Active ingredients: Lormetazepam
Minias 1 mg coated tablets
Minias 2 mg coated tablets
Minias package inserts are available for pack sizes: - Minias 1 mg coated tablets, Minias 2 mg coated tablets
- Minias 2.5 mg / mL oral drops, solution
Indications Why is Minias used? What is it for?
What is Minias and what is it for
Minias belongs to the pharmaceutical category of benzodiazepines, sedative-hypnotic drugs.
Therapeutic indications
This medicine is used for the short-term treatment of insomnia.
Benzodiazepines are indicated only when insomnia is severe, disabling and subjects the subject to severe discomfort.
Contraindications When Minias should not be used
Do not take Minias
If it's:
- allergic to lormetazepam, benzodiazepines or any of the other ingredients of this medicine;
- if you are pregnant or breastfeeding (see "Pregnancy and breastfeeding").
If you suffer from:
- myasthenia gravis (a severe muscle function disorder);
- spinal and cerebellar ataxia (severe movement coordination disorder);
- severe respiratory failure (the inability of the lungs to absorb oxygen and eliminate carbon dioxide effectively eg severe chronic obstructive pulmonary disease);
- severe liver failure (impaired liver function).
If you have:
- sleep apnea (shortness of breath) syndrome;
- narrow-angle glaucoma (rapid increase in pressure in the eye);
- acute intoxication (excessive use) from alcohol, hypnotics (sleeping pills), analgesics (pain relievers) or psychotropic drugs (medicines that affect psychic functions such as neuroleptics, antidepressants, lithium).
Talk to your doctor or pharmacist before taking Minias.
Talk to your doctor especially if:
- have a history of drug or alcohol abuse;
- suffer from spinal and cerebellar ataxia (severe movement coordination disorder) (see "Do not take Minias");
- suffer from chronic respiratory failure (the inability of the lungs to absorb oxygen and eliminate carbon dioxide effectively). In this case, your doctor will prescribe a lower dose due to the risk of respiratory depression (increased level of carbon dioxide in the blood) (see "How to take Minias" and "Do not take Minias").
- suffer from liver failure (impaired liver function). In this case the doctor will decide whether to prescribe a lower dose (see "How to take Minias"), since in patients with severe hepatic insufficiency and / or encephalopathy the use of benzodiazepines can aggravate hepatic encephalopathy (altered level of consciousness and coma due to liver failure).
- suffer from severe kidney failure (reduced kidney function);
- suffer from heart failure (weak heart) and low blood pressure, as in this case you will need to be checked regularly during treatment with this medicine;
- is an elderly person. In this case, your doctor will prescribe a reduced dose, as some adverse reactions may occur, such as lack of coordination in movements.
Benzodiazepines, like this medicine, and benzodiazepine-like agents are only indicated when the disorder is severe, disabling, or makes the person very unwell.
Benzodiazepines are not recommended for the primary treatment of psychotic illnesses and should not be used alone to treat depression or anxiety associated with depression (suicide may have precipitated in such patients) (see "Patients with psychosis").
Treatment with Minias, as with all benzodiazepines, should be as short as possible: maximum four weeks, including a gradual withdrawal period at the end.
Precautions for use What you need to know before taking Minias
Tolerance
After repeated use for a few weeks, some loss of efficacy of the drug's hypnotic effects ("tolerance") may develop.
Addiction and abuse
The use of this medicine and other benzodiazepines can lead to the development of physical and psychological dependence on these medicines. The risk of this increases with dose and duration of treatment, and is greater in patients who use drugs or abuse. alcohol Therefore, if you have a history of alcohol or drug abuse use this medicine with extreme caution The possibility of dependence is reduced when this medicine is used in the appropriate dose with short term treatment.
Abuse of benzodiazepines has been reported.
Withdrawal symptoms
Once physical dependence has developed, abrupt cessation of treatment may be accompanied by withdrawal symptoms (see section "Undesirable effects"). These may consist of:
- extreme anxiety, tension, restlessness, confusion, irritability, headache, muscle aches.
In severe cases, the following symptoms may occur:
- derealization (the sensation of perceiving reality in a distorted way, as unreal or unfamiliar), depersonalization (the loss of a sense of personal identity), hyperacusis (difficulty in tolerating certain sounds), numbness and tingling of the extremities, paresthesia of the limbs ( sensitivity in the limbs), hypersensitivity to light, noise and physical contact, hallucinations (seeing or hearing things that are not present in reality) and seizures.
Other symptoms are:
- depression, insomnia, sweating, persistent tinnitus (noise in the ear), involuntary movements, vomiting, paraesthesia (changes in sensation), perceptual changes, abdominal and muscle cramps, tremor, myalgia (muscle pain), agitation, palpitations, tachycardia (acceleration heartbeat), panic attacks, dizziness, hyper-reflexia (accentuation of reflexes), short-term memory loss, hyperthermia (increased body temperature).
Upon discontinuation of treatment, the following may also occur:
- rebound insomnia, a transient syndrome in which symptoms that led to treatment with benzodiazepines recur in an aggravated form. This can be accompanied by other reactions including: mood changes, anxiety, restlessness or sleep disturbances.
In case of administration of short-acting benzodiazepines, withdrawal symptoms may appear in the dosing interval, particularly at high doses. However, when switching to treatment with Minias after using benzodiazepines with a significantly longer duration of action for a prolonged period of time and / or at high doses, withdrawal symptoms may occur.
Withdrawal symptoms, especially the more severe ones, are more common in those patients who have been taking excessive doses for a long period of time; however, they can also occur after discontinuation of benzodiazepines taken continuously at therapeutic dosages, especially if the suspension occurs abruptly.
Since the risk of withdrawal or rebound symptoms is greater after abrupt discontinuation of treatment, discontinuation of treatment should be done with a gradual decrease in dosage.
Amnesia
Minias can induce anterograde amnesia (difficulty memorizing new information). This happens most often in the first few hours after ingestion of the medicine and therefore, to reduce the risk, make sure you can sleep for 7-8 hours without interruption before taking Minias (see "Possible side effects").
Psychiatric and paradoxical reactions
The use of benzodiazepines, like this medicine, can lead to reactions such as restlessness, agitation, irritability, aggression, delirium, delusion, anger, anger, nightmares, hallucinations (seeing or hearing things that are not present in reality), psychosis (disturbance characterized by detachment from reality), inappropriate behavior and other changes in behavior. If this happens, stop using the medicine. These reactions are more likely to occur in children and the elderly as well as in patients with organic brain syndrome (decreased mental function). While using benzodiazepines, including Minias, a pre-existing depressive state may be unmasked. If you have depression you should use Minias with caution.
Children and adolescents
Minias should not be used in patients under 18 years of age. If children need to be given the medicine, the doctor will first assess the need for treatment. The duration of treatment should be as short as possible (see "Use in children and adolescents").
Senior citizens:
The use of benzodiazepines, including this medicine, may be associated with an increased risk of falls due to side effects such as ataxia (lack of coordination in movement), muscle weakness, dizziness, sleepiness, tiredness and fatigue. In this case, your doctor. will prescribe a reduced dose (see 'Use in the elderly').
Patients with psychosis (mental illness):
Minias should not be used alone for the treatment of insomnia associated with depression.
Benzodiazepines are not recommended for the primary treatment of psychotic illnesses and should not be used alone to treat depression or anxiety associated with depression (the risk of suicide may be increased in these patients).
Interactions Which drugs or foods can modify the effect of Minias
Interactions with other medicines:
- Other psychotropic drugs (medicines that affect the central nervous system); The combination of these medicines with Minias requires special attention and vigilance from the doctor to avoid unexpected undesirable effects from interaction.
- Medicines that depress respiratory function, such as opioids (analgesics [pain relievers], antitussives [against cough], replacement treatments), particularly in elderly patients; the combination with these medicinal products requires special attention.
Medicines that depress the central nervous system (CNS):
- Antipsychotics (medicines to treat mental illnesses), hypnotics (medicines to facilitate sleep), anxiolytics / tranquilizers / sedatives, some antidepressants, narcotic analgesics and opioid anesthetics (pain relievers) particularly if you are an elderly patient, antiepileptics (medicines to treat "epilepsy), anticonvulsants (medicines for seizures) and sedative antihistamines (some medicines to treat allergies that induce sedation)." Concomitant use of these medicines with Minias may increase the "effect of these" last and narcotic analgesics can cause an increase in euphoria leading to an increase in psychic dependence.
- Cytochrome P450 inhibitors (medicines that slow the activity of certain enzymes involved in drug metabolism); they can increase the activity of benzodiazepines.
- Cardiac glycosides (medicines for heart failure); concomitant use may increase the levels of cardiac glycosides in the blood.
- Beta-blocking agents (medicines for the treatment of arrhythmias and heart failure); may increase the clinical effects of Minias.
- Methylxanthines, theophylline or aminophylline (antiasthmatics), rifampicin (antibiotic); can reduce the effect of Minias.
- Medicines containing estrogen (hormones); concomitant use may reduce blood levels of benzodiazepines.
- Clozapine (medicine to treat mental illness); concomitant use with Minias can produce marked sedation, excessive salivation, ataxia (loss of coordination of movements).
Minias with alcohol
Do not drink alcohol while taking Minias. Benzodiazepines cause an additive effect when taken with alcohol.
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.
Do not take this medicine during pregnancy and breastfeeding (see "Do not take Minias").
If you have been prescribed Minias and you are a woman of childbearing potential, please contact your doctor regarding discontinuation of treatment if you intend to become pregnant or suspect that you are pregnant. If, for serious medical reasons, Minias is administered during the last period effects on the newborn such as hypothermia (decrease in body temperature from normal), hypotonia (loss of muscle tone), hypotension (low blood pressure), difficulty in sucking (" infant hypotonia ") and moderate respiratory depression (increased level of carbon dioxide in the blood) due to the" pharmacological action of the medicine.
In addition, infants born to mothers who have taken Minias or other long-term benzodiazepines during late pregnancy may develop physical dependence and may be at some risk of developing withdrawal symptoms in the postpartum period.
As small amounts of this medicine may pass into breast milk, do not take Minias if you are breastfeeding (see "Do not take Minias").
Driving and using machines
Minias significantly affects the ability to drive or use machines as it causes sedation, amnesia (memory loss), impaired concentration and impaired muscle function. If your sleep time has been insufficient, there may be a greater chance that your alertness is altered.
Reactions can be altered in relation to the time of ingestion, its individual sensitivity and the dose taken. This occurs with a "high dose in combination with alcohol (see" MINIAS with alcohol ").
Minias contains lactose
This medicinal product contains lactose. If you have been told by your doctor that you have "intolerance to some sugars, contact your doctor before taking this medicinal product.
Dosage and method of use How to use Minias: Dosage
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
Unless otherwise prescribed, the recommended dose for adults is 1-2 mg, i.e .:
1 mg tablets: 1-2 tablets
2 mg tablets: ½ (half) - 1 tablet
The availability of divisible tablets facilitates the administration of the correct dose. Take the tablets with some liquid, without chewing them, half an hour before bedtime.
The maximum dose should not be exceeded.
Use in children and adolescents
The doctor will prescribe MINIAS to patients under the age of 18 only when absolutely necessary and only after careful consideration. The duration of treatment should be as short as possible.
The dosage will only be determined by the doctor.
Use in the elderly
In elderly patients the single dose is 0.5-1 mg, i.e .:
1 mg tablets: ½ (half) 1 tablet
2 mg tablets: ¼ (quarter) - ½ (half) tablet
Use in patients with chronic respiratory failure or impaired liver and / or renal function
Your doctor will carefully establish the appropriate dosage for you and will evaluate a possible reduction in the above doses.
Duration of treatment
Your doctor will explain to you that the treatment is of limited duration and that the dose can be progressively decreased before the end of the treatment.
Treatment with Minias should be as short as possible. Your doctor will regularly re-evaluate your condition and the need for continued treatment with this medicine, particularly if you are symptom-free.
The duration of treatment generally ranges from a few days to two weeks, up to a maximum of four weeks, including a gradual withdrawal period.
In certain cases, it may be necessary to extend beyond the maximum treatment period, but this will only take place after your doctor has reviewed your condition.
Treatment should be started with the lowest recommended dose and should be increased taking care not to exceed the maximum dose, and be as short as possible.
In case of treatment longer than two weeks, the administration of Minias should not be stopped abruptly, as the sleep disturbances may temporarily recur with a higher intensity. For this reason it is recommended to end the treatment by gradually reducing the doses taken.
Overdose What to do if you have taken too much Minias
If you take more Minias than you should
In case of accidental ingestion / intake of an overdose of Minias, notify your doctor immediately or go to the nearest hospital.
As with other benzodiazepines, an overdose of Minias is not expected to be life-threatening unless concomitant medication which depresses the central nervous system (including alcohol) is taken. Benzodiazepine overdose usually occurs. with varying degrees of central nervous system depression ranging from clouding (momentary blurring of the senses or reason) to coma.
Symptoms of mild intoxication are drowsiness, fatigue, ataxia (loss of coordination of movement), disturbed vision, drowsiness (momentary blurring of the senses or reason), mental confusion and lethargy (predisposition to continuous sleep and failure to respond to normal stimuli ).
Oral administration of higher doses can lead to symptoms ranging from deep sleep to unconsciousness, ataxia (loss of movement coordination), hypotonia (loss of muscle tone), hypotension (low blood pressure), respiratory depression (increased level of anhydride carbon dioxide in the blood), rarely coma and, very rarely, death.
Treatment of overdose
In the treatment of overdose, the possibility that other substances have been taken at the same time will be considered and that respiratory depression (increased level of carbon dioxide in the blood), rarely coma and, very rarely, death may occur.
Patients with milder symptoms of intoxication should sleep under observation. Following an overdose of oral benzodiazepines, vomiting should be induced (within one "hour) if the patient is conscious, or gastric lavage with respiratory protection undertaken if the patient is unconscious.
If no improvement is seen with stomach emptying, activated charcoal should be given to reduce absorption.
Special attention must be paid to respiratory and cardiovascular functions in emergency therapy.
In case of hypotension (low blood pressure), norepinephrine and volume medications should be used. Assisted ventilation is required in case of respiratory compromise, which can also be caused by peripheral muscle relaxation. In the presence of mixed intoxication, hemodialysis and peritoneal dialysis (blood dialysis) may be useful. However, they are not effective in mono-intoxication with Minias.
As an antidote (to nullify the harmful effects of the medicine) Flumazenil may be useful.
Morphine antagonists are contraindicated.
If you stop taking Minias
Discontinuation of treatment with this medicine should be done by gradually reducing the dosage. Discontinuation, especially if abrupt, may be accompanied by withdrawal symptoms (see "Withdrawal Symptoms").
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 Minias
Like all medicines, this medicine can cause side effects, although not everybody gets them.
At the start of treatment, daytime sleepiness, emotional disturbances, depressed consciousness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia (loss of movement coordination) or diplopia (double vision) may occur. they generally disappear with continued treatment.
The most frequently observed adverse reactions in patients receiving Minias are headache, sedation and anxiety.
The most serious adverse reactions in patients receiving Minias are angioedema (swelling of the skin of the face, lips and tongue), suicide or attempted suicide in association with unmasking a pre-existing depression.
Very common side effects (may affect more than 1 in 10 people)
- headache.
Common side effects (may affect up to 1 in 10 people)
- angioedema * (swelling of the skin on the face, lips and tongue),
- anxiety,
- decreased libido (decreased sexual desire),
- dizziness§,
- sedation,
- drowsiness§,
- attention disorder,
- amnesia (memory disorder) §,
- impaired vision,
- speech disorder,
- dysgeusia (altered taste),
- psycho-motor slowdown,
- diplopia (double vision),
- tachycardia (rapid heart rate),
- He retched,
- nausea,
- pain in the upper abdomen,
- constipation (constipation),
- dry mouth,
- itch,
- urination disorder (urination disorder),
- asthenia (reduction in muscle strength),
- hyperhidrosis (excessive sweating).
Rare side effects (may affect up to 1 in 1,000 people)
- anaphylactic / anaphylactoid reactions (severe allergic or allergic-like reactions),
- increased bilirubin (a pigment contained in bile),
- jaundice (yellowing of the skin, mucous membranes and whites of the eyes),
- increased liver transaminases (liver enzymes),
- increased alkaline phosphatase (an enzyme),
- thrombocytopenia (lack of platelets in the blood),
- agranulocytosis (lack of blood cells called granulocytes),
- pancytopenia (deficiency of all types of blood cells),
- syndrome of inappropriate antidiuretic hormone secretion (hormonal disorder).
Undesirable effects with frequency not known (frequency cannot be estimated from the available data)
- suicide (unmasking of pre-existing depression) *,
- attempted suicide (unmasking of pre-existing depression) §
- acute psychosis (mental disorder) §,
- hallucination (seeing or hearing things that are not present in reality) §,
- dependence§ ,
- depression (unmasking of pre-existing depression) §,
- delirium§,
- withdrawal syndrome (rebound insomnia) §,
- agitation§,
- aggression§,
- irritability§,
- restlessness§,
- anger§,
- nightmare§ ,
- abnormal behavior§,
- emotional disturbance,
- confusional state,
- reduction of vigilance,
- ataxia (loss of coordination of movements) §,
- muscle weakness§,
- dizziness,
- urticaria,
- rash (on the skin),
- fatigue,
- fall.
* life-threatening or fatal cases have been reported
§ see "Warnings and precautions"
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
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 about 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 carton after expiry. The expiry date refers to the last day of that month. The expiry date refers to the product in intact packaging, correctly stored.
Keep at a temperature not exceeding 25 ° C.
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.
Contents of the pack and other information
What Minias
- The active ingredient is lormetazepam.
1 mg coated tablets: Each coated tablet contains 1 mg of lormetazepam.
2 mg coated tablets: Each coated tablet contains 2 mg of lormetazepam.
- The other ingredients are: lactose, maize starch, povidone 25,000, magnesium stearate, quinoline yellow SS-E 104 (2 mg tablets only), Eudragit E 30 D, talc, titanium dioxide, macrogol 5/6000, polysorbate 80, sodium caramelose, silicone oil.
Description of the appearance of Minias and contents of the package
Carton with 30 coated tablets.
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
MINIAS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
MINIAS 1 mg coated tablets
Each coated tablet contains:
Active ingredient: lormetazepam 1 mg
Excipient: lactose
For the full list of excipients see section 6.1
MINIAS 2 mg coated tablets
Each coated tablet contains:
Active ingredient: Lormetazepam 2 mg
Excipient: lactose
For the full list of excipients see section 6.1
MINIAS 2.5 mg / ml oral drops, solution
100 ml of solution contain:
Active ingredient: lormetazepam 250 mg
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Coated tablets.
Oral drops, solution.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Short-term treatment of insomnia.
Benzodiazepines are indicated only when insomnia is severe, disabling and subjects the subject to severe discomfort.
04.2 Posology and method of administration
Route of administration
Oral use.
Dosage
Treatment should be as short as possible. The patient should be re-evaluated regularly and the need for continued treatment should be carefully considered, particularly if the patient is symptom-free.
The duration of treatment generally ranges from a few days to two weeks, up to a maximum of four weeks, including a gradual withdrawal period.
In certain cases, extension beyond the maximum treatment period may be necessary; if so, it should not take place without reassessment of the patient's condition.
Treatment should be started with the lowest recommended dose, to be increased taking care not to exceed the maximum dose, and to be as short as possible.
In case of treatment longer than two weeks the administration of MINIAS should not be stopped abruptly, as the sleep disturbances may temporarily recur with a higher intensity. For this reason it is recommended to conclude the treatment by gradually reducing the doses, also facilitated by the pharmaceutical forms.
The maximum dose should not be exceeded.
Unless otherwise prescribed, the single dose in adults is 1-2 mg (1 mg is equivalent to 10 drops).
In elderly patients the single dose is 0.5 - 1 mg.
In the treatment of patients with impaired hepatic and / or renal function, as well as in subjects with chronic respiratory insufficiency, a "possible reduction of the dosages indicated above should be considered.
Pediatric population
Children and adolescents
The administration of MINIAS for the treatment of insomnia to patients under the age of 18 is not recommended without a careful assessment of its need. The single dose for patients under 18 depends on their age, weight and general condition The duration of treatment should be as short as possible.
The availability of divisible tablets and drops makes dosage easier.
The tablets should be taken with a little liquid, without chewing them, half an hour before going to bed.
The drops should be diluted in a little liquid, half an hour before going to bed.
04.3 Contraindications
Hypersensitivity to benzodiazepines or to any of the excipients of Minias
Myasthenia gravis.
Spinal and cerebellar ataxia.
Severe respiratory failure (e.g. severe chronic obstructive pulmonary disease).
Sleep apnea syndrome.
Narrow angle glaucoma.
Severe hepatic insufficiency.
Acute intoxication with alcohol, hypnotic, analgesic or psychotropic drugs (neuroleptics, antidepressants, lithium).
Contraindicated during pregnancy and lactation (see section 4.6).
04.4 Special warnings and appropriate precautions for use
Benzodiazepines and benzodiazepine-like agents are indicated only when the disorder is severe, disabling, or makes the subject very uncomfortable.
Tolerance
After repeated use for a few weeks some loss of efficacy of the hypnotic effects of Minias may develop.
Dependence
The use of MINIAS and other benzodiazepines can lead to the development of physical and mental dependence on these drugs. Abuse of benzodiazepines has been documented. The risk of addiction increases with dose and duration of treatment; it is greater in patients with a history of drug or alcohol abuse. Therefore, Minias should be used with extreme caution in patients with a history of alcohol or drug abuse.
The possibility of dependence is reduced when MINIAS is used in the appropriate dose with short-term treatment.
Withdrawal symptoms
Once physical dependence has developed, abrupt discontinuation of treatment will be accompanied by withdrawal symptoms. These may consist of, extreme anxiety, tension, restlessness, confusion, irritability, headache, muscle aches. In severe cases, the following may occur. symptoms: derealization, depersonalization, hyperacusis, numbness and tingling of the extremities, paraesthesia of the limbs, hypersensitivity to light, noise and physical contact, hallucinations and seizures.
Other symptoms are: depression, insomnia, sweating, persistent tinnitus, involuntary movements, vomiting, paraesthesia, perceptual changes, abdominal and muscle cramps, tremor, myalgia, agitation, palpitations, tachycardia, panic attacks, dizziness, hyper-reflexia, loss of short-term memory, hyperthermia.
There is evidence that, in the case of use of benzodiazepines with a short duration of action, withdrawal symptoms may become manifest within the dosing interval, particularly in the case of high doses. This is unlikely to happen with MINIAS because its elimination half-life is around 10 hours. However, when switching to MINIAS after using benzodiazepines with a significantly longer duration of action for an extended period of time and / or at high doses, withdrawal symptoms may occur.
Rebound insomnia and anxiety
Rebound insomnia, a transient syndrome in which symptoms that led to treatment with benzodiazepines recur in an aggravated form, may occur upon discontinuation of treatment. This can be accompanied by other reactions including: mood changes, anxiety, restlessness or sleep disturbances.
Since the risk of withdrawal or rebound symptoms is greater after abrupt discontinuation of treatment, a gradual decrease in dosage is suggested. Furthermore, it is important that the patient is informed of the possibility of rebound phenomena, in order to minimize the anxious reaction that the possible appearance of such symptoms could trigger when MINIAS is suspended.
Duration of treatment
The duration of treatment should be as short as possible (see section 4.2). It generally ranges from a few days to two weeks up to a maximum of four weeks, including tapering off the dose. Extension of therapy beyond these periods should not occur without re-evaluation of the clinical situation. In some cases it may be necessary to extend therapy beyond the maximum treatment period; in this case, it cannot be undertaken without reassessment of the clinical situation.
The patient should be informed when treatment is initiated that it is of limited duration and it must be clearly explained that the dose may be progressively decreased.
For further information regarding patients below 18 years of age see section 4.2
Amnesia
MINIAS can induce antegrade amnesia. This occurs most often in the first few hours after ingestion of the drug and therefore, to reduce the risk, it should be ensured that the patient can have an uninterrupted sleep of 7-8 hours (see section 4.8).
Psychiatric and paradoxical reactions
It is known that reactions such as restlessness, agitation, irritability, aggression, delirium, delusion, anger, anger, nightmares, hallucinations, psychosis, inappropriate behavior and other behavioral changes may occur with the use of benzodiazepines. "use of the medicinal product should be discontinued.
These reactions are more likely to appear in children and the elderly as well as in patients with organic brain syndrome.
For the time being, the possibility cannot be excluded that in patients in an acute state of endogenous psychosis, especially severe depressive states, symptoms are aggravated by the use of MINIAS. Therefore, MINIAS is not recommended for the primary treatment of psychotic illnesses. MINIAS is not recommended. it should be used alone for the treatment of insomnia associated with depression. The presence of depression must always be excluded in particular in the initial and morning sleep disturbances, since the symptoms are also differently masked and the risks caused by the underlying disease are always present (for example suicidal tendencies).
A pre-existing depressive state may be unmasked during the use of benzodiazepines, including MINIAS. MINIAS should be used with caution in patients with depression.
Specific groups of patients
Pediatric patients
For insomnia, MINIAS should not be administered to patients under the age of 18 without careful consideration of the actual need for treatment; the duration of treatment should be as short as possible (see section 4.2).
Elderly patients
The use of benzodiazepines, including MINIAS, may be associated with an increased risk of falls due to undesirable effects such as ataxia, muscle weakness, dizziness, somnolence, tiredness and fatigue and therefore it is recommended that elderly patients be treated with caution. should take a reduced dose (see section 4.2).
Patients with spinal and cerebellar ataxia
Minias should be administered with caution to patients with spinal and cerebellar ataxia.
Patients with chronic respiratory insufficiency
A lower dose is recommended in patients with chronic respiratory failure due to the risk of respiratory depression (see also section 4.3).
Patients with hepatic insufficiency
Single dose pharmacokinetic data of Minias in patients with mild to moderate hepatic impairment are limited. Reduced plasma clearance in these patients leads to a mean 2-fold increase in maximum concentration and systemic exposure (AUC). However, no pharmacokinetic data from clinical trials with repeat administration of Minias are available in this patient population. recommends that patients with severe hepatic insufficiency and / or encephalopathy be treated with caution as MINIAS like all benzodiazepines can precipitate hepatic encephalopathy.
Patients with severe renal insufficiency
MINIAS should be administered with caution to patients with severe renal insufficiency.
Patients with psychosis
Benzodiazepines are not recommended for the primary treatment of psychotic illness.
Benzodiazepines should not be used alone to treat depression or anxiety associated with depression (suicide can be precipitated in such patients). Benzodiazepines should be used with extreme caution in patients with a history of drug or alcohol abuse.
The same prudential measures should be taken for patients with heart failure and low blood pressure who should be regularly monitored during therapy with MINIAS (as is recommended with other benzodiazepines and other psychopharmacological agents).
Alcohol
MINIAS oral drops contain small amounts of ethanol (ethyl alcohol): less than 100 mg per ml (1ml corresponds to 25 drops). It can be dangerous for patients suffering from alcoholism. To be kept in mind in pregnant or breastfeeding women, in children and in high-risk categories, such as patients with liver disease or epilepsy.
Excipients
This medicinal product contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the lactase deficiency, or glucose / galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Concomitant intake with alcohol is not recommended. Benzodiazepines cause an additive effect when the drug is taken with alcohol or other CNS depressant drugs. Particular care should be taken with drugs that depress respiratory function such as opioids ( analgesics, antitussives, substitution treatments) in particular in elderly patients.
Pay attention
Drugs that depress the CNS
Combination with CNS depressant drugs: the central depressive effect may be enhanced in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics / tranquilizers / sedatives, some antidepressants, narcotic analgesics, antiepileptics, anesthetics, opioids, anticonvulsants and antihistamines Sedatives: Narcotic analgesics can cause increased euphoria leading to increased psychic dependence.
The concomitant use of clozapine and MINIAS can produce marked sedation, excessive salivation, ataxia.
Administration of theophylline or aminophylline may reduce the effects of benzodiazepines.
Inhibitors of cytochrome P450
Compounds that inhibit certain liver enzymes (especially cytochrome P450) may increase the activity of benzodiazepines. To a lesser extent, this also applies to benzodiazepines which are metabolized only by conjugation.
Interaction of benzodiazepines with other drugs (beta-blocking agents, cardiac glycosides, methylxanthines, oral contraceptives, and various antibiotics) has been reported. Patients on beta-blockers, cardiac glycosides, methylxanthines, oral contraceptives, and antibiotics should be treated with caution, especially at the initiation of treatment with MINIAS.
04.6 Pregnancy and lactation
As a precaution, MINIAS should not be used during pregnancy, childbirth and breastfeeding.
Women of childbearing potential
If MINIAS is prescribed to a woman of childbearing age, she will need to contact her doctor, both if she intends to become pregnant and if she suspects she is pregnant, regarding the suspension of the MINIAS.
Pregnancy
If, for serious medical reasons, MINIAS is administered during late pregnancy, or during labor and delivery, effects on the newborn such as hypothermia, hypotonia, hypotension, difficulty in sucking ("infant hypotonia") and moderate respiratory depression due to the pharmacological action of the drug.
Additionally, infants born to mothers who have taken MINIAS or other benzodiazepines chronically during late pregnancy may develop physical dependence and may be at some risk of developing withdrawal symptoms in the postnatal period.
Feeding time
As small amounts of the medicine can and pass into breast milk, MINIAS should not be given to mothers who are breastfeeding (see section 4.3).
04.7 Effects on ability to drive and use machines
MINIAS significantly affects the ability to drive or use machines as it causes sedation, amnesia, difficulty concentrating and impaired muscle function. If sleep duration has been insufficient, the likelihood of impaired alertness may be increased.
Reactions can be altered in relation to time of ingestion, individual sensitivity and dose. This occurs with a high dose in combination with alcohol (see section 4.5).
04.8 Undesirable effects
Summary of the safety profile
Daytime sleepiness, emotional disturbances, depressed consciousness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia or diplopia may occur at the start of treatment. These reactions generally disappear with continued treatment.
Adverse reactions (ADRs) that are most frequently observed in patients receiving MINIAS are headache, sedation and anxiety.
The most serious adverse reactions (ADRs) in patients receiving MINIAS are angioedema, suicide or attempted suicide in association with unmasking of pre-existing depression.
List of adverse reactions in tabular form
Adverse reactions observed with MINIAS are shown in the table below, classified by Systems and Organs according to MedDRA. The most appropriate MedDRA term is used to describe a particular reaction, its synonyms and related conditions.
Adverse reactions from clinical trials (852 patients; administered dose of lormetazepam: 0.5 to 3 mg) are classified by frequency
Adverse reactions identified only during post-marketing surveillance, for which the frequency cannot be defined, are listed under "not known".
Within each frequency category, undesirable effects are presented in descending order of severity.
Table 1: Adverse reactions reported in clinical trials or during post-marketing surveillance in patients treated with MINIAS
* life-threatening or fatal cases have been reported
§ see section 4.4
Description of particular adverse reactions
Dependence
The use of MINIAS and other benzodiazepines can lead to the development of physical and mental dependence on these products.
Once physical dependence has developed, abrupt cessation of treatment may be accompanied by withdrawal symptoms. These may consist of extreme anxiety, tension, restlessness, confusion, irritability, headache and muscle pain. In severe cases they may appear. the following symptoms: derealization, depersonalization, hallucinations, paraesthesia of the limbs, hypersensitivity to light, noise and physical contact, hyperacusis and seizures.
There is evidence that, in the case of use of benzodiazepines with a short duration of action, withdrawal symptoms may become manifest between the interval of one dose and another especially at high doses. This is unlikely to occur with MINIAS as its elimination half-life is approximately 10 hours (see section 5.2).
For more information on addiction / withdrawal symptoms see section 4.4.
Psychiatric disorders
Rebound insomnia
Upon discontinuation of treatment, a transient syndrome such as rebound insomnia may occur, which recurs in an aggravated form following treatment with benzodiazepines. Since, after abrupt discontinuation of treatment, the risk of rebound / withdrawal phenomena is higher, it is recommended to gradually decrease the dose. The patient should be informed of the possibility of rebound phenomena in order to minimize anxiety. caused by these symptoms, which can appear when benzodiazepines are stopped.
Depression
MINIAS is not recommended for the primary treatment of psychotic illnesses. It should not be used alone for the treatment of sleep disorders associated with depression. A pre-existing depressive state may be unmasked during the use of benzodiazepines, including MINIAS. MINIAS should be used with caution in patients with depression.
Psychiatric and paradoxical reactions: MINIAS can cause reactions such as: restlessness, irritability, aggression, delirium, anger, nightmares, hallucinations, psychosis, behavioral changes and other behavioral disorders. Such reactions can be quite severe. They are more likely in children and the elderly.
Nervous system disorders
Amnesia
MINIAS can induce antegrade amnesia.
In addition, other adverse reactions have been reported rarely with benzodiazepines including: increased bilirubin, jaundice, increased liver transaminases, increased alkaline phosphatase, thrombocytopenia, agranulocytosis, pancytopenia, SIAD (syndrome of inappropriate antidiuretic hormone secretion).
04.9 Overdose
As with other benzodiazepines, an overdose of MINIAS should not be life-threatening unless concomitant other CNS depressants (including alcohol) are taken. In the treatment of overdose of any drug, it should be considered. the possibility that other substances have been taken at the same time and that respiratory depression, rarely coma and, very rarely, death can occur.
Benzodiazepine overdose usually results in varying degrees of central nervous system depression ranging from drowsiness to coma.
Symptoms
Symptoms of mild intoxication are drowsiness, fatigue, ataxia, vision disturbances, drowsiness, mental confusion, and lethargy.
Oral administration of higher doses can lead to symptoms ranging from deep sleep to unconsciousness, ataxia, hypotonia, hypotension, respiratory depression, rarely coma and, very rarely, death.
Treatment
Patients with milder symptoms of intoxication should be allowed to sleep under observation. Following an overdose of oral benzodiazepines, vomiting should be induced (within one "hour) if the patient is conscious or gastric lavage with respiratory protection undertaken if the patient is unconscious.
If no improvement is seen with stomach emptying, activated charcoal should be given to reduce absorption.
Special attention must be paid to respiratory and cardiovascular functions in emergency therapy.
In case of hypotension, norepinephrine and volemic drugs for peripheral circulation should be used. Assisted ventilation is required in case of respiratory compromise, which can also be caused by peripheral muscle relaxation.
In the presence of mixed intoxication, hemodialysis and peritoneal dialysis may be useful. However, they are not effective in the case of mono-intoxication with MINIAS.
Flumazenil can be useful as an antidote. For further information regarding the safety of flumazenil, please refer to the Summaries of Characteristics of products containing flumazenil.
Morphine antagonists are contraindicated.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Hypnotics and sedatives - Benzodiazepine derivatives. ATC code: N05CD06
In the course of animal studies for the neuro-pharmacological characterization of the substance, it emerged that lormetazepam possesses the typical sedative spectrum of benzodiazepines.
As for the sedative-hypnotic action, lormetazepam has been shown to have an effect (reduction of motor activity) five times higher than that of lorazepam and ten times greater than that of flurazepam and diazepam. Apart from the effect on the central nervous system, lormetazepam does not exert pharmaco-dynamic actions on the respiratory, cardiocirculatory, renal excretory function. Furthermore, lormetazepam has no interference on hepatic function and on glucose metabolism.
05.2 Pharmacokinetic properties
The classification of lormetazepam among the short-acting hypno-inducing benzodiazepines derives from pharmacokinetic studies in animals and humans. After oral administration the drug is rapidly and completely absorbed with reaching the maximum plasma peak within about 2 hours. Already 30 minutes after administration, unchanged lormetazepam, conjugated to glucuronic acid, is found in the plasma. Benzodiazepine, which does not undergo metabolic breakdowns, binds for more than 85% to plasma proteins. The plasma concentration decreases in two successive phases with half-life times of about 2 hours (distribution phase) and about 10 hours (phase of elimination) Lormetazepam is excreted almost completely via the urine in the form of unchanged substance conjugated with glucuronic acid. Only 5% of the administered dose is found in the urine as the unconjugated N-demethylated metabolite.
05.3 Preclinical safety data
Lormetazepam has very low acute toxicity.
LD50 (mg / kg) after single administration of lormetazepam.
Long-term toxicological studies conducted on rodents, dogs and monkeys have shown that lormetazepam has no chronic toxicity and can therefore be safely used even for long periods.
Finally, no data have emerged indicative of a "possible mutagenic, embryotoxic or teratogenic action, nor, in the very long term, of a" cytotoxic or carcinogenic action.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Coated tablets 1 mg
Lactose, corn starch, povidone 25,000, magnesium stearate, Eudragit E30D, talc, titanium dioxide, macrogol 5/6000, polysorbate 80, sodium caramelose, silicone oil.
Coated tablets 2 mg
Lactose, corn starch, povidone 25,000, magnesium stearate, quinoline yellow SS-E104, Eudragit E30D, talc, titanium dioxide, macrogol 5/6000, polysorbate 80, sodium caramelose, silicone oil.
Oral drops
Sodium saccharin, orange flavor, lemon essence, caramel flavor, glycerol, 95% ethyl alcohol, propylene glycol.
06.2 Incompatibility
Coated tablets: 5 years.
Oral drops: 3 years.
The shelf life after first opening the bottle is 80 days.
06.3 Period of validity
Not relevant.
06.4 Special precautions for storage
Store below 25 ° C.
06.5 Nature of the immediate packaging and contents of the package
Coated tablets: box of 30 tablets of 1 mg or 2 mg in PVC / AL blister.
Oral drops: 20 ml yellow glass bottle complying with the requirements of the Ph.Eur., equipped with a white polypropylene cap with child-resistant closure, and a low density polyethylene dropper.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Bayer S.p.A., Viale Certosa, 130 - 20156 Milan
08.0 MARKETING AUTHORIZATION NUMBER
1 mg coated tablets: A.I.C. n. 023382017
2 mg coated tablets: A.I.C. n. 023382031
Oral drops, 2.5 mg / ml solution: A.I.C. n. 023382029
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
1 mg coated tablets: 12.09.1981 / 01.06.2010
2 mg coated tablets: 18.12.1982 / 01.06.2010
Oral drops, 2.5 mg / ml solution: 12.09.1981 / 01.06.2010
10.0 DATE OF REVISION OF THE TEXT
AIFA Determination of: 05/2013
