Prospect: information for the user

Metasedin 40 mg tablets

Metadone hydrochloride

Read this prospect carefully before starting to take the 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 for 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 is Metasedin and for what it is used

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

3.How to take Metasedin

4.Possible adverse effects

5.Storage of Metasedin

6.Contents of the package and additional information

Metasedin 40 mg tablets is a medication that contains a substance called methadone, belonging to the group of narcotic analgesic drugs. Methadone is a central analgesic of slightly higher potency than morphine. It also produces less euphoria and a withdrawal syndrome similar, although more prolonged.

Metasedin 40 mg tablets is indicated for the substitute maintenance treatment of opioid dependence, within a maintenance program with medical control and together with other medical and psychosocial measures.

Do not take Metasedin

• If you are allergic to methadone or any of the other components of this medication (listed in section 6).
• If you have respiratory or pulmonary problems such as severe obstructive respiratory disease, emphysema, or bronchial asthma. Do not take this medication during an acute asthma attack.
• If you have heart symptoms as a result of chronic pulmonary processes (Cor pulmonale).
• If you have high pressure inside the skull or have had a recent head injury.
• If you are taking monoamine oxidase inhibitors (MAOIs) to treat depression or have taken an MAOI in the last two weeks.
• If you are addicted to other medications.
• During childbirth.
• If you have a condition called pheochromocytoma, a tumor of the adrenal glands.
• If you have a known intestinal problem called paralytic ileus.

Warnings and precautions

Consult your doctor or pharmacist if you experience any of the following symptoms before starting or while taking Metasedin:

• If you have low blood pressure (hypotension).
• If you have liver or kidney problems.
• If you have low thyroid function (hypothyroidism).
• If you have 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.
• If you have bile duct disorders (gallbladder and bile duct).
• If you have an enlarged prostate (prostatic hyperplasia).
• If you have a disease characterized by muscle weakness, called myasthenia gravis.
• If you have inflammatory or obstructive intestinal disorders.
• If you are addicted to alcohol.
• If you have epilepsy.
• If you are pregnant or breastfeeding.
• If you are in shock.
• If you are an elderly person or are extremely ill. In these cases, you may be more sensitive to the medication.
• If you are prone to allergic reactions, you may experience, for example: an exacerbation of asthma, skin redness, etc.
• If you have acute abdominal pain, as the administration of this medication or other similar medications may make it more difficult to diagnose and treat.
• If you have a risk factor for prolongation of the QT interval (alteration of cardiac conduction) such as:

• History of irregular heartbeats,
• History of heart disease,
• Family history of sudden death without apparent cause,
• Low levels of potassium, sodium, or magnesium,
• Liver disease.

• The long-term 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).

• During the induction phase of maintenance treatment with methadone, patients must stop consuming heroin and may experience typical withdrawal symptoms (tearfulness, nasal mucositis, sneezing, yawning, etc.), which must be differentiated from methadone side effects.
• The administration of usual doses of an opioid antagonist to a patient with physical dependence on methadone or other opioids precipitates an acute withdrawal syndrome. The intensity of the symptoms will depend on the degree of dependence of the subject and the dose of antagonist administered.
• Methadone may alter the results of some blood tests (blood levels of hormones such as prolactin and other thyroid-related hormones (such as thyroxine, thyroxine-binding globulin [TBG], and triiodothyronine)).

Tolerance, dependence, and addiction

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

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

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

-You or a family member has a history of alcohol abuse, 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 Metasedin, it could be a sign that you have become dependent or addicted.

-You need to take the medication for longer than recommended by your doctor.

-You need to take more doses than recommended.

-You are using the medication for reasons other than those prescribed, for example, “to calm down” or “to help you sleep”.

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

-You do not feel well when you stop taking the medication 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 appropriate 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 Metasedin”).

Respiratory disorders related to sleep

Methadone can cause respiratory disorders related to sleep such as, for example, 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 somnolence. If you or someone else observes these symptoms, contact your doctor. Your doctor may consider reducing the dose.

Use in athletes

This medication contains a component that can produce a positive result in doping control tests.

Children and adolescents

Metasedin is not recommended for use in children and adolescents under 18 years of age due to the lack of safety and efficacy data in this population..Children are more sensitive to the effects of methadone than adults.

Other medications and Metasedin

There are some medications that can affect the proper functioning of Metasedin or Metasedin itself can reduce the effectiveness of other medications being taken at the same time. These medication interactions can increase or decrease the effect of one of the two medications, and may increase the risk or severity of side effects.

Do not take Metasedin if you are taking monoamine oxidase inhibitors (MAOIs) or have taken an MAOI in the last two weeks.

Inform your doctor or pharmacist if you are using or have recently used other medications, even those obtained without a prescription.

• The simultaneous use of Metasedin and sedative medications such as benzodiazepines or related medications (e.g., opioid analgesics such as codeine, pentazocine, buprenorphine) increases the risk of drowsiness, difficulty breathing (respiratory depression), coma, and is potentially fatal, particularly in elderly patients. Due to this, simultaneous use should only be considered when other therapeutic options are not possible. However, if your doctor prescribes Metasedin along with sedative medications, they will restrict the dose and duration of simultaneous treatment.
• Gabapentin and pregabalin (medications used to treat epilepsy, nerve pain, or anxiety) may increase the risk of opioid overdose, respiratory depression, and may be potentially fatal.
• Inform your doctor of all sedative medications you are taking, and follow the recommended dosage strictly as indicated by your doctor. It may be helpful to inform your friends or family members to be aware of the signs and symptoms described above. If you experience these symptoms, contact your doctor.
• Buprenorphine or pentazocine may precipitate withdrawal symptoms in a patient addicted to methadone.
• Opioid antagonists (naloxone).
• Depressants of the central nervous system, including general anesthetics, medications used to treat schizophrenia and psychosis (phenothiazines), sleep disorder treatment, or other central nervous system sedatives, as methadone may increase the risk of respiratory depression, low blood pressure, and deep sedation or coma.
• However, if your doctor prescribes Metasedin along with sedative medications, they will restrict the dose and duration of simultaneous treatment.
• Inform your doctor of all sedative medications you are taking, and follow the recommended dosage strictly as indicated by your doctor. It may be helpful to inform your friends or family members to be aware of the signs and symptoms described above. If you experience these symptoms, contact your doctor.
• 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)
• Fast pulse, unstable blood pressure, fever
• Increased reflexes, discoordination, muscle rigidity
• Gastrointestinal symptoms (such as nausea, vomiting, diarrhea)

• Medications used to treat migraines, such as sumatriptan.
• Medications used to treat heart conditions, such as verapamil, bepridil, or enalapril.
• Medications that cause electrolyte imbalances and affect cardiac conduction (such as antiarrhythmics, diuretics, or lithium).
• Medications used to treat epilepsy, such as phenytoin, carbamazepine, phenobarbital, and primidone.
• Cannabidiol (a medication used to treat seizures).
• Antibiotics such as ciprofloxacin or macrolide antibiotics such as erythromycin or clarithromycin.
• Medications used to treat fungal infections, such as ketoconazole, itraconazole, miconazole, and fluconazole.
• Rifampicin or phenytoin, which may trigger withdrawal symptoms.
• Cimetidine, which potentiates the effects of methadone.
• Medications that acidify or alkalize the urine and may alter the elimination of methadone, increasing or decreasing its effects (e.g., ascorbic acid (vitamin C) and ammonium chloride).
• Antiretroviral medications for HIV, such as ritonavir, nevirapine, efavirenz, abacavir, and nelfinavir. Your doctor may need to change the dose of methadone you take while taking these medications.
• St. John's Wort, a herbal preparation used for depression.

Taking Metasedin with food, drinks, and alcohol

Alcohol can increase the side effects of methadone, so it should not be taken during treatment with this medication.

Orange juice may modify the effect of methadone, so it should not be taken with Metasedin.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, consult your doctor or pharmacist before using this medication.

Pregnancy

If Metasedin is used during pregnancy, your baby may experience withdrawal symptoms. Be careful if you are taking a pregnancy test, as methadone may interfere with the results.

Metasedin should not be used if you are in labor.

Breastfeeding

Methadone is excreted in breast milk. Metasedin will only be administered to breastfeeding mothers when the benefits for the infant outweigh the potential risks. Breastfeeding in these cases may prevent the onset of withdrawal symptoms in the newborn.

Consult 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 (more than usual), difficulty breathing, or weakness. Immediately contact your doctor if you observe any of these symptoms.

Driving and operating machinery

Methadone may cause drowsiness, dizziness, or other symptoms that may impair your ability to drive. If you experience any of these effects, avoid driving vehicles or operating machinery.

Metasedin contains lactose and croscarmellose sodium

This medication contains lactose. If your doctor has indicated that you have a intolerance to certain sugars, consult with them before taking this medication.

This medication contains less than 23 mg of sodium (1 mmol) per tablets, which is essentially “sodium-free”.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

The dosage must be individualized, so your doctor will establish the appropriate dose for you and make any necessary adjustments.

If you estimate that the action of this medication is too strong or too weak, inform your doctor or pharmacist.

Use in adults:

The dose will be established according to the patient's physical dependence level. Initially, a dose of 20-30 mg/day will be administered. Depending on the clinical response, the dose may be increased up to 40-60 mg/day over1 to2 weeks to avoid the appearance of withdrawal or intoxication symptoms. The maintenance dose is around 60-100 mg/day, achieved through successive weekly increases of 10 mg/day. It is not recommended to exceed a dose of 120 mg/day unless plasma levels can be determined. The dose will be administered in 1 single daily dose. Treatment suspension will be carried out gradually, through gradual reduction of the dose in amounts of5 to10 mg.

The tablets can be dispersed in a glass with water or juice, or swallowed with the help of a little water.

Remember to take your medication.

Your doctor will indicate the duration of treatment with Metasedin.

If you take more Metasedin than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

If you take too much metadone you may experience:

• respiratory problems;
• extreme drowsiness, which may evolve into decreased level of consciousness and coma;
• very small pupils;
• muscle weakness;
• cold skin;
• occasionally, low blood pressure and slow pulse;
• low blood sugar levels;
• a brain disorder (known as toxic leukoencephalopathy).

In case of extreme intoxication, respiratory arrest, circulatory collapse, heart failure, and death may occur.

If you forgot to take Metasedin

Do not take a double dose to compensate for the missed doses.

If you interrupt treatment with Metasedin

Brusque treatment interruption, in physically dependent patients, may precipitate an abstinence syndrome. Your doctor will indicate how to gradually reduce the dose.

Treatment suspension will be carried out gradually, through gradual reduction of the dose in amounts of5 to10 mg (see “How to take Metasedin” section).

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

Like all medications, this medication may cause side effects, although not everyone will experience them.

Generally, methadone causes side effects similar to those of morphine.

The most serious side effects of methadone, as with other opioids, are respiratory depression (difficulty breathing) and, to a lesser extent, a decrease in blood pressure, with cases of respiratory arrest, shock, and cardiac arrest occurring. The most frequent side effects are dizziness, sedation, nausea, vomiting, and excessive sweating. These side effects appear to be more intense in ambulatory patients and those who do not have intense chronic pain. In these patients, it is recommended to use lower doses. Some side effects may be alleviated if the patient lies down.

Inform your doctor immediately if you experience:

• An allergic reaction, such as swelling of the face, lips, tongue, or throat, difficulty breathing, severe swelling and itching of the skin with bumps.
• Cardiac problems, such as changes in heart rhythm (both rapid heartbeats and missed beats), difficulty breathing, and dizziness.
• If your breathing becomes slow and shallow.
• Worsening of intracranial pressure or headache, if you already have this condition after a head injury or brain disease.
• If you have asthma and it worsens.

Other possible side effects may be the following:

Very frequent (may affect more than 1 in 10 patients)

nausea, vomiting.

Frequent (may affect up to 1 in 10 patients)

excessive sweating

fatigue, drowsiness, sedation

weight gain

fluid retention

constipation

eruption, which may appear and disappear

blurred vision, small pupils, dry eyes

dizziness, vertigo

mood changes, feeling too excited (euphoria) or seeing or hearing things that are not real (hallucinations)

Rare (may affect up to 1 in 100 patients)

difficulty breathing (respiratory depression), especially with high doses

worsening of asthma

low blood pressure

headache, syncope, or sudden loss of consciousness

feeling disheartened (disphoria), agitation, confusion, disorientation, difficulty sleeping

You may become dependent on Metasedin, for more information, see section 2 "Warnings and precautions"

itching, skin eruptions, urticaria

dry mouth or nose, inflammation of the tongue, facial redness

difficulty urinating (urinary retention), lower back and abdominal pain caused by muscle spasms

alteration of bile duct movement (may manifest as nausea, vomiting, or both, biliary pain in the upper right abdomen or radiating to the right shoulder area)

low body temperature (hypothermia)

sensation of weakness, fatigue

decreased libido or difficulty achieving or maintaining an erection

menstrual cramps, absence of menstruation

milk secretion from the nipple (galactorrhea)

fluid accumulation in the lungs (pulmonary edema)

Rare (may affect up to 1 in 1000 patients)

changes in heart rhythm (both rapid heartbeats and missed beats)

electrocardiogram (ECG) anomaly, known as QT interval prolongation, which may appear as an alteration in heart rhythm called "torsades de pointes" (especially with high doses of methadone)

cardiac arrest

shock

respiratory arrest

Other reported side effects of unknown frequency are

loss of appetite

swelling, swollen legs (this may be a sign that your body is retaining more water than normal)

increased intracranial pressure (especially with high doses)

involuntary, rapid, and repetitive eye movements, strabismus

reduced visual acuity

sleep apnea (pauses in breathing during sleep)

reduced platelet count, which increases the risk of bleeding or hematomas in patients with chronic hepatitis

low potassium and magnesium levels

decreased production of adrenal and sex hormones

low blood sugar levels

elevated prolactin levels in the blood

If you observe any other reaction not described in this prospectus, consult your doctor or pharmacist.

Reporting of side effects

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

Keep this medication out of the sight and reach of children. Store this medication in a safe and secure location where other individuals cannot access it. It may cause severe harm and be fatal to people who have not been prescribed it.

No special storage conditions are required.

No special storage conditions are required.

Do not use this medication after the expiration date shown on the packaging after CAD. The expiration date is the last day of the month indicated.

Medications should not be disposed of through drains or in the trash. Dispose of the packaging and unused medications at the SIGRE drop-off point at the pharmacy. If in doubt, ask your pharmacist how to properly dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of Metasedin

• The active ingredient is hydrochloride of metadone. Each tablet contains 40 mg of hydrochloride of metadone.
• The other components are lactose, sodium croscarmellose, microcrystalline cellulose, magnesium stearate, and colloidal silicon dioxide.

Appearance of the product and content of the packaging

Metasedin 40 mg tablets are presented in the form of white, elliptical, scored tablets on both faces, with the anagram “4/4” on one face and the other face is anonymous, in packaging with 800 tablets.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Esteve Pharmaceuticals, S.A.

Passeig de la Zona Franca, 109

08038 Barcelona

Spain

Responsible for manufacturing

TOWA Pharmaceutical Europe, S.L.

c/ de Sant Martí, 75-97

08107 Martorelles (Barcelona) Spain

Last review date of this leaflet: March 2023

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/