SUBLANA

Package leaflet: Information for the patient

Sublana, 10 mg/ml, concentrate for solution for oral use
Active substance: methadone hydrochloride
Please read carefully all the information in this leaflet before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Sublana is and what it is 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 pack and other information

1. What Sublana is and what it is used for

Methadone hydrochloride, the active substance in Sublana, is used in the maintenance treatment of opioid dependence (substitution therapy).
Sublana relieves withdrawal symptoms after stopping opioid abuse and reduces the craving to use opioids again.
Substitution therapy for opioid dependence in adult patients should be carried out in combination with medical supervision and appropriate psychological support.

2. Information before taking Sublana

When not to take Sublana:

• if allergic to methadone hydrochloride or any of the other ingredients 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 self-administers the medicine (self-administration), 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 disorders affecting the liver.

Warnings and precautions
Before starting treatment with Sublana, consult a doctor or pharmacist.
Treatment should be carried out with particular caution and under strict medical supervision in the following cases:

• the patient belongs to a high-risk group, e.g. after suicide attempts involving opioids such as heroin, especially in combination with antidepressants, alcohol, and other medicines with depressant effects on the central nervous system (e.g. sleeping pills);
• if the patient has acute abdomen syndrome, because Sublana may mask symptoms of disease and delay diagnosis;
• in case of heart rhythm disorders (palpitations) or other changes in ECG (conduction disorders) or electrolyte imbalances, especially low potassium levels in the blood. QT interval prolongation may occur, as well as tachycardia and accelerated heartbeat, which may lead to life-threatening ventricular fibrillation. The doctor may recommend an ECG examination before starting treatment or during its course, if necessary;
• in case of heart failure;
• in case of low blood pressure;
• if symptoms of shock occur;
• in case of disorders affecting the biliary tract;
• if the patient has inflammatory bowel disease or intestinal obstruction;
• in case of benign prostatic hyperplasia with urinary retention;
• in case of slow heart rate (bradycardia);
• if the patient is taking certain medicines used to treat palpitations (antiarrhythmic drugs class I and III);
• during pregnancy or breastfeeding (see section "Pregnancy and breastfeeding");
• in case of disorders of consciousness;
• if the patient is taking other medicines or substances with depressant effects on the central nervous system or respiratory system (e.g. sedatives, alcohol);
• if the patient has conditions where respiratory depression should be avoided;
• if the patient has sustained a head injury currently or recently;
• in case of increased intracranial pressure;
• during antiviral therapy (see section "Sublana and other medicines" and section 3.);
• in case of pancreatitis;
• if the patient experiences seizures;
• in case of hypothyroidism;
• in case of adrenal insufficiency;
• in case of shock;
• if the patient has a neurological muscle disease (myasthenia gravis).

Inform your doctor or pharmacist if any of the following symptoms occur during treatment with Sublana:

• 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 may lead to decreased levels of sex hormones and increased levels of prolactin. Consult a doctor if the patient experiences symptoms such as decreased libido (sexual desire), impotence, or absence of menstruation.
Sublana may cause dependence when used long-term and repeatedly. Physical and psychological dependence may develop, as well as tolerance. Abrupt discontinuation of treatment may lead to withdrawal symptoms, which may be life-threatening. For this reason, treatment must be discontinued gradually.
Sublana should be used exclusively in opioid-dependent patients, because standard dosing used in substitution therapy may 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 narcotics. Abuse of narcotics and other medicines during substitution therapy may be life-threatening, and therefore should be avoided. Sublana in substitution therapy is intended exclusively for oral administration. Intravenous administration of Sublana may cause severe adverse reactions, including death.
The analgesic effect of Sublana may mask symptoms of other diseases. Consult a doctor if another disease usually causing pain is suspected, even in the absence of pain symptoms or mild pain. If the patient experiences pain, another analgesic may be necessary.
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 experience in treating adolescents from the age of 15.

Sublana and other medicines
Inform your doctor or pharmacist about all medicines currently taken or recently taken, as well as about medicines the patient plans to take.
Be honest about your addiction, ongoing substitution therapy, and current dosage every time you visit a doctor or are hospitalized. This also applies to other medicines taken additionally. This information is important to avoid potentially dangerous combinations with other medicines.
Methadone hydrochloride may affect the action of other medicines. Similarly, other medicines may affect the action of Sublana.
Inform your doctor if the patient is taking any of the following substances:

• strong painkillers (opioid analgesics);
• medicines affecting mental state (e.g. thioridazine, phenothiazine derivatives, haloperidol, sertindole, ziprasidone);
• medicines used for heart disorders such as verapamil and quinidine;
• medicines used to treat depression (desipramine, nefazodone, fluvoxamine, fluoxetine, paroxetine, and sertraline);
• anti-inflammatory and immunosuppressive medicines (e.g. dexamethasone and cyclosporine);
• antiviral medicines, including some used to treat HIV infection or hepatitis C virus (nevirapine, zidovudine, efavirenz, nelfinavir, ritonavir, telaprevir, amprenavir, delavirdine, lopinavir/ritonavir, ritonavir/saquinavir, abacavir, didanosine, and stavudine);
• antibiotics (medicines used to treat bacterial infections), such as ciprofloxacin, levofloxacin, moxifloxacin, and macrolide antibiotics, e.g. clarithromycin, telithromycin, and erythromycin;
• medicines used to treat fungal infections, such as fluconazole, itraconazole, and ketoconazole;
• cimetidine used in the treatment of peptic ulcer disease;
• naloxone used to reverse opioid effects;
• medicines used to block opioid effects such as naltrexone and buprenorphine;
• rifampicin used in the treatment of tuberculosis;
• medicines used to treat epilepsy such as phenytoin, carbamazepine, and phenobarbital;
• medicines that cause urine acidification, such as ascorbic acid (vitamin C) and ammonium chloride;
• medicines used to treat diarrhea (e.g. loperamide, diphenoxylate);
• diuretics (e.g. spironolactone);
• medicines causing drowsiness (sleeping pills, sedatives);
• herbal medicines containing St. John's wort used to treat depression;
• medicines used to treat palpitations (arrhythmia) e.g. sotalol, amiodarone, and flecainide;
• certain medicines used to treat allergies (non-selective classical H--antihistamines e.g. diphenhydramine, doxylamine, dimenhydrinate);
• monoamine oxidase inhibitors (MAO inhibitors used to treat Parkinson's disease);
• metamizole, a medicine used to treat pain and fever.

The risk of adverse reactions increases when methadone is used simultaneously with antidepressants (such as citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, amitriptyline, clomipramine, imipramine, nortriptyline). Contact your doctor if the patient experiences any of the following symptoms:

• changes in mental state (e.g. agitation, hallucinations, delirium)
• rapid heartbeat, unstable blood pressure, fever
• increased reflexes, coordination disorders, muscle stiffness
• gastrointestinal symptoms (e.g. nausea, vomiting, diarrhea).

Concurrent use of Sublana and sedatives such as benzodiazepines or related medicines increases the risk of drowsiness, breathing difficulties (respiratory depression), and coma, which may be life-threatening. For this reason, concurrent use of these medicines should only be considered when no other treatment options are possible.
If the doctor prescribes Sublana together with other sedatives, their dose and duration of use will be limited.
Inform your doctor about all sedatives taken by the patient and strictly follow dosing instructions. It may be helpful to inform friends or relatives so they are aware of the above-mentioned symptoms. Contact your doctor if such symptoms occur.
Marijuana may delay methadone metabolism and lead to increased plasma concentration. This may cause symptoms of poisoning and respiratory depression.
Inform your doctor about all other medicines taken by the patient, as they may be dangerous when used with methadone. In such cases, the doctor may decide that at the beginning of treatment, monitoring of heart function by electrocardiogram (ECG) is necessary to ensure these effects do not occur.
Methadone may affect the results of certain blood and urine tests (including anti-doping test results). Inform your doctor if the patient is taking methadone before any test is performed.

Sublana, food and alcohol
Do not drink alcohol during treatment with Sublana. This impairs respiratory function and consequently leads to life-threatening breathing disorders due to mutual intensification of effects.
Grapefruit juice may delay methadone metabolism and therefore grapefruit juice is not recommended during treatment with Sublana.

Pregnancy, breastfeeding and fertility

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult a doctor before using this medicine.

Pregnancy
Sublana may be used during pregnancy after careful evaluation by the doctor of the benefit-risk ratio, preferably under supervision in a specialized medical center.
Dose increase to twice daily administration may be necessary to maintain treatment efficacy due to metabolic changes during pregnancy.
Long-term use during pregnancy may lead to fetal dependence and withdrawal symptoms after birth, which often require hospital treatment.

Breastfeeding
Sublana passes into human milk. If a woman is breastfeeding or intends to breastfeed during methadone treatment, she should consult a doctor, as the medicine may affect the child. The child should be monitored for abnormal signs and symptoms such as excessive drowsiness (more than usual), breathing difficulties, or floppiness. If any of these symptoms occur, consult a doctor immediately.

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

Driving and operating machinery
This medicine may affect the ability to drive and operate machinery.
Active participation in road traffic is not recommended at the beginning of treatment, during dose adjustment, if withdrawal symptoms occur, and when using substances that may impair cognitive functions.
Psychomotor and cognitive functions (related to perception, thinking, and recognition) are not impaired during stable substitution therapy. Consult your doctor to determine whether the patient is able to drive and operate machinery.

Sublana contains methyl parahydroxybenzoate (E 218) and propyl parahydroxybenzoate (E 216)
This may cause allergic reactions (including delayed-type reactions).

3. How to take Sublana

This medicine should always be taken as directed by the physician or pharmacist. In case of doubt,
consult your doctor or pharmacist.
The effect of hydrochloride methadone lasts for at least 24 hours; therefore, it should be taken daily at the same time, preferably in the morning. The dose of Sublana should be determined based on the presence of withdrawal symptoms and adjusted according to individual needs and personal feelings of the patient. Usually, after dose adjustment, the goal is to maintain treatment with the lowest possible dose.

Sublana must be diluted by an authorized person for immediate use or for later use at home. The dose must be administered exclusively by a physician or a person designated by the physician. The patient must not independently measure the dose or prepare the solution.

Starting treatment
The initial average dose ranges from 20 to 30 mg of hydrochloride methadone. In cases where opioid tolerance is high, the initial dose ranges from 25 to 40 mg. The physician may gradually increase the dose by up to 5 to 10 mg of hydrochloride methadone at a time if efficacy is insufficient (withdrawal symptoms occur).

Maintenance therapy
The maintenance dose is usually achieved within 1 to 6 days. The dose may reach up to 120 mg of hydrochloride methadone, and in justified cases, it may be higher. Doses exceeding 120 to 150 mg of hydrochloride methadone are administered only exceptionally and only if concomitant drug use can be excluded.

At the beginning of treatment and 1 to 2 weeks after increasing the dose, blood levels of methadone may rise. This effect, or additional use of sedatives or illegal drugs, may lead to life-threatening respiratory disorders.

Treatment duration
The duration of treatment depends on the course of substitution therapy, therapeutic goals, and individual patient needs. Treatment duration may be short-term (e.g., substitution therapy for dependence acquired during hospital treatment) or long-term.

Switching from other substitution substances to Sublana
When switching from morphine, buprenorphine, or levomethadone to Sublana, the physician will select a comparable methadone dose and adjust it if necessary.

Dose reduction and discontinuation of treatment
Discontinuation of treatment must be gradual (if possible), in small steps of 5 to 10 mg of hydrochloride methadone over several weeks or even months, based on individual patient needs, with special attention to possible concurrent use of other drugs.

Sudden discontinuation of methadone leads to withdrawal symptoms and a rapid decrease in opioid tolerance. After stopping methadone, a previously well-tolerated dose may cause life-threatening overdose! The same applies to illegal drugs such as heroin.

Use in children and adolescents

Children and adolescents up to 14 years of age
There is insufficient data on the safety and efficacy of Sublana in children and adolescents up to 14 years of age.

Children and adolescents from 15 years of age
The physician will decide whether to use methadone in adolescents aged 15 years and older.

Elderly patients (over 65 years of age)
To prevent overdose, the physician may decide to reduce the dose.

Patients with renal and/or hepatic impairment
In cases of liver or kidney impairment, the physician may extend the intervals between doses or reduce the dose. In cases of chronic, stable liver disease, dose reduction is not necessary.

Pregnant patients
In pregnant patients, it may be necessary to increase the dose to twice daily to maintain treatment efficacy due to metabolic changes occurring during pregnancy (see section "Pregnancy, breastfeeding, and effects on fertility"). The physician will prescribe a dose appropriate for the patient.

Patients receiving antiretroviral therapy
At the beginning or end of antiretroviral treatment (medicines for HIV infection or hepatitis C virus), consider the possibility of withdrawal symptoms or overdose, as antiretroviral drugs may increase or decrease blood levels of methadone.

Taking more than the recommended dose of Sublana
An excessive dose of the medicine may cause a decrease in blood sugar levels. Adverse effects such as drowsiness, pinpoint (maximally constricted) pupils, respiratory disturbances, and low blood pressure may occur as signs of overdose. These may lead to circulatory collapse, deep unconsciousness, and life-threatening respiratory disorders.

There is a serious risk of death due to respiratory arrest!
The risk of overdose increases when substances not prescribed by a physician are taken concurrently.

In case of suspected overdose, seek immediate medical help from the nearest doctor!
The same applies if it is suspected that a child has swallowed Sublana. Even small doses of this medicine may be life-threatening for a child. Medical help must be summoned immediately. Do not wait for symptoms of overdose to appear!

Information for the physician
Information regarding overdose is located at the end of this leaflet.

Missing a dose of Sublana
Do not take a double dose to make up for a missed dose. Take the prescribed dose and continue treatment every 24 hours, or contact your doctor.

Stopping treatment with Sublana
Discontinuing treatment may cause withdrawal symptoms. Opioid tolerance is lost within a short period (a few days), which is extremely dangerous because a previously tolerated dose may become fatal. After stopping the medicine, never take the same daily dose as before! This also applies to relapses of addiction after treatment interruption, even if the addiction lasted for a very long time (several years)! Discontinuation of treatment must only be carried out under strict medical supervision.

Information for the physician
Information regarding discontinuation of treatment is located at the end of this leaflet.

If you have any further questions about using this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
Treatment should be discontinued and immediate medical advice should be sought if the patient experiences any of the following adverse reactions:

• allergic reactions including swelling of the face, lips, tongue or throat, or difficulty breathing or swallowing, or sudden skin rash including skin eruptions;
• heart disorders which may include changes in heart rhythm such as rapid or slow heartbeat, difficulty breathing, and dizziness, if breathing becomes slow and shallow; these adverse reactions are rare and may occur in up to 1 in 1,000 people;
• in case of slow and shallow breathing;
• increased intracranial pressure, if the patient has previously experienced this as a result of brain injury or brain disease.

Do not stop taking the medicine, but seek immediate medical advice if the following adverse reactions occur:

• worsening of asthma

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

• nausea and vomiting

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

• fluid retention, euphoria, seeing or hearing things that do not exist (hallucinations)
• drowsiness
• blurred vision, constricted pupils, dry eye
• dizziness or sensation of spinning
• constipation
• skin rash, sweating
• feeling of fatigue
• weight gain

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

• low mood, agitation, confusion, difficulty falling asleep, reduced sexual desire
• headache, fainting
• low blood pressure, facial flushing
• pulmonary edema
• worsening of asthma
• breathing disorders (including cough), dryness of the nasal mucosa
• dryness of the mouth, inflammation of the tongue
• biliary colic (abdominal pain)
• itching, urticaria, rash
• urine retention, difficulty passing urine
• difficulty achieving or maintaining erection
• menstrual disorders, milk secretion from breasts
• swelling of the legs
• weakness
• low body temperature

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

• heart disorders, slow heart rate, palpitations
• convulsions
• respiratory arrest
• slowed intestinal activity (ileus)

The following adverse reactions may also occur (frequency unknown: cannot be estimated from available data):

• decreased platelet count, increasing the risk of bleeding or bruising
• increased prolactin levels
• loss of appetite
• deficiency of potassium or magnesium in the blood
• hearing loss
• low blood sugar levels

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181 C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions allows more information to be collected regarding the safety of the medicine.

5. How to store Sublana

The medicine should be stored in a place inaccessible and not visible to children.
No special storage instructions apply.
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 stated month.
After first opening, the bottle may be stored for 6 months with the attached dropper applicator and dropper (pack sizes 100, 150, 300 and 500 ml) or tightly closed (pack size 1000 ml).
The solution prepared using high-viscosity diluents (syrups) containing a preservative (for home use) or purified water may be stored for 3 months at room temperature.
The solution prepared using water or fruit juice (e.g. apple or orange juice, except grapefruit juice – see section 2) for immediate use may be stored for 24 hours at room temperature.
Diluted solutions should be stored at a temperature below 25°C in amber glass bottles or protected from light.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. 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 concentrate for oral solution 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 pack
Concentrate for oral solution.
A clear, colourless or yellowish solution with a bitter taste, free from visible particles, in a brown glass bottle with a white safety cap, together with a graduated pipette and a pipette scraper or a measuring device.
Sublana is available in the following pack sizes: 100 ml, 150 ml, 300 ml, 500 ml and 1000 ml.
Not all pack sizes may be marketed.

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

For further information and details on the medicinal product's name in other EEA countries, please contact the representative of the Marketing Authorisation Holder:
G.L. Pharma GmbH Sp. z o.o. Branch in Poland
Al. Jana Pawła II 61
01-031 Warsaw
Poland
Tel: 022/ 636 52 23; 636 53 02
Fax: 022/ 636 50 76

The following information is intended exclusively for healthcare professionals:

Dosage
Adults
This medicinal product must be prepared for administration by a healthcare professional.
The initial dose should be administered in the morning.
The dose must be administered exclusively by a physician or a person designated by the physician.
The patient must not measure the dose independently.
Dosing is based on the presence of withdrawal symptoms and must be individually adjusted for each patient according to their specific situation and needs.

Initiation of treatment
The usual initial dose ranges from 20 to 30 mg. In cases of high opioid tolerance, the initial dose may range from 25 to 40 mg.
If withdrawal symptoms occur, the dose should be gradually increased by increments of no more than 5 to 10 mg of methadone hydrochloride at a time. Dose adjustment is considered complete when withdrawal symptoms cease. Individual tolerance limits must be taken into account.
During dose titration, dosing is performed using the graduated pipette supplied in the package, with markings of 0.25 ml accuracy (corresponding to 2.5 mg of methadone hydrochloride). Information on the preparation of the oral solution is provided under "Method of administration".

Maintenance therapy
Most patients require a daily dose of 60–120 mg to achieve safe and effective maintenance therapy; however, some patients may require higher doses. Methadone is usually administered once daily. The maximum recommended dose of 150 mg per day should be used only in exceptional cases (unless national guidelines recommend otherwise).

Method of administration
Oral administration.
Sublana may be diluted with high-viscosity diluents (syrups) containing a preservative in any desired proportion, or with purified water in a ratio of up to 1:3 (1 part concentrate to up to 2 parts purified water). For immediate use, the concentrate may be diluted with water or fruit juice (e.g. apple or orange juice, except grapefruit juice). The packaging contains a graduated pipette (for 100, 150, 300, 500 ml packs) or a graduated measuring cup (1000 ml pack) intended for measuring the required dose.
To avoid errors, the bottle in use should be labeled with the type of diluent, the concentration of the solution in mg/ml, and the date of preparation.
The daily dose must be taken under supervision and visual control (e.g. at a pharmacy), in accordance with applicable legal regulations and national guidelines, unless national guidelines recommend otherwise.
Patients must be informed that oral administration is the only permitted and safe route of administration for this medicinal product. The physician should also clearly emphasize the potential consequences of incorrect use of the medicinal product.

Toxicity in individuals not previously treated with opioids
Life-threatening toxicity may occur even at doses lower than those used in substitution therapy, particularly in individuals without tolerance (especially children). In opioid-naïve adults, toxicity may occur at a dose of approximately 20 mg of methadone hydrochloride.

Children and adolescents
In children under 5 years of age, toxicity may occur at a dose of approximately 1 mg, and in older children, starting at a dose of approximately 3 mg.

Subjective and objective symptoms of excessive methadone use
The relationship between the development and persistence of opioid tolerance and the dose of methadone hydrochloride is complex. If a patient exhibits subjective and objective symptoms of excessive methadone hydrochloride effects, characterized by "unusual well-being," impaired concentration, drowsiness, and dizziness upon standing, dose reduction is recommended.

Symptoms of overdose
Overdose is characterized by respiratory depression (reduced respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), excessive drowsiness progressing to stupor or coma, pinpoint pupils, skeletal muscle flaccidity, cold and clammy skin, and occasionally bradycardia and hypotension. Severe poisoning, particularly after intravenous administration, may lead to respiratory arrest, circulatory collapse, cardiac arrest, and death.

Treatment of overdose
If necessary, immediate treatment in an intensive care unit should be initiated (e.g. intubation and mechanical ventilation). Specific opioid antagonists (e.g. naloxone) may be effective in treating poisoning symptoms. The doses of individual opioid antagonists vary (refer to manufacturer's information!). Particular attention must be paid to the fact that the respiratory depressant effect of methadone may be prolonged (36–48 hours), whereas opioid antagonists have a short duration of action (1–3 hours). After the antagonistic effect wears off, repeated administration may be necessary. Measures to prevent excessive reduction in body temperature and to maintain adequate fluid volume may be required.
In patients physically dependent on opioids, administration of a standard dose of an opioid antagonist may precipitate acute withdrawal symptoms. Therefore, if possible, the use of antagonists should be avoided in these patients. Particular caution is required if such intervention is necessary to treat severe respiratory depression.
In cases of oral methadone poisoning, gastric lavage may be performed only after antagonist treatment.
Airway protection via intubation is particularly important during gastric lavage and prior to antagonist administration (due to the risk of inducing vomiting).
Alcohol, barbiturates, phenothiazines, and scopolamine must not be used in the treatment of poisoning.
Methadone is not dialyzable.

Discontinuation of methadone hydrochloride
Withdrawal symptoms may appear within 24 hours of a missed dose if the prescribed methadone dose is too low (nasal congestion, gastrointestinal symptoms, diarrhea, muscle pain, anxiety).
The physician supervising treatment should be aware that dosage adjustments may be necessary if the patient reports experiencing withdrawal symptoms.