Misio

Leaflet accompanying the packaging: information for the user

Misyo, 10 mg/ml, concentrate for oral solution preparation

Methadone hydrochloride

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for a specific person. Do not pass it on to others. The medicine may harm them, even if their symptoms are the same as yours.
• If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What is Misyo and what is it used for

This medicine contains methadone hydrochloride, which belongs to a group of medicines called opioid analgesics. It is used to treat dependence to reduce withdrawal symptoms. All patients taking Misyo must be routinely monitored for signs of misuse, abuse, and dependence.

2. Important information before taking Misyo

When not to take Misyo:

• if the patient is allergic to methadone or any of the other ingredients of this medicine (listed in section 6). An allergic reaction includes rash, itching, or difficulty breathing;
• if the patient has an asthma attack (this medicine should not be used during an asthma attack). In case of self-administration, wait until the asthma attack has subsided and full recovery has occurred;
• if the patient is addicted to alcohol;
• if the patient is taking monoamine oxidase inhibitors (MAOIs) used to treat depression or if the patient has taken MAOIs in the last two weeks (see "Taking other medicines");
• if the patient is not opioid-dependent;
• if the patient has heart problems (prolonged QT interval);
• if the patient has severe liver function disorders;
• during childbirth.

In case of uncertainty as to whether any of the above situations apply to the patient, consult a doctor or pharmacist before taking Misyo.

Warnings and precautions

Before starting Misyo, discuss with your doctor or pharmacist if you have:

• -severe breathing difficulties;
• head injury, currently or recently;
• liver or kidney problems;
• epilepsy;
• decreased thyroid function (hypothyroidism);
• adrenal gland problems;
• enlarged prostate;
• low blood pressure;
• shock;
• a disease that causes muscle weakness called myasthenia;
• intestinal problems;
• known risk factors for QT interval prolongation, namely:
• irregular heartbeat in history;
• heart disease in history;
• sudden death without a known cause among family members;
• low potassium, sodium, or magnesium levels;
• pregnancy or breastfeeding;
• severe illness or advanced age. Sensitivity to the medicine may then increase.

If any of the following symptoms occur while taking Misyo, consult a doctor or pharmacist: weakness, fatigue, loss of appetite, nausea, vomiting, or low blood pressure. These symptoms may indicate that the adrenal glands are producing too little cortisol and hormone replacement may be necessary.

• Patient feels the need to take the medicine for longer than prescribed by the doctor.
• Patient feels the need to take a higher dose than recommended.
• Patient uses the medicine for reasons other than the one for which it was prescribed, such as "to calm down" or "to be able to sleep".
• Patient has repeatedly attempted to stop or control the use of the medicine.
• After stopping the medicine, the patient feels unwell and feels better after taking the medicine again ("withdrawal symptoms").

If the patient notices any of the above symptoms, they should talk to their doctor and discuss the best treatment option, including the right time to stop treatment and a safe way to stop treatment (see section 3, Stopping Misyo). If in doubt, consult a doctor or pharmacist before taking Misyo.

Misyo and other medicines

Tell your doctor or pharmacist about all medicines you are taking, or have recently taken, and any medicines you plan to take. Methadone hydrochloride may affect the way some other medicines work. Also, some medicines may affect the way methadone works.

• other opioid painkillers;
• medicines that affect the mind (e.g., thioridazine, phenothiazine derivatives, haloperidol, and sertindol);
• medicines used to treat heart conditions, such as verapamil and quinidine;
• medicines used to treat depression (desipramine, nefazodone, fluvoxamine, fluoxetine, paroxetine, and sertraline);
• anti-inflammatory and immunosuppressive medicines (e.g., dexamethasone and cyclosporine);
• antiviral medicines, including some medicines used to treat HIV infection (nevirapine, zidovudine, efavirenz, nelfinavir, ritonavir, amprenavir, delavirdine, lopinavir/ritonavir, ritonavir/saquinavir, abacavir, didanosine, and stavudine);
• antibiotics (medicines used to treat bacterial infections), such as ciprofloxacin and macrolide antibiotics, e.g., clarithromycin, telithromycin, and erythromycin;
• medicines used to treat fungal infections, such as fluconazole, itraconazole, and ketoconazole;
• cimetidine, used to treat stomach ulcers;
• naloxone, used to reverse the effects of opioids;
• medicines used to counteract the effects of opioid medicines, such as naltrexone and buprenorphine;
• rifampicin, used to treat tuberculosis (TB);
• medicines used to treat epilepsy, such as phenytoin, carbamazepine, phenobarbital, and primidone;
• cannabidiol (a medicine used to treat seizure disorders);
• gabapentin and pregabalin (medicines used to treat epilepsy, nerve pain, or anxiety), may increase the risk of opioid overdose, respiratory depression (breathing difficulties), and may be life-threatening;
• medicines that cause urine acidification, such as ascorbic acid (vitamin C) and ammonium chloride;
• a medicine used to treat diarrhea (e.g., loperamide, diphenoxylate);
• a diuretic (e.g., spironolactone);
• a medicine that increases sleepiness;
• metamizole, a medicine used to treat pain and fever;
• preparations containing St. John's Wort, used to treat depression.

Concomitant use of Misyo and sedatives, such as benzodiazepines or similar medicines, increases the risk of sleepiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. For this reason, concomitant use of these medicines should only be considered when other treatment options are not available.

Misyo with food, drink, and alcohol

Misyo can be taken with or without food. Do not drink alcohol while taking Misyo, as methadone can cause sleepiness and drinking alcohol may increase sleepiness. Do not drink grapefruit juice while taking Misyo, as grapefruit juice may change the effect of methadone.

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 taking this medicine.

Driving and using machines

Methadone can seriously affect your ability to drive and use machines while taking the medicine and afterwards. The time after which such activities can be safely resumed must be determined by your doctor.

Misyo contains sorbitol

This medicine contains 300 mg of liquid, non-crystallizing sorbitol (equivalent to 210 mg of sorbitol) per 1 ml. Sorbitol is a source of fructose. If you have been previously diagnosed with intolerance to some sugars or previously diagnosed with hereditary fructose intolerance, a rare genetic disorder in which your body does not break down fructose, you should consult your doctor before taking or receiving this medicine.

Misyo contains sodium benzoate

This medicine contains 3 mg of sodium benzoate per 1 ml. Although this medicine is not intended for use in newborns, it is important to be aware that sodium benzoate may increase the risk of jaundice (yellowing of the skin and whites of the eyes) in newborns (up to 4 weeks of life).

3. How to take Misyo

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor or pharmacist. Misyo can only be taken orally. Under no circumstances should this medicine be injected, as it may cause serious and permanent damage to the body and may be life-threatening. This medicine is intended to be diluted by qualified medical personnel. You will receive Misyo in a diluted form.

Adults

The usual starting dose is 10-30 mg per day. The dose will be gradually increased until the patient's withdrawal symptoms or intoxication symptoms disappear. The usual dose is 60-120 mg per day. Your doctor will decide what dose to use and when to reduce it.

Elderly (over 65 years) and severely ill patients

If it is necessary to take multiple doses of this medicine, your doctor may want to monitor your condition more closely. In elderly, frail, or patients with liver or kidney disease, caution should be exercised and the dose of the medicine should be reduced.

Use in children

Misyo is not intended for use in children.

Taking a higher dose of Misyo than recommended

If you take too much methadone, you may experience:

• breathing difficulties;
• extreme sleepiness, fainting, or coma;
• pinpoint (maximally constricted) pupils;
• muscle weakness;
• cold and clammy skin;
• low blood sugar;
• slow heartbeat, low blood pressure, heart attack, or shock;
• brain disorders (known as toxic leukoencephalopathy);
• in severe cases, death may occur. In case of overdose, contact a doctor immediately, even if you feel well, as methadone poisoning may occur.

Missing a dose of Misyo

Do not take a missed dose. Wait until the next dose is due and take only that amount of medicine. Do not take a double dose to make up for a missed dose.

Stopping Misyo

Do not stop taking this medicine without your doctor's advice, as you may experience withdrawal symptoms. Your doctor will tell you how to gradually reduce the dose. If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Misyo can cause side effects, although not everybody gets them. Stop taking this medicine and contact a doctor immediately if you experience any of the following symptoms:

• An allergic reaction, which may include: swelling of the face, lips, tongue, or throat, difficulty breathing or swallowing, or severe itching of the skin with a rash.
• Heart problems. Symptoms may include changes in heart rhythm, such as faster heartbeat or pauses in heart function, difficulty breathing, and dizziness with shallow breathing. These side effects are rare and may affect up to 1 in 1000 people.
• Slow and shallow breathing.
• Increased pressure inside the skull, if you have previously had a brain injury or disease.

Continue taking the medicine, but tell your doctor immediately if you experience any of the following side effects:

• Asthma or worsening of asthma.

Other possible side effects include:

Very common (may affect more than 1 in 10 people):

• Nausea or vomiting.

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

• Water retention in the body;
• Feeling of euphoria, seeing or hearing things that are not real (hallucinations);
• Feeling of sleepiness;
• Blurred vision, pinpoint (maximally constricted) pupils, dry eyes;
• Feeling of dizziness or spinning;
• Constipation;
• Skin rash, sweating;
• Feeling of tiredness;
• Weight gain.

Uncommon (may affect up to 1 in 100 people):

• Feeling of dysphoria, agitation, confusion, difficulty sleeping, decreased sex drive;
• Headache, fainting;
• Low blood pressure, hot flashes;
• Breathing difficulties (including coughing), dry nose;
• Dry mouth, tongue inflammation;
• Bile duct spasm (abdominal pain);
• Itching, hives, rash;
• Urinary retention, difficulty urinating;
• Difficulty achieving or maintaining an erection;
• Menstrual disorders, milk production;
• Swelling of the legs;
• Weakness;
• Low body temperature.

Rare (may affect up to 1 in 1,000 people):

• Heart problems, slower heartbeat, feeling of heartbeat;
• Shock;
• Respiratory arrest;
• Slowing of bowel movements (obstruction).

Side effects have also been reported (frequency not known):

• Lower platelet count, which increases the risk of bleeding or bruising;
• Increased prolactin levels;
• Lack of appetite;
• Potassium or magnesium deficiency in the blood;
• Low blood sugar;
• Hearing loss;
• Patient may develop dependence on Misyo (see section 2 "Warnings and precautions");
• Sleep apnea (pauses in breathing during sleep).

Side effects such as potassium or magnesium deficiency, hearing loss, low platelet count may occur with an unknown frequency.

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181 C, PL-02 222 Warsaw, Tel.: +48 22 49 21 301, Fax: + 48 22 49 21 309, Website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder.

5. How to store Misyo

Keep this medicine out of the sight and reach of children. This medicine should be stored in a safe place, out of the reach of other people. Taking this medicine by people it was not prescribed for may lead to serious harm and death. Store in a temperature below 25°C. Store in the original package to protect from light. Do not use this medicine after the expiry date stated on the carton, bottle, or blister after EXP. The expiry date refers to the last day of the month stated. After first opening, store in a temperature below 25°C. Store in the original package to protect from light, for no more than 90 days. The medicine should be used within 90 days of opening. After dilution, the shelf-life of the solution with a concentration of 1 mg/ml or 5 mg/ml is 14 days, provided it is stored in a temperature below 25°C, in a PET bottle without light exposure. The medicine should be used within 14 days of dilution. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Misyo contains

• -The active substance is methadone hydrochloride. 1 ml of the concentrate for oral solution contains 10 mg of methadone hydrochloride.
• -The other ingredients are: liquid, non-crystallizing sorbitol (E420), glycerol (E422), sodium benzoate (E211), citric acid monohydrate (E330), brilliant blue FCF (E133), and purified water.

What Misyo looks like and contents of the pack

Misyo is a clear blue solution. Packaging of 100 ml: A glass bottle containing 100 ml of the concentrate for oral solution with a plastic cap or a plastic cap with a child-resistant closure and an attached leaflet, in a cardboard box. Packaging of 1000 ml: A glass bottle containing 1000 ml of the concentrate for oral solution with a plastic cap or a plastic cap with a child-resistant closure and an attached leaflet, in a cardboard box. Not all pack sizes may be marketed.

Marketing authorization holder

INN-FARM d.o.o. Maleševa ulica 14 1000 Ljubljana Slovenia Tel.: +386 70 390 711 Fax: + 386 5191 116 e-mail: [email protected]

Manufacturer/Importer

ALKALOID-INT d.o.o., Šlandrova ulica 4, 1231 Ljubljana – Črnuče, Slovenia Tel.: 386 1 300 42 90 Fax: 386 1 300 42 91 email: [email protected]

This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

United Kingdom (Northern Ireland) MISYO 10 mg/ml Concentrate for oral solution Austria MISYO 10 mg/ml Konzentrat zur Herstellung einer Lösung zum Einnehmen Czech Republic MISYO 10 mg/ml Germany MISYO 10 mg/ml Konzentrat zur Herstellung einer Lösung zum Einnehmen Hungary MISYO 10 mg/ml Koncentrátum belsőleges oldathoz Poland Misyo Portugal MISYO 10 mg/ml Concentrado para solução oral Romania MISYO 10 mg/ml Concentrat pentru soluţie orală Slovakia MISYO 10 mg/ml Spain MISYO 10 mg/ml Concentrado para solución oral Date of last revision of the leaflet:26.06.2023