Mst continus

Package leaflet: Information for the patient

MST Continus 10, 30, 60, 100, 200 mg,
modified-release coated tablets
Morphini sulfas
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet:

1. What MST Continus is and what it is used for
2. Important information before taking MST Continus
3. How to take MST Continus
4. Possible side effects
5. How to store MST Continus
6. Contents of the pack and other information

1. What MST Continus is and what it is used for

MST Continus contains morphine sulfate as the active substance, a strong analgesic belonging to the group of opioid medicines.
MST Continus is used:

• for the relief of moderate to severe pain not relieved by weaker analgesics;
• for the management of severe postoperative pain from the second day after surgery.

2. Important information before using MST Continus

When not to use MST Continus

• if the patient is allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6), or if the patient has been diagnosed with acute abdomen;
• if the patient has paralytic ileus or suspected intestinal obstruction;
• if the patient has severe respiratory depression with hypoxia and/or hypercapnia (reduced respiratory rate or respiratory arrest);
• if the patient has delayed gastric emptying;
• if the patient has acute liver disease;
• if the patient has severe chronic obstructive pulmonary disease;
• if the patient has severe bronchial asthma.

Tolerance, dependence and abuse
This medicine contains morphine, which is an opioid. Repeated use of opioids may lead to reduced effectiveness of the medicine (the patient becomes accustomed, known as tolerance). Repeated use of MST Continus may lead to dependence and abuse, which can result in life-threatening overdose. The risk of these adverse effects may increase with higher doses and longer duration of treatment.
Dependence or abuse may cause the patient to feel that they have lost control over the dose or frequency of medicine intake.
The risk of dependence varies between patients. The risk of dependence on MST Continus may be higher if:

• the patient or a family member has ever abused or been dependent on alcohol, prescription medicines or drugs;
• the patient smokes cigarettes;
• the patient has had mood disorders (depression, anxiety or personality disorders) or has been treated by a psychiatrist for other mental illnesses.

Warnings and precautions
Administration of MST Continus is not recommended:

• to patients prior to surgery and within 24 hours after surgery (due to increased risk of reduced intestinal peristalsis or respiratory depression);
• to children under 12 years of age;
• to children and adolescents over 12 years of age for the treatment of postoperative pain.

Exercise particular caution when using MST Continus:

• if the patient has been or is currently opioid-dependent;
• if the patient has a history of psychological dependence on drugs, psychotropic substances and/or alcohol;
• if the patient suffers from alcohol delirium (delirium tremens);
• if the patient has disturbances of consciousness;
• if the patient has severe impairment of respiratory centre function (part of the nervous system responsible for respiratory rate and depth) or lung function. The patient should also exercise caution if they have any other condition that may lead to breathing difficulties;
• if the patient has respiratory depression;
• if the patient has severe right ventricular hypertrophy (enlargement of one of the heart's components);
• if the patient has sleep apnoea;
• if the patient has head injury, intracranial lesions or increased intracranial pressure, especially when mechanical ventilation is not used;
• if the patient has low blood pressure, including due to low circulating blood volume (hypotensive arterial hypovolemia);
• if the patient has benign prostatic hyperplasia causing urinary retention (risk of bladder rupture due to urine retention);
• if the patient has urethral stricture;
• if the patient has renal colic;
• if the patient has severe renal impairment;
• if the patient has severe hepatic impairment;
• if the patient has biliary tract dysfunction;
• if the patient has pancreatitis or gallbladder problems due to gallstones;
• if the patient has inflammatory bowel disease;
• if the patient has hypothyroidism;
• if the patient has adrenal insufficiency;
• if the patient has phaeochromocytoma;
• if the patient has epilepsy or increased seizure susceptibility;
• if the patient is elderly;
• if the patient is concurrently using MAO inhibitors or within 2 weeks after discontinuation of MAO inhibitors;
• if the patient is concurrently using central nervous system depressants;
• if the patient has constipation.

Contact a doctor if the patient experiences severe upper abdominal pain radiating to the back, nausea, vomiting or fever, as these may be symptoms of pancreatitis and biliary tract disorders.
If any of the following symptoms occur during treatment with MST Continus, consult a doctor, pharmacist or nurse:

• Increased sensitivity to pain despite increasing the dose of the medicine (hyperalgesia). The doctor will decide whether dosage adjustment or use of a stronger analgesic is necessary (see section 2).
• Weakness, fatigue, loss of appetite, nausea, vomiting or low blood pressure. These may be symptoms of insufficient cortisol production by the adrenal glands, and hormone supplementation may be required.
• Loss of libido, impotence, amenorrhea. This may be due to reduced secretion of sex hormones.
• If the patient has previously been dependent on drugs or alcohol. Also inform the doctor if the patient notices developing dependence on MST Continus during treatment, for example, if they frequently think about taking another dose even when not needed for pain relief.
• Symptoms of withdrawal or dependence. The most common withdrawal symptoms are listed in section 3. In such cases, the doctor may change the medicine or adjust the interval between doses.

When to exercise particular caution when using MST Continus
Acute generalised exanthematous pustulosis (AGEP) has been reported during treatment with MST Continus. Symptoms usually appear within the first 10 days of treatment. Inform the doctor if the patient has ever experienced severe skin rash, skin peeling, blisters and/or oral ulcers after taking MST Continus or other opioids. Discontinue MST Continus and seek immediate medical attention if the patient notices any of the following symptoms: appearance of blisters, extensive skin peeling or pustular lesions accompanied by fever.

Respiratory depression
If the patient has difficulty breathing, shortness of breath or apnoea, they should contact a doctor. Suppression of the respiratory centre in the central nervous system is a significant risk in opioid overdose.

Sleep-related breathing disorders
MST Continus may cause sleep-related breathing disorders such as sleep apnoea (pauses in breathing during sleep) and hypoxemia (low blood oxygen levels), or worsen existing sleep-related breathing disorders. Symptoms may include episodes of stopped breathing during sleep, waking up at night due to breathlessness, difficulty maintaining sleep or excessive daytime sleepiness. Inform the doctor if the patient or someone else observes these symptoms. The doctor may consider reducing the dose.
Children and elderly patients are more sensitive to morphine and should therefore be treated with MST Continus with particular caution.
If the patient has difficulty breathing, shortness of breath or apnoea, they should contact a doctor. Suppression of the respiratory centre in the central nervous system is a significant risk in opioid overdose.
Opioids may cause sleep-related breathing disorders, including central sleep apnoea and sleep-related hypoxia, and may worsen existing sleep apnoea. If the patient has central sleep apnoea, the doctor should consider reducing the total daily dose of the analgesic.

Due to its sphincter-constricting effect, the medicine may cause biliary or renal colic attacks. Use with caution after surgical procedures, especially those involving the biliary tract, and in patients with secondary acute pancreatitis.
If the patient is to undergo cordotomy (cutting certain nerves to eliminate pain) or another pain-blocking procedure, they should inform the doctor that they are taking MST Continus.
If the patient develops symptoms such as poorly localised abdominal pain, vomiting, abdominal distension and retention of gas and stool, with or without low blood pressure (paralytic ileus), contact a doctor.
Morphine may increase the risk of seizures in patients with epilepsy (epilepsy).
If hypersensitivity occurs in a patient previously treated with high doses of morphine sulfate and does not resolve with increased MST Continus dose, it may be necessary to reduce the morphine sulfate dose or switch to another opioid.
Use of MST Continus may lead to physical dependence (development of tolerance), requiring higher doses to achieve the desired analgesic effect.
Morphine has an abuse potential similar to other strong opioid analgesics. MST Continus should be used with particular caution in patients currently or previously dependent on drugs or alcohol, or in individuals with a predisposition to addiction.
Use of opioid analgesics may lead to development of physical and/or psychological dependence or tolerance. The associated risk increases with duration of use and higher doses. These effects can be minimized by adjusting the dose or formulation and gradually tapering morphine.
Sudden discontinuation of treatment may lead to withdrawal syndrome, characterized by symptoms such as diarrhoea, pain and cardiovascular disturbances. If morphine treatment is no longer necessary, the doctor will gradually reduce the dose to prevent withdrawal symptoms (see section "Discontinuation of MST Continus" in section 3).
High doses of morphine should not be used immediately at the beginning of treatment without prior gradual titration of small doses.
Morphine should be used with particular caution in patients concurrently taking MAO inhibitors or within 2 weeks after discontinuation of MAO inhibitors.
If the patient has adrenal cortex dysfunction (e.g. Addison's disease), the doctor may recommend testing plasma cortisol levels and, if necessary, prescribe appropriate medication.
Constipation is a common adverse effect associated with morphine treatment. Discuss this with the doctor. The doctor may recommend using laxatives from the beginning of morphine treatment, especially if the patient had intestinal motility problems before starting morphine.
Administration of MST Continus is not recommended in the perioperative period or within 24 hours after surgery.
Intravenous administration of an oral dose may cause severe adverse effects. Abuse of orally or parenterally administered morphine may result in serious adverse effects that may lead to death.
Concurrent alcohol consumption and use of MST Continus may intensify adverse effects; simultaneous intake should be avoided.

Children
Use of MST Continus is not recommended in children under 12 years of age.

MST Continus and other medicines
Inform the doctor about all medicines currently or recently taken, including those available without prescription, and any medicines planned for future use.
This is particularly important when using MST Continus concurrently with:

• rifampicin, used in the treatment of, for example, tuberculosis;
• certain anticoagulants (e.g. clopidogrel, prasugrel, ticagrelor) may have delayed and reduced effects when taken with morphine;
• sedatives, e.g. benzodiazepines or related drugs, which increase the risk of drowsiness, breathing difficulties (respiratory depression) or coma, potentially life-threatening. Therefore, combined treatment should only be considered when no other treatment options are available. If MST Continus is used together with sedatives, the doctor should limit the dose and duration of concurrent use. The patient should inform the doctor about all sedatives taken and strictly follow the prescribed dose. Informing a relative or close friend about the possibility of the above symptoms may be helpful. If these symptoms occur, consult a doctor;
• monoamine oxidase inhibitors (MAOIs), as they may cause inhibition or stimulation of the central nervous system accompanied by hypertension or hypotension; therefore, morphine should not be used simultaneously or within two weeks after stopping MAO inhibitor treatment;
• other medicines affecting the central nervous system, including other opioids, hypnotics, anxiolytics (including phenothiazines), general anaesthetics and muscle relaxants, gabapentin (an antiepileptic), certain antihypertensives, antiemetics and alcohol, as morphine enhances their effects: excessive sedation, excessively low blood pressure and particularly respiratory depression (manifested by reduced respiratory rate or respiratory arrest), which may lead to coma and even death;
• anticholinergic drugs, e.g. antihistamines (antiallergic), antiemetics and drugs for Parkinson's disease, as they may intensify certain opioid adverse effects: constipation, dry mouth or urinary retention;
• other opioid receptor agonist-antagonist analgesics, i.e. pentazocine, nalbuphine, butorphanol, buprenorphine, as they may cause withdrawal symptoms (see section 3, "Discontinuation of MST Continus");
• cimetidine (used in the treatment of gastric ulcers) and other drugs that impair hepatic metabolic pathways, as they may inhibit morphine metabolism and thus increase morphine plasma concentrations;
• ritonavir (used in the treatment of HIV infection), as it may reduce morphine serum concentration;
• gabapentin or pregabalin used in the treatment of epilepsy and neuropathic pain;
• selective opioid receptor antagonists (e.g. naloxone), as they may reverse the effects of morphine.

If, during treatment with MST Continus, the patient notices any of the following symptoms, it may indicate developing tolerance or dependence:

• the patient needs to take the medicine longer than prescribed by the doctor;
• the patient must take a higher dose than recommended;
• the patient uses the medicine for reasons other than those prescribed by the doctor, e.g. "to stay calm" or "to help with falling asleep";
• the patient has made repeated unsuccessful attempts to discontinue or control medicine use;
• the patient feels unwell after stopping the medicine and feels better after resuming it ("withdrawal effects").

If any of these symptoms occur, discuss with the doctor the best treatment strategy for the patient, including when it is appropriate to discontinue treatment and how to safely stop it (see section 3 "Discontinuation of MST Continus").

MST Continus with food, drink and alcohol
Tablets may be taken independently of meals, either during or between meals.
Remnants of the tablet may be seen in the stool. This is not a cause for concern, as the active substance (morphine) has been released during passage through the gastrointestinal tract.
Alcohol consumption during MST Continus treatment may cause drowsiness or increase the risk of severe adverse effects such as shallow breathing with risk of apnoea and loss of consciousness. Alcohol consumption during MST Continus treatment is contraindicated.

Pregnancy, breastfeeding and effects on fertility
Animal studies have shown harmful effects of morphine on reproduction and offspring development.
MST Continus should not be used during pregnancy unless the doctor considers morphine treatment absolutely necessary. If MST Continus has been used during pregnancy for a prolonged period, there is a risk of neonatal withdrawal syndrome, which should be treated by a doctor. Morphine may prolong or shorten labour duration.
Morphine passes into breast milk; therefore, breastfeeding is not recommended during treatment.
Due to the mutagenic properties of morphine, effective contraception should be used during MST Continus treatment.

Driving and operating machinery
MST Continus affects reaction speed, potentially impairing the patient's ability to respond adequately or quickly to unexpected or sudden events. Consult the doctor regarding the possibility and conditions for driving.

MST Continus contains lactose and sunset yellow FCF
MST Continus 10 mg, 30 mg and 60 mg tablets contain 90 mg, 70 mg and 40 mg of lactose, respectively, as an excipient. If your doctor has informed you that you have an intolerance to certain sugars, contact your doctor before starting MST Continus treatment.
MST Continus 30 mg and 60 mg tablets contain the colouring agent sunset yellow FCF (E110), which may cause allergic reactions.

3. How to use MST Continus

This medicine should always be used exactly as directed by your doctor. If in doubt, consult your doctor or pharmacist.
Before starting treatment and regularly during therapy, your doctor will discuss with you what to expect from using MST Continus, when and for how long it should be taken, when to contact your doctor, and when to stop taking the medicine (see also "Discontinuing MST Continus" in this section).
The dose of MST Continus should be determined based on the intensity of pain, the patient's age, and response to previously used painkillers. Your doctor may start treatment with immediate-release morphine (tablets or solution) to establish the dose required for adequate pain control, before switching to MST Continus.
Modified-release tablets must be swallowed whole and must not be broken, chewed, or crushed. Administering a broken, chewed, or crushed modified-release tablet results in rapid release and absorption of a potentially fatal dose of morphine (see "Taking more MST Continus than you should" in section 3).

Adults
The usual starting dose for patients with low body weight is 10 mg every 12 hours, and for other patients, 30 mg every 12 hours. It is recommended to take the tablets in the morning and evening, always maintaining a 12-hour interval.
The starting dose is then increased until adequate pain control is achieved.
If pain returns before the next dose is due, do not shorten the interval between doses. In case of doubt regarding dosing, consult your doctor. Your doctor may increase the dose of MST Continus appropriately or prescribe an additional medicine containing morphine in the form of fast-acting tablets or injections.
For postoperative pain management, but not earlier than 24 hours after surgery: for patients weighing less than 70 kg, 2 tablets of 10 mg every 12 hours; for patients weighing more than 70 kg, 1 tablet of 30 mg every 12 hours.

Use in adolescents over 12 years of age:
Dosing is strictly at the physician’s discretion. The recommended starting dose is 0.2–0.8 mg of morphine per kg of body weight every 12 hours.
MST Continus is not recommended for the treatment of postoperative pain in adolescents.
MST Continus is not recommended for use in children under 12 years of age.

Elderly patients and patients in generally poor health
Elderly patients (aged 75 years and over) and patients in generally poor health may be more sensitive to morphine. For patients in these groups, your doctor may recommend longer intervals between doses or a lower dose.

Method of administration
Prolonged-release tablets must be swallowed whole and must not be bitten, chewed, crushed, or split. Take with sufficient liquid. The medicine may be taken regardless of meals, either during or between meals.

Duration of treatment
The duration of treatment will be determined by your doctor based on the intensity of the patient's pain.
If you feel that the effect of MST Continus is too strong or too weak, consult your doctor.

Taking more MST Continus than you should
If more MST Continus than recommended has been taken, contact your doctor immediately, as overdose of strong opioids can be fatal.
The patient may experience one or more of the following symptoms: breathing difficulties leading to loss of consciousness and even death, increasing drowsiness up to coma, pinpoint pupils, muscle flaccidity, hypotension, slowed heart rate. Aspiration pneumonia caused by vomiting or foreign bodies may also occur. Symptoms may include shortness of breath, cough, and fever.
Morphine overdose may lead to brain damage (known as toxic leukoencephalopathy).
In case of overdose, the following measures may be helpful while waiting for medical help: keep the patient awake, give breathing instructions, assist breathing by placing the patient in a sitting position. Hospitalization and continuous medical supervision may be necessary.

Missing a dose of MST Continus
Taking less than the recommended dose of MST Continus or missing a dose may result in inadequate pain relief.
Do not take MST Continus more often than every 12 hours.
Do not take a double dose to make up for a missed dose.

Discontinuing MST Continus
Do not stop taking MST Continus unless your doctor advises otherwise. To discontinue MST Continus, consult your doctor, who will decide how to gradually reduce the dose to avoid withdrawal symptoms. Abruptly stopping treatment may lead to withdrawal symptoms, which may include: headache, muscle pain, anxiety, tension, restlessness, confusion, irritability, mood changes, hallucinations, seizures, diarrhea, stomach pain, nausea, flu-like symptoms, rapid heartbeat, and dilated pupils.
The risk of withdrawal symptoms is greater if treatment is stopped suddenly. If treatment is to be discontinued, the dose should be gradually reduced.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
If any of the following symptoms occur, stop taking the medicine
MST Continus and seek immediate medical advice:

• Constipation is a characteristic adverse effect of long-term treatment.
• Intestinal obstruction
• Morphine causes dose-dependent respiratory depression and sedation of variable degree, ranging from mild fatigue to drowsiness.
• Bronchospasm
• Morphine may cause various psychiatric adverse effects, the severity and nature of which vary between individuals (depending on personality and duration of treatment).
• Morphine may cause severe allergic reactions leading to difficulty in breathing or dizziness, fainting (loss of consciousness)
• Clinically significant lowering or raising of blood pressure, heart failure
• Pancreatitis
• Renal colic
• Severe skin reaction with blistering, widespread peeling of the skin, pustular lesions accompanied by fever. This may be a condition known as acute generalized exanthematous pustulosis (AGEP).

In assessing adverse effects, the following frequency of occurrence is considered:
Very common (occurs in more than 1 in 10 people): nausea, constipation.
Common (occurs in less than 1 in 10 people): changes in activity level (usually decreased, but also increased activity), insomnia, changes in cognitive and sensory functions (e.g. perceptual disturbances, confusion), dizziness, headache, involuntary muscle contractions, drowsiness, abdominal pain, loss of appetite, dry mouth, vomiting (especially at the beginning of treatment), loss of appetite, excessive sweating, rash, urinary disorders, weakness, asthenia, fatigue, malaise, itching.
Uncommon (occurs in less than 1 in 100 people): hypersensitivity reactions (allergy), agitation, euphoria, hallucinations, mood changes, seizures, increased tension, paresthesia, fainting (loss of consciousness), visual impairment, dizziness, facial flushing, clinically significant lowering or raising of blood pressure, pulmonary edema, respiratory center depression, bronchospasm, intestinal obstruction, taste disturbances, dyspepsia, increased liver enzyme activity, urticaria, urinary retention, peripheral edema (transient after discontinuation of morphine), tachycardia (rapid heartbeat).
Rare (occurs in less than 1 in 1,000 people): increased pancreatic enzyme levels or pancreatitis, renal colic.
Very rare (occurs in less than 1 in 10,000 people): drug dependence, decreased libido, tremor, increased sensitivity to pain (perceiving pain in situations that do not cause pain in healthy individuals), blurred vision, double vision and nystagmus, shortness of breath, other rashes such as exanthema, muscle spasms, muscle stiffness, syndrome of inappropriate antidiuretic hormone secretion (SIADH) (mainly manifested by low blood sodium levels).

• Frequency not known (cannot be estimated from available data): sleep apnea (episodes of breathing cessation during sleep),
• severe skin reaction with blisters, widespread peeling skin, pustular lesions accompanied by fever. This may be a condition called acute generalized exanthematous pustulosis (AGEP), anaphylactic reactions, anaphylactoid reactions, disturbances in thinking, low mood, pinpoint pupils (miosis), excessive sweating, reduced cough reflex,
• symptoms associated with inflammation of the pancreas and biliary tract, e.g. severe upper abdominal pain radiating to the back, nausea, vomiting or fever. absence of menstruation, decreased libido, erectile dysfunction, withdrawal symptoms or dependence (for information on symptoms, see "Discontinuation of MST Continus" in section 3).

Cases of dental changes have been observed; however, a definite link with morphine treatment has not been established.
Palpitations, decreased heart rate, and heart failure may occur.
Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to: Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, PL-02 222 Warsaw, Tel.: + 48 22 49 21 301, Fax: + 48 22 49 21 309, Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store MST Continus

Store below 25 °C.
Keep the medicine in a place out of sight and reach of children.
Do not use the medicine after the expiry date stated on the packaging following the abbreviation: "Expiry date" or "EXP". The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. Such measures will help protect the environment.

6. Contents of the pack and other information

What MST Continus contains
The active substance is morphine.
Each modified-release coated tablet contains:
10, 30, 60, 100, or 200 mg of morphine sulfate (Morphini sulphas).

The other ingredients are:
MST Continus 10 mg
Anhydrous lactose, hydroxyethylcellulose, cetostearyl alcohol, magnesium stearate, talc.
Coating: Opadry 85F270017 (gold-brown), containing: polyvinyl alcohol, partially hydrolysed, titanium dioxide (E 171), macrogol 3350, talc, yellow iron oxide (E 172), red iron oxide (E 172), black iron oxide (E 172).

MST Continus 30 mg
Anhydrous lactose, hydroxyethylcellulose, cetostearyl alcohol, magnesium stearate, talc.
Coating: Opadry OY-6708 (violet).

MST Continus 60 mg
Anhydrous lactose, hydroxyethylcellulose, cetostearyl alcohol, magnesium stearate, talc.
Coating: Opadry OY-3508 (orange).

MST Continus 100 mg
Hydroxyethylcellulose, cetostearyl alcohol, magnesium stearate, talc.
Coating: Opadry OY-8215 (grey).

MST Continus 200 mg
Hydroxyethylcellulose, cetostearyl alcohol, magnesium stearate, talc.
Coating: Opadry 06B21168 (green), polyethylene glycol 400.

What MST Continus looks like and contents of the pack
Blister packs made of PVC/Aluminium foil in a cardboard box.
Pack sizes: 20, 30 or 60 tablets, in blisters of 10 tablets each.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Mundipharma A/S
Frydenlundsvej 30
2950 Vedbæk, Denmark

Manufacturer
Mundipharma DC B.V.
Leusderend 16
3832 RC Leusden, The Netherlands

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Mundipharma Polska Sp. z o.o., ul. Międzyborska 11B lok.104, 04-041 Warsaw, Poland, tel. +48 22 3824850.