Methadone hydrochloride inn-farm

Package leaflet: Information for the user

Methadone hydrochloride INN-FARM, 1 mg/ml, oral solution
Methadoni hydrochloridum
Please read all of this leaflet carefully before 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.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Methadone hydrochloride INN-FARM is and what it is used for

This medicine contains methadone hydrochloride, which belongs to a group of medicines called opioid analgesics. It is used in the treatment of opioid dependence.
All patients receiving Methadone hydrochloride INN-FARM must be routinely monitored for signs of misuse, abuse, and addiction.

2. Important information before taking Methadone hydrochloride INN-FARM

When not to take Methadone hydrochloride INN-FARM:

• if the patient is allergic to methadone or any of the other ingredients of this medicine (listed in section 6). Allergic reaction includes rash, itching or difficulty breathing;
• if the patient is experiencing an asthma attack (this medicine should not be used during an asthma attack). In case of self-administration, wait until the asthma attack has completely subsided and full recovery has occurred;
• if the patient is breathing very slowly or shallowly (respiratory depression);
• if the patient is alcohol-dependent;
• if the patient has recently suffered a head injury or has increased intracranial pressure;
• if the patient is taking monoamine oxidase inhibitors (MAOIs) used to treat depression, or if the patient has taken MAOIs within the last two weeks (see "Methadone hydrochloride INN-FARM and other medicines");
• if the patient is not opioid-dependent;
• if the patient has heart problems (prolonged QT interval);
• if the patient has severe liver dysfunction;
• if the patient has inflammatory bowel disease, known as ulcerative colitis;
• if the patient has urinary tract spasm (causing lower back pain and difficulty urinating);
• if the patient has biliary tract spasm (causing pain on the right side under the ribs, usually after meals);
• during childbirth.

If in doubt whether any of the above situations apply to the patient,
consult a doctor or pharmacist before taking Methadone hydrochloride INN-FARM.
Warnings and precautions
Before using this medicine, discuss with your doctor or pharmacist if the patient has:

• severe breathing problems;
• current or recent head injury;
• liver or kidney problems;
• epilepsy;
• insufficient pituitary gland function (hypopituitarism);
• reduced thyroid function (hypothyroidism);
• adrenal insufficiency;
• adrenal gland tumour (pheochromocytoma);
• enlarged prostate;
• low blood pressure;
• shock (circulatory failure);
• a disease causing muscle weakness, called myasthenia gravis;
• intestinal problems;
• established risk factors for QT interval prolongation, such as:
• history of irregular heartbeat;
• history of heart disease;
• sudden unexplained death in family members;
• low levels of potassium, sodium or magnesium;
• pregnancy or breastfeeding;
• extremely severe illness or advanced age. Sensitivity to the drug may be increased in such cases.

If any of the following symptoms occur while taking Methadone hydrochloride INN-FARM, consult a doctor or pharmacist: weakness, fatigue, loss of appetite, nausea, vomiting or low blood pressure. These symptoms may indicate insufficient cortisol production by the adrenal glands, and hormone replacement may be necessary (see section 4).
Long-term use may be associated with decreased levels of sex hormones and increased prolactin levels. If symptoms such as low libido, impotence, absence of menstruation or infertility occur, contact a doctor.
Breathing disorders during sleep
Methadone hydrochloride INN-FARM may cause breathing disorders during sleep, such as sleep apnoea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). 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 another person notices such symptoms, contact a doctor. The doctor may consider reducing the dose.
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 effects, known as "tolerance"). Repeated use of Methadone hydrochloride INN-FARM may also lead to dependence, abuse and compulsive use, which may result in life-threatening overdose.
Dependence or compulsive use may cause the patient to feel they have no control over the amount or frequency of medicine intake.
The risk of developing dependence or abuse varies among patients. The patient may be at higher risk of developing abuse or dependence on Methadone hydrochloride INN-FARM 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 INN-FARM, 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 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 talk to their doctor and discuss the best treatment approach, including the appropriate time to stop treatment and a safe way to discontinue treatment (see section 3, Stopping Methadone hydrochloride INN-FARM).
If in doubt whether any of the above situations apply to the patient, consult a doctor or pharmacist before taking Methadone hydrochloride INN-FARM.
Methadone hydrochloride INN-FARM and other medicines
Tell your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines the patient plans to take.
Methadone hydrochloride may affect the action of other medicines. In addition, some medicines may affect the action of methadone.
Do not take Methadone hydrochloride INN-FARM:

• at the same time or within 2 weeks after stopping monoamine oxidase inhibitors (MAOIs).

In particular, the patient should inform the doctor if taking any of the following medicines:

• other opioid painkillers;
• medicines affecting mental state (e.g. thioridazine, phenothiazine derivatives, haloperidol and sertindole);
• medicines used for heart conditions, such as verapamil and quinidine;
• medicines used to treat depression (desipramine, nefazodone, fluvoxamine, fluoxetine, paroxetine and sertraline);
• anti-inflammatory and immunosuppressive medicines (e.g. dexamethasone and cyclosporine);
• antiviral medicines, including some used to treat HIV infection (nevirapine, zidovudine, efavirenz, nelfinavir, ritonavir, amprenavir, delavirdine, lopinavir/ritonavir, ritonavir/saquinavir, abacavir, didanosine and stavudine);
• antibiotics (medicines used to treat bacterial infections), such as ciprofloxacin and macrolide antibiotics, e.g. clarithromycin, telithromycin and erythromycin;
• medicines used to treat fungal infections, such as fluconazole, itraconazole and ketoconazole;
• cimetidine, used to treat peptic ulcer disease;
• naloxone, used to reverse opioid effects;
• medicines used to block opioid effects, such as naltrexone and buprenorphine;
• rifampicin, used to treat tuberculosis (TB);
• medicines used to treat epilepsy, such as phenytoin, carbamazepine, phenobarbital and primidone;
• 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;
• medicines that acidify urine, such as ascorbic acid (vitamin C) and ammonium chloride;
• a medicine used to treat diarrhoea (e.g. loperamide, diphenoxylate);
• a diuretic (e.g. spironolactone);
• a medicine that increases drowsiness;
• metamizole, a medicine used to treat pain and fever;
• St John's wort preparations, used to treat depression.

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 disturbances, muscle stiffness
• gastrointestinal disturbances (e.g. nausea, vomiting, diarrhoea) (see section 4).

Concomitant use of Methadone hydrochloride INN-FARM and sedative medicines such as benzodiazepines or similar medicines increases the risk of drowsiness, breathing problems (respiratory depression), coma and may be life-threatening. Therefore, concomitant use of these medicines should only be considered when other treatment options are unavailable.
If the doctor prescribes Methadone hydrochloride INN-FARM together with sedative medicines, the dose and duration of concomitant treatment should be limited by the doctor.
Inform the doctor about all sedative medicines the patient is taking and strictly follow the doctor's dosage instructions. It may be helpful to inform friends or family members about the above-mentioned symptoms and signs. If such symptoms occur, contact the treating doctor.
Other medicines that may affect heart function (e.g. sotalol, amiodarone and flecainide).
Inform the doctor about all other medicines the patient is taking, as they may be dangerous when used with methadone. In such cases, the doctor may decide that heart monitoring via electrocardiogram (ECG) is necessary at the beginning of treatment to ensure these effects do not occur.
Methadone may also affect certain blood and urine tests (including anti-doping test results). Inform the doctor if the patient is taking methadone before any tests are performed.
Taking Methadone hydrochloride INN-FARM with food, drink and alcohol
Methadone hydrochloride INN-FARM can be taken with or without food.
Do not consume alcohol while taking Methadone hydrochloride INN-FARM. This is because methadone may cause drowsiness and drinking alcohol may worsen this effect.
Do not drink grapefruit juice while taking Methadone hydrochloride INN-FARM, as grapefruit juice may alter the action of methadone.
Pregnancy, breastfeeding and effects on fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant or plans to have a child, she should consult a doctor.
When performing a pregnancy test in urine, the patient should consider that Methadone hydrochloride INN-FARM may interfere with test results.
Do not use this medicine during childbirth.
Consult your doctor if a woman is 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), difficulty breathing or floppiness. If any of these symptoms are observed, inform the doctor immediately.
Driving and using machines
Methadone may seriously affect the ability to drive and operate machinery, both during and after treatment. You may only return to these activities after receiving permission from your doctor.
Methadone hydrochloride INN-FARM contains sorbitol.
This medicinal product contains 21 mg of sorbitol in 1 ml.
Sorbitol is a source of fructose. If the patient has been informed by a doctor of intolerance to certain sugars, or if hereditary fructose intolerance has been diagnosed – a rare genetic disorder causing affected individuals to be unable to metabolise fructose – the patient should contact a doctor before taking the medicine.
In some individuals, sorbitol may affect the amount of methadone absorbed from the ingested dose. In these patients, switching from Methadone hydrochloride INN-FARM to other methadone-containing products that do not contain sorbitol may lead to changes in methadone plasma concentration and recurrence of symptoms. In such cases, contact the treating doctor.
Methadone hydrochloride INN-FARM contains sodium benzoate.
This medicinal product contains 3 mg of sodium benzoate in 1 ml.
Methadone hydrochloride INN-FARM contains the colouring agent Orange Yellow S,
which may cause allergic reactions.
Methadone hydrochloride INN-FARM contains sodium.
This medicine contains 0.478 mg of sodium (main component of table salt) in 1 ml. When taking the maximum daily dose (150 mg) of methadone, the amount of sodium corresponds approximately to 3.59% of the recommended maximum daily sodium intake for an adult.

3. How to take Methadone hydrochloride INN-FARM

This medicine should always be taken exactly as recommended by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
Methadone hydrochloride INN-FARM must only be taken orally. Under no circumstances should
this medicine be injected, as it may cause severe and permanent bodily harm, possibly resulting in death.
Your doctor will inform you how much Methadone hydrochloride INN-FARM to take and how often.
It is important not to take more than the dose agreed upon with your doctor.

Adults
The usual starting dose is 10–30 mg per day. The dose will be gradually increased until withdrawal or intoxication symptoms have resolved. The usual maintenance dose is 60–120 mg per day. Your doctor will decide what dose to use and when to reduce it.

Elderly patients
Your doctor may decide to reduce the dose and monitor your condition more closely.

Patients with kidney or liver disease
Your doctor may decide to reduce the dose and monitor your condition carefully. Patients with severe liver problems should not receive this medicine.

Use in children and adolescents
Methadone hydrochloride INN-FARM is not intended for use in children and adolescents.

Taking more Methadone hydrochloride INN-FARM than recommended
If too much methadone is taken, the following symptoms may occur:

• Breathing difficulties, slow or shallow breathing;
• Extreme drowsiness, fainting, or coma;
• Pinpoint (maximally constricted) pupils;
• Muscle weakness;
• Cold and clammy skin;
• Low blood sugar;
• Slow heart rate, low blood pressure, heart attack, or shock;
• Brain function disorders (known as toxic leukoencephalopathy);
• In severe cases, death may occur. In case of overdose, contact a doctor immediately, even if the patient feels well, as methadone poisoning may still be present.

Missing a dose of Methadone hydrochloride INN-FARM
Do not take the missed dose. Wait until the next scheduled dose and take only the prescribed amount. Do not take a double dose to make up for a missed dose.

Stopping Methadone hydrochloride INN-FARM
Do not stop taking this medicine without your doctor’s instruction, as withdrawal symptoms may occur (see section 4). Your doctor 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 will experience them.
You must stop taking this medicine immediately and contact a doctor without delay if the patient
experiences any of the following symptoms:

• allergic reaction, which may include: swelling of the face, lips, tongue or throat, difficulty breathing or swallowing, or severe skin itching with an urticarial rash;
• serious heart problems. Symptoms may include changes in heart rhythm, such as faster heartbeat or irregular heartbeat, difficulty breathing, dizziness, slow and shallow breathing;
• occurrence of slow and shallow breathing;
• increased intracranial pressure, if the patient previously had brain injury or brain disease.

Continue taking the medicine, but contact your doctor immediately if the patient experiences any of the following adverse reactions:

• asthma or worsening of asthma.

Other possible adverse reactions:
Very common (may occur in more than 1 in 10 people):

• nausea or vomiting.

Common (may occur in up to 1 in 10 people):

• fluid retention in the body;
• feeling of euphoria, seeing or hearing things that are not real (hallucinations), confusion;
• feeling drowsy (sedation);
• blurred vision, pinpoint (maximally constricted) pupils, dry eyes;
• feeling dizzy or experiencing vertigo;
• constipation;
• transient rash, sweating;
• feeling tired, drowsiness;
• weight gain.

Uncommon (may occur in up to 1 in 100 people):

• feeling depressed (dysphoria), restlessness, confusion, difficulty falling asleep, reduced sex drive;
• headache, fainting;
• low blood pressure, hot flushes;
• breathing difficulties (including cough) due to fluid accumulation in the lungs, worsening of asthma, dry nose;
• dry mouth, inflammation of the tongue;
• biliary spasm (abdominal pain);
• itching, urticaria, rash, petechiae;
• urinary retention (difficulty passing urine), reduced urine production;
• reduced potency, menstrual disorders, lactation;
• swelling of legs, oedema;
• weakness;
• low body temperature.

Rare (may occur in up to 1 in 1000 people):

• heart problems, slower heartbeat, palpitations;
• collapse, shock;
• respiratory arrest;
• slowed intestinal motility (obstruction).

The following adverse reactions have also been reported (frequency unknown):

• decreased platelet count, increasing the risk of bleeding or bruising;
• increased prolactin levels;
• adrenal insufficiency (with symptoms such as: nausea or vomiting, loss of appetite, fatigue, weakness, dizziness, low blood pressure);
• loss of appetite;
• low blood potassium or magnesium levels;
• low blood sugar levels;
• serotonin syndrome (see section 2);
• nystagmus (involuntary eye movements);
• hearing loss;
• urinary tract spasm (causing lower back pain and difficulty passing urine);
• prolonged use of methadone is associated with breast enlargement in men, impaired fertility, disturbances in sexual function, and reduced sex hormone levels;
• the patient may develop dependence on Methadone hydrochloride INN-FARM (for more information, see section 2 "Warnings and precautions");
• sleep apnoea (pauses in breathing during sleep).

Withdrawal symptoms may occur after discontinuation of opioids. These include: body aches, diarrhoea, piloerection (goosebumps), eating disturbances, restlessness or irritability, sneezing, runny nose, tremor or shivering, colicky abdominal pain, nausea, sleep disturbances, increased sweating and yawning, weakness and unexplained fever. Some individuals may experience a sensation of slightly faster or stronger heartbeat. With appropriate dose adjustment and gradual discontinuation of opioids, these symptoms are usually mild.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products at 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
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Methadone hydrochloride INN-FARM

Keep this medicine out of the sight and reach of children. This medicine must be stored in a secure place inaccessible to others. Taking this medicine by people for whom it has not been prescribed may result in severe harm or death.
Do not use this medicine after the expiry date stated on the carton and bottle under "Expiry date (EXP)". The expiry date refers to the last day of the stated month.
Store in the original packaging to protect from light.
After first opening, this medicine should be used within 90 days when stored in the original packaging to protect from light.
This medicine does not require any special storage temperature conditions.
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. Such measures help protect the environment.

6. Contents of the package and other information

What Methadone hydrochloride INN-FARM contains

• The active substance is methadone hydrochloride. 1 ml of oral solution contains 1 mg of methadone hydrochloride.
• The other ingredients are: sorbitol liquid, non-crystallizing (E420), glycerol (E422), sodium benzoate (E211), monohydrate citric acid (E330), brilliant blue FCF (E133), sunset yellow (E110), and purified water.

What Methadone hydrochloride INN-FARM contains and contents of the pack
Methadone hydrochloride INN-FARM is a clear, green solution for oral use.
100 ml pack:
A cardboard box containing a glass bottle with 100 ml of oral solution with a child-resistant cap and a leaflet.
1000 ml pack:
A cardboard box containing a bottle with 1000 ml of oral solution with a child-resistant cap and a leaflet.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
INN-FARM d.o.o.
Maleševa ulica 14
1000 Ljubljana
Slovenia
Tel.: +386 70 390 711
Fax: +386 5191 116
e-mail: [email protected]

Importer
ALKALOID-INT d.o.o
Šlandrova ulica 4
1231 Ljubljana-Črnuče
Slovenia

This medicinal product is authorised in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:
Croatia: Metadon Alkaloid 1 mg/ml oral solution
Ireland: Methadone hydrochloride 1 mg/ml oral solution
Malta: Methadone Alkaloid 1 mg/ml oral solution
Poland: Methadone hydrochloride INN-FARM
United Kingdom (Northern Ireland): Methadone Alkaloid 1 mg/ml oral solution