OMTISA 5 mg Коированная Таблетка

Содержание инструкции

1. Cos’è Metadone cloridrato G.L. e a cosa serve
2. Cosa deve sapere prima di prendere Metadone cloridrato G.L.
3. How to take Metadone cloridrato G.L.
4. Possible side effects
5. How to store Metadone cloridrato G.L.
6. Contents of the pack and other information

Methadone Hydrochloride G.L. 5 mg tablets
Methadone Hydrochloride G.L. 10 mg tablets
Methadone Hydrochloride G.L. 20 mg tablets
Methadone Hydrochloride G.L. 40 mg tablets
Methadone Hydrochloride G.L. 60 mg tablets
Methadone Hydrochloride
Generic equivalent medicine (for 5 mg, 10 mg, 40 mg packs)

Read this leaflet carefully before you start taking this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. Cos’è Metadone cloridrato G.L. e a cosa serve

Metadone cloridrato G.L. contains the active ingredient methadone hydrochloride, which belongs to the group
of opioids.
Metadone cloridrato G.L. is used for substitution therapy for opioid dependence in
adults with opioid/opiate dependence as part of an integrated treatment approach that
combines opioid substitution with medical, social and psychosocial care.

2. Cosa deve sapere prima di prendere Metadone cloridrato G.L.

Do not take Metadone cloridrato G.L. if

• you are allergic to methadone or any of the other ingredients of this medicine listed in section 6.
• you are also being treated with MAO inhibitors (medicines used to treat Parkinson's disease or depression) or if you have stopped taking them less than 2 weeks ago.
• you experience respiratory depression, especially if this is accompanied by cyanosis and excessive bronchial secretions.
• you suffer from severe bronchial asthma or other obstructive airway diseases.
• you are having an asthma attack.
• you suffer from alcoholism.
• you have heart problems (prolongation of the QT interval).
• you have an intestinal obstruction due to paralysis of the intestinal muscles (paralytic ileus).
• you suffer from severe liver impairment.
• you suffer from a very rare liver disease in which substances called porphyrins accumulate in the body, negatively affecting the skin or nervous system (porphyria).
• you suffer from uncontrolled diabetes (presence of diabetic ketoacidosis or hyperosmolar hyperglycemic state).
• you suffer from cor pulmonale (pulmonary heart disease).

During treatment with Metadone cloridrato G.L., you should not take any narcotic antagonist or
mixed agonist-antagonist (substances that can eliminate the effect of Metadone cloridrato G.L., for
example pentazocine and buprenorphine), unless these are part of the treatment for overdose.

Warnings and precautions
Talk to your doctor or pharmacist before taking Metadone cloridrato G.L..
Methadone must only be used in patients with opioid/opiate dependence because even normal
doses can lead to severe intoxication and even death in patients not tolerant to
opioids.
In cases where this medicine is prescribed for home therapy, the doctor must
ensure that all reasonable measures are taken to eliminate any risk of
self-harm or harm to others that may result from a home prescription, and to ensure
that the patient uses the prescribed medicine as directed. In case of misuse or abuse by
the patient, the prescription service for home therapy must be discontinued
immediately.
Extreme caution is advised when treating:

• Patients at high risk: Suicide attempts with opioids, especially combined with tricyclic antidepressants, alcohol and other CNS-active substances, are part of the clinical picture of dependence. Individual assessment and treatment planning, including if this involves hospitalization, should be considered for patients who show uncontrolled drug use and who exhibit high-risk behaviors despite adequate pharmacological treatment.
• Acute abdominal conditions: Treatment with Metadone cloridrato G.L. may obscure the diagnosis or clinical course of acute abdominal conditions. This is why patients receiving substitution treatment and showing signs of an acute abdomen should be monitored particularly carefully.
• If you are known or suspected to have a prolonged QT interval or an electrolyte imbalance, in particular a decrease in blood potassium levels.
• If you have a tumor of the adrenal glands (pheochromocytoma)

The concomitant use of Metadone cloridrato G.L. and sedatives such as benzodiazepines or
related active ingredients increases the risk of drowsiness, respiratory difficulties (respiratory
depression), coma and can be life-threatening. For this reason, concomitant use should
be considered only when other treatment options are not possible.
However, if your doctor prescribes Metadone cloridrato G.L. together with sedatives, the dose and
duration of concomitant treatment must be limited by the doctor.
Tell your doctor about all the sedatives you are taking and carefully follow
your doctor's recommendations on dosage.
Urine and/or blood tests are an integral part of
maintenance treatment with methadone to monitor for the presence of narcotics and
psychotropic substances. The doctor will also check for alcohol abuse. It may be helpful to inform
friends or family members to be aware of the signs and symptoms described above. Contact your doctor when
you experience these symptoms. The doctor will adjust the dose appropriately.
Talk to your doctor or pharmacist if you experience any of the following symptoms while taking
Metadone cloridrato G.L.:
Weakness, fatigue, loss of appetite, nausea, vomiting or low blood pressure. This may be a
symptom that the adrenal glands are producing too little cortisol hormone, and you may
need to take a hormone supplement.
Long-term use can cause a decrease in sex hormone levels and an increase in
levels of the hormone prolactin. Contact your doctor if you experience symptoms such as decreased
libido, impotence or absence of menstruation (amenorrhea).
Metadone cloridrato G.L. must be used with particular caution

• If you have an underactive thyroid
• In individuals with adrenal insufficiency
• If you have an underactive pituitary gland
• If you have an enlarged prostate with incomplete bladder emptying or urethral stenosis
• In individuals with circulatory shock
• If you have a biliary disorder
• If you have a condition that causes narrowing or inflammation of the intestine
• If you have a slow heart rate
• If you are also receiving certain medicines that are used to treat heart arrhythmias (antiarrhythmics of class I and III)
• In individuals with pancreatitis
• In disorders requiring the prevention of respiratory depression
• In case of pregnancy or breastfeeding (see section “Pregnancy, breastfeeding and fertility”)
• If you have low blood pressure or reduced blood volume (hypotension due to hypovolemia)
• In subjects with loss of consciousness or in a coma
• When using this medicine simultaneously with other substances that have a depressive effect on central nervous functions (e.g. breathing)
• If you are elderly (in elderly patients methadone can cause confusion (see section “How to take Metadone cloridrato G.L.”).
• In subjects with increased intracranial pressure

In addition, opioids can produce effects that can obscure the clinical course of patients with
head injuries.
Risk of abuse
Methadone is a mu-opioid agonist with a risk level similar to that of morphine. There is
a risk of misuse and unauthorized diversion. The risk of opioid abuse is greater
in patients with a personal or family history of substance abuse (including drug and alcohol abuse or
dependence) or psychiatric disorders (e.g. major depression).
Tolerance and withdrawal
Methadone has a risk of giving rise to dependence and can induce addiction following prolonged or repeated use. This results in physical and psychological dependence and tolerance. An abrupt
cessation or interruption of treatment can lead to severe withdrawal symptoms, some of which
can be life-threatening. Tolerance has been acquired during the course of the disease and can
be lost shortly after discontinuation, so that doses previously tolerated can trigger a
overdose if treatment is continued. This must be taken into account when the
treatment needs to be continued after an interruption with the same dose used previously.
Liver and kidney impairment
Caution should be exercised in the use of methadone in patients with mild to moderate renal or hepatic impairment.
Gastrointestinal motility
Opioids including methadone can cause troublesome constipation, which is particularly
dangerous in patients with severe liver impairment, and measures to prevent constipation
must be started early.
Respiratory system
The main risk associated with the use of methadone is respiratory depression. While severe, life-threatening or even fatal respiratory depression can occur at any time in
patients taking methadone, the risk is higher at the beginning of treatment or following an
increase in dose. The peak of the depressive effect at the respiratory level occurs later, and persists
longer, than the maximum analgesic effect, especially during the initial dosing period. The doctor will monitor you carefully.
To reduce the risk of respiratory depression, the correct dosage and titration of methadone are
essential. Overestimating the dose of methadone in patients switching from
another opioid to methadone can cause a fatal overdose even after the first dose. Respiratory depression has been reported in connection with the use of methadone even in the absence of improper use or
abuse.
Metadone cloridrato G.L. must be used with caution in patients with asthma, chronic obstructive pulmonary disease or heart disease caused by a lung disease (pulmonary heart disease), as
well as in people with severely limited inspiratory reserve volume, pre-existing
decreased respiratory function, reduced oxygen levels in the blood or increased levels of
carbon dioxide in the blood. In these patients, even normal therapeutic doses of narcotics can
decrease the respiratory rate, simultaneously increasing the resistance of the airways up to
the point of respiratory arrest. Exacerbations of pre-existing asthma, skin rashes and changes
in blood composition (eosinophilia) may be observed in patients particularly
predisposed to these types of atopic phenomena.
Cardiac arrhythmias:
There is some evidence from clinical studies that treatment with mu receptor agonists can lead to
prolongation of the QT interval, and therefore to the risk of polymorphic ventricular tachycardia (torsades de pointes). In patients for whom the potential benefits of methadone treatment outweigh the risks of
tachycardia, an ECG should be performed before starting treatment and 2 weeks after the start
of treatment to determine and quantify the effect of methadone hydrochloride on the QT interval. Similarly, ECG monitoring should be performed before a dose increase
administered.
Reduction of sex hormones:
Long-term use can cause a decrease in sex hormone levels and an increase in
levels of the hormone prolactin. Contact your doctor if you experience symptoms such as decreased
libido, impotence or absence of menstruation (amenorrhea).
Improper use
This medicine may be a target for people who abuse prescription drugs and
should be kept in a safe place to protect it from theft (see section 5). Do not give
this medicine to anyone else. It may cause their death or otherwise harm them.
Metadone cloridrato G.L. is for oral use only. Improper use by intravenous injection can
cause serious and potentially fatal side effects, such as sepsis (a life-threatening condition that occurs when the body's response to infection causes injury to its own
tissues and organs), phlebitis (inflammation of the veins), pulmonary embolism (blockage of an artery in the
lungs due to the movement of material from other parts of the body through the bloodstream).
Drug, alcohol and medicine abuse during methadone treatment can cause life-threatening events and must be avoided.
The doctor will regularly perform urine tests to confirm cases of potential drug abuse.
In case of abuse or improper use of the medicine (e.g. intravenous injection), the doctor will
immediately discontinue treatment.
Methadone can also affect some blood and urine tests. Tell your doctor if you are
taking methadone before performing any tests.
Effects of improper use for doping purposes
For those involved in sports: the use of Metadone cloridrato G.L. without therapeutic need
constitutes doping and may still result in a positive doping test.
The improper use of this medicine for doping purposes can be harmful to your health.

Children and adolescents
The safety and efficacy of methadone in children and adolescents under 18 years of age have not
been established.
According to the scientific literature, there is evidence of treatment for opioid dependence in
adolescents starting from the age of 15.

Other medicines and Methadone Hydrochloride G.L.
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicine.
The daily dose required of Methadone Hydrochloride G.L. may change depending on other
medicines you are taking. Tell your doctor if you notice signs of an increased effect or withdrawal symptoms associated with Methadone Hydrochloride G.L..
Do not take any of the following medicines if you are also takingMethadone Hydrochloride G.L.:

• Monoamine oxidase inhibitors (medicines used in the treatment of Parkinson's disease or depression) You must stop taking these medicines at least 14 days before starting treatment with Methadone Hydrochloride G.L.. Otherwise these medicines can cause depressive or stimulant effects on the respiratory and circulatory system which can be life-threatening.
• Pentazocine, buprenorphine, nalbufine, butorphanol (medicines for the treatment of severe pain) and naloxone, naltrexone (opioid antagonists). Concomitant use with Methadone Hydrochloride G.L. can lead to withdrawal symptoms. Do not start taking buprenorphine until at least 24 hours after stopping Methadone Hydrochloride G.L.. These medicines can only be used in conjunction with Methadone Hydrochloride G.L. when they are needed to treat an overdose of Methadone Hydrochloride G.L..

Tell your doctor if you are taking any of the following medicines, as they may affect how Metadone Hydrochloride G.L. works:

• Strong painkillers, including opioids.
• Central nervous system depressant drugs (e.g. sedatives, hypnotics, anesthetics, some antiemetics, phenothiazines, other tranquilizers, alcohol and drugs).
• Medicines used to treat epilepsy, which are called barbiturates, and whose active ingredients usually end in “-tal”, such as phenobarbital.
• Medicines for general anesthesia.
• Some medicines used to treat depression, called tricyclic antidepressants, and other medicines against depression, called selective serotonin reuptake inhibitors (SSRIs).
• Medicines used to treat high blood pressure (for example reserpine, clonidine, urapidil and prazosin).
• Cimetidine (a medicine that helps reduce stomach acid production)
• Medicines used to treat fungal infections (e.g. itraconazole, ketoconazole, voriconazole, fluconazole)
• Antiarrhythmic class I and III medicines that are used to treat heart arrhythmias
• Oral contraceptives
• Carbamazepine and phenytoin (medicines used to treat epilepsy)
• Medicines used to treat some bacterial diseases, such as rifampicin and antibiotics known as macrolides, ciprofloxacin and fusidic acid.
• Medicines containing St John's Wort
• Spironolactone (a diuretic used to remove excess fluid)
• Medicines that inhibit the proliferation of the human immunodeficiency virus (HIV) (e.g. efavirenz, nevirapine, nelfinavir, ritonavir, amprenavir, didanosine, stavudine and zidovudine, abacavir, darunavir+ritonavir, telaprevir, lopinavir+ritonavir, saquinavir+ritonavir, and tipranavir+ritonavir)
• Medicines for urinary tract infections (ammonium chloride)
• Vitamin C (ascorbic acid)
• Medicines that inhibit bowel movements
• Metamizole, a medicine used to treat pain and fever.

The risk of side effects increases if methadone is used in conjunction with 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 status (e.g. agitation, hallucinations, coma)
• rapid heartbeat, unstable blood pressure, fever
• exaggeration of reflexes, impaired coordination, muscle stiffness
• gastrointestinal symptoms (e.g. nausea, vomiting, diarrhea).

Other possible interactions
Desipramine (a type of antidepressant)
Concomitant use with methadone has been observed to lead to high levels of desipramine in
the blood.
Anticholinergics (a type of medicine that suppresses the effect of acetylcholine)
When used in conjunction with opioids, anticholinergics or other medicines with anticholinergic activity can lead to an increased risk of urinary retention and/or severe constipation, which can lead to intestinal obstruction. When methadone and anticholinergics are used
simultaneously, patients should be monitored for signs of urinary retention and reduced
gastric motility.
Medicines potentially causing arrhythmias
Extreme caution is required when any medicine known to have the risk of prolongation
of the QT interval is prescribed in conjunction with methadone.
Interactions may occur following concomitant use of methadone and medicines
potentially causing arrhythmias, such as class I and III antiarrhythmics, some neuroleptics as well as
tricyclic antidepressants and calcium channel blockers.
Similarly, caution is recommended when prescribing methadone in conjunction
with medicines that are able to induce electrolyte imbalances that can cause a
prolongation of the QT interval (hypomagnesemia, hypokalemia). This includes diuretics, laxatives and,
in rare cases, mineralocorticoid hormones.
Cannabis may delay the degradation of methadone and lead to increased plasma concentrations
of methadone. This can cause symptoms of intoxication and respiratory depression.
The occurrence of these interactions will depend on the individual patient's situation, the tolerability
of the opioid used and the patient's overall health. Although not all
possible interactions with methadone have been listed, these are theoretically possible and cannot be excluded.

Methadone Hydrochloride G.L. with food, drinks and alcohol
You should avoid consuming alcohol while taking Methadone Hydrochloride G.L., as there is a
risk of unexpected and mutually potentiating effects that could lead to severe or
even fatal intoxication.
Grapefruit juice may delay the degradation of Methadone Hydrochloride G.L. and is not recommended
during treatment with Methadone Hydrochloride G.L.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you are breastfeeding with
breast milk, ask your doctor for advice before taking this medicine.
Pregnancy
Methadone Hydrochloride G.L. can be used during pregnancy after a careful assessment of
the risk/benefit ratio by a doctor, preferably under control in a specialized medical center.
An increase in the dose up to twice a day may be necessary to maintain the effectiveness of
treatment due to changes in metabolism during pregnancy.
Chronic use during pregnancy can lead to habituation and dependence on methadone in
the fetus, as well as withdrawal symptoms in the newborn after birth, which often require hospital treatment.
Withdrawal syndrome may not appear in the newborn for several days after birth. Therefore,
in addition to initial monitoring for respiratory depression, newborns should be subjected to
prolonged monitoring for signs and symptoms of withdrawal.
Discontinuation of the medicine in the newborn must be carried out in an adequate pediatric intensive care unit, as treatment with methadone can lead to habituation and dependence
in the fetus, as well as withdrawal symptoms in the newborn requiring treatment.
Breastfeeding
Consult your doctor if you are breastfeeding or may be breastfeeding while taking methadone, because
this may have effects on your baby. Check your baby for abnormal signs and symptoms such as
increased drowsiness (more than usual), difficulty breathing or weakness. Consult your doctor immediately if you notice any of these symptoms.
Fertility
Methadone has been reported to cause sexual dysfunction in male patients
in maintenance treatment.

Driving and operating machinery
Methadone Hydrochloride G.L. impairs the ability to drive vehicles and operate machinery as
it causes drowsiness and reduces attention. Active participation in traffic cannot be
recommended at the beginning of treatment, during dose titration, if withdrawal symptoms occur or in case of co-administration of substances that impair cognitive function.
The doctor will decide whether you are allowed to drive vehicles, operate machinery or perform other
dangerous activities. He will take into account your reactivity and your dose of Methadone Hydrochloride G.L..

Methadone Hydrochloride G.L. contains lactose and sucrose.
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking
this medicine.

3. How to take Metadone cloridrato G.L.

Maintenance therapy with methadone must be prescribed by a doctor experienced in the treatment
of opioid/opiate dependence. This treatment is preferably administered in centers
specialized in the treatment of opioid dependence. The doctor will also consider
national recommendations.
Take this medicine following exactly the instructions of your doctor or pharmacist. If
you have any doubts, ask your doctor or pharmacist.
The doctor will determine the best dose for you. The doctor may decide to adjust the dose during the
treatment - even if you have not requested it.
Use the medicine once a day, at the dose prescribed by the doctor.

Methadone withdrawal
If the prescribed dose of methadone is too low, withdrawal symptoms may develop during
the 24-hour dosing interval (nasal congestion, lower abdominal pain [abdominal symptoms],
diarrhea, muscle pain, anxiety). Treating physicians must be aware that dose adjustments may be
necessary if patients report having withdrawal symptoms.
Tell your doctor if your craving for drugs has not been completely suppressed. An adequate dose will ensure that no more withdrawal symptoms develop. A dose that is too high, however, may
lead to sedation or drowsiness.
The dose of Metadone cloridrato G.L. must be titrated based on the appearance of withdrawal symptoms
and is adjusted according to individual needs and the patient's personal perception. In general,
after dose adjustment, the goal is to administer the lowest possible maintenance dose.

Elderly patients over 65 years of age
In order to prevent overdose, the doctor may reduce the dose.

Patients with impaired renal and/or hepatic function
If hepatic or renal function is impaired, the doctor may reduce the dose. If you suffer from stable chronic liver disease, it is not necessary to reduce the dose.

Pregnant patients
An increase in the dose up to twice a day may be necessary to maintain the effectiveness of
treatment due to changes in metabolism during pregnancy (see paragraph
“pregnancy and breastfeeding”). The doctor will prescribe the appropriate dose.

Patients undergoing treatment with antiretroviral drugs
At the start or end of treatment with antiretroviral drugs (drugs for the treatment
of HIV or hepatitis C), potential withdrawal or overdose symptoms must be considered,
as antiretroviral substances may increase or decrease methadone levels in the blood.

Use in children and adolescents
The safety and efficacy of methadone in children under 18 years of age have not been established.
Therefore, the use of Metadone cloridrato G.L. is not recommended under 18 years of age.
There is experience in the treatment of opioid dependence in adolescents starting from 15
years of age.

Method of administration
The tablets are for oral use and must not be injected.
The oral route is the only effective and safe route of administration for this medicine.
The tablets can be taken whole or can be readily dissolved in water, orange or apple juice.
The solution is intended to be taken immediately.
This medicine can be taken with or without food.

Duration of treatment
The duration of treatment will depend on the specificities of each individual case and its evolution and will
be determined by the doctor according to the criteria of substitution treatment. There are no limitations for
regarding the maximum duration of treatment.
Discontinuation of Metadone cloridrato G.L. must occur gradually, with a reduction of
treatment over several weeks or months. Any dose reduction must be guided
by the patient's subjective experience of symptoms.

If you take more Metadone cloridrato G.L. than you should
This can cause dangerous poisoning, especially in non-tolerant individuals (especially
children) even at doses that are lower than those normally used as part of substitution treatment. This can occur from a dose of approximately 1 mg in children up to 5 years of age, of
approximately 3 mg in older children and of approximately 20 mg in non-tolerant adults.
It can cause a drop in blood sugar.
Consult a doctor immediately. An overdose of Metadone cloridrato G.L. can be
life-threatening. Take this leaflet and show it to the doctor.

If you forget to take Metadone cloridrato G.L.
If you have taken less than the prescribed amount of Metadone cloridrato G.L. and have developed withdrawal symptoms, take the remaining dose as soon as you remember. Do not increase in any case the dose
daily that has been established for that specific day. Tell your doctor if you have not developed
withdrawal symptoms after taking a reduced amount of the medicine, so that your dose
daily can be adjusted.

If you stop taking Metadone cloridrato G.L.
An abrupt interruption can lead to severe withdrawal symptoms, some of which may be
life-threatening. Therefore, you should not stop treatment or interrupt it prematurely.
Long-term treatment must be discontinued gradually.
If you have further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Symptoms associated with opioid withdrawal are common at the start of maintenance treatment and
include anxiety, loss of appetite, involuntary contractions and jerky movements, intestinal spasms,
depression, diarrhoea, vomiting, fever, alternating hot flushes and chills, yawning,
goosebumps, weight loss, increased heart rate, runny nose, sneezing, dilated pupils,
irritability, drowsiness, muscle pain, feeling faint, excessive sweating, excessive tearing,
nausea, restlessness, abdominal cramps and chills.
Other possible side effects of Metadone cloridrato G.L.:
The side effects indicated with a (#) appear to be more common in outpatients and in
those receiving oral therapy.
Very common: may affect more than 1 in 10 people:

• Dizziness#
• Drowsiness#
• Nausea#
• Vomiting#
• Dry mouth#
• Constipation
• Prolonged gastric emptying time
• Sweating#
• Prolonged use in men has been reported to be associated with the development of gynecomastia and decreased fertility

Common: may affect up to 1 in 10 people:

• Vertigo
• Confusion#
• Lethargy
• Clouded state of consciousness
• Facial flushing
• Itching
• Increased tone of the external sphincter
• Urinary retention
• Increased bladder volume
• Decreased libido and/or sexual dysfunction

Uncommon: may affect up to 1 in 100 people:

• Loss of appetite
• Mental apathy
• Euphoria
• Dysphoria
• Agitation
• Insomnia
• Headache
• Visual disturbances (miosis)
• Bradycardia
• Reduced blood pressure
• Respiratory depression
• Pulmonary edema
• Biliary dyskinesia

Rare: may affect up to 1 in 1,000 people:

• Hallucinations
• Changes in ECG, including prolongation of the QT interval and torsades de pointes, usually in patients who have risk factors or who are receiving methadone at high doses
• Syncope

Not known (frequency cannot be estimated from the available data):

• Disorientation
• Convulsions
• Spasm of the bile ducts
• Skin rash
• Urticaria
• Spasm of the renal tract, antidiuretic effect
• Weakness
• Edema
• Low blood sugar levels
• A reversible decrease in the number of platelets, which can cause bleeding and bruising (thrombocytopenia) has been reported in opioid-dependent patients with chronic hepatitis.
• Low potassium levels, low magnesium levels
• Hearing loss

Withdrawal syndrome (abstinence): chronic use of opioid analgesics can be associated with
the development of physical dependence. Abrupt discontinuation of opioids or the administration of
opioid antagonists can trigger a withdrawal syndrome.
The following withdrawal symptoms may be observed after stopping opioid use:
muscle pain, diarrhoea, goosebumps, loss of appetite, nervousness or restlessness, runny nose,
sneezing, chills or tremors, abdominal cramps, nausea, sleep disturbances, unusually increased
sweating and yawning, weakness, palpitations and fever of unknown origin. With appropriate
dose adjustments and gradual discontinuation, these symptoms are usually mild.
Important
Once the maintenance dose is reached, the side effects will gradually decrease in
frequency and severity over a few weeks. Constipation and increased sweating,
however, often persist permanently, but can be alleviated with appropriate measures.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet. You can also report side effects directly through the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Metadone cloridrato G.L.

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on blister/label and on the package
after Exp. The expiry date refers to the last day of that month.
Store in the original package to protect the medicine from light.
Tablet container:
After first opening: do not use for more than 6 months.
Solutions of dissolved tablets are stable for up to 3 hours.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how
to eliminate medicines that you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Metadone Hydrochloride G.L. contains

• The active ingredient is metadone hydrochloride. Metadone Hydrochloride G.L. 5 mg tablets: 1 tablet contains 5 mg of metadone hydrochloride, equivalent to 4.473 mg of metadone. Metadone Hydrochloride G.L. 10 mg tablets: 1 tablet contains 10 mg of metadone hydrochloride, equivalent to 8.947 mg of metadone. Metadone Hydrochloride G.L. 20 mg tablets: 1 tablet contains 20 mg of metadone hydrochloride, equivalent to 17.893 mg of metadone. Metadone Hydrochloride G.L. 40 mg tablets: 1 tablet contains 40 mg of metadone hydrochloride, equivalent to 35.786 mg of metadone. Metadone Hydrochloride G.L. 60 mg tablets: 1 tablet contains 60 mg of metadone hydrochloride, equivalent to 53.679 mg of metadone.
• The other ingredients are: microcrystalline cellulose; pregelatinized starch (corn); lactose monohydrate, sucrose; magnesium stearate.

Description of the appearance of Metadone Hydrochloride G.L. and contents of the pack
Metadone Hydrochloride G.L. is available in 5 mg, 10 mg, 20 mg, 40 mg, 60 mg tablets. The
tablets are described below.
5 mg
Round tablet, from white to off-white in colour, convex on one side, with the inscription “5”
embossed on one side, score line on the other side, with a diameter of 7.1 ± 0.2 mm and a
thickness of 2.8 ± 0.5 mm. The tablet can be divided into equal doses.
10 mg
Round tablet, from white to off-white in colour, convex on one side with the inscription “10” in
relief on one side, score line on the other side, with a diameter of 9.2 ± 0.2 mm and a thickness of
3.9 ± 0.5 mm. The tablet can be divided into equal doses.
20 mg
Oblong tablet, from white to off-white in colour, biconvex with the inscription “20” embossed in relief
on one side, score line on the other side, with a length of 13.5 ± 0.2 mm, a width of 5.5
± 0.2 mm and a thickness of 3.6 ± 0.5 mm. The tablet can be divided into equal doses.
40 mg
Round tablet, from white to off-white in colour, convex on one side with the inscription “40” in
relief on one side, score line on the other side, with a diameter of 12.1 ± 0.2 mm and a thickness
of 4.8 ± 0.6 mm. The tablet can be divided into equal doses.
60 mg
Oval tablet, from white to off-white in colour, biconvex with the inscription “60” in relief on one side,
score line on the other side, with a length of 17.5 ± 0.2 mm, a width of 9.0 ± 0.2 mm
and a thickness of 6.2 ± 0.8 mm. The tablet can be divided into equal doses.
Metadone Hydrochloride G.L. is available in opaque blisters of 10, 20, 30, 50 or 75 tablets or in
opaque tablet containers with child-resistant closure containing 50, 100 or 500 tablets
(Metadone Hydrochloride G.L. 5 mg / Metadone Hydrochloride G.L. 10 mg), 50 or 500 tablets (Metadone
Hydrochloride G.L. 20 mg tablets), 100 or 250 tablets (Metadone Hydrochloride G.L. 40 mg /
Metadone Hydrochloride G.L. 60 mg tablets)
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
G.L. Pharma GmbH, Schlossplatz 1, 8502 Lannach, Austria

This medicinal product is authorised in the Member States of the European Economic Area with the
following names:
Germany Methadon G.L. Pharma 5 mg Tabletten
Methadon G.L. Pharma 10 mg Tabletten
Methadon G.L. Pharma 20 mg Tabletten
Methadon G.L. Pharma 40 mg Tabletten
Methadon G.L. Pharma 60 mg Tabletten
Italy Metadone cloridrato G.L.
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The following information is only for physicians or healthcare professionals:
Substitution therapy with methadone must be initiated by a physician experienced in the treatment of
opioid/opiate dependence. Metadone Hydrochloride G.L. is not suitable for the acute withdrawal
syndrome. Depending on national requirements, such treatment should preferably be administered in
specialised centres for the treatment of opioid/opiate dependence. The recommendations of national
guidelines should also be taken into consideration.

Posology
Start of treatment
The dosage must be based on the withdrawal symptoms and must be adjusted on a case-by-case basis, depending on the
individual patient’s condition and their subjective experience of withdrawal. Methadone substitution therapy must be started when patients are otherwise stable and medically fit. After stabilisation of the dose, it is generally desirable to aim for the lowest effective maintenance dose, administered every 24 hours.
If the patient’s opioid tolerance is unknown or uncertain, the average starting dose is 20 mg of
methadone hydrochloride per day; in patients with long-term opioid dependence with a known level of
opioid tolerance, the dose is up to 40 mg of methadone hydrochloride.
The patient must be observed for 3-4 hours after taking the first dose. If the
patient shows signs of overdose, the patient must continue to be monitored at fifteen-minute intervals. If the patient becomes comatose, naloxone should be administered as a prolonged infusion.
In patients with low or unknown tolerance (e.g. after release from prison), the lowest initial dose should be selected as loss of opioid tolerance can occur within
a few days after stopping/reducing the use of the usual opioid.
The initial dose should be administered in the morning. In some cases, an additional dose may be necessary in the evening on the first day, depending on subjective and
objective effects, in order to prevent withdrawal symptoms. However, this dose must be administered under
strict medical supervision and may require hospitalisation of the patient.

Dose titration and maintenance therapy
If withdrawal symptoms develop, the dose must be increased gradually, in increments
of 5-10 mg of methadone hydrochloride. Patients must be monitored medically for
one week between dose increments. Dose adjustment is completed as soon as
withdrawal symptoms disappear. Individual limits of tolerability must be taken into
consideration during this process. The maintenance dose can reach up to 120 mg of
methadone hydrochloride per day and may in some cases be even higher.
A dose higher than 100-120 mg of methadone hydrochloride should only be administered in cases in
which this is justified, and in which the use of other drugs has been definitively ruled out. It is recommended to
test plasma levels of methadone.
The maximum recommended dose, which should be used rarely, is 150 mg/day of methadone
hydrochloride (unless national guidelines recommend otherwise). The reasons for this
limitation are the increased frequency of QT interval prolongation, torsades de pointes and cases of
cardiac arrest with higher dose ranges.

Route of administration
For oral use. Physicians must warn patients that the oral route is the only effective and safe route of administration
for this medicinal product.
The tablets can be taken whole with sufficient liquid or can
be easily dissolved in water, orange or apple juice.
The solution is intended for immediate consumption.
Care must be taken to ensure that the daily dose is taken under supervision and visual control according to
the legal basis of the respective national regulations or unless national guidelines recommend otherwise.
In the case of home therapy, the physician must ensure that:

• the risks to the patient and others resulting from home therapy are excluded as far as possible
• the patient uses the prescribed substitute exclusively as intended.

Home prescription is not acceptable if the examinations and investigations by the physician reveal that the
patient consumes substances that are dangerous when combined with substitution treatment, taking into
account the development of tolerance, failure to achieve a stable maintenance dose, or substance abuse by the patient.
Home therapy must be discontinued immediately if the substance is misused by the patient.