cases;
other pain medicines (morphine agonist analgesics, such as alfentanil, codeine, dextromoramide, dextropropoxyphene, dihydrocodeine, fentanyl, oxycodone, pethidine, phenoperidine, remifentanil, sufentanil, tramadol);
medicines used to treat cough (morphine antitussives, such as codeine, and morphine-like agents such as dextromethorphan);
other sedative medicines (neuroleptics), used to treat depression (antidepressants), muscle stiffness (muscle relaxants), allergies (antihistamines), or to induce anaesthesia (anaesthetics), as they may increase morphine’s effects on respiration and on your ability to drive or operate machinery (see section “Driving and use of machinery”);
medicines used to prevent blood clotting (oral anticoagulants, including dicoumarol). Morphine may enhance the effects of these medicines;
medicines used to increase fluid elimination (diuretics). Morphine may reduce the effect of these medicines and cause urine retention (urinary retention), especially if you suffer from prostate problems (early prostatism).

MORPHINE HYDROCHLORIDE S.A.L.F. with alcohol
Consumption of alcoholic beverages or medicines containing alcohol is not recommended during treatment with MORPHINE HYDROCHLORIDE S.A.L.F., as alcohol may increase sedative effects and breathing disturbances.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.

Pregnancy
Do not use MORPHINE HYDROCHLORIDE S.A.L.F. during pregnancy, except in cases of absolute necessity, such as severe pain.
This medicine, like other similar medicines (narcotic analgesics), may cause breathing problems (respiratory depression) in the newborn or withdrawal symptoms, if used continuously during pregnancy.
If MORPHINE HYDROCHLORIDE S.A.L.F. is used for a prolonged period during pregnancy, there is a risk that the newborn may experience withdrawal symptoms requiring medical treatment.
Administration should be avoided during premature labour or during the second stage of labour (when the cervix is dilated to 4–5 cm).

Breastfeeding
Morphine passes into breast milk. Your doctor will assess whether breastfeeding or treatment should be discontinued.

Driving and use of machinery
This medicine may cause effects that significantly impair your ability to drive vehicles or operate machinery. Avoid driving and operating machinery during treatment with this medicine.
These effects may be greater if you take this medicine in combination with alcohol or other sedative medicines (see sections “MORPHINE HYDROCHLORIDE S.A.L.F. and alcohol” and “MORPHINE HYDROCHLORIDE S.A.L.F. and other medicines”).

3. How to use MORPHINE HYDROCHLORIDE S.A.L.F.

This medicine will be administered to you by a doctor or nurse, under the skin (subcutaneous route), into a muscle (intramuscular route), into a vein (intravenous route), or into the epidural space if the medicine does not contain preservatives.
The contents of the vial may be diluted in physiological saline (sodium chloride 0.9%) or in another solvent (5% glucose).
The doctor will adjust the dose according to your age and health condition.

Use in adults
Treatment of acute pain:

Subcutaneous or intramuscular administration: the recommended dose is 10 mg, repeated every 4 hours if necessary.
Direct intravenous administration: the recommended dose is between 2 mg and 10 mg per 70 kg of body weight, administered over 4–5 minutes.

Treatment of post-surgical pain:

Epidural administration: the recommended dose is between 2 mg and 5 mg. This dose provides pain relief for 24 hours. If necessary, the doctor may decide to increase the dose by 1–2 mg at regular intervals to assess effectiveness. Do not exceed 10 mg within 24 hours.
Continuous intravenous infusion: the recommended initial dose is 2–4 mg over 24 hours. The doctor may decide to increase the dose by 1–2 mg if necessary.

Treatment of pain associated with lung problems (acute pulmonary edema)
The recommended dose is between 5 mg and 10 mg, administered by slow intravenous injection (2 mg per minute).

Treatment of pain associated with heart activity block (myocardial infarction)
The recommended dose is 10 mg, followed by another 10 mg if necessary, administered by slow intravenous injection (2 mg per minute).

Use in newborns

Slow intravenous administration (bolus): the recommended dose is between 40 and 100 micrograms per kg of body weight, administered over at least 5–10 minutes, every 4–6 hours.
Intravenous infusion:
- In premature infants: the recommended initial dose is between 25 and 50 micrograms per kg of body weight, followed by a second dose (loading dose) of 5 micrograms per kg of body weight per hour.
- In full-term infants: the recommended initial dose is between 50 and 100 micrograms per kg of body weight, followed by 10–20 micrograms per kg of body weight per hour.

Use in children up to 12 years of age
Use this medicine in children under 12 years of age only when strictly necessary:

Intravenous administration (bolus): the recommended dose is between 100 and 200 micrograms per kg of body weight, up to 6 times daily.
Infusion: must only be performed after an initial dose (bolus administration). The recommended dose is between 10 and 30 micrograms per kg of body weight per hour.

Use in adolescents aged 12 to 18 years:

Intravenous administration (bolus): the recommended dose is between 2.5 mg and 10 mg, up to 6 times daily.
Infusion: must only be performed after an initial dose (bolus administration). The recommended dose is between 10 and 30 micrograms per kg of body weight per hour.

Use in elderly and debilitated patients
The doctor will decide whether to reduce the dose based on your health condition (see section “Warnings and precautions”).

Use in patients with kidney or liver problems
If you suffer from liver or kidney problems (hepatic and/or renal insufficiency), the doctor will reduce the dose. In severe cases, the dose may be halved.

If you use more MORPHINE HYDROCHLORIDE S.A.L.F. than you should
This medicine will be administered by a doctor or nurse, so overdose is unlikely. However, if you think you have been given too much of this medicine, inform your doctor immediately or go to the nearest hospital.
People who have taken an excessive dose may develop aspiration pneumonia due to inhaling vomit or foreign bodies, with symptoms such as dyspnea, cough, and fever.
People who have taken an excessive dose may also experience breathing difficulties leading to unconsciousness or even death.
Symptoms of morphine overdose may include:

Breathing problems (respiratory depression, respiratory arrest), collapse, and coma;
Circulatory problems;
Altered state of consciousness;
Constriction of the pupil (miosis);
Lowered body temperature (hypothermia);
Muscle flaccidity, breakdown of muscle cells (rhabdomyolysis), leading to impaired kidney function (renal failure).

In severe cases, inadequate blood circulation (circulatory failure), coma, collapse, and death may occur. During coma, relaxation of organs (sphincter relaxation) and enlargement of the pupils (mydriasis) may occur.
In milder cases, symptoms may include:

Nausea, vomiting;
Tremors;
Behavioral changes (dysphoria);
Decreased body temperature (hypothermia);
Decreased blood pressure (hypotension).

If you have taken an excessive dose of this medicine, contact your doctor immediately or go to the nearest hospital.

If you forget to use MORPHINE HYDROCHLORIDE S.A.L.F.
This medicine will be administered by a doctor or nurse, so it is unlikely that a dose will be missed. However, do not take a double dose to make up for a forgotten dose.

If you stop using MORPHINE HYDROCHLORIDE S.A.L.F.
Do not stop treatment with MORPHINE HYDROCHLORIDE S.A.L.F. without consulting your doctor. If you intend to stop treatment, ask your doctor how to gradually reduce the dose to avoid withdrawal symptoms. Withdrawal symptoms may include muscle pain, tremors, diarrhea, stomach pain, nausea, flu-like symptoms, rapid heartbeat, and dilated pupils.
Psychological symptoms include intense feelings of dissatisfaction, anxiety, and irritability.

If you have any questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
The following side effects may occur:
Important side effects or symptoms to monitor and what to do if you experience them:

Severe allergic reaction causing breathing difficulties or dizziness.

If you experience these serious side effects, seek medical advice immediately.
Not known (Insufficient data available to determine the frequency of individual listed side effects)

Increased sensitivity to pain
Sweating
Dry mouth
Changes in hormone levels (decrease in CRF, ACTH, LH, FSH, androgens, estrogens; increase in prolactin, ADH)
Excitation, irritability, agitation, behavioral changes (euphoria, dysphoria)
Sleep loss (insomnia)
Sedation
Reduced mood tone
Feeling of weakness (asthenia)
Confusion (mental obtundation), states of indifference
Headache (cephalalgia)
Dizziness
Increased intracranial pressure, which may worsen pre-existing brain disorders
Vision problems, pupil constriction (miosis)
Sensation of dizziness due to drop in blood pressure upon standing (orthostatic hypotension)
Temporary loss of consciousness (syncope)
Breathing problems (respiratory depression, respiratory arrest), even severe if you suffer from bronchial or lung disorders (atelectasis)
Circulatory depression
Collapse
Nausea, vomiting
Digestive blockage (closure of the sphincter of Oddi and increased biliary pressure which may cause nausea and colicky pain)
Decreased gastric and intestinal secretions, increased tone of intestinal smooth muscle, and slowed peristalsis leading to constipation (spastic constipation)
Flushing of the face, neck, and chest, sweating, itching, skin irritation (urticaria and other skin alterations)
Withdrawal or dependence symptoms (for symptoms, see section 3: If you stop taking Morfina Cloridrato S.A.L.F.)
Reduced urine output (hormonally-induced oliguria); morphine prolongs bladder emptying time, but rapid tolerance develops to this effect.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. You can also report side effects directly via the national reporting system at the following website:
http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store MORPHINE HYDROCHLORIDE S.A.L.F.

Keep this medicine out of the reach and sight of children.
Do not use this medicine after the expiry date stated on the packaging after "EXP.". The expiry date refers to the last day of that month.
Store the vials in their original packaging to protect the medicine from heat and light.
Warning: do not use solutions of Morphine Hydrochloride S.A.L.F. 10 mg/ml injectable solution if they appear coloured.
Do not use solutions of Morphine Hydrochloride S.A.L.F. 20 mg/ml injectable solution if they are more intensely coloured than a slight yellow tint.
The vials are for single use only; discard any unused solution.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What MORFINA CLORIDRATO S.A.L.F. contains
MORFINA CLORIDRATO S.A.L.F. 10 mg/ml Injectable solution

The active substance is morphine hydrochloride. Each vial contains 10 mg of morphine hydrochloride trihydrate.
The other components are hydrochloric acid and water for injections.

MORFINA CLORIDRATO S.A.L.F. 20 mg/ml Injectable solution

The active substance is morphine hydrochloride. Each vial contains 20 mg of morphine hydrochloride trihydrate.
The other components are hydrochloric acid and water for injections.

Description of the appearance of MORFINA CLORIDRATO S.A.L.F. and contents of the pack
MORFINA CLORIDRATO S.A.L.F. 10 mg/ml Injectable solution: Carton pack containing 5 vials of 10 mg/ml.
MORFINA CLORIDRATO S.A.L.F. 20 mg/ml Injectable solution: Carton pack containing 5 vials of 20 mg/ml.
Marketing Authorization Holder and Manufacturer
S.A.L.F. S.p.A. Laboratorio Farmacologico – Via Marconi, 2 - Cenate Sotto (BG)

The following information is intended exclusively for physicians or healthcare professionals:
Physical-chemical incompatibility (precipitate formation) has been demonstrated between solutions of morphine sulfate and 5-fluorouracil.