Levomethadone hydrochloride molteni

Patient Information Leaflet

Levomethadone Hydrochloride Molteni, 5 mg/mL, oral solution
Levomethadoni hydrochloridum
Please read all of this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet as you may need to read it again.
• Speak to your doctor or pharmacist if you have any further questions.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If any of the side effects worsens or if you notice any side effects not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet:

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

1. What Levomethadone Hydrochloride Molteni is and what it is used for

Levomethadone Hydrochloride Molteni contains the active substance levomethadone hydrochloride. It belongs to a group of medicines that act on the patient's nervous system.
Levomethadone Hydrochloride Molteni is used in the treatment of adult patients addicted to substances known as "opioids" or "opioid analgesics" – such as heroin and morphine. It works as a substitute for the addictive substance.

2. Information before using Levomethadone Hydrochloride Molteni

When not to use Levomethadone Hydrochloride Molteni:

• if the patient is allergic to levomethadone or any of the other ingredients of this medicine (listed in section 6);
• if the patient is taking medicines for depression called "MAO inhibitors" (monoamine oxidase inhibitors) or has taken them within the last 2 weeks (see “Other medicines and Levomethadone Hydrochloride Molteni”);
• if the patient is taking medicines used to treat addiction or strong painkillers (see “Other medicines and Levomethadone Hydrochloride Molteni”);
• if the patient has difficulty breathing or lung problems;
• if the patient is not addicted to opioid substances.

This medicine should not be used in children and adolescents under 18 years of age.
Do not take Levomethadone Hydrochloride Molteni if any of the above apply to the patient. If the patient has any doubts, consult a doctor or pharmacist before using Levomethadone Hydrochloride Molteni.
Warnings and precautions
Before starting Levomethadone Hydrochloride Molteni, consult a doctor or pharmacist if the patient:

• does not feel fully alert or conscious (has "reduced levels of consciousness");
• has low blood pressure;
• has ever had heart-related disorders, such as heart disease or heart rhythm disorders. This medicine may affect the electrical signals controlling the heartbeat, especially at high doses. Therefore, inform the doctor if the patient has ever had heart problems;
• has ever had breathing difficulties or lung problems, such as asthma or "COPD" (chronic obstructive pulmonary disease);
• has difficulty passing urine;
• has prostate-related problems;
• has gallbladder or biliary tract disorders;
• has inflammatory pancreas disease;
• has intestinal function disorders;
• has hypothyroidism;
• has increased intracranial pressure;
• has adrenal gland dysfunction – hyperactivity or a certain type of tumour (called “pheochromocytoma”);
• has previously been informed by a doctor about electrolyte imbalances, such as “hypokalaemia”.

If any of the above conditions apply to the patient (or if uncertain), discuss them with a doctor or pharmacist before starting Levomethadone Hydrochloride Molteni.
Contact a doctor or pharmacist if any of the following symptoms occur while taking Levomethadone Hydrochloride Molteni:

• weakness, fatigue, loss of appetite, nausea, vomiting, or low blood pressure. These may be signs that the adrenal glands are producing too little cortisol hormone, and hormone replacement may be necessary.

Long-term use of opioid painkillers may lead to decreased sex hormone levels and increased prolactin hormone levels. Contact a doctor or pharmacist if symptoms such as reduced libido, impotence, or absence of menstruation occur.
 When using levomethadone, it is very important to note that it has approximately twice the potency of methadone (see also section 3 “How to use Levomethadone Hydrochloride Molteni”).
 Levomethadone Hydrochloride Molteni is intended for oral use only and must not be injected. Injecting this medicine is dangerous and may cause serious complications: the patient may develop systemic infection, veins may become painful and swollen, or the patient may experience a blocked blood vessel in the lungs.
Tolerance, dependence, and compulsive use
This medicine contains levomethadone, which is an opioid medicine. Repeated use of opioids may lead to reduced effectiveness of the medicine (the patient's body becomes accustomed to the medicine, known as "tolerance"). Repeated use of Levomethadone Hydrochloride Molteni may also lead to abuse, dependence, and compulsive use, which may result in life-threatening overdose.
Dependence or compulsive use may cause the patient to feel a lack of control over the amount or frequency of medicine intake.
The risk of developing dependence or abuse varies among patients.
The patient may have an increased risk of developing abuse or dependence on Levomethadone Hydrochloride Molteni if:

• the patient or a family member has ever abused or been dependent on alcohol, prescription medicines, or illegal drugs ("addiction");
• the patient smokes cigarettes;
• the patient has ever had mood disorders (depression, anxiety disorders, or personality disorders) or has been treated by a psychiatrist for other mental illnesses.

If the patient notices any of the following symptoms while taking Levomethadone Hydrochloride Molteni, this may indicate the development of dependence or abuse:

• The patient feels the need to take the medicine longer than prescribed by the doctor.
• The patient feels the need to take a higher dose than recommended.
• The patient uses the medicine for reasons other than those for which it was prescribed, e.g., "to calm down" or "to be able to sleep".
• The patient has repeatedly made unsuccessful attempts to stop or control the use of the medicine.
• After stopping the medicine, the patient feels unwell and feels better after taking it again ("withdrawal symptoms").

If the patient notices any of the above symptoms, they should speak with their doctor to discuss the best treatment approach, including the appropriate time to stop treatment and a safe way to discontinue treatment (see section 3, Discontinuing Levomethadone Hydrochloride Molteni).
Sleep-related breathing disorders
Levomethadone Hydrochloride Molteni may cause sleep-related breathing disorders, such as sleep apnoea (pauses in breathing during sleep) and sleep-related hypoxaemia (low oxygen levels in the blood). Symptoms may include pauses in breathing during sleep, waking up at night due to breathlessness, difficulty maintaining sleep, or excessive daytime sleepiness. If the patient or someone else notices such symptoms, contact a doctor. The doctor may consider reducing the dose.
Effect on test results
Using Levomethadone Hydrochloride Molteni may lead to positive results in sports doping tests ("anti-doping tests"). Do not use Levomethadone Hydrochloride Molteni as a doping agent – it may seriously harm health.
Children and adolescents
This medicine must not be used in children and adolescents under 18 years of age.
Levomethadone Hydrochloride Molteni and other medicines
Inform the doctor or pharmacist about all medicines currently or recently taken, as well as any medicines the patient plans to take. This includes over-the-counter medicines, including herbal medicines. This is important because Levomethadone Hydrochloride Molteni may affect the action of certain medicines, and other medicines may affect the action of Levomethadone Hydrochloride Molteni.
Do not take Levomethadone Hydrochloride Molteni and inform the doctor or pharmacist if the patient is taking any of the following medicines:

• antidepressants called MAO inhibitors (monoamine oxidase inhibitors), or if they have been taken within the last 2 weeks – including moclobemide, phenelzine, and tranylcypromine;
• medicines used to treat addiction – such as buprenorphine. At least 20 hours must pass after stopping Levomethadone Hydrochloride Molteni before starting buprenorphine;
• strong painkillers – such as morphine, butorphanol, nalbuphine, and pentazocine.

If any of the above apply to the patient (or if uncertain), do not take Levomethadone Hydrochloride Molteni and inform the doctor or pharmacist.
Inform the doctor or pharmacist before starting Levomethadone Hydrochloride Molteni if the patient is taking any of the following medicines:

• medicines used to treat severe mental disorders called "psychoses", such as chlorpromazine;
• medicines that reduce sensory perception, including:
• other antidepressants – such as amitriptyline and clomipramine;
• sleeping medicines – including anaesthetics;
• medicines for high blood pressure – such as reserpine, clonidine, urapidil, and prazosin;
• spironolactone – a diuretic;
• antifungal medicines – such as fluconazole, itraconazole, voriconazole, and ketoconazole;
• medicines for heart rhythm disorders – such as quinidine, verapamil, and diltiazem;
• cimetidine – used to treat peptic ulcer disease;
• rifampicin – an antibiotic;
• macrolide antibiotics, e.g. clarithromycin, telithromycin, and erythromycin;
• medicines used to treat certain bacterial infections – such as ciprofloxacin, fusidic acid;
• herbal medicines containing St John's wort (Hypericum perforatum);
• antiviral medicines, including some medicines used to treat HIV, e.g. amprenavir, nevirapine, zidovudine, efavirenz, nelfinavir, ritonavir, lopinavir, saquinavir, abacavir, delavirdine, didanosine, and stavudine;
• oral contraceptives ("birth control pills");
• 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, neuropathic pain, or anxiety), which may increase the risk of opioid overdose, respiratory depression (difficulty breathing), and may be life-threatening;
• metamizole, a medicine used to treat pain and fever;
• sedatives called benzodiazepines, such as diazepam or flunitrazepam. Concurrent use of Levomethadone Hydrochloride Molteni and sedatives such as benzodiazepines or medicines with similar effects increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. For this reason, concurrent use should only be considered if no other treatment options are available. If a doctor prescribes Levomethadone Hydrochloride Molteni together with sedatives, the doctor should also limit the dose and duration of concurrent treatment. Inform the doctor about all sedatives the patient is taking and strictly follow the doctor's dosage instructions. It may be helpful to inform friends or family members so they are aware of the possibility of the above-mentioned signs and symptoms. If any of the above symptoms occur, contact a doctor.

The risk of adverse effects increases if the patient takes levomethadone simultaneously with antidepressants (such as citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, amitriptyline, clomipramine, imipramine, nortriptyline). Contact a doctor if the following symptoms occur:

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

If any of the above apply to the patient (or if uncertain), discuss them with a doctor or pharmacist before starting Levomethadone Hydrochloride Molteni.
Levomethadone Hydrochloride Molteni and alcohol
Do not drink alcohol while taking this medicine, as alcohol may intensify the adverse effects of Levomethadone Hydrochloride Molteni and lead to severe poisoning with symptoms such as drowsiness, shallow and weak breathing, and coma, which may be fatal.
Pregnancy, breastfeeding, and fertility
Consult a doctor before using Levomethadone Hydrochloride Molteni if the patient is pregnant, suspects she may be pregnant, or is planning pregnancy. Discuss this with a doctor or pharmacist before starting this medicine.
Pregnancy

• Levomethadone Hydrochloride Molteni may be used during pregnancy after careful consideration by the doctor of the benefit-risk ratio, preferably under the supervision of a specialist medical centre. Due to metabolic changes during pregnancy, it may be necessary to increase the number of doses to twice daily to maintain treatment effectiveness. The doctor may also recommend dividing the daily dose.
• Chronic use during pregnancy may lead to the foetus becoming accustomed to and dependent on levomethadone, and withdrawal symptoms may occur after birth, often requiring hospital treatment.

Breastfeeding

• Levomethadone passes into human milk. Before using Levomethadone Hydrochloride Molteni, if the patient is breastfeeding or plans to breastfeed while taking levomethadone, consult a doctor, as this may affect the child. The decision on whether the patient can breastfeed during substitution treatment with Levomethadone Hydrochloride Molteni is made by the doctor. The patient should monitor the child for any unusual signs and symptoms, such as increased sleepiness (more than usual), breathing difficulties, or floppiness. Consult a doctor immediately if any of these symptoms are observed.

Fertility

• There have been reports that methadone may cause male fertility problems during maintenance treatment.

Driving and operating machinery
Do not drive or operate tools or machinery while taking Levomethadone Hydrochloride Molteni, as the patient may feel drowsy and have reduced alertness while taking this medicine and sometimes even after stopping it.
The patient may drive or operate tools or machinery only after prior approval from a doctor.
Levomethadone Hydrochloride Molteni contains methyl parahydroxybenzoate (E218)
It may cause allergic reactions (possibly delayed).

3. How to use Levomethadone Hydrochloride Molteni

This medicine should always be used exactly as directed by the doctor. If in doubt, consult the
doctor or pharmacist.
Recommended dose
The doctor will determine the dose for the patient:

• according to the individual needs of the patient;
• based on the speed of onset of withdrawal symptoms.

Always take the dose prescribed by the doctor:

• do not take more or less of this medicine than the prescribed dose;
• do not take this medicine more or less frequently than instructed.

Initial dose:

• The usual initial dose is 3 to 4 mL of oral solution per day (i.e. 15 to 20 mg of levomethadone hydrochloride).

Dose increase:

• The doctor may increase the patient's dose by 1 to 2 mL per day (i.e. 5 to 10 mg of levomethadone hydrochloride). This will depend on how the medicine affects the patient.
• The usual dose may generally be increased up to 12 mL of oral solution per day (i.e. up to 60 mg of levomethadone hydrochloride). In exceptional cases, the doctor may prescribe a higher dose to the patient.

Elderly and seriously ill patients
The dose may be reduced if the patient is over 65 years old. Dosing may also be reduced if the patient is in a serious general condition or has severe renal impairment or severe, chronic hepatic dysfunction. In such cases, the doctor may wish to monitor the patient more frequently.
Method of administration

• Levomethadone Hydrochloride Molteni is a liquid for oral use only.
• The patient may take this medicine undiluted or diluted with water or non-alcoholic drinks—such as orange juice.
• The patient's dose will be measured and dispensed by the doctor or pharmacist.

Use of more than the recommended dose of Levomethadone Hydrochloride Molteni
If the patient takes more Levomethadone Hydrochloride Molteni than prescribed, speak to the
doctor or go to hospital immediately. Take the medicine packaging with you. The following symptoms of overdose may occur:

• breathing difficulties;
• extreme drowsiness, near loss of consciousness ("unresponsiveness") or coma;
• constricted pupils;
• cold and clammy skin;
• very slow heart rate;
• muscle weakness;
• low blood sugar levels;
• brain dysfunction (known as toxic leukoencephalopathy). In extreme cases, respiratory or circulatory arrest and heart attack may occur.

Missed dose of Levomethadone Hydrochloride Molteni
If the patient forgets to take a dose, skip the missed dose and take the next dose at the scheduled time. Do not take a double dose to make up for a missed dose.
Stopping Levomethadone Hydrochloride Molteni
Do not stop using Levomethadone Hydrochloride Molteni without first discussing it with the doctor.
Sudden discontinuation of the medicine may cause adverse effects. If discontinuation of Levomethadone Hydrochloride Molteni is necessary, the doctor will gradually discontinue treatment.
If there are any further questions regarding the use of this medicine, consult the
doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the adverse reactions listed below occur, you should
inform your doctor:
Adverse reactions are more likely at the beginning of treatment:

• feeling restless, depression, irritability or drowsiness;
• loss of appetite (anorexia), weight loss or malaise (nausea);
• stomach or intestinal cramps, diarrhoea or nausea (vomiting);
• fever, alternating chills and hot flushes, yawning, goosebumps, runny nose, sneezing;
• uncoordinated and rapid movements or tremors (shaking);
• faster heartbeat (tachycardia);
• very small pupils;
• generalised body pain;
• weakness or motor restlessness;
• excessive sweating or tearing of the eyes.

Other adverse reactions include:
Uncommon (may affect up to 1 in 100 people) to common (may affect up to 1 in 10 people):

• slow or shallow breathing;
• headache or visual disturbances;
• weakness, dizziness, fainting, confusion or disorientation;
• excessive sleepiness or insomnia;
• euphoric-dysphoric mood;
• palpitations or slower heartbeat;
• reduced sexual drive;
• decreased libido or difficulties achieving and maintaining erection in men;
• increased sweating;
• skin rash, including urticaria and other types of itchy rash;
• dry mouth;
• loss of appetite, nausea or vomiting;
• constipation;
• fluid retention (‘oedema’), ‘biliary spasm’ which may cause pain in the upper abdomen or back;
• urinary disorders, including reduced urine output.

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

• flushed skin and sensation of heat (‘flushing’);
• internal bleeding;
• respiratory arrest;
• low blood pressure occurring after rapid change to upright position;
• cardiac arrest, heart attack, circulatory disorders, onset of shock.

Frequency not known:

• low blood sugar levels;
• sleep apnoea (pauses in breathing during sleep);
• the patient may develop dependence on Levomethadone Hydrochloride Molteni.

It should be noted that the severity of some adverse reactions decreases over time. However,
constipation and excessive sweating tend to persist. You should talk to your doctor or pharmacist about
treatment to help relieve these adverse reactions.
Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed
in this leaflet, you should inform your doctor or pharmacist. Adverse reactions can be reported
directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: + 48 22 49 21 301, fax: + 48 22 49 21 309. Website: https://smz.ezdrowie.gov.pl.
Reporting adverse reactions helps to provide more information on the safety of this medicine.

5. How to store Levomethadone Hydrochloride Molteni

• Keep this medicine out of sight and reach of children. This medicine should be stored in a secure place inaccessible to others. Taking this medicine by someone for whom it has not been prescribed may lead to severe harm or death.
• Do not use this medicine after the expiry date stated on the label and carton after: “EXP”. The expiry date refers to the last day of the specified month.
• Store below 25°C.
• Shelf life (oral solution): 12 weeks after first opening.
• Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Levomethadone Hydrochloride Molteni contains

• The active substance is levomethadone hydrochloride. Each millilitre (mL) of oral solution contains 5 milligrams (mg) of levomethadone hydrochloride.
• The other ingredients are: methyl parahydroxybenzoate (E218), betaine hydrochloride, glycerol, purified water.

What Levomethadone Hydrochloride Molteni looks like and contents of the pack

• Levomethadone Hydrochloride Molteni is a clear, colourless oral solution.
• It is available in pack sizes of: 100 mL, 3 x 100 mL, 500 mL and 1000 mL. The 100 mL pack: amber glass bottle with child-resistant closure and adapter (pipette adapter). A 5 mL pipette calibrated from 0.25 mL to 5 mL in 0.25 mL increments is supplied with the bottle.
• Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
L. Molteni & C. dei F.lli Alitti Società di Esercizio S.p.A.,
Strada Statale 67, Loc. Granatieri
50018 Scandicci (Firenze),
Italy
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Molteni Farmaceutici Polska Sp. z o.o
Tel.: +48 (12) 653 15 71
e-mail: [email protected]
This medicinal product is authorised in the European Economic Area countries under the following names:
Germany Levomethadon Molteni
Italy Ellepalmiron
Poland Levomethadone Hydrochloride Molteni
Spain Levometadona Molteni