Prospecto: information for the patient

MISYO 10 mg/ml Concentrated oral solution

Methadone, hydrochloride

Read this prospect carefully before starting to take this medicine, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section 4.

1. What Misyo is and for what it is used

2. What you need to know before starting to take Misyo

3. How to take Misyo

4. Possible adverse effects

5. Storage of Misyo

6. Contents of the container and additional information

This medication contains metadone hydrochloride, which belongs to the group of narcotic analgesic medications. 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, misuse, and addiction during treatment.

Do not take Misyo:

• if you are allergic to methadone, benzyl alcohol or any of the other ingredients of this medicine (listed in section 6). An allergic reaction may include a rash, itching, or difficulty breathing;
• if you have asthma attacks (you should not take this medicine during an asthma attack). If you are self-administering the 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 these types of medicines in the last two weeks (see "Taking other medicines");
• if you are not addicted to opioid drugs;
• if you have heart problems (prolongation of the QT interval);
• if you have severe liver problems;
• if you are pregnant.

If you are unsure about any of the above situations that may apply to your case, consult your doctor or pharmacist before taking Misyo.

Warnings and precautions

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

• severe respiratory problems;
• recently suffered a head injury;
• liver or kidney problems;
• epilepsy;
• slow thyroid function (hypothyroidism);
• adrenal gland problems;
• enlarged prostate;
• low blood pressure;
• shock;
• myasthenia gravis, a condition characterized by muscle weakness;
• gastrointestinal problems;
• one of the verified risk factors for prolongation of the QT interval:
• history of irregular heartbeat;
• history of heart disease;
• family history of sudden death without apparent cause;
• low levels of potassium, sodium, or magnesium;
• pregnant or breastfeeding;
• very ill or elderly. 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. This may be a sign that your adrenal glands are producing very low levels of cortisol, so you may need to take a hormone supplement.

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

Respiratory problems related to sleep

Misyo may cause respiratory problems related to sleep, such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). Symptoms may include pauses in breathing during sleep, nocturnal awakenings due to lack of breath, difficulty maintaining sleep, or excessive daytime sleepiness. If you or someone else observes these symptoms, contact your doctor. Your doctor may consider reducing the dose.

Tolerance, dependence, and addiction

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

Dependence or addiction may make you feel like you no longer have control over the amount of medicine you need to take or how often you need to take it.

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

- You or a family member has a history of alcohol, prescription medication, or illicit substance abuse ("addiction").

- You are a smoker.

- You have had problems with your mood (depression, anxiety, or personality disorder) or have received treatment from a psychiatrist for other mental health conditions.

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 a longer period than recommended by your doctor.

- You need to take more doses than recommended.

- You are using the medicine for reasons other than those prescribed, such as "to calm down" or "to help you sleep".

- You have made repeated and unsuccessful attempts to stop or control your use of the medicine.

- You do not feel well 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 address the most suitable treatment strategy for your case, including when it is appropriate to stop taking it and how to do it safely (see section 3 "If you interrupt treatment with Misyo").

If you are unsure about any of the above situations that may apply to your case, consult your doctor or pharmacist before taking Misyo.

Taking Misyo with other medicines

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medicine.

Methadone, hydrochloride may affect how other medicines work. Like other medicines, they may affect the way methadone works.

You should not take Misyo if:

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

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

• other opioid analgesics;
• medicines that may affect mental state (e.g. thioridazine, phenothiazines, haloperidol, and sertindol);
• medicines for heart problems such as verapamil and quinidine;
• medicines for depression (desipramine, nefazodone, fluvoxamine, fluoxetine, paroxetine, and sertraline);
• anti-inflammatory and immunosuppressive agents (e.g. dexamethasone and ciclosporin);
• 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 such as clarithromycin, telithromycin, and erythromycin;
• medicines used to treat fungal infections, such as fluconazole, itraconazole, and ketoconazole;
• cimetidine, used to treat stomach ulcers;
• naloxone to reverse the effects of opioid medicines;
• medicines to prevent opioid medicines from working, such as naltrexone and buprenorphine;
• rifampicin, used to treat tuberculosis (TB);
• medicines to treat 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, difenoxin);
• diuretics (e.g. spironolactone);
• medicines that cause drowsiness;
• metamizole, a medicine used to treat pain and fever;
• hypericum (a herb 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 fatal. Therefore, concomitant use is only considered when there are no alternative treatment options.

In cases where your doctor prescribes Misyo along with other tranquilizers, the dose and duration of concomitant treatment should be limited by your doctor.

You should inform your doctor about all sedatives you are taking, and follow your doctor's recommendations exactly about the dose. It may be helpful to inform your friends and family about the symptoms described above. Consult your doctor if you experience any of these symptoms.

The risk of side effects increases if metadone 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 (such as restlessness, hallucinations, coma)
• rapid pulse, unstable blood pressure, fever
• exaggerated reflexes, discoordination, muscle rigidity
• gastrointestinal symptoms (such as nausea, vomiting, diarrhea)

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

You should inform your doctor about any other type of medicine you are taking, as they may be hazardous if taken with methadone. In these cases, your doctor will decide whether to control the heart with an electrocardiogram (ECG) before starting treatment to avoid these effects.

Methadone may also affect some blood and urine tests (including antidoping tests). Please inform your doctor if you are taking methadone before undergoing any type of test.

Taking Misyo with food, drinks, and alcohol

Misyo can be taken with food or without it.

Do not drink alcohol while taking Misyo, as methadone may cause drowsiness and alcohol will make you feel even sleepier.

Do not drink grapefruit juice while taking Misyo, as grapefruit juice may modify the effect of methadone.

Pregnancy, breastfeeding, and fertility

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

Pregnancy

Misyo may be used during pregnancy after a careful evaluation of the risk-benefit ratio by a doctor, preferably under the supervision of a specialized medical center. The dose may need to be increased to a maximum of twice a day to maintain the effectiveness of the treatment due to changes in metabolism during pregnancy.

Long-term use during pregnancy may cause changes in the fetus's habituation and addiction to methadone, as well as symptoms of withdrawal after birth, which usually require hospitalization.

Be careful if you are taking a pregnancy test, as Misyo may interfere with the results.

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

Breastfeeding

Talk to your doctor if you are breastfeeding or planning to do so while taking methadone, as it may affect your baby. Monitor your baby for any abnormal signs and symptoms, such as excessive sleepiness, difficulty breathing, or weakness. Immediately consult your doctor if you observe any of these symptoms.

Fertility

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

Driving and operating machinery

Methadone may severely affect your ability to drive or operate machinery, both while taking it and after taking it. You can only resume these activities after obtaining your doctor's permission.

Misyo contains sorbitol

This medicine contains 300 mg of liquid non-crystallizable 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 some sugars, or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person is unable to 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 concentrated oral solution to other methadone-based medicines that do not contain sorbitol may modify the methadone concentration in the blood and may cause symptoms to 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 essential to know that sodium benzoate increases the risk of jaundice (yellow skin and eyes) in newborns (up to 4 weeks old).

This medicine contains less than 1 mmol of sodium (23 mg) per ml, so it is considered "sodium-free".

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

Misyo should only be taken orally. Under no circumstances should this medication be injected, as injection could cause severe and permanent damage to the body or have fatal consequences. This medication should 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 essential not to take more than the dose indicated by your doctor.

Adults

The usual dose is initially 10 to 30 mg per day. The dose will gradually increase until you no longer show signs of withdrawal or intoxication. The usual dose is 60 to 120 mg per day. Your doctor will decide what dose you need and when to reduce it.

Older patients and people with severe illnesses

If you need multiple doses of this medication, your doctor may monitor you closely. If you are an older patient, are ill, or have liver or kidney disorders, you should be closely monitored and the dose reduced.

Use in children

Misyo is not suitable for children.

If you take more Misyo than you should

If you take too much metadone, the following symptoms may appear:

• Respiratory 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 can be fatal.

In case of overdose, seek medical assistance immediately. Although you may feel well, you may be intoxicated by metadone.

If you forget to take Misyo

If you forget a dose, do not take it. Wait until the next one and take only that amount. Do not take a double dose to compensate for the missed doses.

If you interrupt treatment with Misyo

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

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

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

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

• Allergic reaction that may consist of any of the following symptoms: swelling of the face, lips, tongue, or throat, or difficulty breathing or severe swelling or itching of the skin with blisters.
• Cardiac disorders. The signs of this type of disorder may be changes in the way the heart beats, both rapid heartbeats and omission of some heartbeats, difficulty breathing, 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 the pressure inside the head, if you already suffer from this condition after a head injury or brain disease.

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

• If you have asthma and it worsens.

Other possible side effects may be the following:

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

• Feeling unwell.

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

• Water retention.
• Feeling excited (euphoria), seeing or hearing things that are not real (hallucinations).
• Feeling sleepy.
• Blurred vision, very small pupils, dry eyes.
• Sensation of dizziness or feeling that everything is spinning.
• Constipation.
• Erythema, sweating.
• Tiredness.
• Weight gain.

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

• Feeling flat (disphoria), agitation, confusion, difficulty sleeping, reduced sexual appetite.
• Headache, fainting.
• Low blood pressure, facial erythema.
• Difficulty breathing (even with coughing), dry nose.
• Dry mouth, inflammation of the tongue.
• Biliary spasms (abdominal pain).
• Itching, urticaria, rash.
• Urinary retention, difficulty urinating.
• Difficulty achieving or maintaining an erection.
• Menstrual and lactation disorders.
• Swelling of the legs.
• Weakness.
• Low body temperature.

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

• Cardiac disorders, slow pulse, feeling heartbeats (palpitations).
• Shock
• Respiratory arrest.
• Reduced intestinal motility (ileus).

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

• Low platelet count in the blood, which increases the risk of bleeding or petechiae.
• Increased prolactin.
• Loss of appetite.
• Low potassium or magnesium levels in the blood.
• Low blood sugar
• Loss of hearing.
• You may become dependent on Misyo (for more information, see section 2 “Warnings and precautions);
• Sleep apnea (pauses in breathing during sleep).

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

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use, www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children. Store this medication in a safe and protected place where other people cannot access it. It can cause serious harm and be fatal to people when not prescribed.

Do not use this medication after the expiration date that appears on the box, the bottle after CAD. The expiration date is the last day of the month indicated.

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

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

Once the concentration of 1 mg/ml or 5 mg/ml has been diluted, it has a duration of 14 days if stored in PET bottles below 25 °C and protected from light. Use before 14 days from opening.

Medicines should not be thrown down the drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This way, you will help protect the environment.

Composition of Misyo

• The active principle is methadone.

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

• The other components are: sorbitol, non-crystallizing liquid (E420); glycerol (E422); sodium benzoate (E211); citric acid monohydrate (E330), brilliant blue FCF dye (E 133) and purified water.

Appearance of the product and contents of the package

Misyo is a clear blue solution.

100 ml package:

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

1000 ml (clinical package):

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

Only some package 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]

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Laboratorios Tillomed Spain S.L.U.

C/ Cardenal Marcelo Spínola 8, 1º, F

28016 Madrid, Spain

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

AustriaMISYO 10 mg/ml Konzentrat zur Herstellung einer Lösung zum Einnehmen

Czech RepublicMISYO 10 mg/ml

GermanyMISYO 10 mg/ml Konzentrat zur Herstellung einer Lösung zum Einnehmen

HungaryMISYO 10 mg/ml koncentrátum belsoleges oldathoz

PolandMISYO

PortugalMISYO 10 mg/ml Concentrado para solução oral

RomaniaMISYO 10 mg/ml Concentrat pentru solutie orala

Slovak RepublicMISYO 10 mg/ml

SpainMISYO 10 mg/ml Concentrado para solución oral

Last review date of this leaflet: 06/2023