TWICE 10 mg Капсулы С Пролонгированным Высвобождением

Содержание инструкции

1. TWICE 10 mg, prolonged-release hard capsules, 30 mg, prolonged-release hard capsules, 60 mg, prolonged-release hard capsules, 100 mg, prolonged-release hard capsules
   1. What is TWICE and what is it used for
   2. What you need to know before you take TWICE
   3. How to use TWICE
   4. Possible side effects
   5. How to store TWICE
   6. Contents of the pack and other information

TWICE 10 mg, prolonged-release hard capsules, 30 mg, prolonged-release hard capsules, 60 mg, prolonged-release hard capsules, 100 mg, prolonged-release hard capsules

Morphine sulfate

Read this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

• 1. What TWICE is and what it is used for
• 2. What you need to know before you take TWICE
• 3. How to take TWICE
• 4. Possible side effects
• 5. How to store TWICE
• 6. Contents of the pack and other information

1. What is TWICE and what is it used for

TWICE contains the active ingredient morphine sulfate, belonging to the group of opioid analgesics.
TWICE is indicated to control severe and/or resistant chronic (long-lasting) pain to other
painkillers, in particular pain of cancer origin (associated with a tumor).

2. What you need to know before you take TWICE

Do not take TWICE:

• if you are allergic to morphine and its derivatives or to any of the other ingredients of this medicine (listed in section 6);
• if you experience a rapid-onset, sudden and severe abdominal pain (acute abdomen);
• if you have an intestinal obstruction (paralytic ileus);
• if you suffer from delayed gastric emptying;
• if you have acute liver diseases;
• if you suffer from severe hepatic insufficiency (impaired liver function);
• if you have symptoms such as drowsiness or difficulty with coordination, blurred vision, difficulty speaking or loss of contact with reality (signs of central nervous system depression);
• if you have abused alcohol (acute alcoholism);
• if you suffer from a state of psychosis or a confused state caused by alcohol withdrawal (delirium tremens);
• if you have had a head injury (cranio) or have a disease that causes increased pressure in the head (intracranial hypertension);
• if you suffer from convulsions (involuntary, sudden and uncontrolled muscle movements);
• if you have severe difficulty breathing (respiratory depression);
• if you suffer from bronchial asthma (a disease that causes narrowing and inflammation of the bronchi);
• if you suffer from right heart failure (the heart's inability to provide an adequate amount of blood to the lungs);
• if you suffer from arrhythmias (irregular heartbeat);
• if you are already taking medicines called MAOIs, used as antidepressants or in the treatment of Parkinson's disease (a disease that causes tremor, rigidity and slowness of movement), or if you have stopped taking them less than two weeks ago;

Warnings and precautions
Talk to your doctor or pharmacist before taking TWICE.
Tell your doctor:

• if you are elderly or debilitated;
• if you have chronic lung diseases, especially if accompanied by increased mucus production, or conditions that cause difficulty breathing such as kyphoscoliosis (curvature of the spine) and obesity;
• if you suffer from reduced thyroid activity (hypothyroidism);
• if you have fluid accumulation under the skin caused by severe thyroid disorders (myxedema);
• if you have decreased function of the adrenal glands (small glands located above each of the two kidneys); if you suffer from severe hypotension (low blood pressure);
• in case of shock (decreased blood flow reaching the organs and tissues of the body due to decreased heart activity);
• if you suffer from diseases of the biliary tract (ducts that carry bile from the liver to the intestine);
• if you suffer from prostatic hypertrophy (enlargement of the prostate);
• if you have urethral stenosis (narrowing or obstruction of the urethra which is the channel that carries urine from the bladder to the outside);
• if you suffer from constipation;
• if you suffer from a condition that causes frequent interruptions of breathing during sleep (sleep apnea syndrome);
• if you are being treated with medicines used for the prevention of thrombotic events (formation of clots that prevent blood flow);
• if you are affected by a genetic and hereditary blood disease that causes a deformation of red blood cells (sickle cell disease);
• if you have inflammatory or obstructive bowel diseases;
• if you suffer from low blood pressure (hypotension) associated with hypovolemia (reduced blood volume);
• if you have inflammation of the pancreas (pancreatitis);
• if you have reduced kidney or liver function;
• if you have undergone surgery to reduce pain in the last 24 hours;
• if you have a history of epilepsy (a disease that causes loss of consciousness and violent involuntary muscle contractions). Contact your doctor or pharmacist if you notice any of the following symptoms while taking TWICE:
• Increased sensitivity to pain despite taking increasing doses (hyperalgesia). The doctor will decide if a dose adjustment or treatment change is necessary.
• Weakness, fatigue, loss of appetite, nausea, vomiting, dizziness or low blood pressure. These may be signs of reduced adrenal activity; this effect is reversible, must be monitored and treated.
• Constipation.
• Loss of sexual desire (decreased libido), inability to achieve and maintain an erection (impotence), cessation of the menstrual cycle (amenorrhea). This may be due to a decrease in certain hormones (prolactin, cortisol and testosterone).
• If you have been addicted to drugs, narcotics (psychoactive substances capable of altering the psycho-physical state) or alcohol in the past. Also, tell them if you feel you are becoming addicted to TWICE while using it, if you find yourself thinking a lot about when you can take the next dose, even if you don't need it for pain. BE CAREFUL:
• Prolonged use of TWICE for a prolonged period of time may result in a loss of its effectiveness with a consequent need to increase the dosage to be able to get pain relief. This effect is called tolerance. The doctor will establish the dose and duration of treatment most suitable for you. The treatment will be of limited duration;
• This medicine can lead to abuse and mental and physical dependence (possible need to gradually increase the dosage). Therefore, treatment should be short-term. Undesirable effects can be minimized with the shortest possible duration of treatment needed to control symptoms. This risk increases with the dose and duration of treatment and is more frequent if you have a history of drug abuse, narcotics or alcohol. Once physical dependence has developed, abrupt discontinuation of treatment will be accompanied by withdrawal symptoms, such as increased sensitivity to pain, dilation of the pupil, headache, high blood pressure, diarrhea, muscle pain, anxiety, restlessness, confusion and irritability (see "Possible side effects"). Because the risk of withdrawal symptoms is greater after abrupt discontinuation of treatment, the doctor will explain how to gradually reduce the dose until discontinuation;
• The concomitant use of TWICE with sedative drugs such as benzodiazepines, such as hypnotics (medicines that induce sleep), sedatives (calmants), anxiolytics (which reduce anxiety) increases the risk of drowsiness, difficulty breathing (respiratory depression), coma (state of deep unconsciousness) and can be life-threatening. For this reason, concomitant use should only be considered when other treatment options are not possible. However, if the doctor prescribes TWICE together with

medicines with a sedative effect, the dose and duration of concomitant treatment must
be limited by the doctor. Tell your doctor about all sedative medicines you are
taking and carefully follow their recommendations on dosage. It may be helpful
to inform friends or family members so that they are aware of the signs and symptoms described
above. If you experience these symptoms, contact your doctor.

Children and adolescents
Do not use TWICE in children and adolescents.

Other medicines and TWICE
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
TWICE should not be used at the same time as some antidepressant drugs called
monoamine oxidase inhibitors or if you have taken these medicines in the last two
weeks (see also section Do not take TWICE). The association of these drugs can
induce the development of a serotonin syndrome characterized by the following symptoms: nausea,
low blood pressure, neuromuscular hyperactivity (tremor, involuntary muscle contractions),
sweating, fever, rapid heartbeat, increased breathing rate,
pupil dilation, agitation, excitement, confusion, up to cardiac arrest and
death.
The concomitant use of TWICE and sedative medicines such as benzodiazepines or related medicines
increases the risk of drowsiness, difficulty breathing (respiratory depression), coma
(state of unconsciousness) and can be life-threatening.
The dose and duration of treatment must be limited (see “Warnings and precautions”).
Tell your doctor if you are taking:

• opioids (analgesics), anesthetics (medicines that induce sedation, reduce pain sensitivity and muscle relaxation), hypnotics (medicines that induce sleep), sedatives (calmants), anxiolytics (medicines that reduce anxiety), neuroleptics (medicines to treat mental disorders, such as chlorpromazine), antidepressants, antihistamines (medicines for the treatment of allergies);
• procarbazine (an antitumor);
• methocarbamol (a medicine that relieves muscle spasms);
• amphetamines (psychostimulants);
• diuretics (medicines that lower blood pressure);
• muscle relaxants (medicines that reduce muscle tone) and neuromuscular blockers (medicines that cause muscle relaxation);
• rifampicin an antibiotic used to treat infections caused by bacteria;
• antithrombotics, medicines used for the prevention of thrombotic events (formation of clots that prevent blood flow);
• anticoagulants (medicines that delay blood clotting).

TWICE with alcohol
The concomitant use of alcohol and TWICE should be avoided because it can increase the
undesirable effects of TWICE.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you are breastfeeding
with breast milk, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
TWICE is not recommended during pregnancy. The administration of TWICE during pregnancy
should only be considered if the expected benefit to the mother outweighs the risk to the
fetus or child. Take this medicine under strict medical supervision.
It can cause respiratory depression and withdrawal syndrome in the newborn, who should therefore be
carefully monitored.
The use of TWICE should be avoided near delivery.
Breastfeeding
This medicine is excreted in breast milk. Therefore, if you are breastfeeding, talk to your
doctor who will assess whether to discontinue breastfeeding and continue to
take TWICE or, conversely, continue breastfeeding avoiding the administration of
the medicine.
Fertility
Studies in animals have shown that morphine can reduce fertility.

Driving and using machines
TWICE impairs the ability to drive vehicles and operate machinery; because the morphine contained in
TWICE causes drowsiness and slows down reflexes.

TWICE contains sucrose.If your doctor has diagnosed you with intolerance to some sugars, contact
them before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per capsule, i.e. essentially
`sodium-free'.

TWICE 60 mg contains: yellow orange S E 110. It may cause allergic reactions.
For those who play sports: the use of the drug without therapeutic necessity constitutes doping and
may still result in positive doping tests.

3. How to use TWICE

Take this medicine following exactly the instructions of your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
The doctor, based on the severity of your symptoms and the type of illness, will establish the correct dose and the
duration of treatment
Adults
The initial dose is 1 or 2 capsules of 10 mg twice a day.
2 administrations per day are recommended with an interval of 12 hours between them. In
elderly patients, the initial dose is lower.
In case of persistent pain or if tolerance to the medicine occurs, the doctor may modify the
dosage regimen according to the needs of achieving the optimal dosage.

Patients already being treated with other medicines containing morphine administered via
parenteral route (intramuscular or intravenous).

• If you were being treated with morphine injections and are switching to TWICE therapy, your doctor will prescribe a higher dose. The increase can vary from approximately 50% to 100%.
• Do not exceed the recommended dose.
• If you have any doubts, consult your doctor or pharmacist. Children and adolescentsDo not use TWICE in children and adolescents. Route of administration The capsules must be swallowed whole and must not be broken, chewed or crushed. For patients with difficulty swallowing, the contents of the capsules can be administered via a gastric tube (a tube that goes into the stomach, used to provide artificial nutrition to patients who are unable or refuse to eat normally).

If you take more TWICE than you should
In case of overdose, the following symptoms may occur:
decrease in pupil diameter (miosis), reduction in heart rate, severe
difficulty breathing (respiratory depression) up to arrest, aspiration pneumonia
(inflammation of the lungs caused by the entry of foreign material into the bronchi due to a
incorrect swallowing), drowsiness that may become deep to the point of stupor or
coma (complete state of unconsciousness, absence of any type of sensitivity and voluntary
motility), hypothermia (reduction in body temperature), rhabdomyolysis (muscle injury)
leading to renal failure (altered kidney function), low blood pressure, collapse (sudden
loss of consciousness), circulatory failure (inability of the heart to provide an adequate amount of
blood to the body) and death.
Pupil dilation (mydriasis) is added to the deep coma.
The use of broken, chewed or crushed capsules determines the immediate release of morphine
which may be responsible for a fatal overdose.

If you forget to take TWICE
Do not take a double dose to make up for a missed dose.

If you stop taking TWICE
Treatment with TWICE should not be stopped abruptly.
The doctor will explain how to gradually reduce the dose until discontinuation.
Abrupt discontinuation of treatment will be accompanied by withdrawal symptoms (see
“Warnings and precautions”).
If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Tell your doctor immediately in case of difficulty breathing, wheezing, swelling of the face, lips, mouth, tongue or throat which can cause difficulty in breathing and swallowing, rash or itching, especially if widespread over your body because these are the signs and symptoms of serious allergic reactions (anaphylactic and anaphylactoid reaction).
The following side effects have been reported:

Common (may affect up to 1 in 10 people):

• Confusion, drowsiness,
• involuntary muscle contractions,
• dizziness (sense of movement or rotation),
• abdominal pain,
• anorexia (reduced or absent appetite),
• vomiting,
• itching,
• malaise,
• fatigue. Uncommon (may affect up to 1 in 100 people):
• allergic reaction,
• hallucinations (perception of things that do not exist in reality),
• mood alterations,
• convulsions (uncontrolled body movements),
• hypertonia (increased muscle tone),
• paresthesia (sensation of numbness, tingling),
• vertigo,
• hot flashes (feeling of warmth),
• low blood pressure,
• pulmonary edema (fluid accumulation in the lungs),
• bronchospasm (contraction of the bronchial muscles),
• ileus (intestinal obstruction),
• altered taste,
• dyspepsia (difficult digestion),
• increased liver enzymes (proteins that increase in case of liver damage),
• urinary retention (inability to urinate or empty the bladder),
• peripheral edema (fluid accumulation),
• neonatal abstinence syndrome which manifests with irritability, acute crying, tremor, difficulty sucking, respiratory problems, sleep disturbances, sweating and diarrhea), Not known (frequency cannot be estimated based on available data):
• anaphylactic and anaphylactoid reaction (severe allergic reactions),
• altered thinking,
• dysphoria (mood alteration),
• dependence (see “Warnings and precautions”),
• excitation,
• insomnia (alteration of the amount and quality of sleep),
• agitation,
• euphoria,
• depression of mood,
• indifference,
• irritability,
• headache,
• hyperalgesia (increased sensitivity to pain),
• increased intracranial pressure (high pressure in the head),
• allodynia (pain elicited by a stimulus that is normally not able to provoke a painful sensation),
• hyperhidrosis (excessive sweating),
• sleep apnea syndrome (frequent interruptions of breathing during sleep),
• sedation,
• mental dullness (reduction of the level of consciousness),
• syncope (sudden and transient loss of consciousness),
• miosis (constriction of the pupils),
• visual disturbances,
• vertigo (sense of movement or rotation),
• low blood pressure,
• vasodilation of the extremities,
• orthostatic hypotension (lowering of blood pressure when getting up),
• cardiovascular collapse (rapid drop in blood pressure),
• reduced cough,
• respiratory depression (severe difficulty breathing),
• atelectasis (collapse of the lung alveoli),
• respiratory arrest,
• dry mouth,
• nausea,
• retching (attempts to vomit),
• constipation,
• epigastric discomfort (“under the spoon”),
• reduction of stomach acidity,
• intestinal motility disorders,
• pain in the biliary tract,
• increased pressure in the biliary tract,
• spasm of the sphincter of Oddi (contraction of a muscle that opens and closes to allow digestive juices to pass),
• biliary colic (acute and intermittent pain in the upper right region of the abdomen),
• facial flushing,
• erythema (redness of the skin),
• sweating,
• itching,
• urticaria (skin rash),
• rash (skin irritation),
• oliguria (decreased urine production),
• difficulty emptying the bladder,
• amenorrhea (cessation of menstruation),
• decreased libido (sexual desire),
• erectile dysfunction (erection disorders),
• tolerance (see “Warnings and precautions”),
• withdrawal syndrome,
• asthenia (weakness),
• reduction in the amount of certain hormones in the blood (ACTH, cortisol, LH, FSH and testosterone),
• increase in the amount of certain hormones (ADH and prolactin). Description of some side effects: respiratory depression is mild or moderate and without consequences in healthy subjects; it can be severe in subjects affected by bronchopulmonary diseases; : intestinal motility disorders can slow down the transit of feces; : increased pressure in the biliary tract can accentuate the feeling of nausea and discomfort under the spoon and accentuate or trigger pain from biliary colic (acute and intermittent pain in the upper right region of the abdomen); : withdrawal syndrome manifests with muscle pain, tremors, restless legs syndrome (sleep disorder that manifests with tingling, itching or pain in the legs, associated with an urgent and irresistible need to move the legs), diarrhea, abdominal colic (acute and intermittent pain in the abdomen), nausea, flu-like symptoms, tachycardia (increased heart rate), mydriasis (dilation of the pupils), mood alterations, anxiety and irritability; : in men, increased prolactin can accentuate disorders related to reduced testosterone production.

Reporting of side effects
If you get any side effects, even if not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly through the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store TWICE

Keep this medicine out of sight and reach of children.
Do not store at a temperature above 25°C.
Do not use this medicine after the expiry date which is stated on the packaging. The expiry date refers to the last day of that month.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What TWICE contains
The active ingredient is morphine sulfate.
TWICE 10 mg
Each 10 mg capsule contains: 10 mg of morphine sulfate equivalent to 7.5mg of morphine.
The other ingredients are: sucrose and corn starch microgranules, macrogol 4000, aquacoat
ECD 30, dibutyl sebacate, talc, gelatin, quinoline yellow E 104, titanium dioxide E 171, iron
oxide black.
TWICE 30 mg
Each 30 mg capsule contains: 30 mg of morphine sulfate equivalent to 22.5 mg of morphine.
The other ingredients are: sucrose and corn starch microgranules, macrogol 4000, aquacoat
ECD 30, dibutyl sebacate, talc, gelatin, titanium dioxide E 171, erythrosine E 127, iron oxide
black.
TWICE 60 mg
Each 60 mg capsule contains: 60 mg of morphine sulfate equivalent to 45 mg of morphine.
The other ingredients are: sucrose and corn starch microgranules, macrogol 4000, aquacoat
ECD 30, dibutyl sebacate, talc, gelatin, titanium dioxide E 171, yellow orange S E 110, iron
oxide black.
TWICE 100 mg
Each 100 mg capsule contains: 100 mg of morphine sulfate equivalent to 75 mg of morphine.
The other ingredients are: sucrose and corn starch microgranules, macrogol 4000, aquacoat
ECD 30, dibutyl sebacate, talc, gelatin, titanium dioxide E 171, iron oxide black.

Description of the appearance of TWICE and contents of the pack
Prolonged-release hard capsules of 10 mg, 30 mg, 60 mg and 100 mg in Al/PVC blisters

Marketing Authorisation Holder
Ethypharm, 194 Bureaux de la Colline, Bâtiment D, 92 213 Saint Cloud cedex – France.

Manufacturer
Ethypharm – Chemin de la Poudrière – 76120 Grand-Quevilly (France).