Package leaflet: Information for the patient

Omtisa 5 mg tablets, 10 mg tablets, 20 mg tablets, 40 mg tablets, 60 mg tablets

hydrochloride methadone
Equivalent medicinal product (for 5 mg, 10 mg, 40 mg pack sizes)
Please read 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 questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it could be harmful.
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Omtisa is and what it is used for
What you need to know before taking Omtisa
How to take Omtisa
Possible side effects
How to store Omtisa
Contents of the pack and other information

1. What Omtisa is and what it is used for

Omtisa contains the active substance methadone hydrochloride, which belongs to the group of opioids.
Omtisa is used for opioid substitution therapy in adults with opioid dependence, as part of an integrated treatment approach combining opioid replacement with medical, social, and psychosocial care.

2. What you should know before taking Omtisa

Do not take Omtisa if

you are allergic to methadone or any of the other ingredients of this medicine listed in section 6.
you are currently 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 have respiratory depression, especially if accompanied by cyanosis and excessive bronchial secretions.
you suffer from severe bronchial asthma or other obstructive airway diseases.
you are experiencing an asthma attack.
you suffer from alcoholism.
you have heart problems (prolongation of the QT interval).
you have intestinal obstruction due to paralysis of the intestinal muscles (paralytic ileus).
you suffer from severe hepatic impairment.
you have 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 hyperglycaemic hyperosmolar state).
you suffer from cor pulmonale (pulmonary heart disease).

During treatment with Omtisa, you must not take any narcotic antagonists or mixed agonist-antagonists (substances that may eliminate the effect of Omtisa, such as pentazocine and buprenorphine), except when these are part of treatment for overdose.
Warnings and precautions
Talk to your doctor or pharmacist before taking Omtisa.
Methadone should only be used in patients with opioid dependence, as even normal doses may lead to severe intoxication and even death in patients not tolerant to opioids.
In cases where this medicine is prescribed for home treatment, the doctor must ensure that all reasonable measures are taken to eliminate any risk of self-harm or harm to others that could arise from home prescribing, and to guarantee that the patient uses the prescribed medicine as directed. In case of misuse or abuse by the patient, the prescription service for home treatment must be immediately discontinued.
Extreme caution is advised when treating:

High-risk patients: Suicide attempts with opioids, especially combined with tricyclic antidepressants, alcohol, and other central nervous system (CNS) active substances, are part of the clinical picture of addiction. Individualized assessment and treatment planning, including possible hospitalization, should be considered for patients who show uncontrolled drug use and engage in high-risk behaviors despite adequate pharmacological treatment.
Acute abdominal conditions: Treatment with Omtisa may obscure the diagnosis or clinical course of acute abdominal conditions. Therefore, patients receiving substitution therapy who show signs of acute abdomen should be closely monitored.
If you are known or suspected to have QT interval prolongation or an electrolyte imbalance, particularly low blood potassium levels.
If you have a tumour of the adrenal glands (pheochromocytoma).

The concomitant use of Omtisa and sedative medicines such as benzodiazepines or related active substances increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and can be life-threatening. For this reason, concomitant use should only be considered when no other treatment options are possible.
However, if your doctor prescribes Omtisa together with sedative medicines, the dose and duration of concomitant treatment must be limited by the doctor.
Inform your doctor about all sedative medicines you are taking and carefully follow the doctor’s recommendations regarding dosage. Urine and/or blood testing is an integral part of methadone maintenance treatment to monitor the presence of psychoactive and narcotic substances. Your doctor will also monitor for possible alcohol abuse. It may be helpful to inform friends or relatives to be aware of the signs and symptoms listed above. Contact your doctor if you experience such symptoms. The doctor will adjust the dose appropriately.
Contact your doctor or pharmacist if you experience any of the following symptoms while taking Omtisa:
Weakness, fatigue, loss of appetite, nausea, vomiting, or low blood pressure. These may be symptoms indicating that your adrenal glands are producing insufficient cortisol hormone, and you may need to take a hormonal supplement.
Long-term use may cause decreased levels of sex hormones and increased levels of prolactin hormone. Contact your doctor if symptoms such as decreased libido, impotence, or absence of menstruation (amenorrhea) occur.
Omtisa should 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 tract disorder.
if you have a condition causing narrowing or inflammation of the intestine.
if you have a slow heart rate.
if you are also receiving certain medicines used to treat cardiac arrhythmias (Class I and III antiarrhythmics).
in individuals with pancreatitis.
in disorders requiring prevention of respiratory depression.
during pregnancy or breastfeeding (see section “Pregnancy, breastfeeding and fertility”).
if you have low blood pressure or reduced blood volume (hypotension due to hypovolemia).
in individuals with loss of consciousness or in coma.
when this medicine is used simultaneously with other substances that have a depressant effect on central nervous system functions (e.g., respiration).
if you are elderly (in elderly patients, methadone may cause confusion (see section “How to take Omtisa”).
in individuals with increased intracranial pressure.

Additionally, opioids may produce effects that may obscure the clinical course of patients with cranial trauma.
Tolerance and dependence
This medicine contains methadone, which is an opioid medicine. Repeated use of opioids may cause the drug to become less effective (you become accustomed, a phenomenon known as tolerance). Repeated use of Omtisa may also cause dependence and abuse, which can lead to potentially fatal overdose.
Dependence may cause you to lose control over how much medicine you take or how often you take it.
The risk of becoming dependent varies from person to person. You may have a higher risk of becoming dependent on Omtisa if:

you or someone in your family has ever abused or been dependent on alcohol, prescription medicines, or illegal drugs (“addiction”).
you smoke.
you have ever had mood disorders (depression, anxiety, or a personality disorder) or have been treated by a psychiatrist for other mental illnesses.

If you notice any of the following signs while taking Omtisa, it could be a sign that you have become dependent.

You need to take the medicine for longer than recommended by your doctor.
You need to take a higher dose than recommended.
You are using the medicine for reasons other than those for which it was prescribed, e.g., to “stay calm” or “help you sleep.”
You have made repeated unsuccessful attempts to stop or control the use of the medicine.
When you stop taking the medicine, you feel unwell and feel better when you resume taking it (“withdrawal effects”).

If you notice any of these signs, contact your doctor and discuss the best treatment approach for you, including when it is appropriate to stop and how to stop safely (see section 3 If you stop taking Omtisa).
Risk of abuse
Methadone is a mu-opioid agonist with a risk level similar to morphine. There is a risk of misuse and unauthorized diversion. The risk of opioid abuse is higher in patients with a personal or family history of substance abuse (including drug or alcohol abuse or dependence) or psychiatric disorders (e.g., major depression).
Tolerance and withdrawal
Abrupt discontinuation or interruption of treatment may lead to severe withdrawal symptoms, some of which may be life-threatening. Tolerance has been acquired during the disease and may be lost shortly after discontinuation, so that previously tolerated doses may trigger overdose if treatment is continued. This must be considered when treatment is resumed after interruption with the same dose previously used.
Hepatic and renal impairment
Caution should be exercised when using methadone in patients with mild to moderate renal or hepatic impairment.
Gastrointestinal motility
Opioids, including methadone, may cause troublesome constipation, which is particularly dangerous in patients with severe hepatic impairment, and measures to prevent constipation should be initiated early.
Respiratory system
The main risk associated with methadone use is respiratory depression. While severe, life-threatening, or even fatal respiratory depression may occur at any time in patients taking methadone, the risk is higher at the beginning of treatment or after a dose increase. The peak of respiratory depressant effect occurs later and persists longer than the peak analgesic effect, especially during the initial dosing period. Your doctor will monitor you closely.
To reduce the risk of respiratory depression, correct dosing and titration of methadone are essential. Overestimating the methadone dose in patients switching from another opioid to methadone may result in fatal overdose even after the first dose. Respiratory depression has been reported in association with methadone use even in the absence of misuse or abuse.
Omtisa should be used cautiously in patients with asthma, chronic obstructive pulmonary disease (COPD), or heart disease caused by lung disease (cor pulmonale), as well as in individuals with severely limited inspiratory reserve volume, pre-existing respiratory function impairment, low blood oxygen levels, or elevated blood carbon dioxide levels. In these patients, even normal therapeutic doses of narcotics may reduce respiratory rate, simultaneously increasing airway resistance 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 atopic phenomena.
Sleep-related breathing disorders
Omtisa 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, nighttime awakenings due to breathlessness, difficulty maintaining sleep, or excessive daytime sleepiness. If you or someone else observes these symptoms, contact your doctor, who may consider reducing the dose.
Cardiac arrhythmias:
There is some evidence from clinical studies that treatment with mu-receptor agonists may lead to QT interval prolongation and thus 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 initiation of treatment to determine and quantify the effect of methadone hydrochloride on the QT interval. Similarly, ECG monitoring should be performed before increasing the administered dose.
Reduction of sex hormones:
Long-term use may cause decreased levels of sex hormones and increased levels of prolactin hormone. Contact your doctor if symptoms such as decreased libido, impotence, or absence of menstruation (amenorrhea) occur.
Misuse
This medicine may be targeted by individuals who abuse prescription medicines and must be stored in a safe place to protect it from theft (see section 5). Do not give this medicine to anyone else. It could cause their death or otherwise harm them.
Omtisa is for oral use only. Misuse by intravenous injection may cause serious adverse effects that may be fatal, such as sepsis (a life-threatening condition occurring when the body’s response to infection causes injury to its own tissues and organs), phlebitis (inflammation of veins), or pulmonary embolism (blockage of an artery in the lungs due to material moving from other parts of the body via the bloodstream).
Omtisa contains water-insoluble excipients that form particles which may cause life-threatening events if administered by intravenous injection.
Abuse of drugs, alcohol, and medicines during treatment with methadone may cause life-threatening events and must be avoided.
Your doctor will regularly perform urine tests to confirm potential drug abuse. In case of abuse or misuse of the medicine (e.g., intravenous injection), your doctor will immediately discontinue treatment.
Methadone may also affect certain blood and urine tests. Inform your doctor if you are taking methadone before undergoing any tests.
Effects of misuse for doping purposes
For athletes: the use of Omtisa without therapeutic need constitutes doping and may result in a positive anti-doping test.
Misuse of this medicine for doping purposes may 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 scientific literature, there is evidence for the treatment of opioid dependence in adolescents starting from age 15.
Other medicines and Omtisa
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The daily dose of Omtisa required may change depending on other medicines you are taking. Inform your doctor if you notice signs of increased effect or withdrawal symptoms associated with Omtisa.
Do not take any of the following medicines if you are also taking Omtisa:

Monoamine oxidase inhibitors (medicines used to treat Parkinson’s disease or depression). You must stop taking these medicines at least 14 days before starting treatment with Omtisa. Otherwise, these medicines may cause depressant or stimulant effects on the respiratory and circulatory systems that may be life-threatening.
Pentazocine, buprenorphine, nalbuphine, butorphanol (medicines for the treatment of severe pain) and naloxone, naltrexone (opioid antagonists). Concomitant use with Omtisa may lead to withdrawal symptoms. Do not start taking buprenorphine until at least 24 hours after stopping Omtisa. The only time these medicines may be used concomitantly with Omtisa is when they are required to treat Omtisa overdose.

Inform your doctor if you are taking any of the following medicines, as they may affect how Omtisa works:

Strong painkillers, including opioids.
Centrally acting depressant medicines (e.g., sedatives, hypnotics, anaesthetics, certain antiemetics, phenothiazines, other tranquillisers, alcohol, and drugs).
Medicines used to treat epilepsy, known as barbiturates, whose active ingredients usually end in “-tal”, such as phenobarbital.
Medicines for general anaesthesia.
Certain medicines used to treat depression, called tricyclic antidepressants, and other antidepressants known as selective serotonin reuptake inhibitors (SSRIs).
Medicines used to treat hypertension (e.g., reserpine, clonidine, urapidil, prazosin).
Cimetidine (a medicine that helps reduce gastric acid production).
Medicines used to treat fungal infections (e.g., itraconazole, ketoconazole, voriconazole, fluconazole).
Class I and III antiarrhythmic medicines used to treat cardiac arrhythmias.
Oral contraceptives.
Carbamazepine and phenytoin (medicines used to treat epilepsy).
Medicines used to treat certain bacterial infections, 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 human immunodeficiency virus (HIV) replication (e.g., efavirenz, nevirapine, nelfinavir, ritonavir, amprenavir, didanosine, stavudine, 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 intestinal motility.
Metamizole, a medicine used to treat pain and fever.
Cannabidiol (a medicine used to treat seizures).
Gabapentin and pregabalin (medicines used to treat epilepsy, neuropathic pain, or anxiety) may increase the risk of opioid overdose, respiratory depression (difficulty breathing), and may be potentially fatal.

The risk of side effects increases if methadone is used concomitantly 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
exaggerated reflexes, impaired coordination, muscle rigidity
gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea).

Other possible interactions
Desipramine (a type of antidepressant)
Concomitant use with methadone has been observed to lead to elevated blood levels of desipramine.
Anticholinergics (a type of medicine that suppresses the effect of acetylcholine)
When used concomitantly with opioids, anticholinergics or other medicines with anticholinergic activity may increase the risk of urinary retention and/or severe constipation, which may lead to intestinal obstruction. When methadone and anticholinergics are used simultaneously, patients should be monitored for signs of urinary retention and reduced gastric motility.
Potentially arrhythmogenic medicines
Extreme caution is required when any medicine known to carry a risk of QT interval prolongation is prescribed concomitantly with methadone.
Interactions may occur with concomitant use of methadone and potentially arrhythmogenic medicines, such as Class I and III antiarrhythmics, certain neuroleptics, tricyclic antidepressants, and calcium channel blockers.
Similarly, caution is recommended when prescribing methadone concomitantly with medicines that can induce electrolyte imbalances leading to QT interval prolongation (hypomagnesemia, hypokalemia). This includes diuretics, laxatives, and, in rare cases, mineralocorticoid hormones.
Cannabis may delay methadone degradation and lead to increased plasma concentrations of methadone. This may cause symptoms of intoxication and respiratory depression.
The occurrence of these interactions depends on the individual patient's condition, opioid tolerance, and overall health. Although not all possible interactions with methadone have been listed, these are theoretically possible and cannot be excluded.
Omtisa with food, drinks, and alcohol
You must avoid consuming alcohol during treatment with Omtisa, as there is a risk of unexpected and mutually enhancing effects that could lead to severe or even fatal intoxication.
Grapefruit juice may delay the breakdown of Omtisa and is not recommended during treatment with Omtisa.
Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.
Pregnancy
Omtisa may be used during pregnancy after careful evaluation of the risk-benefit ratio by a doctor, preferably under supervision in a specialized medical centre.
Dose increases up to twice daily may be necessary to maintain treatment efficacy due to metabolic changes during pregnancy.
Chronic use during pregnancy may lead to methadone dependence and addiction in the fetus, as well as withdrawal symptoms in the newborn after birth, often requiring hospital treatment.
Withdrawal syndrome may not manifest in the newborn for several days after birth. Therefore, in addition to initial monitoring for respiratory depression, newborns should be monitored for prolonged signs and symptoms of withdrawal.
Discontinuation of the medicine in the newborn must be performed in an appropriate paediatric intensive care unit, as methadone treatment may lead to dependence and addiction in the fetus, as well as withdrawal symptoms in the newborn requiring treatment.
Breastfeeding
Talk to your doctor if you are breastfeeding or may breastfeed while taking methadone, as this may affect your baby. Monitor your baby for unusual signs and symptoms such as increased drowsiness (more than usual), breathing difficulties, or weakness. Contact your doctor immediately if you notice any of these symptoms.
Fertility
It has been reported that methadone may cause sexual dysfunction in male patients undergoing maintenance treatment.
Driving and using machines
Omtisa impairs the ability to drive vehicles and operate machinery because 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 when co-administered with substances that impair cognitive function.
Your doctor will decide whether you are allowed to drive vehicles, operate machinery, or perform other hazardous activities. He will take into account your reaction time and your dose of Omtisa.
Omtisa 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 Omtisa

Methadone maintenance therapy must be prescribed by a physician experienced in the treatment of opioid dependence. It is preferable that this treatment be administered in specialized centers for the treatment of opioid dependence. The physician will also take into account national recommendations.
Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Your doctor will determine the best dose for you. Your doctor may decide to adjust the dose during treatment—even if you have not requested it.
Use the medicine once daily, at the dose prescribed by your doctor.

Methadone withdrawal
If the prescribed dose of methadone is too low, withdrawal symptoms may develop during the 24-hour dosing interval (nasal congestion, abdominal pain [abdominal symptoms], diarrhea, muscle pain, anxiety). Treating physicians should be aware that dose adjustments may be necessary if patients report withdrawal symptoms.
Inform your doctor if your craving for drugs is not fully suppressed. An adequate dose will prevent the occurrence of withdrawal symptoms. However, an excessively high dose may lead to sedation or drowsiness.
The dose of Omtisa must be titrated according to the appearance of withdrawal symptoms and adjusted based on 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
To prevent overdose, the doctor may reduce the dose.

Patients with impaired renal and/or hepatic function
If liver or kidney function is impaired, the doctor may reduce the dose. If you have stable chronic liver disease, dose reduction is not necessary.

Pregnant patients
An increase in dosing up to twice daily may be necessary to maintain treatment efficacy due to metabolic changes during pregnancy (see section “Pregnancy and breastfeeding”). Your doctor will prescribe the appropriate dose.

Patients receiving antiretroviral therapy
When starting or stopping treatment with antiretroviral medicines (medicines for the treatment of HIV or hepatitis C), potential withdrawal or overdose symptoms should be considered, as antiretroviral agents may increase or decrease methadone blood levels.

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 Omtisa is not recommended in individuals under 18 years of age.
There is experience with opioid dependence treatment in adolescents from 15 years of age onwards.

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

Duration of treatment
The duration of treatment will depend on the individual characteristics and clinical evolution of each case, and will be determined by the physician according to substitution treatment criteria. There are no limitations regarding the maximum duration of treatment.
Discontinuation of Omtisa must be gradual, with tapering of the dose over several weeks or months. Any dose reduction must be guided by the patient's subjective experience of symptoms.

If you take more Omtisa than you should
This may cause dangerous poisoning, particularly in non-tolerant individuals (especially children), even at doses lower than those normally used in substitution treatment. This may occur starting from a dose of approximately 1 mg in children up to 5 years of age, about 3 mg in older children, and about 20 mg in non-tolerant adults.
It may cause low blood sugar. A brain disorder (known as toxic leukoencephalopathy).
Contact a doctor immediately. An overdose of Omtisa can be life-threatening.
Take this leaflet with you and show it to the doctor.

If you forget to take Omtisa
If you have taken less than the prescribed amount of Omtisa and have developed withdrawal symptoms, take the missed dose as soon as you remember. Do not under any circumstances increase the daily dose established for that particular day. Inform your doctor if you do not experience withdrawal symptoms after taking a reduced amount of the medicine, so that your daily dose can be adjusted.

If you stop taking Omtisa
Sudden discontinuation may lead to severe withdrawal symptoms, some of which may be life-threatening. Therefore, do not stop or discontinue treatment prematurely. Long-term treatment must be discontinued gradually.

If you have further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.

Symptoms associated with opioid withdrawal are common at the beginning 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 aches, feeling faint, excessive sweating, excessive tearing, nausea, restlessness, abdominal cramps and chills.

Other possible side effects of Omtisa:

Side effects marked with a (#) appear to be more common in outpatients and in patients 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 gynaecomastia and reduced fertility

Common: may affect up to 1 in 10 people:

Vertigo
Confusion#
Lethargy
Clouded 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
Reduction in blood pressure
Respiratory depression
Pulmonary oedema
Biliary dyskinesia

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

Hallucinations
ECG abnormalities, including QT interval prolongation and torsades de pointes, usually in patients with risk factors or receiving high-dose methadone
Syncope

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

Disorientation
Seizures
Biliary tract spasm
Rash
Urticaria
Renal tract spasm, antidiuretic effect
Weakness
Oedema
Low blood sugar levels
A reversible decrease in platelet count, which may cause bleeding and bruising (thrombocytopenia), has been reported in opioid-dependent patients with chronic hepatitis.
Low potassium levels, low magnesium levels
Hearing loss
You may become dependent on Omtisa (for further information, see section 2 Warnings and precautions)
Sleep apnoea (pauses in breathing during sleep)

Withdrawal syndrome (abstinence): chronic use of opioid analgesics may lead to the development of physical dependence. Abrupt discontinuation of opioids or administration of opioid antagonists may trigger a withdrawal syndrome.

The following withdrawal symptoms may occur after stopping opioid use: muscle aches, diarrhoea, goosebumps, loss of appetite, nervousness or restlessness, runny nose, sneezing, chills or tremors, abdominal cramps, nausea, sleep disturbances, unusual sweating and yawning, weakness, palpitations and unexplained fever. With appropriate dose adjustments and gradual discontinuation, these symptoms are usually mild.

Important
Once the maintenance dose has been reached, side effects gradually decrease in frequency and severity over several weeks. Constipation and increased sweating, however, often persist permanently but can be alleviated with appropriate measures.

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

5. How to store Omtisa

Keep this medicine out of the sight and reach of children. Store this medicine in a safe place where others cannot access it. It may cause serious harm and could be fatal to people for whom it has not been prescribed.
Do not use this medicine after the expiry date stated on the blister/label and on the carton after "Exp". The expiry date refers to the last day of that month.
Store in the original packaging to protect the medicine from light.
Tablet container:
After first opening: do not use beyond 6 months.
Solutions of dissolved tablets are stable for up to 3 hours.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package Contents and Other Information

What Omtisa Contains

The active substance is methadone hydrochloride.
Omtisa 5 mg tablets: 1 tablet contains 5 mg of methadone hydrochloride, equivalent to 4.473 mg of methadone.
Omtisa 10 mg tablets: 1 tablet contains 10 mg of methadone hydrochloride, equivalent to 8.947 mg of methadone.
Omtisa 20 mg tablets: 1 tablet contains 20 mg of methadone hydrochloride, equivalent to 17.893 mg of methadone.
Omtisa 40 mg tablets: 1 tablet contains 40 mg of methadone hydrochloride, equivalent to 35.786 mg of methadone.
Omtisa 60 mg tablets: 1 tablet contains 60 mg of methadone hydrochloride, equivalent to 53.679 mg of methadone.
The other components are: microcrystalline cellulose; pregelatinized starch (maize); lactose monohydrate, sucrose; magnesium stearate.

Description of the Appearance of Omtisa and Contents of the Package
Omtisa is available as 5 mg, 10 mg, 20 mg, 40 mg, and 60 mg tablets. The tablets are described below.

5 mg
Round tablet, white to off-white in colour, convex on one side only, with the number “5” engraved in relief on one side and a 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, white to off-white in colour, convex on one side only, with the number “10” engraved in relief on one side and a 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, white to off-white in colour, biconvex, with the number “20” engraved in relief on one side and a 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, white to off-white in colour, convex on one side only, with the number “40” engraved in relief on one side and a 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, white to off-white in colour, biconvex, with the number “60” engraved in relief on one side and a 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.

Omtisa is available in opaque blisters containing 10, 20, 30, 50 or 75 tablets, or in opaque child-resistant tablet containers containing 50, 100 or 500 tablets (Omtisa 5 mg / Omtisa 10 mg tablets), 50 or 500 tablets (Omtisa 20 mg tablets), or 100 or 250 tablets (Omtisa 40 mg / Omtisa 60 mg tablets).
Not all pack sizes may be marketed.

Marketing Authorization Holder
G.L. Pharma GmbH, Schlossplatz 1, 8502 Lannach, Austria.

Manufacturer
G.L. Pharma GmbH
Industriestraße 1
8502 Lannach, Austria

Sales Licensee:
G.L. Pharma Italy S.r.l., [email protected].

This medicinal product is authorized in the European Economic Area Member States under 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: Omtisa
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The following information is intended exclusively for physicians or healthcare professionals:
Methadone substitution therapy must be initiated by a physician experienced in the treatment of opioid dependence. Omtisa is not suitable for the treatment of acute withdrawal syndrome. Depending on national requirements, it is preferable that such treatment be administered in specialized centres for the treatment of opioid dependence. National treatment guidelines should also be taken into account.

Dosage
Initiation of Treatment
Dosage should be based on withdrawal symptoms and must be individually adjusted according to the patient's specific situation and subjective experience of withdrawal. Methadone substitution therapy should be initiated only when patients are otherwise medically stable and suitable. After dose stabilization, it is generally advisable to aim for the lowest effective maintenance dose, administered every 24 hours.

If the patient's opioid tolerance is unknown or uncertain, the average initial dose is 20 mg of methadone hydrochloride per day. In patients with long-term opioid dependence and a known level of opioid tolerance, the initial dose may be up to 40 mg of methadone hydrochloride.

The patient must be observed for 3–4 hours after taking the first dose. If signs of overdose occur, monitoring should continue at 15-minute intervals. If the patient lapses into coma, 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 may occur within a few days after cessation or reduction of usual opioid use.

The initial dose should be administered in the morning. In some cases, an additional dose may be necessary on the evening of the first day, depending on subjective and objective effects, to prevent withdrawal symptoms. However, this additional dose must be administered under strict medical supervision and may require hospitalization.

Dose Titration and Maintenance Therapy
If withdrawal symptoms occur, the dose should be gradually increased in increments of 5–10 mg of methadone hydrochloride. Patients should be medically monitored for one week between dose increases. Dose adjustment is considered complete once withdrawal symptoms have disappeared. Individual tolerability limits must be taken into account during this process. The maintenance dose may reach up to 120 mg of methadone hydrochloride per day, and in some cases may be even higher.

A dose exceeding 100–120 mg of methadone hydrochloride should be administered only when clearly justified and only after concomitant use of other drugs has been definitively ruled out. Methadone plasma level testing is recommended.

The maximum recommended dose, which should be used only rarely, is 150 mg/day of methadone hydrochloride (unless national guidelines recommend otherwise). The rationale for this limitation is the increased frequency of QT interval prolongation, torsades de pointes, and cases of cardiac arrest associated with higher dose ranges.

Method of Administration
For oral use. Physicians must inform patients that the oral route is the only effective and safe route of administration for this medicinal product.

The tablets may be taken whole with sufficient water, or may be easily dissolved in water, orange juice, or apple juice.

The solution is intended for immediate consumption.

It must be ensured that the daily dose is taken under visual supervision and control, in accordance with the legal basis of the respective national regulations, unless national guidelines recommend otherwise.

In the case of home-based therapy, the physician must ensure that:

risks to the patient and others arising from home-based therapy are minimized as much as possible,
the patient uses the prescribed substitute substance strictly as intended.

Home dispensing is not acceptable if medical examinations and assessments reveal that the patient is using substances that are dangerous when combined with substitution therapy, taking into account the development of tolerance, failure to achieve a stable maintenance dose, or substance abuse by the patient.

Home-based therapy must be discontinued immediately if the substance is misused by the patient.