LEVOMETADONE MOLTENI 5 mg/mL ORAL SOLUTION

Introduction

Package Leaflet: Information for the User

Levometadona Molteni 5 mg/ml Oral Solution

Levometadona, hydrochloride

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

1. What is Levometadona Molteni and what is it used for
2. What you need to know before you take Levometadona Molteni
3. How to take Levometadona Molteni
4. Possible side effects
5. Storage of Levometadona Molteni
6. Contents of the pack and other information

1. What is Levometadona Molteni and what is it used for

Levometadona Molteni contains the active substance levometadona hydrochloride. This belongs to a group of medicines that act on the nervous system.

Levometadona Molteni is used to treat adults who are addicted to substances called «opioids» or «narcotic analgesics», such as heroin or morphine. It acts as a substitute for addictive drugs.

2. What you need to know before you take Levometadona Molteni

Do not take Levometadona Molteni if:

• you are allergic to levometadona hydrochloride or any of the other ingredients of this medicine (listed in section 6)
• you are taking medicines for depression called MAOIs (monoamine oxidase inhibitors) or have taken them in the last 2 weeks (see «Taking Levometadona Molteni with other medicines»)
• you are taking medicines to treat addiction or strong painkillers (see «Taking Levometadona Molteni with other medicines»)
• you have severe respiratory or lung problems
• you are not addicted to opioid medicines or drugs.

Children and adolescents under 18 years of age should not take this medicine.

Do not take this medicine if you meet any of the above circumstances. If you are not sure, consult your doctor or pharmacist before starting to take Levometadona Molteni.

Warnings and precautions

Consult your doctor or pharmacist before starting to take this medicine if

• you do not feel alert or fully awake (you have «low levels of consciousness»)
• you have low blood pressure
• you have ever had heart problems, including heart disease or problems with your heartbeat. This medicine may affect the electrical signals that control your heart's contractions, particularly at high doses. Therefore, inform your doctor if you have a history of heart problems.
• you have ever had respiratory or lung problems such as asthma or «COPD» (chronic obstructive pulmonary disease)
• you are unable to urinate
• you are a man with prostate problems
• you have problems with your gallbladder or bile duct
• you have an inflamed pancreas
• you have bowel problems
• your thyroid gland is underactive
• you have high pressure inside your skull
• you have problems with your adrenal glands, either an overactive adrenal gland or a type of tumor (called «pheochromocytoma»)
• your doctor has told you that you have an «electrolyte imbalance» such as «hypokalemia».

If you meet any of the above circumstances (or are not sure), consult your doctor or pharmacist before starting to take Levometadona Molteni.

Consult your doctor or pharmacist if you experience any of the following symptoms while taking Levometadona Molteni:

• Weakness, fatigue, loss of appetite, nausea, vomiting, or low blood pressure. This may be a symptom that your adrenal glands are producing very little cortisol hormone, and you may need to take a hormonal supplement.

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

• When using levometadona, it is essential to consider that it is approximately twice as active as methadone(see also section 3 «How to take Levometadona Molteni»).
• This medicine is for oral use only and should not be injected. Its use by injection is dangerous and can seriously harm your health: you may have an infection in your body, your veins may become painful and swollen, or you may have a blockage of a blood vessel in your lungs.

Tolerance, dependence, and addiction

This medicine contains an opioid medicine called levometadona. Repeated use of opioids can reduce the effectiveness of the medicine (your body gets used to the medicine, this is what is known as tolerance). Repeated use of Levometadona Molteni 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 medicine 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 higher risk of becoming dependent or addicted to Levometadona Molteni if:

• You or a family member have a history of abuse or dependence on alcohol, prescription medicines, or illegal substances («addiction»).
• You are a smoker.
• You have ever had problems with your mood (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 Levometadona Molteni, it could 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 more doses than recommended.
• You are using the medicine for reasons other than those prescribed, for example, «to calm down» or «to help you sleep».
• You have made repeated attempts to stop or control the use of the medicine without success.
• 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 appropriate therapeutic strategy in your case, including when it is appropriate to stop taking it and how to do it safely (see section 3 «If you stop taking Levometadona Molteni»).

Sleep-related breathing disorders

Levometadona Molteni may cause sleep-related breathing disorders, 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, nighttime 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.

Effects on laboratory test results

The use of this medicine may result in positive results in sports drug tests (doping tests). Do not use Levometadona Molteni as a doping medicine, as it can cause serious harm to your health.

Children and adolescents

Children and adolescents under 18 years of age should not take this medicine.

Taking Levometadona Molteni with other medicines

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

This includes medicines obtained without a prescription and herbal medicines. This is because Levometadona may affect how some medicines work. Also, some medicines may affect how Levometadona works.

Do not take Levometadona Molteni and tell your doctor or pharmacist if you are taking any of the following:

• medicines for depression called MAOIs (monoamine oxidase inhibitors), or have taken them in the last 2 weeks. This includes moclobemide, phenelzine, and tranylcypromine
• medicines to treat addiction, such as buprenorphine. You should wait at least 20 hours after stopping Levometadona Molteni before starting to take buprenorphine.
• strong painkillers, such as morphine, butorphanol, nalbuphine, and pentazocine.

If you meet any of the above circumstances (or are not sure), do not take Levometadona Molteni and consult your doctor or pharmacist.

Consult your doctor or pharmacist before starting to take Levometadona Molteni if you are taking any of the following:

• medicines for a serious mental health problem called «psychosis», such as chlorpromazine
• medicines that make you feel drowsy, including:

• other medicines for depression, such as amitriptyline and clomipramine
• medicines to help you sleep, including anesthetics
• medicines for high blood pressure, such as reserpine, clonidine, urapidil, and prazosin
• spironolactone - a diuretic medicine
• medicines for fungal infections, such as fluconazole, itraconazole, voriconazole, and ketoconazole
• medicines for heart problems, such as quinidine, verapamil, and diltiazem
• cimetidine, to treat stomach ulcers
• rifampicin, an antibiotic
• macrolide antibiotics, such as clarithromycin, telithromycin, and erythromycin
• medicines to treat certain bacterial infections, such as ciprofloxacin, fusidic acid
• herbal medicines that contain St. John's Wort (Hypericum perforatum)
• antiviral medicines, including some medicines used to treat HIV, such as amprenavir, nevirapine, zidovudine, efavirenz, nelfinavir, ritonavir, lopinavir, saquinavir, abacavir, delavirdina, didanosine, and stavudine
• oral contraceptives («the pill»)
• medicines for epilepsy, including barbiturates, such as phenytoin and carbamazepine.
• 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 (breathing difficulties), and can be potentially fatal.
• metamizole, a medicine used to treat pain and fever
• medicines to calm you down, called benzodiazepines, such as diazepam or flunitrazepam. The concomitant use of Levometadona Molteni and sedative medicines like benzodiazepines or related medicines increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and can be potentially fatal. Due to this, concomitant use should only be considered when other treatment options are not possible. However, if your doctor prescribes Levometadona Molteni with sedative medicines, your doctor should limit the dose and duration of concomitant treatment. Inform your doctor about all sedative medicines you are taking and follow your doctor's recommendations regarding the dose carefully. It may be helpful to inform friends or family members who are aware of the signs and symptoms indicated above. Contact your doctor when you experience such symptoms.

The risk of side effects increases if you use levometadona at the same time as antidepressants (such as citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, amitriptyline, clomipramine, imipramine, nortriptyline). Contact your doctor if you experience symptoms such as:

• Changes in mental state (e.g., agitation, hallucinations, coma)
• Rapid heartbeat, unstable blood pressure, fever
• Exaggerated reflexes, altered coordination, muscle stiffness
• Gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea)

If you meet any of the above circumstances (or are not sure), consult your doctor or pharmacist before starting to take this medicine.

Taking Levometadona Molteni with alcohol

Do not drink alcohol while taking this medicine. This is because alcohol can increase the adverse effects of this medicine and cause severe poisoning with signs such as drowsiness, shallow and weak breathing, and coma, which can be fatal.

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 for advice before taking this medicine.

Pregnancy

• Levometadona Molteni can be used during pregnancy after a careful benefit-risk assessment by a doctor, preferably under supervision in a specialized medical center. It may be necessary to increase the dose up to twice a day to maintain the effectiveness of the treatment due to changes in metabolism during pregnancy. Your doctor may also recommend dividing the daily dose.
• Chronic use during pregnancy can lead to habituation and addiction of the fetus to levometadona, as well as withdrawal symptoms after birth, which often requires hospital treatment.

Breastfeeding

• Levometadona is excreted in breast milk. Consult your doctor if you are breastfeeding or planning to breastfeed while being treated with levometadona, as it may affect your baby. Your doctor will decide whether breastfeeding is allowed during treatment with Levometadona Molteni. Monitor your baby for unusual signs and symptoms, such as increased sleepiness (more than usual), breathing difficulties, or floppiness. Consult your doctor immediately if you notice any of these symptoms.

Fertility

• It has been reported that methadone causes sexual dysfunction in male patients undergoing maintenance treatment.

Driving and using machines

Do not drive or use any tools or machines while taking Levometadona Molteni.

This is because you may feel drowsy and less alert while taking the medicine and for some time after stopping it.

You can only drive or use tools or machines if your doctor tells you to do so.

Levometadona Molteni contains methyl parahydroxybenzoate (E218)

This may cause allergic reactions (possibly delayed).

3. How to take Levometadona Molteni

Follow exactly the administration instructions of this medicine given by your doctor. In case of doubt, consult your doctor or pharmacist again.

How much to take

Your dose will be decided by your doctor:

• it is chosen for you individually
• it is based on how soon your withdrawal symptoms start.

Always take the dose that your doctor tells you:

• do not take more or less of this medicine than you have been told
• do not take this medicine more or less frequently than you have been told.

Initial dose:

• The usual initial dose is between 3 and 4 ml of the oral solution per day (equal to between 15 and 20 mg of levometadona hydrochloride).

Dose increase:

• Your doctor may increase your dose by 1 to 2 ml per day (equal to 5 to 10 mg of levometadona hydrochloride). This will depend on how the medicine affects you.
• The usual dose may be up to 12 ml of the oral solution per day (equal to 60 mg of levometadona hydrochloride). In some cases, your doctor may prescribe a higher dose.

Elderly patients and people who are very ill

Your dose may be reduced if you are over 65 years old. It may also be reduced if you are in very poor health or have severe kidney problems or long-term liver problems. In these cases, your doctor may want to monitor you more closely.

Method of administration

• Levometadona Molteni is a solution for oral use only.
• You can take this medicine on its own or diluted with water or non-alcoholic drinks, such as orange juice.
• Your doctor or pharmacist will measure and administer your dose.

If you take more Levometadona Molteni than you should

In case of overdose or accidental ingestion, consult your doctor immediately or go immediately to the hospital. You can also consult your pharmacist or the Toxicology Information Service, phone 915 620 420, indicating the medicine and the amount ingested.

Take the medicine package with you. The following effects may appear:

• breathing problems
• feeling very drowsy, about to faint («unconscious») or go into a coma
• pupils very small in the eyes
• cool and clammy skin
• very slow pulse
• muscle weakness
• low blood sugar levels
• a brain disorder (known as toxic leukoencephalopathy).

In extreme cases, your breathing or blood flow may stop, and you may have a heart attack.

If you forget to take Levometadona Molteni

If you miss a dose, skip the missed dose and take your next dose as usual. Do not take a double dose to make up for a missed dose.

If you stop taking Levometadona Molteni

Do not stop taking Levometadona Molteni without consulting your doctor first. This is because you may experience side effects. If you need to stop taking Levometadona Molteni, your doctor will gradually withdraw the medicine.

If you have any other 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 all people suffer from them.

Consult your doctor if you observe any of the following adverse effects:

Adverse effects that may occur with greater probability at the start of treatment:

• feeling of anxiety, depression, irritability, or drowsiness
• loss of appetite (anorexia), weight loss, or feeling of discomfort (nausea)
• stomach or intestinal cramps, diarrhea, or discomfort (vomiting)

• fever, alternating chills and hot flashes, yawning, goosebumps, runny nose, sneezing

• rapid and spasmodic movements or tremors (tremor)
• increased heart rate (tachycardia)
• very small pupils in the eyes
• general body pain
• feeling of weakness or restlessness
• excessive sweating or tearing.

Other adverse effects include:

Between uncommon (may affect up to 1 in 100 people) and common (may affect up to 1 in 10 people):

• slow or shallow breathing
• headache or vision problems
• feeling of weakness, dizziness, fainting, confusion, or disorientation
• feeling very sleepy or being unable to sleep
• feeling of euphoria or depression
• palpitations or decreased heart rate
• decreased sexual desire
• decreased libido or difficulty achieving and maintaining an erection in men
• sweating
• skin rashes, including hives and other types of itchy skin rashes
• dry mouth
• loss of appetite, nausea, or vomiting
• constipation
• fluid retention ("edema"), "biliary colic" that can cause pain in the upper abdomen or back
• urinary problems, including urinating very little.

Between rare (may affect up to 1 in 1,000 people) and very rare (may affect up to 1 in 10,000 people):

• red skin and feeling of heat ("flushing")
• reduced bleeding inside the body
• stopping breathing
• low blood pressure when standing or sitting up quickly
• absence of heartbeats, heart attack, problems pumping blood throughout the body, going into "shock".

Frequency not known:

• low blood sugar levels.
• sleep apnea (breathing pauses during sleep)
• you may become dependent on Levometadona Molteni (for more information, see section 2 "Warnings and precautions").

You may notice that some adverse effects become less intense over time. However, it is unlikely that constipation or excessive sweating will improve. Consult your doctor or pharmacist about treatment to alleviate the symptoms of these adverse effects.

Reporting Adverse Effects

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

5. Storage of Levometadona Molteni

• Keep this medicine out of the sight and reach of children. Store this medicine in a safe and protected place, where other people cannot access it. It can cause serious harm and be fatal to people who have not been prescribed it.
• Do not use this medicine after the expiration date that appears on the label and box after CAD. The expiration date is the last day of the month indicated.
• Store below 25°C.
• Once the bottle is opened, use the oral solution within 12 weeks.
• Medicines should not be thrown away through drains or into the trash. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Levometadona Molteni

• The active ingredient is levometadone hydrochloride. Each milliliter (ml) of oral solution contains 5 milligrams (mg) of levometadone hydrochloride
• The other components are methyl parahydroxybenzoate (E218), betaine hydrochloride, glycerol, purified water.

Appearance of the Product and Package Contents

• Levometadona Molteni is a clear and colorless oral solution.
• It is available in package sizes of 100 ml, 3 x 100 ml, 500 ml (clinical package), and 1000 ml (clinical package).

100 ml size: glass bottle with a safety cap and a pipette adapter. Includes a graduated dosing pipette from 0.25 to 5 ml, divided into 0.25 ml. Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

• Molteni & C. dei F.lli Alitti Società di Esercizio S.p.A.

Strada Statale 67, Loc. Granatieri

50018 Scandicci (Florence)

Italy

Manufacturer:

• Molteni & C. dei F.lli Alitti Società di Esercizio S.p.A.

Strada Statale 67, Loc. Granatieri

50018 Scandicci (Florence)

Italy

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Laboratorios Gebro Pharma, S.A.

Avenida Tibidabo, 29

08022 Barcelona – Spain

Phone: 93 205 86 86

This medicine is authorized in the member states of the European Economic Area under the following names:

Germany Levomethadon Molteni

Italy Ellepalmiron

Poland Levomethadone Hydrochloride Molteni

Spain Levometadona Molteni

Date of the last revision of this prospectus:July 2024