Package leaflet: Information for the patient

Agovadin 2.5 mg tablets, 5 mg tablets, 10 mg tablets, 20 mg tablets, 30 mg tablets

levomethadone hydrochloride
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 questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it could be harmful.
If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Agovadin is and what it is used for

Agovadin is a medicine belonging to the opioid group. The active substance is levomethadone hydrochloride.
Agovadin is used for opioid substitution therapy in adults.
Substitution therapy, also called opioid replacement therapy, is carried out under intensive medical, social, and psychosocial support.

2. What you need to know before taking Agovadin

Do not take Agovadin if

you are allergic to levomethadone or to any of the other ingredients of this medicine listed in section 6.
you are currently using monoamine oxidase inhibitors (medicines for Parkinson’s disease or depression), or you have discontinued them less than two weeks ago.
you are taking medicines that may reverse or interfere with the action of Agovadin, such as pentazocine and buprenorphine: however, these medicines may be used to treat an overdose of Agovadin.
you suffer from respiratory depression.
you have obstructive respiratory diseases.
you are dependent on non-opioid substances.

Further information is available in section 2 “Other medicines and Agovadin”.
Warnings and precautions
Talk to your doctor or pharmacist before taking Agovadin if any of the following apply to you.
Your doctor will only initiate treatment if it is essential. This is particularly true for:

pregnancy and breastfeeding.
disorders of consciousness.
concomitant use of other medicines that inhibit certain brain functions (e.g., control of respiration) (see also “Other medicines and Agovadin” and “Agovadin with beverages and alcohol”).
concomitant use of Agovadin and sedative medicines such as benzodiazepines or related active substances, which increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. For this reason, concomitant use should only be considered when no other treatment options are possible. However, if your doctor prescribes Agovadin 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 follow the doctor’s dose recommendations carefully. 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.
diseases in which respiratory impairment must be avoided, such as
- asthma
- lung diseases with chronically narrowed airways
- heart failure due to severe lung disease
- moderate to severe respiratory impairment and labored breathing
- low levels of oxygen in the blood
- increased levels of carbon dioxide in the blood. With these conditions, even at usual doses of Agovadin, breathing may become more difficult, up to respiratory arrest. In particular, if you are prone to allergies, existing asthma may worsen, or skin rashes and changes in blood count may occur.
increased intracranial pressure: this may be intensified.
low blood pressure in case of dehydration.
enlarged prostate with incomplete emptying of the urinary bladder.
inflammation of the pancreas.
diseases of the bile duct.
intestinal diseases with narrowing and inflammation of the intestine.
pheochromocytoma, a tumor of the adrenal gland that produces hormones.
underactive thyroid.
risk of suicide: Suicide attempts with opioids, particularly in relation to certain antidepressant medicines (tricyclic antidepressants), alcohol, and other substances such as benzodiazepines, are part of the clinical picture of substance dependence. If you are unable to stop taking such medicines, consult your doctor or a specialized counseling center.
severe diseases of the abdominal cavity: Treatment with Agovadin may mask even severe abdominal diseases. At the first signs of an abdominal disease, you must undergo regular medical monitoring until the exact cause is clarified.
patients with cardiac arrhythmia or prolonged ventricular activity, known as QT interval prolongation, or disturbances in mineral balance, especially due to low levels of potassium in the blood. Some opioids, such as levomethadone, may affect cardiac conduction (prolongation of the QT interval on ECG). This may lead to a dangerous heart rhythm disorder (excessively rapid, irregular heartbeat, “Torsades de Pointes”). If you experience irregular heartbeat or fainting, inform your doctor immediately.
treatment with antiarrhythmic medicines of classes I and III.
slow heartbeat.

Tolerance and dependence
This medicine contains levomethadone, which is an opioid medicine. Repeated use of opioids
may cause the medicine to become less effective (you become accustomed, a phenomenon known as tolerance).
Repeated use of Agovadin may also cause dependence and abuse, which may lead to a
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 Agovadin if:

you or someone in your family has ever abused or been dependent on alcohol, prescription medicines, or illegal drugs (“dependence”).
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 Agovadin, it may 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 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, consult 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 treatment with Agovadin).
Contact your doctor or pharmacist if you experience any of the following symptoms while taking
Agovadin:

Weakness, fatigue, loss of appetite, nausea, vomiting, or low blood pressure. This may be a symptom that your adrenal glands are producing too little cortisol hormone, and you may need to take a hormonal supplement.

Sleep-related breathing disorders
Agovadin may cause sleep-related breathing disorders such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). Symptoms may include breathing pauses during sleep, nighttime awakenings due to labored breathing, difficulty maintaining sleep, or excessive daytime sleepiness. If you or someone else observes these symptoms, contact your doctor, who may consider reducing the dose.
Additional information
Avoid drug, alcohol, and medicine abuse during treatment, as this may lead to potentially fatal episodes. Your doctor may perform urine tests to detect possible substance abuse.
Do not give this medicine to anyone else. It may cause their death or other harm.
Agovadin is for oral use only. Improper use 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 traveling from other parts of the body via the bloodstream).
Agovadin contains excipients insoluble in water that form particles which may cause life-threatening events if administered by intravenous injection.
Long-term use of opioids may cause a decrease in sex hormone levels and an increase in prolactin hormone levels. Contact your doctor if symptoms such as decreased libido, impotence, or absence of menstruation (amenorrhea) occur.
Doping
For individuals engaged in sports: the use of Agovadin without therapeutic need constitutes doping and may result in a positive anti-doping test.
The use of Agovadin as a doping agent may be harmful to health.
Other medicines and Agovadin
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
The daily dose of Agovadin required may vary due to the use of other medicines. Consult your doctor if you notice signs of increased effect or withdrawal symptoms from Agovadin.
For further information on these two aspects, see the third-to-last section of section 3 and the beginning of section 4.
The risk of adverse effects increases if you use levomethadone 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 state (e.g., agitation, hallucinations, coma).
Rapid heartbeat, unstable blood pressure, fever.
Exaggerated reflexes, impaired coordination, muscle stiffness.
Gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

The following medicines must not be taken concomitantly with Agovadin:

monoamine oxidase inhibitors: medicines for depression or Parkinson’s disease. These medicines must be discontinued at least 14 days before starting treatment with Agovadin. Otherwise, potentially fatal depressive or stimulating effects on respiration and circulation may occur.
pentazocine, buprenorphine: medicines for severe pain. Withdrawal symptoms may occur when used concomitantly with Agovadin. Buprenorphine must not be used for at least 20 hours after discontinuation of Agovadin treatment. Exceptionally, these medicines may be used concomitantly with Agovadin if used to treat an overdose of Agovadin.

Inform your doctor if you are taking any of the following substances, as they may affect the effects
of Agovadin:

other medicines that suppress certain brain functions (e.g., control of respiration), such as:
o strong painkillers, including opioids;
o certain psychiatric medicines whose active ingredients usually end in “-azine,” such as phenothiazine;
o sedatives and sleeping pills, the so-called benzodiazepines whose active ingredients usually end in “-zepam,” such as diazepam, flunitrazepam, and other sleeping pills;
o medicines for epilepsy, the so-called barbiturates, whose active ingredients usually end in “-tal,” such as phenobarbital;
o narcotics; or
o certain antidepressants, the so-called tricyclic antidepressants (e.g., trimipramine and doxepine). When used concomitantly, they may have a mutually enhancing effect on brain function, leading, for example, to drowsiness or shallow, weak breathing (see “Warnings and precautions”). Please follow your doctor’s dose recommendations exactly.
certain antidepressants, the selective serotonin reuptake inhibitors (“SSRIs,” e.g., sertraline, fluvoxamine, fluoxetine, and paroxetine);
medicines for high blood pressure (e.g., reserpine, clonidine, urapidil, and prazosin);
cimetidine, a medicine to reduce gastric acid production;
antifungal medicines (e.g., itraconazole, ketoconazole, voriconazole, and fluconazole);
medicines for cardiac arrhythmias (e.g., class I and III such as amiodarone);
oral contraceptives;
carbamazepine and phenytoin, medicines for epilepsy;
medicines for certain bacterial diseases, such as rifampicin, the so-called macrolide antibiotics, ciprofloxacin, fusidic acid;
St. John’s wort preparations, Cannabis;
spironolactone, a diuretic (dehydrating medicine);
medicines that inhibit the replication of human immunodeficiency virus (e.g., efavirenz, nevirapine, nelfinavir, ritonavir, amprenavir, didanosine, stavudine, and zidovudine);
medicines that may reduce the effect of opioids (such as naloxone, naltrexone, nalmefene, pentazocine, nalbuphine, butorphanol, buprenorphine);
substances that may affect the ECG;
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.
Agovadin with beverages and alcohol
Do not drink alcohol or grapefruit juice during treatment with Agovadin. Alcohol may unpredictably increase its effect and cause severe poisoning with symptoms such as drowsiness, shallow and weak breathing, and coma, possibly resulting in death.
Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, are planning pregnancy, or are breastfeeding, consult your doctor before taking this medicine.
Pregnancy
Agovadin may be used during pregnancy after careful assessment of the risk-benefit ratio by a doctor, preferably under supervision in a specialized medical center.
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 withdrawal symptoms in the newborn after birth, often requiring hospital treatment.
Breastfeeding
Consult your doctor if you are breastfeeding or may breastfeed while taking levomethadone, as this may affect your baby. Monitor your baby for unusual signs and symptoms such as increased sleepiness (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
Agovadin 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 if substances that impair cognitive function are co-administered.
Your doctor will decide whether you are allowed to drive vehicles, operate machinery, or perform other hazardous activities. He or she will take into account your reaction time and your dose of Agovadin.
Agovadin contains lactose and sucrose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him or her before taking this medicine.

3. How to take Agovadin

Take this medicine exactly as directed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
The dose is individually adjusted by your doctor and depends on your response and your
specific condition. Your doctor will also consider national guidelines.
If not otherwise prescribed by your doctor, the usual dose is:

Initial dose On the morning of the first day, you will receive a dose of 15 to 20 mg of levomethadone hydrochloride. Depending on the effect of this initial dose, you may receive an additional dose of 10 to 25 mg of levomethadone hydrochloride on the evening of the first day.
Daily dose Within 1 to 6 days, the initial dose will be adjusted to a daily dose taken once in the morning. This adjustment occurs in increments of 5 mg of levomethadone hydrochloride per day. If withdrawal symptoms occur, your doctor may increase the daily dose by 5 to 10 mg of levomethadone hydrochloride. The daily dose may reach up to 60 mg of levomethadone hydrochloride. In justified cases, the daily dose may be considerably higher. The lowest possible maintenance dose should always be aimed for.
Discontinuation of treatment Treatment discontinuation should occur over several weeks or months. The dose should be reduced in the smallest possible steps. If necessary, a levomethadone solution may be used to taper the therapy.

Elderly patients and patients with impaired renal and/or hepatic function
Your doctor may reduce the dose.
Pregnant patients
Your doctor may adjust the dose according to the effectiveness of this medicine, as metabolism may
change during pregnancy.
Children and adolescents under 18 years of age
Due to insufficient data on the safety and efficacy of Agovadin in children and
adolescents, administration is not recommended.

Method of administration
Agovadin is for oral use.
The oral route is the only effective and safe route of administration for this medicine.
Take the prescribed dose immediately after receiving it with a glass of water.
Alternatively, the tablets can be easily dissolved in water, orange juice, or apple juice. The
solution should be taken immediately.
The tablets must be removed from the blister pack only immediately before use. Tablets
must not be removed prematurely from the packaging for later administration.

Duration of treatment
Your doctor will determine the duration of treatment. This depends on the course of therapy and your
individual response and is therefore not time-limited. However, the goal of treatment is complete
abstinence from drug use.

If you take more Agovadin than you should
Contact your nearest doctor immediately, even in case of suspected overdose!
Please keep this leaflet for immediate reference by the doctor. The doctor
will immediately initiate emergency medical measures.
Signs of overdose include:

"feeling strange"
poor concentration
drowsiness
dizziness when standing up
clammy skin
reduced breathing with lips that may turn blue
slowed heart rate and low blood pressure
pinpoint pupils
relaxation of skeletal muscles
extreme drowsiness, ranging from altered consciousness to coma
a brain disorder (known as toxic leukoencephalopathy)

It may cause a drop in blood sugar levels.
Significant poisoning can lead to respiratory arrest, circulatory failure, cardiac arrest, and death.
Taking Agovadin by individuals not accustomed to it may result in death due to
respiratory failure. This applies to:

children up to 5 years of age with a dose of 0.5 mg of levomethadone hydrochloride;
older children with a dose of 1.5 mg of levomethadone hydrochloride;
opioid-naïve adults with a dose of 10 mg of levomethadone hydrochloride.

Never give Agovadin to other people!
If you forget to take Agovadin
Repeat the dose on the same day only if you have taken less Agovadin than prescribed and
withdrawal symptoms occur. Under no circumstances should you increase the daily dose! Inform your doctor if
you do not experience withdrawal symptoms after taking a reduced amount of Agovadin, so that
your daily dose can be adjusted.
If you stop taking Agovadin
Do not stop abruptly or discontinue treatment after prolonged use. Sudden discontinuation
of Agovadin may lead to withdrawal symptoms ranging from severe to life-threatening.
Long-term treatment should be discontinued gradually.
Discuss any desired changes in treatment with your doctor.
If you have further questions about the use of this medicine, please consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following side effects occur commonly at the beginning of treatment (may affect up to 1 in 10 people):

anxiety
loss of appetite
involuntary muscle contractions
depression
intestinal spasms, abdominal cramps
nausea, vomiting
diarrhoea
fever, alternating with chills and hot flushes
yawning
goosebumps
weight loss
rapid heartbeat
runny nose, sneezing
dilated pupils
irritability
drowsiness
physical pain
fainting
excessive sweating
increased tear production
restlessness and tremor

Other possible side effects occur with the following frequencies:
From common (may affect up to 1 in 10 people) to uncommon (may affect up to 1 in 100 people):

shallow and weak breathing
nausea, vomiting, constipation, biliary cramp
palpitations, slow heartbeat
confusion, disorientation
drowsiness, dampness
urticaria and other skin rashes, itching
decreased sexual desire and/or impotence
reduced urination, bladder emptying disorders
fluid retention in tissues
insomnia, restlessness
loss of appetite, fatigue, weakness
feeling high and feeling low
profuse sweating, dry mouth
visual disturbances
headache
weight gain

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

skin flushing, including sensation of warmth
respiratory arrest
cardiac arrest
drop in blood pressure upon standing
circulatory dysfunction
short-term fainting due to irregular heartbeat
shock
haemorrhage

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

low blood sugar levels
you may become dependent on Agovadin (for further information see section 2 Warnings and precautions)
sleep apnoea (breathing pauses during sleep)

Note
Once the regular daily dose has been reached, side effects may decrease within a few weeks. Constipation and increased sweating often persist and can be relieved with appropriate measures. Please consult your doctor about this.

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
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Agovadin

Keep this medicine out of sight and reach of children. Store this medicine in a safe place, where other people cannot access it. It may cause serious harm or be fatal to individuals for whom it has not been prescribed.
Do not use this medicine after the expiry date stated on the blister, label, and 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 for longer than 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 Agovadin contains

The active substance is levomethadone hydrochloride.

Agovadin 2.5 mg tablets
1 tablet contains 2.5 mg of levomethadone hydrochloride, equivalent to 2.237 mg of
levomethadone.
Agovadin 5 mg tablets
1 tablet contains 5 mg of levomethadone hydrochloride, equivalent to 4.473 mg of levomethadone.
Agovadin 10 mg tablets
1 tablet contains 10 mg of levomethadone hydrochloride, equivalent to 8.947 mg of levomethadone.
Agovadin 20 mg tablets
1 tablet contains 20 mg of levomethadone hydrochloride, equivalent to 17.893 mg of
levomethadone.
Agovadin 30 mg tablets
1 tablet contains 30 mg of levomethadone hydrochloride, equivalent to 26.840 mg of
levomethadone.

The other components are: microcrystalline cellulose; pregelatinized maize starch; lactose monohydrate; sucrose; magnesium stearate.

Description of the appearance of Agovadin and contents of the pack
Agovadin is available as 2.5 mg, 5 mg, 10 mg, 20 mg, and 30 mg tablets. The tablets are described below.
2.5 mg:
Round tablet, white to off-white in colour, convex on one side with the inscription “L2” in relief 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.
5 mg:
Round tablet, white to off-white in colour, convex on one side with the inscription “L5” 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.
10 mg:
Oblong tablet, white to off-white in colour, biconvex with the inscription “L10” 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.
20 mg:
Round tablet, white to off-white in colour, convex on one side with the inscription “L20” 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.
30 mg:
Oval tablet, white to off-white in colour, biconvex with the inscription “L30” 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.
The tablets are packaged in opaque blisters or in opaque white tablet containers made of HDPE, closed with a child-resistant and tamper-proof PP screw cap.
Agovadin 2.5 mg tablets / 5 mg tablets:
Agovadin is available in packs of 7, 28, 30, 50, 56 and 98 tablets in PVC/PVdC//Al blisters and in packs of 50, 100 and 500 tablets in HDPE containers.
Agovadin 10 mg tablets:
Agovadin is available in packs of 7, 28, 30, 50, 56 and 98 tablets in PVC/PVdC//Al blisters and in packs of 50 and 500 tablets in HDPE containers.
Agovadin 20 mg tablets / 30 mg tablets:
Agovadin is available in packs of 7, 28, 30, 50, 56 and 98 tablets in PVC/PVdC//Al blisters and in packs of 100 and 250 tablets in HDPE containers.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
G.L. Pharma GmbH, Schlossplatz 1, 8502 Lannach, Austria
Marketing Authorization Holder in Italy:
G.L. Pharma Italy S.r.l., [email protected]

This medicinal product is authorized in the European Economic Area countries under the following names:
Germany Levomethadon G.L. Pharma 2.5 mg Tabletten
Levomethadon G.L. Pharma 5 mg Tabletten
Levomethadon G.L. Pharma 10 mg Tabletten
Levomethadon G.L. Pharma 20 mg Tabletten
Levomethadon G.L. Pharma 30 mg Tabletten
Italy Agovadin
<--------------------------------------------------------------------------------------------------------------------------->
The following information is intended exclusively for physicians or healthcare professionals:
Levomethadone replacement therapy must be initiated by a physician experienced in the treatment of opioid dependence. Agovadin is not suitable for the treatment of acute withdrawal syndrome. Depending on national requirements, it is preferable that this treatment be administered in specialized centres for the treatment of opioid dependence. National guideline recommendations should also be taken into account.

Dosage
Levomethadone is approximately twice as potent as racemic methadone.
The dosage must be based on withdrawal symptoms and adjusted on an individual basis according to the patient's specific situation and subjective experience of withdrawal. Levomethadone replacement therapy should be initiated when patients are otherwise stable and medically suitable. After dose stabilization, it is generally advisable to aim for the lowest effective maintenance dose, administered every 24 hours.
To avoid overdose, 15–20 mg of levomethadone hydrochloride should be taken on the first morning. Depending on subjective and objective effects, an additional 10–25 mg of levomethadone hydrochloride may be administered in the evening of the first day. In patients with low or unknown tolerance (e.g. after release from prison), the initial dose must not exceed 15 mg of levomethadone hydrochloride.
After 1–6 days, the daily dose should be changed to a single morning dose. The transition to a single morning dose is usually achieved by increments of 5 mg of levomethadone hydrochloride.
If efficacy is insufficient (withdrawal symptoms occur), the treating physician may increase the dose by 5 to 10 mg of levomethadone hydrochloride per day.
A dose exceeding 50–60 mg of levomethadone hydrochloride may be administered only in exceptional cases of proven necessity, after excluding the misuse of psychoactive substances for medical reasons.

Method of administration
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.

Precautions
In general, it is recommended to perform an ECG before starting therapy, after two weeks of treatment, before any dose increase, and as an annual check-up, in order to monitor cardiac function for signs of cardiac arrhythmia.

Overdose
Even doses lower than those normally used as part of substitution treatment may cause life-threatening poisoning, especially in non-tolerant individuals (particularly children). This may occur in children up to 5 years of age starting from a dose of approximately 0.5 mg of levomethadone, in older children from approximately 1.5 mg of levomethadone, and in non-tolerant adults from approximately 10 mg of levomethadone.
Dose reduction is recommended if patients show signs and symptoms of excessive levomethadone activity, characterized by discomfort such as “feeling strange”, poor concentration, drowsiness, and orthostatic dizziness.
Furthermore, overdose is characterized by respiratory depression (Cheyne-Stokes respiration, cyanosis), extreme drowsiness progressing to stupor or coma, miosis, skeletal muscle relaxation, clammy skin, and sometimes bradycardia and hypotension. Severe intoxication may lead to respiratory arrest, circulatory collapse, cardiac arrest, and death. Hypoglycaemia has been reported.
Emergency measures or, if necessary, intensive care interventions (e.g. intubation and ventilation) must be initiated immediately. Specific opioid antagonists (e.g. naloxone) may be used to treat intoxication symptoms. Individual opioid antagonists differ in dosage (product information must be consulted!). In particular, it should be noted that the respiratory depressant effect of levomethadone may be long-lasting (up to 75 hours), whereas opioid antagonists are short-acting substances (1 to 3 hours). After the antagonist effect wears off, additional injections may be required. Measures to prevent hypothermia and volume replacement therapy may also be necessary.
In cases of oral levomethadone intoxication, gastric lavage should only be performed after treatment with an antagonist.
Maintaining airway patency through intubation is particularly important during gastric lavage and prior to antagonist administration (induction of emesis may be possible).
Alcohol, barbiturates, bemegride, phenothiazines, and scopolamine must not be used in the treatment of intoxication.
Levomethadone cannot be dialysed.