MisyO 10 mg/ml oral solution concentrate

Patient Information Leaflet

Introduction

Package leaflet: Information for the patient

MISYO 10 mg/ml Oral Concentrate Solution

Methadone hydrochloride

Read the entire leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this leaflet, as 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, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

1. What Misyo is and what it is used for
2. What you need to know 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 Misyo is and what it is used for

This medicine contains methadone hydrochloride, which belongs to the group of narcotic analgesic medicines. It is indicated for the treatment of addiction, as it reduces withdrawal symptoms.

All patients taking Misyo must be regularly monitored to identify signs of medication misuse, abuse, and addiction during treatment.

2. What you need to know before taking Misyo

Do not take Misyo:

• if you are allergic to methadone, benzoate, or any of the other ingredients of this medicine (listed in section 6). The allergic reaction may include rash, itching, or difficulty breathing;
• if you have asthma attacks (you must not take this medicine during an asthma attack). If you self-administer this medicine, wait until the asthma attack has passed and you have fully recovered;
• if you are an alcoholic;
• if you are taking monoamine oxidase inhibitors (MAOIs) for depression, or if you have taken such medicines within the last two weeks (see "Taking other medicines");
• if you are not addicted to opioid drugs;
• if you have heart problems (QT prolongation);
• if you have severe liver disorders;
• if you are in labor.

If you have any doubts about whether any of the above situations apply to you, consult your doctor or pharmacist before taking Misyo.

Warnings and precautions

Talk to your doctor or pharmacist before starting to take Misyo if you:

• have severe respiratory disorders;
• have recently suffered a head injury;
• have liver or kidney disorders;
• have epilepsy;
• have slow thyroid function (hypothyroidism);
• have adrenal gland disorders;
• have an enlarged prostate;
• have low blood pressure;
• are in shock;
• have a disease characterized by muscle weakness called myasthenia gravis;
• have intestinal disorders;
• have any of the confirmed risk factors for QT prolongation:
  • history of irregular heartbeat;
  • history of heart disease;
  • family history of sudden unexplained death;
  • low levels of potassium, sodium, or magnesium;
• are pregnant or breastfeeding;
• are severely ill or are an elderly patient. In these cases, you may be more sensitive to the medicine.

Talk to your doctor or pharmacist if you experience any of the following symptoms while taking Misyo:

• weakness, fatigue, loss of appetite, nausea, vomiting, or low blood pressure. These may be signs that your adrenal glands are producing very low levels of the hormone cortisol, and you may need to take a hormonal supplement.

Long-term use may cause a decrease in sex hormone levels and an increase in prolactin hormone. Consult your doctor if you experience symptoms such as decreased libido, impotence, or absence of menstruation (amenorrhea).

Sleep-related breathing disorders

Misyo may cause sleep-related breathing disorders such as sleep apnea (breathing pauses during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). Symptoms may include breathing pauses during sleep, waking up at night due to shortness of breath, difficulty maintaining sleep, or excessive daytime sleepiness. If you or someone else notices these symptoms, contact your doctor. Your doctor may consider reducing your dose.

Tolerance, dependence, and addiction

This medicine contains an opioid medicine called methadone. Repeated use of opioids may reduce the effectiveness of the medicine (your body becomes accustomed to the medicine, known as tolerance). Repeated use of Misyo may also lead to dependence, abuse, and addiction, which may result in potentially fatal overdose.

Dependence or addiction may make you feel that you no longer have control over how much medicine you need to take or how often.

The risk of becoming dependent or addicted varies from person to person. You may have a higher risk of becoming dependent or addicted to Misyo if:

• you or a family member has a history of alcohol, prescription medicine, or illicit substance abuse or dependence ("addiction");
• you are a smoker;
• you have ever had mood disorders (depression, anxiety, or a personality disorder) or have received treatment from a psychiatrist for other mental illnesses.

If you notice any of the following signs while taking Misyo, it may be a sign that you have become dependent or addicted:

• you need to take the medicine for longer than recommended by your doctor;
• you need to take higher doses than recommended;
• you are using the medicine for reasons other than prescribed, e.g., "to calm down" or "to help you sleep";
• you have made repeated unsuccessful attempts to stop or control your use of the medicine;
• you feel unwell when you stop taking the medicine and feel better when you take it again ("withdrawal symptoms").

If you notice any of these signs, talk to your doctor to discuss the most appropriate treatment strategy for your case, including when it is appropriate to stop taking the medicine and how to do so safely (see section 3 "If you stop taking Misyo").

If you have any doubts about whether any of the above situations apply to you, consult your doctor or pharmacist before taking Misyo.

Taking Misyo with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Methadone hydrochloride may affect how other medicines work. Likewise, other medicines may affect how methadone works.

You must not take Misyo if:

• you are currently taking, or have taken within the last two weeks, monoamine oxidase inhibitors (MAOIs).

In particular, inform your doctor if you are taking any of the following medicines:

• other opioid painkillers;
• medicines that may affect mental state (e.g., thioridazine, phenothiazines, haloperidol, and sertindole);
• medicines for heart conditions such as verapamil and quinidine;
• medicines for depression (desipramine, nefazodone, fluvoxamine, fluoxetine, paroxetine, and sertraline);
• anti-inflammatory and immunosuppressive medicines (e.g., dexamethasone and cyclosporine);
• antivirals, such as those 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 macrolides like 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 effect of opioid medicines;
• medicines to block the action of opioids such as naltrexone and buprenorphine;
• rifampicin, used to treat tuberculosis (TB);
• medicines for epilepsy such as phenytoin, carbamazepine, phenobarbital, and primidone;
• cannabidiol (a medicine used to treat seizures);
• gabapentin and pregabalin (medicines used to treat epilepsy, nerve pain, or anxiety). These may increase the risk of opioid overdose, respiratory depression (difficulty breathing), and may be potentially fatal;
• medicines that make the urine acidic, such as ascorbic acid (vitamin C) and ammonium chloride;
• medicines to treat diarrhea (e.g., loperamide, diphenoxylate);
• diuretics (e.g., spironolactone);
• medicines that cause drowsiness;
• metamizole, a medicine used to treat pain and fever;
• St. John’s wort (an herbal remedy used to treat depression).

The concomitant use of Misyo and other sedatives such as benzodiazepines or related drugs increases the risk of drowsiness, difficulty breathing (respiratory depression), coma, and may be life-threatening. Therefore, concomitant use should only be considered when no alternative treatment options are available.

If your doctor prescribes Misyo together with other sedative medicines, the dose and duration of concomitant treatment should be limited by your doctor.

You must inform your doctor about all sedatives you are taking and strictly follow your doctor's recommendations regarding dosage. It may be helpful to inform your friends and family about the signs and symptoms described above. Consult your doctor if you experience any of these symptoms.

The risk of side effects increases if methadone is taken simultaneously with antidepressants (such as citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, amitriptyline, clomipramine, imipramine, nortriptyline). Consult your doctor if you experience symptoms such as:

• changes in mental state (e.g., restlessness, hallucinations, coma);
• rapid pulse, unstable blood pressure, fever;
• increased reflexes, lack of coordination, muscle stiffness;
• gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

Other medicines you may be taking can also affect the heart (e.g., sotalol, amiodarone, and flecainide).

You must inform your doctor about any other medicines you are taking, as they may be dangerous when taken with methadone. In such cases, your doctor may decide to monitor your heart with an electrocardiogram (ECG) before starting treatment to prevent these effects.

Methadone may also affect certain blood and urine tests (including doping tests). Please inform your doctor if you are taking methadone before undergoing any tests.

Taking Misyo with food, drinks, and alcohol

Misyo can be taken with or without food.

Do not drink alcohol if you are taking Misyo, as methadone can cause drowsiness and alcohol will increase this effect.

Do not drink grapefruit juice if you are taking Misyo, as grapefruit juice may alter the effect of methadone.

Pregnancy, breastfeeding, and fertility

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

Pregnancy

Misyo may be used during pregnancy after careful assessment of the risk-benefit ratio by a doctor, preferably under the supervision of a specialized medical center. Dose increases up to twice daily may be necessary to maintain treatment efficacy due to metabolic changes during pregnancy.

Chronic use during pregnancy may lead to fetal adaptation and addiction to methadone, as well as withdrawal symptoms after birth, which usually require hospitalization.

Be cautious if undergoing a pregnancy test, as Misyo may interfere with test results.

You must not take this medicine if you are in labor.

Breastfeeding

Talk to your doctor if you are breastfeeding or planning to breastfeed while taking methadone, as it may affect your baby. Monitor your baby for any abnormal signs or symptoms, such as excessive sleepiness (more than usual), difficulty breathing, or floppiness. Seek immediate medical attention if you observe any of these symptoms.

Fertility

Methadone has been reported to cause sexual dysfunction in male patients undergoing maintenance treatment.

Driving and using machines

Methadone may seriously impair your ability to drive or use machines, both during and after taking it. You should only resume these activities with your doctor's approval.

Misyo contains sorbitol

This medicine contains 300 mg of non-crystallizable liquid sorbitol (equivalent to 210 mg of sorbitol) in 1 ml.

Sorbitol is a source of fructose. If your doctor has told you that you are intolerant to certain sugars, or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot metabolize fructose, consult your doctor before taking this medicine.

In some cases, sorbitol may alter the amount of methadone absorbed compared to the amount ingested. In such cases, switching from Misyo 10 mg/ml oral solution concentrate to other methadone-containing medicines that do not contain sorbitol may alter methadone blood levels and symptoms may reappear. If this occurs, contact your doctor.

Misyo contains sodium benzoate

This medicine contains 3 mg of sodium benzoate in 1 ml.

Although this medicine should not be used in newborns, it is important to know that sodium benzoate increases the risk of jaundice (yellowing of the skin and eyes) in newborn babies (up to 4 weeks of age).

This medicine contains less than 1 mmol of sodium (23 mg) per ml and is therefore considered practically "sodium-free".

3. How to take Misyo

Always take this medicine exactly as instructed by your doctor or pharmacist. Ask your doctor or pharmacist if you have any doubts.

Misyo is for oral use only. Under no circumstances should this medicine be injected, as injection could cause serious and permanent harm to the body or be fatal. This medicine must be diluted by a healthcare professional. You will receive Misyo in a solution.

Your doctor will tell you how much Misyo to take and how often. It is important not to take more than the dose prescribed by your doctor.

Adults

The usual starting dose is 10 to 30 mg daily. The dose will be increased gradually until there are no signs of withdrawal or intoxication. The usual dose is 60 to 120 mg daily. Your doctor will decide the dose you need and when to reduce it.

Elderly patients and seriously ill persons

If you require multiple doses of this medicine, your doctor may monitor you more closely. If you are elderly, seriously ill, or have hepatic or renal disorders, caution is required and the dose should be reduced.

Use in children

Misyo is not suitable for children.

If you take more Misyo than you should

If you take too much methadone, the following effects may occur:

• breathing problems;
• extreme drowsiness, unconsciousness, or coma;
• very small pupils;
• muscle weakness;
• cold and clammy skin;
• low blood sugar;
• slow pulse, low blood pressure, heart attack, or shock;
• a brain disorder (known as toxic leukoencephalopathy);
• in severe cases, it may be fatal.

In case of overdose, seek immediate medical help. Even if you feel well, you may still be intoxicated with methadone.

If you forget to take Misyo

If you miss a dose, do not take it. Wait until the next scheduled dose and take only that amount. Do not take a double dose to make up for a missed dose.

If you stop taking Misyo

Do not stop taking this medicine unless your doctor tells you to, as you may experience withdrawal symptoms. Your doctor will advise you on how to gradually reduce the dose.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Stop taking this medicine and consult a doctor immediately if you experience any of the following effects:

• Allergic reaction which may include any of the following symptoms: swelling of the face, lips, tongue or throat, difficulty breathing, or severe skin swelling or itching with lumps.
• Heart disorders. Signs of these disorders may include changes in heartbeat, both rapid heartbeat and missed beats, breathing difficulties and dizziness if breathing becomes slow and shallow. These side effects are rare and may affect 1 in 1,000 patients.
• If your breathing becomes slow and shallow.
• Worsening of increased pressure inside the head, if you already suffer from this condition due to brain injury or illness.

Continue taking this medicine, but consult a doctor immediately if any of the following effects occur:

• If you have asthma and it worsens.

Other possible side effects may include:

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

• Feeling unwell.

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

• Fluid retention.
• Feeling excited (euphoria), seeing or hearing things that are not real (hallucinations).
• Feeling sleepy.
• Blurred vision, very small pupils, dry eyes.
• Dizziness or sensation of spinning (vertigo).
• Constipation.
• Erythema, sweating.
• Fatigue.
• Weight gain.

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

• Feeling down (dysphoria), agitation, confusion, difficulty sleeping, reduced sexual appetite.
• Headache, fainting.
• Low blood pressure, facial erythema.
• Breathing difficulties (including cough), dry nose.
• Dry mouth, tongue swelling.
• Biliary tract spasm (abdominal pain).
• Itching, hives, rash.
• Urinary retention, difficulty urinating.
• Difficulty achieving or maintaining an erection.
• Menstrual disorders and disturbances in breast milk production.
• Swelling of the legs.
• Weakness.
• Low body temperature.

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

• Heart disorders, slow pulse, awareness of heartbeat (palpitations).
• Shock.
• Respiratory arrest.
• Reduced intestinal motility (ileus).

The following side effects have also been reported (frequency unknown):

• Low platelet count in blood, increasing the risk of bleeding or bruising.
• Increased prolactin.
• Loss of appetite.
• Deficiency of potassium or magnesium in blood.
• Low blood sugar.
• Hearing loss.
• You may become dependent on Misyo (for further information, see section 2 “Warnings and precautions”).
• Sleep apnea (breathing pauses during sleep).

Deficiency of potassium or magnesium in blood, hearing loss, or low platelet count in blood may also occur, but the frequency is unknown.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Misyo

Keep this medicine out of the sight and reach of children. Store this medicine in a safe and secure place, where others cannot access it. It may cause serious harm and be harmful to individuals when not prescribed to them.

Do not use this medicine after the expiry date stated on the carton and on the vial after CAD. The expiry date refers to the last day of the month indicated.

Store below 25 °C in the original container and protected from light.

After first opening, store below 25 °C in the original container and protected from light, for no more than 90 days. Use within 90 days of opening.

Once diluted, the 1 mg/ml or 5 mg/ml solution remains stable for 14 days if stored in PET bottles at a temperature below 25 °C and protected from light. Use within 14 days of dilution.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Misyo

• The active substance is methadone.

Each ml of oral concentrate solution contains 10 mg of methadone hydrochloride.

• The other components are: sorbitol, non-crystallizable liquid (E420); glycerol (E422); sodium benzoate (E211); citric acid monohydrate (E330); brilliant blue FCF (E133); and purified water.

Appearance of the product and contents of the pack

Misyo is a light blue solution.

100 ml pack:

Carton box containing a glass bottle with 100 ml of oral concentrate solution, with a plastic cap or child-resistant plastic cap, and the package leaflet inside.

1000 ml pack (clinical pack):

Carton box containing a glass bottle with 1000 ml of oral concentrate solution, with a plastic cap or child-resistant plastic cap, and the package leaflet inside.

Only certain pack sizes may be marketed.

Marketing Authorization Holder

INN-FARM d.o.o., Maleševa ulica 014, 1000 Ljubljana, Slovenia

Telephone: +386 70 390 711

Fax: +386 5191 116

E-mail: [email protected]

Manufacturer

ALKALOID-INT d.o.o., Šlandrova ulica 4, 1231 Ljubljana – Crnuce, Slovenia

Telephone: +386 1 300 42 90

Fax: +386 1 300 42 91

E-mail: [email protected]

This medicinal product is authorized in the European Economic Area (EEA) Member States 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 belsoleges oldathoz

Poland: MISYO

Portugal: MISYO 10 mg/ml Concentrado para solução oral

Romania: MISYO 10 mg/ml Concentrat pentru solutie orala

Slovak Republic: MISYO 10 mg/ml

Spain: MISYO 10 mg/ml Concentrado para solución oral

Date of the most recent revision of this leaflet: 06/2023