Active ingredients: Lorazepam
LORANS 1 mg tablets
LORANS 2.5 mg tablets
LORANS 2 mg / ml oral drops, solution
Indications Why is Lorans used? What is it for?
Pharmacotherapeutic group
Anxiolytic
Therapeutic indications
Anxiety, tension and other somatic or psychiatric manifestations associated with anxiety syndrome. Insomnia.
Benzodiazepines are indicated only when the disorder is severe, disabling and subjects the subject to severe distress.
Contraindications When Lorans should not be used
Hypersensitivity to the active substance, to benzodiazepines or to any of the excipients. Myasthenia gravis. Severe respiratory insufficiency. Severe hepatic insufficiency. Sleep apnea syndrome. Narrow angle glaucoma. Do not administer during pregnancy.
Precautions for use What you need to know before taking Lorans
Specific groups of patients
Benzodiazepines should not be given to children without careful consideration of the actual need for treatment; the duration of treatment should be as short as possible.
It is not recommended to use the product under 12 years of age.
Due to the highly variable reactivity to psychotropic drugs, elderly or debilitated patients and those with organic brain changes (especially atherosclerotic) should be treated with low doses. The same prudential measures should be taken for patients with low blood pressure, chronic renal, cardiac and respiratory failure due to the risk of respiratory depression. Such patients should be monitored regularly during LORANS therapy (as recommended with other benzodiazepines and other psychopharmacological agents).
Benzodiazepines are not indicated in patients with severe hepatic insufficiency as they can precipitate encephalopathy. Benzodiazepines are not recommended for the primary treatment of psychotic illness. Benzodiazepines should not be used alone to treat depression or anxiety associated with psychotic illness. 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.
In case of prolonged treatment it is advisable to carry out checks on the blood picture and liver function.
Interactions Which drugs or foods can modify the effect of Lorans
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
The association with other psychotropic drugs requires particular caution and vigilance on the part of the physician in order to avoid unexpected undesirable effects from interactions.
Concomitant intake with alcohol should be avoided. The sedative effect may be enhanced when the medicinal product is taken in conjunction with alcohol. This adversely affects the ability to drive or use machines.
Association with CNS depressants: the central depressive effect may be enhanced in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics / sedatives, antidepressants, analgesics, narcotics, antiepileptics, anesthetics and sedative antihistamines. In the case of narcotic analgesics increased euphoria may occur leading to an increase in psychic dependence.
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 metabolised only by conjugation. The cytochrome P450 system has not been shown to be involved in the metabolism of lorazepam. No interactions involving the cytochrome P450 system were observed.
Cases of marked sedation, ataxia have been reported when lorazepam is co-administered with clozapine
Co-administration of lorazepam with valproate may result in increased plasma concentrations and reduced elimination of lorazepam.
Co-administration of lorazepam with probenecid may result in a more rapid onset or prolongation of the effect of lorazepam due to an increased half-life of lorazepam. Cases of excessive stupor, significant reduction in respiratory rate and, in one case, hypotension have been reported when lorazepam was administered concomitantly with loxapine.
Warnings It is important to know that:
Tolerance
Some loss of efficacy to the hypnotic effects of benzodiazepines may develop after repeated use for a few weeks.
Dependence
The use of benzodiazepines can lead to the development of physical and psychological dependence on these drugs. The risk of dependence increases with dose and duration of treatment, and is greater in patients with a history of drug or alcohol abuse.
Once the physical dependence has developed, the abrupt termination of treatment will be accompanied by withdrawal symptoms. These can consist of headache, body aches, extreme anxiety, tension, restlessness, confusion and irritability. In severe cases, the following symptoms may occur: derealization, depersonalization, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or seizures.
Rebound insomnia and anxiety: A transient syndrome in which symptoms that led to treatment with benzodiazepines recur in an aggravated form may occur on discontinuation of treatment. It may be accompanied by other reactions, including mood changes, anxiety, restlessness or disturbances As the risk of withdrawal or rebound symptoms is greater after abrupt discontinuation of treatment, a gradual decrease in dosage is suggested.
Duration of treatment
The duration of treatment should be as short as possible (see dose, method and time of administration) depending on the indication, but should not exceed four weeks for insomnia and eight to twelve weeks for anxiety, including a gradual withdrawal period. Extension of therapy beyond these periods should not occur without reassessment of the clinical situation. It may be helpful to inform the patient when treatment is started that it will be of limited duration and to explain precisely how the dosage should be progressively decreased. It is also important that the patient is informed of the possibility of rebound phenomena, thus minimizing anxiety about these symptoms should they occur when the drug is discontinued.
Amnesia
Benzodiazepines can induce antegrade amnesia. This occurs most often several hours after ingestion of the drug and, therefore, to reduce the risk it should be ensured that patients can have an uninterrupted sleep of 7-8 hours (see side effects).
Psychiatric and paradoxical reactions
When benzodiazepines are used it is known that reactions such as restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes can occur. Should this occur, the use of the medicinal product should be discontinued. These reactions are more frequent in children and the elderly.
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Do not administer; taking benzodiazepines during pregnancy can cause fetal harm. An increased risk of congenital malformations associated with the use of anxiolytic agents (chlordiazepoxide, diazepam, meprobamate) during the first trimester of pregnancy has been suggested in several studies; therefore, always avoid the administration of benzodiazepines during the first trimester.
If the product is prescribed to a woman of childbearing age, she should contact her doctor, both if she intends to become pregnant and if she suspects that she is pregnant, regarding discontinuation of the medicine.
If, for serious medical reasons, the product is administered during the last period of pregnancy, or during labor at high doses, effects on the newborn may occur such as hypothermia, hypotonia and moderate respiratory depression, due to the pharmacological action of the drug. Additionally, infants born to mothers who have taken benzodiazepines chronically during late pregnancy may develop physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period. Since benzodiazepines are excreted in breast milk, they should not be given to breastfeeding mothers.
Effects on ability to drive and use machines
Sedation, amnesia, impaired concentration and muscle function can adversely affect the ability to drive and use machines.If sleep duration has been insufficient, the likelihood of impaired alertness may be increased (see interactions).
Important information about some of the ingredients
Tablets: Due to the presence of lactose, patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Drops: for those who carry out sporting activities, the use of medicines containing ethyl alcohol can determine positive doping tests in relation to the alcohol concentration limits indicated by some sports federations.
Dosage and method of use How to use Lorans: Dosage
Due to the characteristics of Lorans, which associates a considerable activity with good tolerability, the best results will be achieved by adapting the dosage to the individual patient and to the characteristics of the clinical picture in progress.
The lowest effective dose should be prescribed for the shortest time possible.
In all patients, treatment should be withdrawn gradually to reduce possible withdrawal symptoms.
Anxiety
Treatment should be as short as possible. The patient should be reassessed regularly and the need for continued treatment should be reassessed carefully, particularly if the patient is symptom-free. The overall duration of treatment should generally not exceed 8-12 weeks, including a gradual withdrawal period.
In certain cases, extension beyond the maximum treatment period may be necessary, in which case this should not be done without reassessment of the patient's condition.
As an indication, we recommend:
- General medicine: 1 tablet of 1 mg, 1-3 times a day or 10-20 drops, 1-3 times a day.
- For particularly severe cases, the dosage can be increased to ½-1 tablet of 2.5 mg, 1-3 times a day or 20-50 drops, 1-3 times a day.
Insomnia
Treatment should be as short as possible. 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.
As an indication, we recommend:
Sleep disturbances: 1 to 2.5 mg in the evening or 20-50 drops in the evening.
Treatment should be started with the lowest recommended dose. The maximum dose should not be exceeded.
In the treatment of elderly patients, the posology must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above, however an initial dosage of 1-2mg per day in divided doses is recommended, to be adapted according to needs and tolerability.
Patients with impaired liver and / or renal function should take reduced dosages
Instructions for use of the bottle:
- To open the bottle, press and unscrew at the same time.
- Then press the plastic cap to get the powder to fall and shake until completely dissolved.
- To get the drops out, remove the cap and turn the bottle upside down.
- To close, press and screw at the same time.
- To reopen, press and unscrew at the same time.
The solution is valid for 30 days.
Overdose What to do if you have taken too much Lorans
In case of accidental ingestion / intake of an excessive dose of Lorans, notify your doctor immediately or go to the nearest hospital.
As with other benzodiazepines, an overdose is not expected to be life-threatening unless concomitant other CNS depressants (including alcohol) are taken.
In the treatment of overdosing of any drug, the possibility that other substances have been taken at the same time should be considered. Following an overdose of benzodiazepines for oral use, vomiting should be induced (within one "hour) if the patient is conscious. or undertook gastric lavage with respiratory protection if the patient is unconscious. The usefulness of a dialysis treatment has not been established.
If no improvement is observed with stomach emptying, activated charcoal should be given to reduce absorption. Special attention should be paid to respiratory and cardiovascular functions in emergency therapy. Overdosage of benzodiazepines usually results in varying degrees of central nervous system depression ranging from clouding to coma. In mild cases, symptoms include drowsiness, mental confusion, and lethargy. In severe cases, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, rarely coma, and very rarely death. Flumazenil can be useful as an antidote.
Physicians should be aware of the risk of seizures in association with flumazenil treatment, particularly in those who have been using benzodiazepines for a long time and in case of overdose of cyclic antidepressants.
If you have any questions about the use of Lorans, ask your doctor or pharmacist.
Side Effects What are the side effects of Lorans
Like all medicines, Lorans can cause side effects, although not everybody gets them.
Lorans is normally well tolerated and, in general, does not affect physical and mental abilities when the dosage is properly adapted.
The most frequently observed side effects include:
Psychiatric disorders: emotional blunting, confusion
Nervous system disorders: somnolence, decreased alertness, headache, dizziness, ataxia (unsteadiness in walking)
Musculoskeletal and connective tissue disorders: muscle weakness
General Disorders and Administration Site Conditions: Fatigue
Eye disorders: diplopia
These phenomena occur mainly at the beginning of therapy and usually disappear with subsequent administrations.
Side effects observed occasionally are:
Blood and lymphatic system disorders: thrombocytopenia
Immune system disorders: hypersensitivity reactions, anaphylactic / anaphylactoid reactions
Metabolism and Nutrition Disorders: Hyponatremia
Psychiatric disorders: sleep disturbances, changes in libido, agitation, aggression, mood swings, depression, irritability, delirium, anger, nightmares, hallucinations, psychosis, addiction
Nervous system disorders: tremors, dysarthria, amnesia
Eye disorders: visual disturbances
Vascular disorders: hypotension
Respiratory, thoracic and mediastinal disorders: respiratory depression, apnea
Gastrointestinal disorders: dry mouth, drooling
Hepatobiliary disorders: jaundice
Skin and subcutaneous tissue disorders: skin reactions
General disorders and administration site conditions: paradoxical irritability
Investigations: increased bilirubin, increased liver transaminases, increased alkaline phosphatase
Amnesia
Anterograde amnesia can also occur at therapeutic dosages, the risk increases at higher dosages. Amnesic effects may be associated with behavioral changes (see special warnings).
Depression
During the use of benzodiazepines a pre-existing depressive state can be unmasked. Benzodiazepines or benzodiazepine-like compounds can cause reactions such as: restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes.
Such reactions can be quite severe: they are more likely in children and the elderly.
Dependence
The use of benzodiazepines (even at therapeutic doses) can lead to the development of physical dependence: discontinuation of therapy can cause rebound or withdrawal phenomena (see special warnings). Psychic dependence may occur. Abuse of benzodiazepines has been reported.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.
Expiry and Retention
Expiry: see the expiry date printed on the package.
The expiry date indicated refers to the product in intact packaging, correctly stored.
Warning: do not use the medicine after the expiry date shown on the package.
Tablets: Store at a temperature not exceeding 25 ° C
Drops:
In intact packaging: this medicine does not require any special storage conditions.
After first opening: Store the bottle in the refrigerator (2 ° C - 8 ° C).
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Keep this medicine out of the reach and sight of children.
Composition
LORANS 1 mg tablets
One tablet contains
Active ingredient: lorazepam 1 mg
Excipients: lactose monohydrate, pregelatinised maize starch, povidone, magnesium stearate, sunset yellow (E 110)
LORANS 2.5 mg tablets
One tablet contains:
Active ingredient: lorazepam 2.5 mg
Excipients: lactose monohydrate, pregelatinised maize starch, povidone, magnesium stearate
LORANS 2 mg / ml oral drops, solution
10 ml contain in the tank cap:
Active ingredient: lorazepam 20 mg 20 drops (0.5 ml) contain: 1 mg of lorazepam
Excipients: mannitol, ethanol, purified water
Pharmaceutical form and content
Tablets:
LORANS 1 mg tablets - 20 tablets
LORANS 2.5 mg tablets - 20 tablets
LORANS 1 mg tablets - 30 tablets
LORANS 2.5 mg tablets - 30 tablets
Oral drops, solution:
LORANS 2 mg / ml oral drops, Solution - 10 ml bottle
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
LORANS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
LORANS 1 mg tablets
One tablet contains:
Active ingredient: lorazepam 1 mg
LORANS 2.5 mg tablets
One tablet contains:
Active ingredient: lorazepam 2.5 mg
LORANS 2 mg / ml oral drops, solution
10 ml contain in the tank cap:
Active ingredient: lorazepam 20 mg
20 drops (0.5 ml) contain: 1 mg of lorazepam
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Tablets.
Oral drops, solution.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Anxious reactions, nervous tension. Anxiety-depressive syndromes. Sleep disorders.
Benzodiazepines are only indicated when the disorder is severe, disabling, or makes the subject very uncomfortable.
04.2 Posology and method of administration
Due to the characteristics of LORANS, which associates a considerable activity with good tolerability, the best results will be achieved by adapting the dosage to the individual patient and to the characteristics of the clinical picture in progress.
The lowest effective dose should be prescribed for the shortest time possible.
In all patients, treatment should be discontinued gradually to reduce possible withdrawal symptoms (see section 4.4).
Anxiety
Treatment should be as short as possible. The patient should be reassessed regularly and the need for continued treatment should be reassessed carefully, particularly if the patient is symptom-free. The overall duration of treatment should generally not exceed 8-12 weeks, including a gradual withdrawal period.
In certain cases, extension beyond the maximum treatment period may be necessary, in which case this should not be done without reassessment of the patient's condition.
Insomnia
Treatment should be as short as possible. 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.
As an indication, we recommend:
general medicine: 1 tablet of 1 mg, 1-3 times a day or 10-20 drops, 1-3 times a day.
Neuropsychic affections: ½-1 tablet of 2.5 mg, 1-3 times a day or 20-50 drops, 1-3 times a day.
Sleep disturbances: 1 to 2.5 mg in the evening or 20-50 drops in the evening.
Treatment should be started with the lowest recommended dose. The maximum dose should not be exceeded.
In the treatment of elderly patients the posology must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above, however an initial dosage of 1-2 mg per day in divided doses is recommended, to be adapted according to the needs and tolerability.
Patients with impaired liver and / or renal function should take reduced dosages.
04.3 Contraindications
Hypersensitivity to the active substance, to benzodiazepines, or to any of the excipients. Myasthenia gravis. Severe respiratory insufficiency. Severe hepatic insufficiency. Sleep apnea syndrome. Narrow angle glaucoma. Do not administer during pregnancy (see section 4.6).
04.4 Special warnings and appropriate precautions for use
Tolerance
Some loss of efficacy to the hypnotic effects of benzodiazepines may develop after repeated use for a few weeks.
Dependence
The use of benzodiazepines can lead to the development of physical and psychological dependence on these drugs. The risk of dependence increases with dose and duration of treatment, and is greater in patients with a history of drug or alcohol abuse.
Once the physical dependence has developed, the abrupt termination of treatment will be accompanied by withdrawal symptoms. These can consist of headache, body aches, extreme anxiety, tension, restlessness, confusion and irritability. In severe cases, the following symptoms may occur: derealization, depersonalization, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or seizures.
Rebound insomnia and anxiety: A transient syndrome in which symptoms that led to treatment with benzodiazepines recur in an aggravated form may occur on discontinuation of treatment. It may be accompanied by other reactions, including mood changes, anxiety, restlessness or disturbances As the risk of withdrawal or rebound symptoms is greater after abrupt discontinuation of treatment, a gradual decrease in dosage is suggested.
Duration of treatment
The duration of treatment should be as short as possible (see section 4.2) depending on the indication, but should not exceed four weeks for insomnia and eight to twelve weeks for anxiety, including a gradual withdrawal period. Extending therapy beyond these periods should not occur without reassessment of the clinical situation. It may be helpful to inform the patient when treatment is started that it will be of limited duration and to explain precisely how the dosage should be progressively decreased.
It is also important that the patient is informed of the possibility of rebound phenomena, thus minimizing anxiety about these symptoms should they occur when the drug is discontinued.
Amnesia
Benzodiazepines can induce antegrade amnesia. This occurs most often several hours after ingestion of the drug and, therefore, to reduce the risk it should be ensured that patients can have 7-8 hours of uninterrupted sleep (see section 4.8).
Psychiatric and paradoxical reactions
When benzodiazepines are used it is known that reactions such as restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes can occur.Should this occur, the use of the medicinal product should be discontinued. These reactions are more frequent in children and the elderly.
Specific groups of patients
Benzodiazepines should not be given to children without careful consideration of the actual need for treatment; the duration of treatment should be as short as possible. Use of the product under 12 years of age is not recommended.
Due to the highly variable reactivity to psychotropic drugs, elderly or debilitated patients and those with organic brain changes (especially atherosclerotic) should be treated with low doses.
The same prudential measures should be taken for patients with low blood pressure, chronic renal, cardiac and respiratory failure due to the risk of respiratory depression. Such patients should be monitored regularly during LORANS therapy (as recommended with other benzodiazepines and other psychopharmacological agents). Benzodiazepines are not indicated in patients with severe hepatic insufficiency as they can precipitate encephalopathy. Benzodiazepines are not recommended for the primary treatment of psychotic illness. Benzodiazepines should not be used alone to treat depression or anxiety associated with psychotic illness. 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.
In case of prolonged treatment it is advisable to carry out checks on the blood picture and liver function.
Due to the presence of lactose, patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
The association with other psychotropic drugs requires particular caution and vigilance on the part of the physician in order to avoid unexpected undesirable effects from interactions.
Concomitant intake with alcohol should be avoided. The sedative effect may be enhanced when the medicinal product is taken in conjunction with alcohol. This adversely affects the ability to drive or use machines.
Association with CNS depressants: the central depressive effect may be enhanced in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics / sedatives, antidepressants, analgesics, narcotics, antiepileptics, anesthetics and sedative antihistamines. In the case of narcotic analgesics increased euphoria may occur leading to an increase in psychic dependence.
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 metabolised only by conjugation. The cytochrome P450 system has not been shown to be involved in the metabolism of lorazepam. No interactions involving the cytochrome P450 system were observed.
There have been reports of marked sedation, ataxia when lorazepam is co-administered with clozapine.
Co-administration of lorazepam with valproate may result in increased plasma concentrations and reduced elimination of lorazepam.
Co-administration of lorazepam with probenecid may result in a more rapid onset or prolongation of the effect of lorazepam due to an increased half-life of lorazepam.
Cases of excessive stupor, significant reduction in respiratory rate and, in one case, hypotension have been reported when lorazepam was administered concomitantly with loxapine.
04.6 Pregnancy and lactation
Pregnancy
Do not administer during pregnancy. Taking benzodiazepines during pregnancy can cause fetal harm. An increased risk of congenital malformations associated with the use of anxiolytic agents (chlordiazepoxide, diazepam, meprobamate) during the first trimester of pregnancy has been suggested in several studies; therefore, always avoid the administration of benzodiazepines during the first trimester.
If the product is prescribed to a woman of childbearing age, she should contact her doctor, both if she intends to become pregnant and if she suspects that she is pregnant, regarding discontinuation of the medicine.
If, for serious medical reasons, the product is administered during the last period of pregnancy, or during labor at high doses, effects on the newborn may occur such as hypothermia, hypotonia and moderate respiratory depression due to the pharmacological action of the drug.
Additionally, infants born to mothers who have taken benzodiazepines chronically during late pregnancy may develop physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.
Feeding time
Since benzodiazepines are excreted in breast milk, they should not be given to breastfeeding mothers.
04.7 Effects on ability to drive and use machines
Sedation, amnesia, impaired concentration and muscle function can adversely affect the ability to drive and use machines. If sleep duration has been insufficient, the likelihood of impaired alertness may be increased (see section 4.5).
04.8 Undesirable effects
LORANS is normally well tolerated and generally does not affect physical and mental abilities when the dosage is properly adapted.
The most frequently observed side effects include:
Psychiatric disorders: emotional dulling, confusion.
Nervous system disorders: sleepiness, decreased alertness, headache, dizziness, ataxia (unsteadiness in walking).
Musculoskeletal and connective tissue disorders: muscle weakness.
General disorders and administration site conditions: fatigue.
Eye disorders: diplopia.
These phenomena occur mainly at the beginning of therapy and usually disappear with subsequent administrations.
Side effects observed occasionally are:
Disorders of the blood and lymphatic system: thrombocytopenia.
Disorders of the immune system: hypersensitivity reactions, anaphylactic / anaphylactoid reactions.
Metabolism and nutrition disorders: hyponatremia.
Psychiatric disorders: sleep disturbances, libido changes, agitation, aggression, mood swings, depression, irritability, delirium, anger, nightmares, hallucinations, psychosis, addiction.
Nervous system disorders: tremors, dysarthria, amnesia.
Eye disorders: visual disturbances.
Vascular pathologies: hypotension.
Respiratory, thoracic and mediastinal disorders: respiratory depression, apnea.
Gastrointestinal disorders: dry mouth, drooling.
Hepatobiliary disorders: jaundice.
Skin and subcutaneous tissue disorders: skin reactions.
Diagnostic tests: increased bilirubin, increased liver transaminases, increased alkaline phosphatase.
Amnesia
Anterograde amnesia can also occur at therapeutic dosages, the risk increases at higher dosages: amnesic effects may be associated with behavioral alterations (see section 4.4).
Depression
A pre-existing depressive state may be unmasked during the use of benzodiazepines.
Benzodiazepines or benzodiazepine-like compounds can cause reactions such as: restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, behavioral changes.
Such reactions can be quite severe: they are more likely in children and the elderly.
Dependence
The use of benzodiazepines (even at therapeutic doses) can lead to the development of physical dependence: discontinuation of therapy may cause rebound or withdrawal phenomena (see section 4.4). Psychic dependence may occur. Abuse of benzodiazepines has been reported.
04.9 Overdose
As with other benzodiazepines, an overdose is not expected to be life-threatening unless concomitant other CNS depressants (including alcohol) are taken.
In the treatment of overdose of any drug, the possibility that other substances have been taken at the same time should be considered.
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. This has not been established. the usefulness of a dialysis treatment.
If no improvement is observed with stomach emptying, activated charcoal should be given to reduce absorption. Special attention should be paid to respiratory and cardiovascular functions in emergency therapy. Overdosage of benzodiazepines usually results in varying degrees of central nervous system depression ranging from clouding to coma. In mild cases, symptoms include drowsiness, mental confusion, and lethargy. In severe cases, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, rarely coma, and very rarely death. Flumazenil can be useful as an antidote.
Physicians should be aware of the risk of seizures in association with flumazenil treatment, particularly in those who have been using benzodiazepines for a long time and in case of overdose of cyclic antidepressants.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: anxiolytics, benzodiazepine derivatives.
ATC code: N05BA06
Active ingredient of LORANS is lorazepam: 7-chloro-1,3-dihydro-3-hydroxy-5 (o-chlorophenyl) -2H-1,4-benzodiazepin-2-one.
The results of the investigations aimed at verifying the possible cardiocirculatory and respiratory effects have shown that lorazepam, administered orally or endoperitoneally, does not exert any influence on systemic arterial pressure, on the electrocardiogram and on the pneumogram.
From the experimental tests aimed at evaluating its pharmacological activity, it was found that LORANS:
it induces sleep following non-hypnotic doses of Esobarbital and prolongs it by hypnotic doses of the same barbiturate;
possesses anticonvulsant activity, demonstrated against chemical (strychnine, pentamethylenetetrazole) and physical (electroshock) convulsive agents;
it has an inhibiting effect on spontaneous motor activity;
it has significant inhibitory activity against methamphetamine-induced hypermotility.
This pharmacological spectrum is characteristic of psychoactive benzodiazepine derivatives, commonly referred to as anxiolytics.
05.2 "Pharmacokinetic properties
Lorazepam administered orally is rapidly absorbed.
Pharmacokinetic studies have found that the highest serum concentrations of lorazepam (free and conjugated) are acquired 2-3 hours after administration: the pharmacological effects generally disappear by the 6th-8th hour, although serum levels are also appreciable at 24th hour.
The plasma half-life of unconjugated lorazepam is approximately 12-16 hours.
Lorazepam binds 85-90% to plasma proteins.
About 2/3 of the administered doses are excreted in the urine, in the form of glucuronide, by the 96th hour, while the faeces contain less than 1% of free lorazepam.
In infants it appears that lorazepam conjugation occurs slowly as its glucuronide is detectable in the urine for more than seven days. Lorazepam glucuronidation can competitively inhibit bilirubin conjugation, leading to hyperbilirubinemia in the newborn.
There is no evidence of excessive accumulation of lorazepam when administered for up to 6 months, nor is there any evidence of induction of drug-metabolizing enzymes. Lorazepam is not a substrate for N-dealkylating enzymes of the cytochrome P450 system, nor is it significantly hydrolyzed.
The volume of distribution is 1.3 l / kg.
Comparative studies in young and elderly subjects have shown that the pharmacokinetics of lorazepam remain unchanged with advancing age. In patients with hepatic diseases (hepatitis, alcoholic cirrhosis) no changes in absorption, distribution, metabolism and excretion have been reported. As with other benzodiazepines, the pharmacokinetics of lorazepam may be altered in renal insufficiency.
05.3 Preclinical safety data
In the toxicity tests on animals, the product did not show potential for both acute treatment (LD50> 4000 mg / kg / os in mice and rats) and protracted.
Dilation of the esophagus was observed in rats treated with lorazepam for more than one year with a dosage of 6 mg / kg / day. The dose at which this effect did not occur was 1.25 mg / kg / day ( about 6 times the maximum therapeutic dose in humans, which is 10 mg / day). The effect was reversible only if the treatment was stopped within two months of the first observation of the phenomenon. The clinical significance of this is not known.
No teratogenic or embryotoxic effects were shown in rats, mice and rabbits for oral administration.
No evidence of carcinogenic (rats, mice) and mutagenic potential emerged from the studies conducted.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
LORANS 1 mg:
lactose monohydrate, pregelatinised maize starch, povidone, magnesium stearate, sunset yellow (E110).
LORANS 2.5 mg tablets:
lactose monohydrate, pregelatinised maize starch, povidone, magnesium stearate.
LORANS 2 mg / ml oral drops, solution:
Tank cap: mannitol
Bottle: ethanol, purified water.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
In intact packaging: Tablets - 2 years.
Drops - 3 years.
After reconstitution of the product: drops - 30 days.
06.4 Special precautions for storage
Tablets: Do not store above 25 ° C.
06.5 Nature of the immediate packaging and contents of the package
The tablets are housed in blisters of polyvinyl chloride opacified with titanium dioxide, coupled and heat-sealed to an aluminum foil.
LORANS 1 mg tablets - 20 tablets.
LORANS 2.5 mg tablets - 20 tablets.
LORANS 1 mg tablets - 30 tablets.
LORANS 2.5 mg tablets - 30 tablets.
Glass bottle with solvent and reservoir cap containing the active ingredient in powder form, with built-in polypropylene dropper. The bottle is closed with a flip off cap and overcap.
LORANS 2 mg / ml oral drops, solution - 10 ml bottle.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
UCB Pharma S.p.A.
Via Gadames, 57
20151 Milan
08.0 MARKETING AUTHORIZATION NUMBER
LORANS 1 mg tablets - 20 tablets n. 023001086
LORANS 2.5 mg tablets - 20 tablets n. 023001098
LORANS 1 mg tablets - 30 tablets n. 023001023
LORANS 2.5 mg tablets - 30 tablets n. 023001047
LORANS 2 mg / ml oral drops, solution - 10 ml bottle No. 023001074
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
LORANS 1 mg tablets - 20 tablets 31.12.1973 / June 2005
LORANS 2.5 mg tablets - 20 tablets 31.12.1973 / June 2005
LORANS 1 mg tablets - 30 tablets 31.12.1973 / June 2005
LORANS 2.5 mg tablets - 30 tablets 31.12.1973 / June 2005
LORANS 2 mg / ml oral drops, solution - 10 ml bottle
21.08.1989 / June 2005
10.0 DATE OF REVISION OF THE TEXT
AIFA Determination of April 19, 2010
