Prospect: information for the user

Metasedin 10 mg/ml injectable solution

Hydrochloride of metadone

Read the prospect carefully before starting to use the medication, because it contains important information for you.

• Keep this prospect, as you may have to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication 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.
• Ifyou experience adverse effects, consult your doctor or pharmacist, even if they areadverse effects that do not appear 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 use Metasedin

3.How to use Metasedin

4.Possible adverse effects

5.Storage of Metasedin

6. Contents of the package and additional information

Metasedin 10 mg/ml injectable solution 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 10 mg/ml injectable solution is indicated for intense pain of any etiology. Postoperative, post-traumatic, neoplastic, neuritic, burn pain, whenever not responding to minor analgesics. Treatment of narcotic withdrawal syndrome.

No use 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 head injury recently.
• If you are taking monoamine oxidase inhibitors (MAOIs) to treat depression or if you 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 using 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 condition 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 manage the condition.

• 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 the side effects of methadone.
• The administration of regular 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.

The risk of adverse effects may increase with a higher dose and longer duration of use.

Dependence or addiction may 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. When used to treat pain, you may feel like you need to continue taking the medication, even if it no longer helps to alleviate your pain.

The risk of becoming dependent or addicted to Metasedin 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 abuse or dependence on alcohol, prescription medications, or illicit substances (“addiction”).

-You are a smoker.

-You have had problems with your mood (depression, anxiety, or a 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 may be a sign that you have become dependent or addicted.

-You need to take the medication for a longer period 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 therapeutic 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 may 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 may 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. Additionally, children are more sensitive to the effects of methadone than adults.

Other medications and Metasedin

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

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

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication such as:

• 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). These may increase the risk of opioid overdose, respiratory depression (difficulty breathing), 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.
• Medications used to reverse the effects of opioid medications (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 adverse 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 that are serotoninergic and 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 a withdrawal syndrome.
• Cimetidine, which potentiates the effects of methadone.

• Medications that acidify or alkalize 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.

Use of Metasedin with food, drinks, and alcohol

Alcohol may 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 lactation

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.

Lactation

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 sodium

This medication contains less than 23 mg (1 mmol) of sodium per ampoule, so it is considered essentially “sodium-free”.

Before starting treatment and at regular intervals during it, your doctor will discuss with you what you can expect from using Metasedin, when and for how long you should take it, when to contact your doctor, and when to stop taking it (also see “If you interrupt treatment with Metasedin”).

Metasedin should only be administered by qualified healthcare personnel with adequate knowledge of its use. The administration of the product and the handling of needles should be done with caution.

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

If you think the effect of this medication is too strong or too weak, inform your doctor or pharmacist.

Use in adults:

Half to one ampoule per dose, subcutaneously, according to the intensity of the pain. This dose may be repeated as deemed necessary by a healthcare professional.

Remember to use your medication.

Your doctor will indicate the duration of treatment with Metasedin.

If you receive more Metasedin than you should

Your doctor will ensure that you receive the appropriate dose for your condition. In case of overdose, you may experience more side effects. If you think you have received too much Metasedin, contact your doctor immediately.

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 progress to 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 cerebral disorder (known as toxic leukoencephalopathy).

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

If you forget to use Metasedin

You should not use a double dose to compensate for missed doses.

If you interrupt treatment with Metasedin

Abruptly stopping treatment, in patients with physical dependence, may precipitate withdrawal syndrome.

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

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

Methadone generally 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 drop 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 outpatients and in 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 hives.
• 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 pressure inside the head 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 common (may affect more than 1 in 10 patients)

nausea, vomiting.

Common (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

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

Uncommon (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 “torsade 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 Medicines for Human Use, Website: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 secure location where other individuals cannot access it. It may cause severe harm and be fatal to people who have not been prescribed it.

Do not store at a temperature above 25°C.

Do not use this medication after the expiration date that appears 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 medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Metasedin

• The active principle is hydrochloride of methadone. Each ampoule contains 10 mg of hydrochloride of methadone.
• The other components are sodium chloride and water for injectable preparations.

Appearance of the product and content of the container

Metasedin 10 mg/ml injectable solution is a colorless and transparent solution, and it is presented in containers of 12 ampoules.

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

B. Braun Medical, S.A.

Ronda de los Olivares, parcela 11

Polígono Industrial Los Olivares

23009 Jaén

Spain

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/