Sublana

Leaflet included in the packaging: patient information

Sublana, 10 mg/ml, concentrate for solution for oral use

The active substance is methadone hydrochloride.
You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.
for the patient.

• You should keep this leaflet, so that you can read it again if necessary.
• In case of any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed to you for a specific person. Do not pass it on to others. The medicine can harm another person, even if the symptoms of their illness are the same.
• If the patient experiences any undesirable effects, including any undesirable effects not mentioned in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What is Sublana and what is it used for

Methadone hydrochloride, the active substance of Sublana, is used in the maintenance treatment of opioid dependence (substitution therapy).
Sublana suppresses withdrawal symptoms after stopping opioid abuse and the desire to take them again.
Substitution therapy for opioid dependence in adult patients is carried out in combination with medical supervision and appropriate psychological care.

2. Important information before taking Sublana

When not to take Sublana:

• In case of hypersensitivity to methadone hydrochloride or any of the excipients of this medicine listed in section 6. Allergic reactions include rash, itching or hives;
• In case of severe asthma or during an asthma attack (this medicine should not be used during an asthma attack). If the patient is taking the medicine themselves (self-administration), they should wait until the asthma attack has passed and the patient feels well;
• In case of moderate to severe respiratory disorders;
• In case of heart disorders (QT interval prolongation);
• In case of intestinal obstruction caused by intestinal muscle paralysis or acute gastrointestinal disorders;
• In case of severe liver disorders.

Warnings and precautions

Before starting Sublana, you should consult a doctor or pharmacist.
Treatment should be carried out with special caution and under close medical supervision in the following cases:

• The patient is at high risk, e.g. after attempted suicide with opioids such as heroin, especially in combination with antidepressants, alcohol, and other drugs with a depressant effect on the central nervous system (e.g. "sleeping pills");
• If the patient has acute abdominal syndrome, because Sublana can mask the symptoms of the disease and delay diagnosis;
• In case of heart rhythm disorders (palpitations) or other changes in the ECG (conduction disorders) or electrolyte disorders, especially in case of low potassium levels in the blood. QT interval prolongation may occur, as well as accelerated heart rate and accelerated heartbeat, which can lead to life-threatening ventricular fibrillation. The doctor may recommend an ECG before starting treatment or during its duration, if necessary;
• In case of heart failure;
• In case of low blood pressure;
• If withdrawal symptoms occur;
• In case of biliary tract disorders;
• If the patient has inflammatory bowel disease or intestinal obstruction;
• In case of prostate enlargement with urinary retention;
• In case of slow heart rate (bradycardia);
• If the patient is taking certain medications for arrhythmia (class I and III anti-arrhythmic medications);
• In case of pregnancy or breastfeeding (see "Pregnancy and breastfeeding");
• In case of impaired consciousness;
• If the patient is taking other medications or substances that have a depressant effect on the central nervous system or respiratory system (e.g. sedatives, alcohol);
• If the patient has disorders in which respiratory depression should be avoided;
• If the patient has recently had a head injury;
• In case of increased intracranial pressure;
• In case of antiviral therapy (see "Sublana and other medications" and section 3);
• In case of pancreatitis;
• If the patient has seizures;
• In case of hypothyroidism;
• In case of adrenal insufficiency;
• In case of withdrawal;
• If the patient has a neurological muscle disease (myasthenia gravis).

You should inform your doctor or pharmacist if, while taking Sublana, the patient experiences any of the following symptoms:

• Weakness, fatigue, loss of appetite, nausea, vomiting, or low blood pressure. This may indicate that the adrenal glands are producing too little hormone - cortisol, and hormonal supplementation may be necessary.

Long-term use of the medicine can lead to a decrease in the level of sex hormones and an increase in the level of prolactin. You should consult a doctor if the patient experiences symptoms such as decreased libido (sexual desire), impotence, or absence of menstruation.
Sublana can cause dependence in case of long-term and repeated use.
Physical and psychological dependence may occur, as well as tolerance. Sudden discontinuation of treatment can lead to life-threatening withdrawal symptoms. Therefore, discontinuation of treatment must be gradual.
Sublana should only be used in patients dependent on opioids, as the usual dosage used in substitution therapy can lead to severe poisoning, respiratory depression, and death in patients without opioid tolerance.
The doctor may order periodic urine tests to detect possible concurrent use of other drugs.
Drug abuse and other medication use during substitution therapy can be life-threatening and should be avoided.
Sublana for substitution therapy is intended for oral use only.
Parenteral administration of Sublana can cause severe side effects, including death.
The analgesic effect of Sublana can mask the symptoms of other diseases. You should consult a doctor if it is suspected that another disease is present, which usually causes pain, even if there are no pain symptoms or only mild pain. If the patient experiences pain, it may be necessary to administer another pain medication.
The doctor may, if necessary, reduce the dose in case of kidney or liver disease or if the patient is in poor general condition.

Children and adolescents

There is insufficient data on the safety and efficacy of Sublana in children and adolescents under 14 years of age. However, there is evidence of its use in adolescents from 15 years of age.

Sublana and other medications

You should tell your doctor or pharmacist about all medications you are currently taking or have recently taken, as well as any medications you plan to take.
You should honestly inform about your addiction, ongoing substitution therapy, and current dosage every time you visit your doctor or are hospitalized.
This also applies to other medications taken in addition to Sublana. This information is important to avoid potentially hazardous interactions with other medications.
Methadone hydrochloride can affect the action of other medications. Similarly, other medications can affect the action of Sublana.
You should inform your doctor if you are taking any of the following substances:

• Strong painkillers (opioid painkillers);
• Medications that affect mental state (e.g. thioridazine, phenothiazine derivatives, haloperidol, sertindole, and ziprasidone);
• Medications used in heart disorders, such as verapamil and quinidine;
• Medications used in the treatment of depression (desipramine, nefazodone, fluvoxamine, fluoxetine, paroxetine, and sertraline);
• Anti-inflammatory and immunosuppressive medications (e.g. dexamethasone and cyclosporine);
• Antiviral medications, including some medications used to treat HIV or hepatitis C virus infection (nevirapine, zidovudine, efavirenz, nelfinavir, ritonavir, telaprevir, amprenavir, delavirdine, lopinavir/ritonavir, ritonavir/saquinavir, abacavir, didanosine, and stavudine);
• Antibiotics (medications used to treat bacterial infections), such as ciprofloxacin, levofloxacin, moxifloxacin, and macrolide antibiotics, such as clarithromycin, telithromycin, and erythromycin;
• Medications used to treat fungal infections, such as fluconazole, itraconazole, and ketoconazole;
• Cimetidine used to treat stomach ulcers;
• Naloxone used to reverse opioid effects;
• Medications used to counteract opioid effects, such as naltrexone and buprenorphine;
• Rifampicin used to treat tuberculosis;
• Medications used to treat epilepsy, such as phenytoin, carbamazepine, and phenobarbital;
• Medications that cause urine acidification, such as ascorbic acid (vitamin C) and ammonium chloride;
• Medications used to treat diarrhea (e.g. loperamide, diphenoxylate);
• Diuretics (e.g. spironolactone);
• Sedative medications (sleeping pills, sedatives);
• Herbal medications containing St. John's wort used to treat depression;
• Medications used to treat arrhythmia (e.g. sotalol, amiodarone, and flecainide);
• Certain medications used to treat allergies (non-selective classic H1-antihistamine medications, e.g. diphenhydramine, doxylamine, dimenhydrinate);
• Monoamine oxidase inhibitors (MAO inhibitors used to treat Parkinson's disease);
• Metamizole, a medication used to treat pain and fever.

The risk of side effects increases when methadone is used concurrently with antidepressant medications (such as citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, amitriptyline, clomipramine, imipramine, nortriptyline). You should consult a doctor if the patient experiences any of the following symptoms:

• Changes in mental state (e.g. agitation, hallucinations, drowsiness)
• Rapid heartbeat, unstable blood pressure, fever
• Increased reflexes, coordination disorders, muscle stiffness
• Gastrointestinal symptoms (e.g. nausea, vomiting, diarrhea)

Concomitant use of Sublana and sedative medications, such as benzodiazepines or related medications, increases the risk of drowsiness, respiratory depression, drowsiness, which can be life-threatening. Therefore, concomitant use of these medications may only be considered if there are no other treatment options.
If the doctor prescribes Sublana together with other sedative medications, their dose and duration of use will be limited.
You should inform your doctor about all sedative medications taken by the patient and follow the dosage instructions carefully. It may be helpful to inform friends or relatives to be aware of the above symptoms. You should consult a doctor if these symptoms occur.
Marijuana can delay the breakdown of methadone and lead to an increase in its concentration in the blood. This can cause symptoms of poisoning and respiratory depression.
You should inform your doctor about all other medications taken by the patient, as they may be hazardous if used with methadone. In such cases, the doctor may decide to monitor heart activity using an electrocardiogram (ECG) at the beginning of treatment to ensure that these effects do not occur.
Methadone can affect the results of some blood and urine tests (including doping tests). You should inform your doctor if you are taking methadone before undergoing any tests.

Sublana with alcohol and drinking

You should not drink alcohol while taking Sublana. This impairs respiratory function and can lead to life-threatening respiratory disorders due to the mutual enhancement of effects.
Grapefruit juice can delay the breakdown of methadone, and therefore, it is not recommended to drink grapefruit juice while taking Sublana.

Pregnancy, breastfeeding, and fertility

If you are pregnant, breastfeeding, or think you may be pregnant, or plan to have a child, you should consult a doctor before using this medication.

Pregnancy

Sublana can be used during pregnancy after careful consideration by the doctor of the benefit-to-risk ratio, preferably under the supervision of a specialized medical center.
An increase in dose to twice daily may be necessary to maintain the effectiveness of treatment due to changes in metabolism during pregnancy.
Long-term use during pregnancy can lead to dependence and withdrawal symptoms in the newborn, which often require hospital treatment.

Breastfeeding

Sublana passes into breast milk. If a woman is breastfeeding or plans to breastfeed while taking methadone, she should consult a doctor, as the medication may affect the baby. You should monitor the baby for abnormal signs and symptoms, such as increased drowsiness (more than usual), respiratory difficulties, or limpness. If any of these symptoms occur, you should consult a doctor immediately.

Fertility

There are reports of sexual disorders caused by methadone in men during maintenance therapy.

Driving and using machines

This medicine can affect your ability to drive and use machines.
You should not actively participate in traffic at the beginning of treatment, during dose adjustment, if withdrawal symptoms occur, or when taking substances that can impair cognitive functions.
Psychomotor and cognitive functions (related to perception, ability to think, and recognition) are not impaired during stable substitution therapy. You should consult a doctor to determine if you are able to drive and use machines.

Sublana contains methyl parahydroxybenzoate (E 218) and propyl parahydroxybenzoate (E 216)

This may cause allergic reactions (possible late-type reactions).

3. How to take Sublana

This medicine should always be taken according to the doctor's or pharmacist's instructions. In case of doubts, you should consult a doctor or pharmacist.
The effect of methadone hydrochloride lasts for at least 24 hours, and therefore, it should be taken daily at the same time, preferably in the morning. The dose of Sublana should be determined based on the occurrence of withdrawal symptoms and adjusted to the individual needs and personal feelings of the patient. Usually, after dose adjustment, the goal is to administer the smallest possible maintenance dose.
Sublana must be diluted by an authorized person for immediate use or for later use at home. The dose of the medicine must be administered only by a doctor or a person designated by the doctor. The patient cannot measure the dose or prepare the solution themselves.
Starting treatment
The average initial dose is 20-30 mg of methadone hydrochloride. In cases where opioid tolerance is high, the initial dose may be 25-40 mg. The doctor may increase the dose gradually by a maximum of 5-10 mg of methadone hydrochloride at a time if the effectiveness is insufficient (withdrawal symptoms occur).
Maintenance therapy
The maintenance dose is usually achieved after 1-6 days. The dose may be up to 120 mg of methadone hydrochloride, and in justified cases, it may be higher. Doses higher than 120-150 mg of methadone hydrochloride are administered only in exceptional cases and only if it is possible to exclude concurrent drug abuse.
At the beginning of treatment and after 1-2 weeks after dose increase, the methadone concentration in the blood may increase. This effect or additional use of sleeping pills or illegal drugs can lead to life-threatening respiratory disorders.
Duration of treatment
The duration of treatment depends on the course of substitution therapy, the therapeutic goal, and the individual needs of the patient. The duration of treatment may be short (e.g. substitution therapy for dependence acquired during hospital treatment) or long-term.
Switching from other substitution medications to Sublana
In case of switching from morphine, buprenorphine, or levomethadone to Sublana, the doctor will choose a comparable dose of methadone and adjust it if necessary.
Dose reduction and treatment discontinuation
Treatment discontinuation must be gradual (if possible), with small steps of 5-10 mg of methadone hydrochloride over several weeks or even months, based on the individual needs of the patient, with special consideration of possible concurrent use of other drugs.
Sudden discontinuation of methadone leads to withdrawal symptoms and a decrease in opioid tolerance in a very short time.
After discontinuing methadone, a dose that was previously well-tolerated may become life-threatening! The same applies to relapses of dependence after treatment discontinuation, even if the dependence lasted a very long time (several years)! Treatment discontinuation can only be carried out under close medical supervision.

Use in children and adolescents

Children and adolescents under 14 years of age
There is insufficient data on the safety and efficacy of Sublana in children and adolescents under 14 years of age.
Children and adolescents from 15 years of age
The doctor will decide on the use of methadone in adolescents from 15 years of age.
Patient over 65 years of age
To avoid overdose, the doctor may decide to reduce the dose.

Patients with renal and/or hepatic impairment

In case of hepatic or renal impairment, the doctor may prolong the intervals between doses or reduce the dose. In case of chronic stabilized liver disease, dose reduction is not necessary.

Pregnant women

In pregnant women, it may be necessary to increase the dose to twice daily to maintain the effectiveness of treatment due to changes in metabolism during pregnancy (see "Pregnancy, breastfeeding, and fertility"). The doctor will prescribe a dose suitable for the patient.

Patients undergoing antiretroviral therapy

At the beginning or end of antiretroviral therapy (medications for HIV or hepatitis C virus infection), it should be considered that antiretroviral medications may increase or decrease the methadone concentration in the blood, which may lead to withdrawal symptoms or overdose.

Taking a higher dose of Sublana than recommended

Taking too much of the medicine can cause a decrease in blood sugar levels. Side effects such as drowsiness, pinpoint pupils, respiratory disorders, and low blood pressure may occur, which can lead to circulatory arrest, deep loss of consciousness, and life-threatening respiratory disorders.
There is a serious risk of life due to respiratory arrest!

Missed dose of Sublana

You should not take a double dose to make up for a missed dose. You should take the prescribed dose and continue treatment every 24 hours or consult a doctor.

Discontinuation of Sublana

Treatment discontinuation can lead to withdrawal symptoms. Within a short period (a few days), tolerance to Sublana is lost; this is very dangerous, as a previously well-tolerated dose may become fatal. After discontinuing methadone, a dose that was previously well-tolerated should never be taken again! This also applies to relapses of dependence after treatment discontinuation, even if the dependence lasted a very long time (several years)! Treatment discontinuation can only be carried out under close medical supervision.
Information for the doctor
Information on treatment discontinuation can be found at the end of this leaflet.
In case of any further doubts related to the use of this medicine, you should consult a doctor or pharmacist.

4. Possible side effects

Like all medications, Sublana can cause side effects, although not everybody gets them.
You should stop taking the medicine and consult a doctor immediately if you experience any of the following side effects:

• Allergic reactions, including face, mouth, tongue, or throat swelling, or difficulty breathing or swallowing, or severe skin itching, including skin rash;
• Heart disorders, which can include changes in heart rhythm, such as accelerated or slowed heartbeat, breathing difficulties, and dizziness, if breathing becomes slow and shallow; these side effects are rare and may occur in up to 1 in 1000 people;
• In case of slow and shallow breathing;
• Increased intracranial pressure, if the patient has had this in the past as a result of brain injury or brain disease.

You should not stop taking the medicine but consult a doctor immediately if you experience any of the following side effects:

• In case of worsening asthma

Other possible side effects:

Very common (may affect up to 1 in 10 people):

• Nausea and vomiting

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

• Fluid retention, euphoria, seeing and hearing things that do not exist (hallucinations)
• Drowsiness
• Blurred vision, pinpoint pupils, dry eye
• Dizziness or feeling of spinning
• Constipation
• Skin rash, sweating
• Feeling of fatigue
• Weight gain

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

• Decreased mood, agitation, confusion, difficulty sleeping, decreased sexual desire
• Headache, fainting
• Low blood pressure, facial flushing
• Pulmonary edema
• Asthma worsening
• Respiratory disorders (including cough), dryness of the nasal mucosa
• Dry mouth, pharyngitis
• Biliary colic (abdominal pain)
• Itching, hives, rash
• Urinary retention, difficulty urinating
• Difficulty achieving or maintaining an erection
• Menstrual disorders, milk secretion from the breasts
• Leg swelling
• Weakness
• Low body temperature

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

• Heart disorders, slow heart rate, palpitations
• Seizures
• Respiratory arrest
• Intestinal slowing (constipation)

The following side effects may also occur (frequency unknown: cannot be estimated from the available data):

• Decreased platelet count, which can increase the risk of bleeding or bruising
• Increased prolactin levels
• Loss of appetite
• Potassium or magnesium deficiency in the blood
• Hearing loss
• Low blood sugar

Reporting side effects

If you experience any side effects, including any side effects not mentioned in the leaflet, you should tell your doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181 C, 02-222 Warsaw, Tel: +48 22 49 21 301, Fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medication.

5. How to store Sublana

The medicine should be stored in a place that is out of sight and reach of children.
There are no special recommendations for storing the medicine.
Do not use this medicine after the expiry date stated on the packaging after EXP.
The expiry date refers to the last day of the month stated.
After the first opening, the bottle can be stored for 6 monthswith the attached pipette and dropper (packaging of 100, 150, 300, and 500 ml) or tightly closed (packaging of 1000 ml).
The solution prepared using diluents with high viscosity (syrups) containing a preservative (for home use) or purified water can be stored for 3 monthsat room temperature.
The solution prepared using water or fruit juice (e.g. apple or orange, except grapefruit juice - see section 2), for immediate use, can be stored for 24 hoursat room temperature.
Diluted solutions should be stored at a temperature below 25°C in brown glass bottles or protected from light.
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Sublana contains

• The active substance is methadone hydrochloride. 1 ml of the concentrate for solution for oral use contains 10 mg of methadone hydrochloride.
• The other ingredients are methyl parahydroxybenzoate (E 218), propyl parahydroxybenzoate (E 216), citric acid monohydrate, sodium citrate, purified water.
• The density of Sublana 10 mg/ml concentrate is 1.00 g/ml at 20°C.

What Sublana looks like and contents of the packaging

Concentrate for solution for oral use.
Clear, colorless or yellowish solution with a bitter taste, without visible particles in the brown glass bottle with a white closure and a pipette with graduations or a measuring cup.
Sublana is available in the following packaging sizes: 100 ml, 150 ml, 300 ml, 500 ml, and 1000 ml.
Not all packaging sizes may be marketed.

Marketing authorization holder and manufacturer

G.L. Pharma GmbH, Schloßplatz 1, 8502 Lannach, Austria