Methadone hydrochloride molteni

Package leaflet: Information for the patient

Methadone Hydrochloride Molteni
1 mg/ml, syrup
Methadoni hydrochloridum
Please read the entire leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm others, even if their symptoms are the same.
• If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet:

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

1. WHAT METHADONE HYDROCHLORIDE MOLTENI IS AND WHAT IT IS USED FOR

Methadone Hydrochloride Molteni is an opioid analgesic (it acts on opioid receptors which influence pain perception). It acts on the central nervous system in a manner similar to morphine.
Methadone Hydrochloride Molteni is available as a syrup and should be administered orally only.
Indications:

• Treatment of opioid withdrawal syndrome (a condition following opioid discontinuation characterized by, among others, headaches, muscle pain, fatigue, and irritability);
• Maintenance or substitution treatment in individuals dependent on morphine or heroin;
• Relief of severe pain, particularly in cancer diseases and following surgical procedures.

2. IMPORTANT INFORMATION BEFORE TAKING METHADONE

HYDROCHLORIDE MOLTENI
When not to take Methadone Hydrochloride Molteni

• if the patient is allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6). If allergy is suspected, consult a doctor;
• in children and adolescents under 18 years of age;
• if the patient has had or currently has respiratory disorders, such as respiratory failure or chronic obstructive pulmonary disease (COPD) (obstructed airflow in the airways, symptoms of which include, among others: shortness of breath even at rest, persistent cough, wheezing), because the medicine may worsen symptoms of these diseases;
• if the patient has had or currently has asthma attacks;
• during childbirth as an anaesthetic agent;
• if the patient has kidney function disorders;
• if the patient has liver function disorders;
• if the patient has organic heart disease (heart rhythm disorders);
• if the patient has cor pulmonale (right ventricular hypertrophy due to chronic lung diseases);
• if the patient has diabetes;
• if the patient has low blood pressure (hypotension);
• if the patient has recently suffered head trauma;
• if the patient has increased intracranial pressure;
• if the patient has porphyria (inherited or acquired disorder characterized by impaired activity of enzymes involved in heme formation (the red pigment in blood));
• if the patient has oligemia (reduced blood volume circulating in blood vessels).

Warnings and precautions
Tolerance, dependence and compulsive use
This medicine contains methadone, 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's action, known as "tolerance"). Repeated use of Methadone Hydrochloride Molteni
may also lead to dependence, abuse and compulsive use, which may result in life-threatening
overdose. The risk of adverse effects may increase with higher doses and longer duration of use.
Dependence or compulsive use may cause the patient to feel that they have no control over the
amount or frequency of medicine intake. When used in pain treatment, the patient may feel that
they need to continue taking the medicine, even if it does not relieve pain.
The risk of developing dependence or abuse varies among patients. The patient may have a
higher risk of developing abuse or dependence on Methadone 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, while taking Methadone Hydrochloride Molteni, the patient notices any of the symptoms
listed below, 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 prescribed.
• 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 medicine use.
• 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 talk to their doctor and discuss
the best treatment approach for them, including the appropriate time to stop treatment and a
safe way to discontinue treatment (see section 3, Stopping treatment with Methadone
Hydrochloride Molteni).
Important information before taking Methadone Hydrochloride Molteni
Sleep-related breathing disorders
Methadone Hydrochloride Molteni may cause sleep-related breathing disorders, such as
sleep apnoea (pauses in breathing during sleep) and sleep-related hypoxemia (low blood
oxygen levels). Symptoms may include breathing pauses 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.
Before starting Methadone Hydrochloride Molteni, discuss this with your doctor or pharmacist.
The medicine should be used with caution, especially if the patient:

• is elderly (over 65 years of age);
• is debilitated;
• has hypothyroidism;
• has Addison's disease (adrenal insufficiency);
• has benign prostatic hyperplasia;
• has urethral stricture;
• has severe constipation;
• has cardiac conduction disorders;
• has advanced heart disease, including ischemic heart disease;
• has liver diseases;
• has a family history of sudden deaths;
• has electrolyte imbalances (low blood potassium levels, low blood magnesium levels);
• is being treated simultaneously with medicines that prolong the QT interval visible on electrocardiogram (ECG), such as atazanavir, azithromycin;
• is being treated simultaneously with medicines that may cause electrolyte imbalances (e.g., hydrochlorothiazide);
• is being treated simultaneously with medicines such as ketoconazole, erythromycin;
• is being treated with metamizole, a medicine used to treat pain and fever.

If any of the following symptoms occur during treatment with Methadone Hydrochloride
Molteni, consult a doctor or pharmacist:

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

Do not take this medicine if any of the above warnings apply or have applied to the patient in
the past.
If in doubt, contact a doctor or pharmacist before taking the medicine.
Long-term use may lead to decreased sex hormone levels and increased prolactin levels. If
symptoms such as low libido, impotence or absence of menstruation occur, contact a doctor.
Children and adolescents
Do not use in children and adolescents under 18 years of age.
Methadone Hydrochloride Molteni and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking, have recently
taken or plan to take.
Inform your doctor if you are taking any of the following medicines:

• 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. These medicines may affect the occurrence of adverse effects of Methadone Hydrochloride Molteni.

Do not use Methadone Hydrochloride Molteni with the following medicines:

• antibiotics (rifampicin, clarithromycin, erythromycin);
• antifungal medicines (fluconazole, itraconazole, ketoconazole);
• antiviral medicines (delavirdine, nevirapine, didanosine, stavudine, zidovudine, ritonavir, efavirenz);
• antiepileptic medicines (barbiturates, carbamazepine, phenytoin);
• antidiarrheal medicines (diphenoxylate, loperamide);
• antidepressants (such as citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, amitriptyline, clomipramine, imipramine, nortriptyline). The risk of adverse effects increases when methadone is used concomitantly with antidepressants (such as citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, amitriptyline, clomipramine, imipramine, nortriptyline). If any of the following symptoms occur, contact a doctor:
• changes in mental state (e.g., agitation, hallucinations, coma);
• rapid heartbeat, unstable blood pressure, fever;
• exaggerated reflexes, coordination disorders, muscle stiffness;
• gastrointestinal disturbances (e.g., nausea, vomiting, diarrhea);
• sedatives and hypnotics (including barbiturates, benzodiazepine derivatives). Concomitant use of Methadone Hydrochloride Molteni and sedatives such as benzodiazepines or similar medicines increases the risk of drowsiness, breathing difficulties (respiratory depression), coma and may be life-threatening. Therefore, concomitant use should only be considered if no other treatment options are available. If a doctor prescribes Methadone Hydrochloride Molteni together with sedatives, the doctor should also limit the dose and duration of concomitant 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 relatives so they are aware of the possible occurrence of the symptoms listed above. If any of the above symptoms occur, contact a doctor;
• strong analgesics (morphine, butorphanol, nalbuphine, pentazocine); substances that reduce urine pH (ammonium chloride);
• medicines used for heart and blood vessel diseases (quinidine, verapamil);
• naloxone and naltrexone (medicines used to treat morphine and heroin addiction); octreotide (used to treat certain tumour diseases).

Methadone Hydrochloride Molteni with food and drink
Do not drink alcohol while taking this medicine. Alcohol may worsen adverse effects such as
respiratory disorders and reduced blood pressure.
Do not drink grapefruit juice while taking Methadone Hydrochloride Molteni.
Grapefruit juice may alter the effect of this medicine.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to
have a child, she should consult a doctor or pharmacist before taking this medicine.
Do not use Methadone Hydrochloride Molteni during pregnancy. The medicine may harm the
developing unborn child.
Breastfeeding women should consult a doctor before taking any medicine.
Do not use Methadone Hydrochloride Molteni in breastfeeding women. The medicine passes
into breast milk and may cause dependence in the infant.
Consult your doctor if you are breastfeeding or considering breastfeeding while taking
methadone, as the medicine may affect the child. Monitor the breastfed infant for abnormal
symptoms such as increased drowsiness (more than usual), breathing difficulties or floppiness.
If any of these symptoms are observed, inform the doctor immediately.
Driving and operating machinery

Do not drive, operate machinery or use dangerous tools while taking Methadone
Hydrochloride Molteni. The medicine negatively affects the mental and physical abilities
required to perform these activities.
Warnings regarding excipients
The medicine contains sucrose, glycerol, sodium benzoate (E 211)
1 ml of syrup contains 400 mg of sucrose. 15 ml of syrup contains 6 g of sucrose. This should be
taken into account in patients with diabetes. If the patient has previously been diagnosed with
intolerance to certain sugars, the patient should contact a doctor before taking this medicine.
The medicine contains glycerol – the medicine may cause headache, gastrointestinal
disturbances and diarrhoea.
The medicine contains sodium benzoate (E 211). This medicine contains 0.5 mg of sodium
benzoate per 1 ml.

• Sodium – this medicine contains less than 1 mmol of sodium per ml, meaning the medicine is considered "sodium-free".
• This medicine contains 0.8 mg of alcohol (ethanol) per unit volume, equivalent to 0.08% w/v. The amount of alcohol in 10 ml of this medicine is equivalent to less than 1 ml of beer or 1 ml of wine. The small amount of alcohol in this medicine will not cause noticeable effects.

3. HOW TO TAKE METHADONE HYDROCHLORIDE MOLTENI

This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult
your doctor or pharmacist.
Do not change the prescribed dose on your own.
Do not use the medicine for longer than prescribed by your doctor.
This medicine is intended for oral use only. The medicine is ready for direct use.
1 ml of syrup contains 1 mg of active substance (methadone hydrochloride).
Before starting treatment and regularly during therapy, your doctor will discuss with you what to
expect from using Methadone Hydrochloride Molteni, when and for how long to take it, when to contact
your doctor, and when to discontinue the medicine (see also “Discontinuing Methadone Hydrochloride Molteni”).

Addiction
The usual starting dose is 15 to 20 ml of syrup (15 mg to 20 mg of methadone hydrochloride) once daily.
In cases of addiction to high doses of narcotics, your doctor may increase the dose.
In the treatment of heroin and morphine addiction, your doctor should combine dosing with a detoxification program (toxin removal) and adjust the dose according to the degree of the patient's addiction.
Do not exceed the dose prescribed by your doctor.

Pain
2.5 ml to 10 ml of syrup (2.5 mg to 10 mg of methadone hydrochloride), the dose should be repeated as needed every 3 to 8 hours.
Your doctor should adjust the dosing according to the severity of pain and the patient's response.

Use in children and adolescents
Do not use in children and adolescents under 18 years of age.

Taking more Methadone Hydrochloride Molteni than prescribed
If you take more medicine than prescribed, you must seek immediate medical advice or go to a hospital.
Take the medicine packaging with you.
The following symptoms of overdose may occur:
respiratory disturbances (reduced breathing rate, decreased volume of inhaled air);
deep drowsiness progressing to coma;
pupil constriction;
cold and clammy skin;
muscle weakness;
very slow heart rate; decreased blood pressure;
brain dysfunction (known as toxic leukoencephalopathy).
In severe cases of overdose, respiratory arrest, sudden cardiac arrest, and death may occur.
Taking more Methadone Hydrochloride Molteni than prescribed may result in low blood sugar levels.

Missing a dose of Methadone Hydrochloride Molteni
If a dose is missed:
if there is still plenty of time before the next dose, take the missed dose. In this case, adjust the time of the next dose accordingly;
if it is almost time for the next dose, skip the missed dose and wait until the next scheduled time. Continue treatment as prescribed by your doctor.
Do not take a double dose to make up for a missed dose.

Discontinuing Methadone Hydrochloride Molteni
Do not stop treatment suddenly without consulting your doctor. Abrupt discontinuation may cause withdrawal symptoms (occurring after sudden cessation of Methadone Hydrochloride Molteni).
The following withdrawal symptoms may occur:
anxiety, sudden mood changes, depression;
insomnia, difficulty falling asleep;
nervousness, restlessness, difficulty concentrating;
muscle tremors, muscle and joint pain;
tearing, pupil dilation, yawning;
sensation of increased heart activity (palpitations);
headache;
sweating;
nausea, vomiting, loss of appetite, diarrhea;
pallor.
If your doctor decides that Methadone Hydrochloride Molteni can be discontinued, they will advise you on how to gradually reduce the dose.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
The most significant adverse effects of methadone are: respiratory depression, circulatory collapse,
respiratory arrest, shock, and cardiac arrest.
The most commonly observed adverse reactions are a feeling of emptiness in the head, dizziness
(increased upon standing), sedation, nausea, vomiting, sweating, and low blood pressure
(especially after assuming an upright position). Some of these effects, more frequently observed
in outpatients, may be reduced by placing the patient in a lying position.

Other adverse reactions

Very common: occurs in more than 1 in 10 patients

• nausea and vomiting

Common: occurs in not more than 1 in 10 patients

• weakness
• euphoria, dysphoria, insomnia, agitation, disorientation
• miosis (pupil constriction), visual disturbances
• constipation

Uncommon: occurs in not more than 1 in 100 patients

• headache, transient loss of consciousness
• respiratory depression
• hypotension
• dryness of the oral mucosa
• pruritus, urticaria, other skin reactions, edema, and less frequently hemorrhagic urticaria
• urinary retention and difficulty in urination, antidiuretic effect
• biliary tract spasms
• decreased libido, impotence

Rare: occurs in not more than 1 in 1000 patients

• tachycardia or bradycardia, extrasystoles, and cardiac arrhythmias. After large doses, torsade de pointes arrhythmias may occur.

Frequency unknown: frequency cannot be estimated from available data

• anorexia, hypoglycemia
• sleep apnea (breathing pauses during sleep)
• dependence on Methadone Hydrochloride Molteni may develop in the patient (for more information, see section 2 "Warnings and precautions"). Other adverse reactions not listed in this leaflet may occur in some patients during treatment with Methadone Hydrochloride Molteni. If any adverse reactions occur, including any possible adverse reactions not listed in this leaflet, consult a doctor or pharmacist immediately.

Reporting of adverse reactions
If any adverse reactions occur, including those not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department for Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309. Website: https://smz.ezdrowie.gov.pl.
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. HOW TO STORE METHADONE HYDROCHLORIDE MOLTENI

Keep this medicine out of the sight and reach of children. This medicine must be stored in a secure place to which others do not have access. Taking this medicine by people to whom it has not been prescribed may lead to serious harm or death.
Keep the medicine in its original packaging to protect it from light.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Storage period after first opening the bottle: 2 months.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. CONTENTS OF THE PACKAGE AND OTHER INFORMATION

What Methadone Hydrochloride Molteni contains

• The active substance is methadone hydrochloride. 1 ml of syrup contains 1 mg of methadone hydrochloride.
• Other excipients: sucrose, glycerol (E 422), sodium benzoate (E 211), lemon flavouring agent, citric acid monohydrate, purified water.

What Methadone Hydrochloride Molteni looks like and contents of the pack
Methadone Hydrochloride Molteni is a clear, colourless or slightly yellow lemon-flavoured syrup.
The medicine is supplied in bottles with a capacity of 10 ml, 20 ml, 60 ml, 100 ml, or 1000 ml.
The 10 ml or 20 ml bottle is made of amber glass, closed with an HDPE cap with child-resistant closure and packaged in a cardboard box.
The 60 ml bottle is made of transparent amber PVC, closed with an aluminium cap with a polyethylene seal and packaged in a cardboard box, or made of amber glass, closed with an aluminium cap with a polyethylene seal and packaged in a cardboard box.
The 100 ml bottle is made of amber glass with a child-resistant closure made of polyethylene (HDPE/LDPE), fitted with a polyethylene (LDPE) pipette adapter and packaged in a cardboard box. A 5 ml polypropylene/polyethylene (HDPE) measuring pipette is included in the pack.
The 1000 ml bottle is made of transparent amber PVC, closed with a polypropylene cap with a polyethylene seal and packaged in a cardboard box, or made of amber glass, closed with a polypropylene cap with a polyethylene seal and packaged in a cardboard box.

Marketing Authorisation Holder and Manufacturer
L. Molteni & C. dei F.lli Alitti Società di Esercizio S.p.A.,
Strada Statale 67, Località Granatieri, 50018 Scandicci (Florence), Italy.

For further information about this medicine, please contact the Marketing Authorisation Holder's representative:
Molteni Farmaceutici Polska Sp. z o.o.,
ul. Józefa Korzeniowskiego 39, 30–214 Kraków,
tel.: (12) 653 15 71 or 72