Active ingredients: Methadone
METHADONE HYDROCHLORIDE MOLTENI 1 mg / ml oral solution
METHADONE HYDROCHLORIDE MOLTENI 5 mg / ml oral solution
Why is Methadone - Generic Drug used? What is it for?
METHADONE HYDROCHLORIDE MOLTENI contains the active substance methadone hydrochloride, which belongs to a group of medicines that act on the nervous system, opioid analgesics.
This medicine is used for:
- the treatment of severe pain that is unresponsive to other pain relieving medicines;
- treatment of opioid drug addiction (eg heroin) and for maintenance therapy. Detoxification treatment and maintenance treatment should be performed under medical supervision
Contraindications When Methadone - Generic Drug should not be used
Do not take MOLTENI METHADONE HYDROCHLORIDE
- if you are allergic to methadone or any of the other ingredients of this medicine (listed in section 6);
- if you suffer from severe constipation;
- if you have heart problems (organic heart disease);
- if you have severe liver and kidney problems;
- if you suffer from changes in the amount of glucose in your blood (uncompensated diabetes);
- if you have porphyria (a rare blood disorder);
- if you have low blood pressure (hypotension);
- if you have "high pressure" in the skull (intracranial hypertension);
- if you have head trauma (cranioencephalic trauma);
- if you suffer from acute asthma attacks or other lung diseases (chronic obstructive pulmonary disease);
- if you have breathing problems (respiratory failure);
- if you have an enlarged heart due to lung disease (cor pulmonale);
- if you have a low volume of blood circulating (hypovolaemia);
The use of methadone is not indicated during pregnancy, during lactation and in the treatment of birth pains, since its long duration of action increases the likelihood of respiratory problems in the newborn. Furthermore, the use of this medicine is not indicated in children.
Precautions for use What you need to know before taking Methadone - Generic Drug
Talk to your doctor or pharmacist before taking MOLTENI METHADONE HYDROCHLORIDE.
Methadone therapy can cause physical and mental dependence and tolerance towards the drug. This means that the dose taken will be less effective. Therefore it must be prescribed and taken with the same caution that is taken for morphine.
Pay special attention to the use of methadone and tell your doctor:
- if you take drugs that affect the central nervous system (narcotic analgesics, general anesthetics, antipsychotics (phenothiazines), other sedative hypnotic tranquilizers, tricyclic antidepressants), or even substances such as alcohol because they can cause depression, deep sedation or coma;
- if anxious states appear during the course of treatment. This medicine has no anti-anxiety action, so higher doses should not be used;
- if you have acute abdominal problems;
- if you have low blood volume (hypovolaemia) or are being treated with phenothiazine or anesthetics because you may have severe low blood pressure;
- if you feel dizzy when standing up due to a rapid drop in blood pressure (orthostatic hypotension);
- if you are elderly or debilitated;
- if you have a thyroid malfunction (hypothyroidism);
- if you have adrenal gland disease (Addison's disease);
- if you have an enlarged prostate (prostatic hypertrophy);
- if you have difficulty urinating due to a narrowing of the urethra;
- if you have head trauma (head injuries) and an increase in intracranial pressure;
- if you have heart disease which can alter your heart rate (QT interval prolongation) or are being treated with medicines which can cause this.
If you are physically addicted to narcotics, the administration of the antagonists should be done with caution as it can trigger a withdrawal crisis.
If you are an athlete, taking MOLTENI METHADONE HYDROCHLORIDE can give a positive result in doping tests.
Children
The use of this medicine, in the treatment of pain, is contraindicated in children.
Interactions Which drugs or foods can modify the effect of Methadone - Generic Drug
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Your doctor may decide to increase the dose of methadone, to avoid withdrawal attacks, if you are taking other medicines such as:
- medicines for epilepsy such as barbiturates, carbamazepine, phenytoin;
- medicines for the treatment of AIDS such as nevirapine and efavirenz;
- medicines for tuberculosis such as rifampicin;
- medicines used for stomach problems such as cimetidine;
- medicines used to acidify urine such as ammonium chloride.
Your doctor may decide to decrease the methadone dose if you are taking other medicines such as:
- medicines used to regulate the heartbeat (quinidine);
- medicines to lower blood pressure (verapamil);
- cannabinoids
- medicines against bacteria such as clarithromycin and erythromycin;
- medicines to treat AIDS such as delavirdine and ritonavir;
- antidepressants such as nefazodone and selective serotonin reuptake inhibitors;
- medicines used to treat fungal infections such as itraconazole, ketoconazole and fluconazole.
Methadone can interfere with the work of other medicines, tell your doctor if you are taking:
- medicines for AIDS therapy such as didanosine, stavudine and zidovudine;
- medicines that affect cardiac conduction or drugs that can affect the salt concentration;
- opioid antagonists, naloxone and naltrexone, used for drug and alcohol addiction;
- medicines used in pain management such as butorphanol, nalbuphine, pentazocine;
- medicines that exert a depressive action on the CNS such as analgesics, tranquilizers;
- medicine used in the treatment of diarrhea such as diphenoxylate, loperamide and octeotride;
- antimuscarinic medicine;
- medicines used for depression such as monoamine oxidase (MAO) inhibitors.
MOLTENI METHADONE HYDROCHLORIDE with drinks and alcohol
During treatment with methadone, do not drink alcoholic substances, which could cause drowsiness, and avoid taking grapefruit juice, which interacts with the activity of this medicine.
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Methadone is contraindicated in pregnancy, due to possible effects on the development of the fetus, and during lactation.
However, the physician may decide to undertake methadone maintenance treatment in the event that there is an "obvious inability to discontinue" heroin use.
Any suspension of treatment must take place under medical supervision and must be carried out not before the 14th week of gestation and not after the 32nd to avoid, respectively, the risk of abortion and pre-term birth.
Driving and using machines
MOLTENI METHADONE HYDROCHLORIDE may affect the ability to drive and use machines.
MOLTENI METHADONE HYDROCHLORIDE contains glycerol and sucrose
METHADONE HYDROCHLORIDE MOLTENI 1 mg / ml oral solution contains:
Glycerol: which can cause headache, stomach upset and diarrhea at methadone doses> 100 mg per day. Sucrose: if you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
The maximum daily dose (120 ml, equal to 120 mg of methadone hydrochloride) contains 48 g of sucrose. To be taken into consideration if you have problems with unstable blood glucose levels (diabetes mellitus).
The medicine can be harmful to the teeth.
METHADONE HYDROCHLORIDE MOLTENI 5 mg / ml oral solution contains:
Sucrose: if you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
The maximum daily dose (24 ml, equal to 120 mg of methadone hydrochloride) contains 9.6 g of sucrose. To be taken into consideration if you have problems with unstable blood glucose levels (diabetes mellitus).
The medicine can be harmful to the teeth.
Dosage and method of use How to use Methadone - Generic Drug: Dosage
Always take this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
This medicine is a solution to be taken by mouth (orally), do not use it by injection.
The dosage will be appropriately adjusted by the doctor according to the severity of your condition and your response to therapy. The recommended dosages are given below.
Pain relief
The average dose varies from 5 to 20 mg for one or more doses per day, according to the doctor's instructions. Sometimes, in cases of exceptionally severe pain or in cases where the usual dose is found to be ineffective, your doctor may prescribe a higher dose.
Treatment of opioid drug addiction
The medicine will be given to you daily according to your doctor's opinion and treatment schedule. A detox treatment course will not exceed 21 days and cannot be repeated until 4 weeks after the previous cycle has ended.
Normally the starting dose of 15-20 mg per day can counteract withdrawal crises. This dose may be increased by your doctor, usually to 40 mg per day, in single or divided doses, for people dependent on high amounts of opioids.
The dose will be stable for 2-3 days and then the amount of methadone will gradually decrease.
Maintenance treatment
Your doctor may decide to give methadone for more than three weeks as maintenance therapy.
Methadone therapy can abolish heroin craving and dominate the addict's anxiety state.
The recommended doses range from 50 to 120 mg per day depending on the degree of tolerance and the ability to metabolize the drug.
Use in older people:
In elderly patients, methadone should be administered with caution and the starting dose should be reduced.
The packages are equipped with a child resistant closure.
To open: press and simultaneously rotate anticlockwise.
To close: press and simultaneously rotate clockwise.
Overdose What to do if you have taken too much Methadone - Generic Drug
If you take more METHADONE HYDROCHLORIDE MOLTENI than you should In case of accidental ingestion / intake of an overdose of MOLTENI METHADONE HYDROCHLORIDE, notify your doctor immediately or go to the nearest hospital.
Overdose is manifested by the following symptoms:
- difficulty in breathing (irregular and shallow breathing, bluish discoloration of the skin due to lack of oxygen)
- extreme sleepiness leading to stupor or coma
- narrowing of the pupils (miosis)
- cold and clammy skin
- flaccidity of the muscles
- slow heart rate (bradycardia)
- low blood pressure (hypotension).
In severe overdosage, especially intravenously, the following may occur:
- interruption of breathing (apnea)
- circulatory collapse
- cardiac arrest
- death
If you forget to take MOLTENI METHADONE HYDROCHLORIDE
Do not take a double dose to make up for a forgotten dose.
If you stop using MOLTENI METHADONE HYDROCHLORIDE
Stopping treatment with this drug abruptly can cause side effects, even serious ones. Follow your doctor's instructions carefully on how to gradually decrease the use of this medicine.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Methadone - Generic Drug
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Below are the side effects of methadone hydrochloride. Insufficient data are available to establish the frequency of the individual effects listed.
The main risks of methadone are represented by:
- severe breathing problems (depression and respiratory arrest);
- severe circulation problems (circulatory depression);
- severe heart problems (shock and cardiac arrest).
- heart disease which can affect heart rate (QT prolongation and torsades de pointes).
The other side effects observed are:
- a feeling of emptiness in the head, dizziness and sleepiness;
- nausea, vomiting, sweating;
- feeling of dizziness when standing up due to a drop in blood pressure (orthostatic hypotension);
- mood disorders (euphoria, dysphoria);
- weakness, headache, sleeplessness, agitation;
- disorientation and visual disturbances;
- dry mouth, loss of appetite (anorexia), constipation and gallbladder problems;
- flushing of the face, slow heart rate (bradycardia), perception of heartbeat (palpitations);
- feeling faint and unconscious (syncope);
- urinary retention or difficulty urinating, fluid retention;
- loss of sexual desire (libido) and / or sexual impotence;
- itching, hives, other skin reactions;
- swelling due to fluid accumulation (edema).
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the package after "EXP". The expiry date refers to the last day of that month.
METHADONE HYDROCHLORIDE MOLTENI 1 mg / ml oral solution
After first opening the 100 ml, 500 ml or 1000 ml multidose bottles, the medicine should be used within 2 months. After this period, the residual medicinal product must be discarded.
METHADONE HYDROCHLORIDE MOLTENI 5 mg / ml oral solution
After first opening the multidose bottle, the medicine should be used within 8 months. After this period, the residual medicinal product must be discarded.
Keep in the original package tightly closed to protect the medicine from light.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What does METHADONE HYDROCHLORIDE MOLTENI contain
- The active ingredient is methadone hydrochloride. Each ml of solution contains 1 or 5 mg of methadone hydrochloride
- The other ingredients are sucrose, glycerol, sodium benzoate, lemon flavoring, citric acid, purified water (see section 2 "METHADONE HYDROCHLORIDE MOLTENI contains glycerol and sucrose")
Description of the appearance of MOLTENI METHADONE HYDROCHLORIDE and contents of the pack
METHADONE HYDROCHLORIDE MOLTENI 1 mg / ml oral solution
Bottles of 5 mg, 10 mg, 20 mg, 40 mg, 60 mg;
Multidose bottles of 100 ml, 500 ml, 1000 ml
The multidose packs of 100 ml, 500 ml and 1000 ml are equipped with a measuring cup calibrated up to 30 ml for multiples of 5 ml.
METHADONE HYDROCHLORIDE MOLTENI 5 mg / ml oral solution
Bottles of 25 mg, 50 mg, 100 mg;
1000 ml multidose bottle
The 1000 ml multidose package is equipped with a calibrated measuring cup from 1 to 6 ml, equal to 5-30 mg of methadone hydrochloride.
Packages subject to special medical prescription have a child-resistant closure.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
METHADONE HYDROCHLORIDE MOLTENI ORAL SOLUTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Methadone hydrochloride MOLTENI 1 mg / ml oral solution
1 ml of oral solution contains:
Active ingredient: methadone hydrochloride 1 mg
1 bottle of 5 ml contains: 5 mg methadone hydrochloride.
1 bottle of 10 ml contains: 10 mg methadone hydrochloride.
1 bottle of 20 ml contains: methadone hydrochloride 20 mg.
1 bottle of 40 ml contains: 40 mg methadone hydrochloride.
1 bottle of 60 ml contains: methadone hydrochloride 60 mg.
1 bottle of 100 ml contains: 100 mg methadone hydrochloride.
1 bottle of 500 ml contains: 500 mg methadone hydrochloride.
1 bottle of 1000 ml contains: 1000 mg methadone hydrochloride.
Excipients: glycerol, sucrose.
Methadone hydrochloride MOLTENI 5 mg / ml oral solution
1 ml of oral solution contains:
Active ingredient: methadone hydrochloride 5 mg
1 bottle of 5 ml contains: methadone hydrochloride 25 mg.
1 bottle of 10 ml contains: methadone hydrochloride 50 mg.
1 bottle of 20 ml contains: 100 mg methadone hydrochloride.
1 bottle of 1000 ml contains: 5000 mg methadone hydrochloride.
Excipients: glycerol, sucrose.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Oral solution.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Painful syndromes of severe entity in patients who no longer respond to sequential treatment with analgesic, non-steroidal anti-inflammatory, steroidal, weak opioid drugs. Narcotic-drug cessation treatment.
Detoxification treatment and maintenance treatment must be performed under medical supervision.
If methadone is given to treat heroin addiction for more than three weeks, the procedure switches from treatment of acute withdrawal syndrome to maintenance therapy.
04.2 Posology and method of administration
The medicine is a methadone solution for oral administration only and should not be used by injection.
For pain relief
The dosage should be adjusted according to the severity of the pain and the patient's response.
Sometimes, in cases of exceptionally severe pain or in patients who have become tolerant to the analgesic effect of narcotics, it may be necessary to exceed the usual recommended dose.
The average dosage for adults varies from 5 to 20 mg once or more times a day, according to the doctor's instructions.
For the treatment of opioid drug addiction states
The drug will be administered daily according to the doctor's opinion and treatment schedule. A detox treatment course will not exceed 21 days and cannot be repeated until 4 weeks after the previous cycle has ended.
The dosage schedules given below are recommended but may be changed depending on clinical judgment. Initially, a single dose of 15-20 mg of methadone will often be sufficient to suppress withdrawal symptoms. More methadone can be given if the withdrawal symptoms are not eliminated or if they reappear. When patients are physically dependent on high doses, these levels may need to be exceeded. Usually 40 mg per day in single or divided doses is an adequate dose level. Stabilization can be continuous for 2-3 days and then the amount of methadone will gradually decrease. The frequency at which methadone is decreased will be determined individually for each patient. In hospitalized patients, a daily reduction of 20% of the total per day dose is generally well tolerated. In outpatients, a slower tapering schedule may be needed.
If methadone is given for more than three weeks, the procedure is considered no more detoxification or treatment of acute withdrawal syndrome, but maintenance, although the aim and intent may be total abstinence.
Maintenance treatment can be performed in the case of opioid users with proven stabilized dependence, when previous multidisciplinary interventions have not yielded positive results. This treatment is also indicated in patients with proven opioid dependence and HIV infection, in compromised immune situations or with full-blown AIDS if the doctor believes that another type of program gives less chance of abstention from the use of opioids.
Substitution therapy, if well conducted, succeeds in abolishing craving, that is, the compulsive pursuit of heroin and in dominating the anxiety state of the addict.
For use on subjects in a state of consolidated addiction to heroin, already known to the health facility, it is not necessary to carry out checks by means of the systemic test of naloxone, but it is certainly essential to search for the presence of morphine in biological liquids.
It must be emphasized that urinalysis is an integral part of maintenance treatment with methadone, for the control of the presence of narcotic and psychotropic substances.
Possible alcohol abuse must also be checked.
If the urine is positive for opioids, it is essential to reassess the case.
The dosage must be individually defined by the doctor, in order to prevent the onset of the need for heroin, taking into account the psychophysical conditions of the subject and the related pathologies.
During the maintenance phase, some patients receive the same dose of methadone for years; for others, however, this must be periodically changed more or less. In any case, it must be fixed so that the effects of the administration are prolonged for a period of at least 24 hours. Purely as an indication, it should be borne in mind that most patients benefit from doses between 50 and 120 mg / day, depending on the degree of tolerance and the ability to metabolise the drug.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Severe constipation.
Organic heart disease.
Severe hepatic and renal impairment.
Uncompensated diabetes.
Porphyria.
Feeding time.
Hypotension.
Intracranial hypertension.
Cranioencephalic trauma.
Acute asthmatic attack.
Chronic obstructive pulmonary disease.
Respiratory failure.
Pulmonary heart.
Hypovolemia.
Methadone is contraindicated in pregnancy, due to possible effects on fetal development, and during lactation, except in the cases indicated in section 4.6.
Methadone is not indicated in obstetric analgesia since its long duration of action increases the likelihood of respiratory depression in the newborn.
Methadone is not recommended as an analgesic in children, as documented clinical experience has been insufficient to establish a suitable dosing schedule for pediatric subjects.
04.4 Special warnings and appropriate precautions for use
Drug addiction
Methadone can cause morphine drug dependence.
After repeated administration, psychic dependence, physical dependence and tolerance can occur and therefore it must be prescribed and administered with the same caution that is adopted for morphine.
Interaction with other central nervous system depressants
Methadone should be used with caution and at a reduced dose in patients receiving concomitant other narcotic analgesics, general anesthetics, phenothiazines, other sedative hypnotic tranquilizers, tricyclic antidepressants and other central nervous system depressants, including alcohol. Depression and sedation may occur. deep or coma.
Anxiety
Methadone has no anti-anxiety action, so anxiety symptoms that appear during treatment should not be treated by increasing the dose of methadone.
The action of methadone in the treatment of addiction is limited to the control of narcotic symptoms and is ineffective for the relief of anxiety.
Head injuries and increased intracranial pressure
The respiratory depression effects of methadone and its ability to increase cerebrospinal fluid pressure can be greatly enhanced in the presence of increased intracranial pressure; moreover, narcotics produce side effects that can confuse the clinical course of patients with head injuries. In such patients, methadone is contraindicated (see section 4.3).
Asthma and other respiratory affections
In patients with acute asthma attack, in those with chronic obstructive pulmonary disease or cor pulmonale and in individuals with substantially reduced respiratory reserve in pre-existing respiratory depression, hypoxia and hypercapnia, even the usual therapeutic doses of narcotics can reduce respiratory stimuli. and on the other hand increase the resistance of the airways up to apnea, so the use of the drug is contraindicated in these pathologies (see section 4.3).
Acute abdominal affections
Administration of methadone or other narcotics can confuse the diagnosis and clinical course in patients with acute abdominal disease.
Hypotensive effect
Administration of Methadone can cause severe hypotension in hypovolaemic subjects or in concomitant treatment with drugs such as phenothiazine or certain anesthetics.
Use in outpatients
In outpatients, methadone can cause orthostatic hypotension.
Use of narcotic antagonists
In an individual with physical narcotic addiction, administration of the usual dose of a narcotic antagonist will trigger an acute withdrawal syndrome. The severity of this syndrome will depend on the degree of physical dependence and the dose of antagonist administered.
The use of narcotic antagonists in this subject should be avoided if possible.
If it is to be used to treat severe respiratory depression in the physically dependent patient, the antagonist should be administered with extreme caution and graduated with lower than usual doses.
Special risk patients
Methadone should be administered with caution and the starting dose should be reduced in elderly and debilitated patients and in patients with hypothyroidism, Addison's disease, prostatic hypertrophy, urethral stricture.
Cases of QT interval prolongation and torsades de pointes have been reported with methadone treatment, particularly at high doses> 100 mg / day. QT interval, e.g. in case of a history of QT prolongation, advanced heart disease, concomitant treatment with drugs that can prolong QT.
Important information about some of the ingredients
MOLTENI METHADONE HYDROCHLORIDE contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose / galactose malabsorption or sucrase / isomaltase insufficiency should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Pharmacokinetic interactions
Methadone is a substrate of P-glycoprotein, therefore drugs that inhibit it (quinidine, verapamil) can increase serum concentrations of methadone. Methadone is metabolized by the CYP3A4 isoenzyme. Inducers of this isoenzyme (barbiturates, carbamazepine, phenytoin, nevirapine, rifampicin) can induce hepatic metabolism of methadone, which will be more significant if the inducer is added after it has been started. methadone therapy.
As a result of these interactions, cases of withdrawal syndrome have been reported, requiring increased doses of methadone.
When CYP3A4 inducer therapy is discontinued, the methadone dose should be reduced. CYP3A4 inhibitors (cannabinoids, clarithromycin, delavirdine, erythromycin, fluconazole, grapefruit juice, selective serotonin reuptake inhibitors, itraconazole, ketoconazole and nefazodone) may cause increased methadone concentration.
Methadone decreases the AUC and Cmax of didanosine and stavudine, reducing the bioavailability of these drugs.
Methadone can also slow the absorption and increase the first pass metabolism of these drugs.
Methadone increases the plasma concentration of zidovudine both orally and intravenously, and also causes an increase in the AUC of zidovudine by the oral route, higher than that by the intravenous route. These effects are due to the inhibition of the glucuronidation of zidovudine and its reduced renal clearance.
During treatment with methadone, patients should be monitored for possible zidovudine toxicity and the zidovudine dose may need to be reduced.
Patients receiving both drugs may develop symptoms typical of opioid withdrawal syndrome (headache, myalgia, fatigue and irritability).
Antiretroviral protease inhibitors can inhibit the metabolism of methadone to varying degrees, but the most significant reactions occur with ritonavir, while the possible interaction with abacavir generally does not require dose adjustments. Efavirenz induces the metabolism of methadone. through the cytochrome P4503A4 pathway.
Following 3-week therapy with efavirenz, mean peak methadone concentrations and AUC decreased by 48% and 57%, respectively.
Some reports suggest that if efavirenz is added to a patient on methadone therapy, a withdrawal syndrome may develop, which usually begins after two weeks of efavirenz therapy, but can last for up to 28 days. the dose may need to be adjusted.
Methadone excretion decreases when co-administered with drugs that inhibit CYP3A4, such as some anti-HIV agents, macrolide antibiotics, cimetidine, azole antifungals (since the metabolism of methadone is mediated by the CYP3A4 isoenzyme) .
In patients taking drugs that affect cardiac conduction or drugs that can affect electrolyte balance there may be a risk of cardiac events with concomitant methadone. In such cases it may be useful to perform an ECG.
Methadone is a weak base. Urinary acidifiers (ammonium chloride) can increase the renal clearance of methadone. In this situation, the methadone doses need to be increased.
Pharmacodynamic interactions
Opioid antagonists (naloxone and naltrexone) have a "pharmacological action opposite to that of methadone. These drugs can block their action and cause withdrawal syndrome. Agonists / antagonists (butorphanol, nalbuphine, pentazocine) can partially block the" analgesia, respiratory depression and central nervous system depression due to methadone. Used simultaneously they can cause an increase in neurological, respiratory and hypotensive effects.
The additive or antagonistic effects depend on the dose of methadone; antagonistic effects are more frequent when methadone is used in low or moderate doses. In patients on chronic methadone therapy, these drugs can cause withdrawal syndrome.
The concomitant administration of methadone and drugs that exert a CNS depressant action (other narcotic analgesics, general anesthetics, phenothiazines, other tranquilizers, hypnotic sedatives, tricyclic antidepressants and other central nervous system depressants including alcohol) can cause an increase respiratory depression, hypotension and profound sedation or coma, therefore it may be necessary to reduce the dose of one or both drugs.
The concomitant use of methadone and antidiarrheals (diphenoxylate, loperamide) can lead to severe constipation and possibly to an increase in CNS depression.
Opioid analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
Octreotide may reduce the analgesic effect of methadone and morphine, therefore if there is a loss or reduction in pain control, discontinuation of octreotide should be considered.
Interactions with monoamine oxidase (MAO) inhibitors
Because of the possibility of severe reactions, if methadone is necessary in patients treated with MAO inhibitors, a sensitivity test should be performed, in which small increasing doses are administered over several hours during which the patient must be treated. carefully checked.
04.6 Pregnancy and lactation
Methadone is contraindicated in pregnancy, due to possible effects on fetal development, and during lactation.
Moreover, in the presence of an "evident inability of the pregnant drug addict to stop the use of heroin, the doctor can decide to implement maintenance treatment with methadone."
This treatment must be continued until the end of pregnancy at basically stable dosages, in order to avoid the possible appearance of withdrawal symptoms in the mother and fetus.
If necessary, methadone doses can be increased during the later stages of pregnancy to maintain adequate drug levels and thus avoid any withdrawal from therapy.
However, as with any other pharmacological treatment, the risk and benefit aspects that it entails must be carefully evaluated.
The reduction of the drug, if necessary, must be very gradual, since the onset of withdrawal symptoms must be avoided.
Any suspension of treatment, for which the supervision of an obstetric specialist is essential, must be carried out no earlier than the 14th week of gestation and not after the 32nd week, respectively, to avoid the risk of abortion and pre-term birth.
04.7 Effects on ability to drive and use machines
Methadone can alter the mental and / or physical abilities needed to perform potentially dangerous jobs such as driving a car or operating machines.
The patient must therefore be advised.
04.8 Undesirable effects
The following are the side effects of methadone hydrochloride, organized according to the MedDRA classification. Insufficient data are available to establish the frequency of the individual effects listed.
The main risks of methadone are respiratory depression and to a lesser extent circulatory depression, respiratory arrest, shock and cardiac arrest.
Rare cases of QT interval prolongation and torsades de pointes have been reported.
The most frequently observed side effects include: lightheadedness, dizziness, sedation, nausea, vomiting, sweating and orthostatic hypotension. Some of these effects, which are more common in outpatient treatment, can be avoided by keeping patients lying down.
Other side effects are the following.
Nervous system disorders
Euphoria, dysphoria, weakness, headache, insomnia, agitation, disorientation and visual disturbances.
Gastrointestinal disorders
Dry mouth, anorexia, constipation and spasm of the biliary tract.
Cardiac and vascular diseases
Facial flushing, bradycardia, palpitations, fainting and syncope.
Renal and urinary disorders
Urinary retention or difficulty urinating, antidiuretic effect.
Diseases of the reproductive system and breast
Reduced libido and / or sexual impotence.
Disorders of the immune system
Itching, hives, other skin reactions, edema and rarely hemorrhagic urticaria.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "Street address:
www.agenziafarmaco.gov.it/it/
04.9 Overdose
Symptoms
Respiratory depression (decrease in respiratory rate and / or vital capacity, Cheyne-Stokes breathing, cyanosis), extreme drowsiness leading to stupor or coma, considerable miosis, flaccidity of skeletal muscles occurs following a significant overdose of methadone , cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdose, especially intravenously, there can be: apnea, circulatory collapse, cardiac arrest and death.
Treatment
Particular attention must be paid to restoring adequate respiratory exchange by freeing the airways and instituting assisted and controlled ventilation.
If a non-tolerant person, especially a child, accidentally takes or takes a high dose of methadone, effective narcotic antagonists are available to counteract life-threatening respiratory depression.
It must be remembered, however, that methadone is a long-acting depressant (36 to 48 hours), while the antagonists used to treat overdose act for much shorter periods (1 to 3 hours).
Therefore, the patient should be continuously monitored for a recurrence of respiratory depression and should be treated repeatedly with the narcotic antagonist, as needed.
If the diagnosis is correct and respiratory depression is due only to an overdose of methadone, the use of other breath stimulants is not indicated. An antagonist should not be administered in the absence of clinically significant respiratory or cardiovascular depression.
Intravenous narcotic antagonists (naloxone, nalorphine and levallorfane) are drugs of choice for eliminating symptoms of intoxication.
These drugs must be administered repeatedly until the patient's condition remains satisfactory.
The risk of the narcotic antagonist further depressing breathing is less likely if naloxone is used. Depending on the indication, oxygen, intravenous fluids, vasopressors and other supportive measures should be employed.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: drugs used in opioid addiction.
ATC code: N07BC02.
Methadone hydrochloride is a synthetic opioid analgesic, an agonist of mc receptors, with pharmacological activities qualitatively similar to those of morphine.
The effects of the administration of methadone, also active orally, are the rapid onset of analgesia, the long duration of action in the suppression of withdrawal symptoms in physically dependent subjects and, after repeated administration, the tendency to exert persistent effects.
Withdrawal of the drug causes a withdrawal syndrome similar, in qualitative terms, to that of morphine, diversifying for a more gradual onset, a course that is on average longer lasting and with less severe symptoms.
The oral use causes a gradual onset, a decrease in the maximum level and a longer duration of the analgesic effect.
05.2 "Pharmacokinetic properties
Methadone is rapidly absorbed by oral administration (thanks to an action mediated by P-glycoprotein - see section 4.5) and is recovered in the plasma within 30 minutes of administration, reaching maximum blood concentration in the following 3-4 hours (with an analgesic effect that begins 45 minutes after administration. After subcutaneous or intramuscular administration the analgesic effect begins after 15 minutes).
Approximately 85% of the methadone present in plasma circulates bound to proteins; in vitro it was observed that 44% binds to albumin, 17% to gamma globulins, so from the comparison with the data for total proteins, no it follows that a fraction also binds to alpha-globulins and beta-globulins.
Methadone is distributed in the tissues, passes the placental barrier and is excreted in the milk.
Methadone is mainly metabolised by the liver (by the CYP3A4 isoenzyme - see section 4.5).
Unchanged methadone and its hepatic metabolites (mainly products of N-demethylation and cyclization) are excreted with the bile and in the urine.
Pharmacokinetics show wide interindividual variations and differences following single or repeated administration.
The elimination half-life can vary considerably (15 to 60 hours), resulting in the need for careful dosage adjustment.
In non-tolerant subjects, the mean apparent half-life after a single dose is approximately 15 hours, while after chronic administration, the apparent half-life is 22 hours.
05.3 Preclinical safety data
Racemic methadone hydrochloride showed an LD50 of 95 mg / kg orally in rats, while intravenously the LD50 was 32 mg / kg in mice and 29 mg / kg in dogs.
Administration during pregnancy can cause effects on the central nervous system and on growth in newborns.
In particular, the minimum dose at which toxic effects on the newborn are evident is, intraperitoneally in the pregnant rat, equal to a total of 135 mg / kg, administered between the 1st and 22nd day of gestation.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Sucrose, glycerol, sodium benzoate, lemon flavor, citric acid, purified water
06.2 Incompatibility
Not known.
06.3 Period of validity
Methadone hydrochloride MOLTENI 1 mg / ml oral solution
Packs of 5 ml, 10 ml and 20 ml: two years.
Packs of 40 ml 60 ml, 100 ml, 500 ml and 1000 ml: five years.
After first opening the multidose bottle (100 ml, 500 ml and 1000 ml): 2 months.
Methadone hydrochloride MOLTENI 5 mg / ml oral solution
Two years.
After first opening the multidose bottle (1000 ml): 8 months.
06.4 Special precautions for storage
Keep in the original package tightly closed to protect the medicine from light.
06.5 Nature of the immediate packaging and contents of the package
Methadone hydrochloride MOLTENI 1 mg / ml oral solution
Packs of 5 ml, 10 ml and 20 ml, 40 ml, 60 ml, 100 ml and 500 ml: amber PVC bottle with screw cap and polyethylene seal.
Package of 1000 ml: amber PVC bottle closed with safety seal and screw cap with polyethylene gasket.
Packages subject to special medical prescription have a child-resistant closure.
The packs of 100 ml, 500 ml and 1000 ml are supplied with a 30 ml measuring cup, calibrated at 5-10-15-20-25-30 ml.
Methadone hydrochloride MOLTENI 5 mg / ml oral solution
Packs of 5 ml, 10 ml and 20 ml: amber PVC bottle with screw cap and polyethylene seal.
Package of 1000 ml: amber PVC bottle closed with safety seal and screw cap with polyethylene gasket.
Packages subject to special medical prescription have a child-resistant closure.
The 1000 ml pack is supplied with a calibrated measuring cup from 1 to 6 ml, equal to 5-30 mg of methadone hydrochloride.
06.6 Instructions for use and handling
No special instructions.
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
L. Molteni & C. dei F.lli Alitti Company of Exercise SpA, S.S. 67, Hamlet of Granatieri, Scandicci (FI)
08.0 MARKETING AUTHORIZATION NUMBER
1 mg / ml oral solution 5 ml bottle with child resistant closure AIC n. 029610019
1 mg / ml oral solution 5 ml bottle AIC n. 029610134
1 mg / ml oral solution 10 ml bottle with child resistant closure AIC n. 029610021
1 mg / ml oral solution 10 ml bottle AIC n. 029610146
1 mg / ml oral solution 20 ml bottle with child resistant closure AIC n. 029610033
1 mg / ml oral solution 20 ml bottle AIC n. 029610159
1 mg / ml oral solution 40 ml bottle with child resistant closure AIC n. 029610072
1 mg / ml oral solution 40 ml bottle AIC n. 029610173
1 mg / ml oral solution 60 ml bottle with child resistant closure AIC n. 029610084
1 mg / ml oral solution 60 ml bottle AIC n. 029610185
1 mg / ml oral solution 100 ml bottle with child resistant closure AIC n. 029610045
1 mg / ml oral solution 100 ml bottle AIC n. 029610161
1 mg / ml oral solution 500 ml bottle AIC n. 029610058
1 mg / ml oral solution 1000 ml bottle AIC n. 029610060
5 mg / ml oral solution 5 ml bottle with child resistant closure AIC n. 029610096
5 mg / ml oral solution 5 ml bottle AIC n. 029610197
5 mg / ml oral solution 10 ml bottle with child resistant closure AIC n. 029610108
5 mg / ml oral solution 10 ml bottle AIC n. 029610209
5 mg / ml oral solution 20 ml bottle with child resistant closure AIC n. 029610110
5 mg / ml oral solution 20 ml bottle AIC n. 029610211
5 mg / ml oral solution 1000 ml bottle AIC n. 029610122
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
December 1993 / December 2008
10.0 DATE OF REVISION OF THE TEXT
September 2015
