LORAZEPAM 1 mg Film-Coated Tablets

Зміст інструкції

1. LORAZEPAM ALMUS 1 mg film-coated tablets, 2.5 mg film-coated tablets
   1. WHAT IS LORAZEPAM ALMUS AND WHAT IS IT USED FOR
   2. BEFORE YOU TAKE LORAZEPAM ALMUS
   3. HOW TO TAKE LORAZEPAM ALMUS
   4. POSSIBLE SIDE EFFECTS
   5. HOW TO STORE LORAZEPAM ALMUS
   6. OTHER INFORMATION

LORAZEPAM ALMUS 1 mg film-coated tablets, 2.5 mg film-coated tablets

Generic medicine

Read this leaflet carefully before taking this medicine.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not give it to other people, even if their symptoms are the same as yours, as it could be dangerous.
• If any of the side effects gets worse, or if you notice any side effect not listed in this leaflet, tell your doctor or pharmacist.

Contents of this leaflet:

• 1. What Lorazepam Almus is and what it is used for
• 2. Before taking Lorazepam Almus
• 3. How to take Lorazepam Almus
• 4. Possible side effects
• 5. How to store Lorazepam Almus
• 6. Further information

1. WHAT IS LORAZEPAM ALMUS AND WHAT IS IT USED FOR

Lorazepam Almus belongs to a group of medicines known as benzodiazepines.
Lorazepam Almus is used in the treatment of states of anxiety or nervous tension, nervous insomnia and
anxious depression.
Benzodiazepines are indicated only when the disorder is severe, disabling or subjects the
patient to severe distress.

2. BEFORE YOU TAKE LORAZEPAM ALMUS

Do not take Lorazepam Almus

• if you are allergic (hypersensitive) to lorazepam, to other benzodiazepines or to any of the excipients of Lorazepam Almus
• if you suffer from myasthenia gravis
• if you suffer from severe respiratory failure (e.g. severe chronic obstructive pulmonary disease)
• if you suffer from sleep apnea syndrome
• if you suffer from narrow-angle glaucoma
• if you suffer from severe liver failure
• if you have acute alcohol intoxication, hypnotic drugs, analgesics or psychotropic drugs (neuroleptics, antidepressants, lithium)
• if you are pregnant or breastfeeding

Take special care with Lorazepam Almus
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking
this medicine.
The use of benzodiazepines, including Lorazepam Almus, can lead to potentially fatal respiratory depression.
Severe anaphylactic/anaphylactoid reactions have been reported with the use of benzodiazepines. Cases of
angioedema involving the tongue, glottis or larynx have been reported in patients after
taking the first dose or subsequent doses of benzodiazepines. Some patients taking
benzodiazepines have had additional symptoms such as dyspnea, throat closure, or nausea and vomiting.
Some patients have needed emergency room therapy. If angioedema involves the
tongue, glottis, or larynx, airway obstruction may occur which could be
fatal.
Patients who develop angioedema after treatment with benzodiazepines should not be
retreated with the drug.

Tolerance. After repeated use for a few weeks, a certain loss of effectiveness of the
hypnotic effects of benzodiazepines may develop.

Dependence. The use of lorazepam and other benzodiazepines can lead to the development of physical and psychic dependence on these drugs. The risk of dependence increases with the dose and duration of
treatment; it is greater in patients with a history of drug or alcohol abuse. Therefore, benzodiazepines must be used with extreme caution in patients with a history of abuse of
alcohol or drugs.
The possibility of dependence is reduced when Lorazepam Almus is used at the appropriate dose with a
short-term treatment.

Withdrawal symptoms. Once physical dependence has developed, abrupt discontinuation of
treatment will be accompanied by withdrawal symptoms. These may consist of headaches, muscle
pain, extreme anxiety, tension, restlessness, confusion, irritability, rebound phenomena,
dysphoria, dizziness, nausea, diarrhea, loss of appetite. In severe cases, the following
symptoms may occur: derealization, depersonalization, hyperacusis, numbness and tingling of the extremities,
paresthesia of the limbs, hypersensitivity to light, noise and physical contact, hallucinations and
seizures.
Other symptoms are: depression, insomnia, sweating, persistent tinnitus, involuntary movements,
vomiting, paresthesia, perceptual alterations, abdominal and muscle cramps, tremor, myalgia, agitation,
palpitations, tachycardia, panic attacks, vertigo, hyperreflexia, short-term memory loss, hyperthermia.
There is evidence to suggest that, in the case 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 lorazepam because its
elimination half-life is approximately 12-16 hours. However, when switching to lorazepam 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.

Rebound insomnia and anxiety. Upon discontinuation of treatment, a transient syndrome may occur
in which the symptoms that led to treatment with benzodiazepines recur in an aggravated form. This may be accompanied by other reactions including: mood changes, anxiety,
restlessness or sleep disturbances.
Because the risk of withdrawal or rebound symptoms is greater after abrupt discontinuation of
treatment, a gradual reduction in dosage is suggested.
In addition, it is important that the patient is informed of the possibility of rebound phenomena, in order to
minimize the anxious reaction that the eventual appearance of these symptoms may trigger when lorazepam is discontinued.

Amnesia. Benzodiazepines can induce anterograde amnesia. This happens more often several
hours after ingestion of the drug and, therefore, to reduce the risk, it is necessary to ensure that the patient
can have an uninterrupted sleep of 7-8 hours (see “Possible side effects”).

Psychiatric and paradoxical reactions. It is known that reactions such as restlessness, agitation, irritability, aggression, delirium, delusion, anger, rage, nightmares, hallucinations, psychosis, inappropriate behavior and other alterations in behavior can occur with the use of benzodiazepines. If
this should happen, the use of the medicine should be discontinued.
These reactions are more likely to occur in the elderly as well as in patients with organic cerebral syndrome.
At present, it is not possible to exclude the possibility that in patients in acute states of endogenous psychosis, especially severe depressive states, the symptoms are aggravated by the use of lorazepam. Therefore, benzodiazepines are not recommended for the primary treatment of psychotic illnesses. The presence of depression must always be excluded, particularly in initial and morning sleep disturbances, as the symptoms are moreover differently masked and there are always risks caused by the underlying disease (e.g. suicidal tendencies).

Specific patient groups
Pediatric patients: lorazepam should not be administered to patients under 18 years of age
without careful assessment of the actual need for treatment; the duration of treatment should be
as short as possible.
Elderly patients: the use of benzodiazepines may be associated with an increased risk of falls,
due to side effects such as ataxia, muscle weakness, dizziness, drowsiness, fatigue and
exhaustion and therefore caution is recommended when treating elderly patients.
The elderly should take a reduced dose or should not be treated at all.
Patients with chronic respiratory failure: a lower dose is recommended in patients with
chronic respiratory failure due to the risk of respiratory depression (see also “Do not
take Lorazepam Almus”).
Patients with severe liver failure: caution is recommended in treating patients with severe
liver failure and/or hepatic encephalopathy as lorazepam, like all benzodiazepines, can
precipitate hepatic encephalopathy.
Patients with renal failure: lorazepam should be administered with caution in patients with
severe renal failure.
Patients with psychosis: benzodiazepines are not recommended for the primary treatment of psychotic illnesses. Benzodiazepines should not be used alone to treat depression or anxiety
associated with depression (suicide may be precipitated in such patients). Benzodiazepines
should be used with extreme caution in patients with a history of drug or alcohol abuse.
The same precautionary measures must be adopted for patients with heart failure and low
blood pressure who must be subjected to regular checks during therapy with
Lorazepam Almus (as is recommended with other benzodiazepines and other psychopharmacological agents).

Duration of treatment
The duration of treatment should be as short as possible depending on the indication, but should not
exceed 4 weeks for insomnia and 8-12 weeks for anxiety disorders, including a
period of gradual withdrawal. Extension of therapy beyond these periods should not occur
without reassessment of the clinical situation. It is useful to inform the patient when starting treatment
that it is of limited duration and to clearly explain how the dose should be gradually
reduced.

Taking Lorazepam with other medicines
Tell your doctor or pharmacist if you are taking or have recently taken any other
medicines, including those without a prescription.
In particular, be careful in the following cases:

• Drugs that depress the Central Nervous System: The central depressant effect may be increased in cases of concomitant use of drugs that depress the Central Nervous System such as antipsychotics (neuroleptics), hypnotics, anxiolytics/tranquilizers/sedatives, antidepressants, narcotic analgesics, antiepileptics, anesthetics and sedative antihistamines. Narcotic analgesics can cause an increase in euphoria leading to increased psychic dependence.
• Cytochrome P450 inhibitors: Compounds that inhibit certain liver enzymes (especially cytochrome P450) can increase the activity of benzodiazepines. To a lesser extent, this also applies to benzodiazepines metabolized only by conjugation.
• Clozapine: Concomitant use of clozapine and lorazepam can produce marked sedation, excessive salivation, ataxia.
• Valproate: The concomitant administration of lorazepam with valproate may determine an increase in plasma concentrations and a reduced elimination of lorazepam. The dosage of Lorazepam Almus must be reduced by 50% when co-administered with valproate.
• Probenecid: The concomitant administration of lorazepam with probenecid may determine an earlier onset or a prolongation of the effect of lorazepam due to a greater half-life or a decreased total elimination. The dosage of Lorazepam Almus must be reduced by 50% when co-administered with probenecid.
• Theophylline and aminophylline: The administration of theophylline or aminophylline may reduce the effects of benzodiazepines.
• Loxapine: Cases of excessive stupor, significant reduction in respiratory rate and, in one case, hypotension have been reported when lorazepam was administered concomitantly with loxapine

Taking Lorazepam Almus with food and drink
Alcohol: The concomitant intake of the medicine with alcohol should be avoided. The sedative
effect may be increased when the medicine is taken together with alcohol, this negatively
affects the ability to drive or operate machinery.

Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Do not take Lorazepam Almus during pregnancy, labor and breastfeeding.
If you are of childbearing potential, you should contact your doctor, whether you intend to become pregnant,
or suspect you are 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 such as hypothermia, hypotension,
difficulty in sucking (“infant hypotonia”) and moderate respiratory depression may occur
due to the pharmacological action of the medicine.
In addition, newborns born to mothers who have taken benzodiazepines chronically during the advanced stages
of pregnancy may develop physical dependence and may be at certain risk of
developing withdrawal symptoms in the postnatal period.
It appears that in newborns the conjugation of lorazepam occurs slowly, its glucuronide
being traceable in the urine for more than 7 days. The glucuronidation of lorazepam may competitively inhibit
the conjugation of bilirubin, leading to hyperbilirubinemia in the newborn.

Breastfeeding
Since benzodiazepines are excreted in breast milk, they should not be administered to
mothers who are breastfeeding.

Driving and using machines
Do not drive and do not use tools or machines because sedation, amnesia, altered concentration and
impaired muscle function may negatively affect the ability to drive
or operate machinery.
Reactions may be altered in relation to the time of ingestion, individual sensitivity and
the dose. This occurs with a high dose in association with alcohol.
If the duration of sleep has been insufficient, the probability that vigilance is altered may be
increased.

Important information about some excipients of Lorazepam Almus
The tablets contain lactose. Patients with rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this
medicine.

3. HOW TO TAKE LORAZEPAM ALMUS

Always take Lorazepam Almus exactly as your doctor has instructed. If you have any doubts, consult your doctor or pharmacist.

Route of administration
Oral use

How much Lorazepam Almus to take
To achieve optimal results, the dose, frequency of administration and duration of therapy must be individually adjusted according to your response.
The minimum effective dose should be prescribed for the shortest possible time.
Because the risk of withdrawal or rebound symptoms is greater after abrupt discontinuation of treatment, a gradual reduction of the dosage is suggested.

Anxiety
Treatment should be as short as possible.
You should be regularly reassessed and the need for continued treatment should be carefully evaluated, especially if you are symptom-free. The overall duration of treatment should generally not exceed 8-12 weeks, including the period of gradual discontinuation.
In certain cases, an extension beyond the maximum treatment period may be necessary; in such cases, this should not occur without a reassessment of your condition.
In general, a daily dosage of 2-3 mg is recommended for mild forms and 7.5-10 mg for severe forms. It is advisable to take the highest dose in the evening, before bedtime.
In the treatment of elderly patients, the dosage must be carefully established by the doctor, who will have to assess a possible reduction of the dosages mentioned above. In general, in elderly or debilitated patients, an initial dosage of 1-2 mg per day in divided doses is recommended, to be adjusted according to needs and tolerability.
Patients with impaired liver and/or kidney function should take a reduced dose.

Insomnia
Treatment should be as short as possible. In general, the duration of treatment varies from a few days to 2 weeks, up to a maximum of 4 weeks, including the period of gradual discontinuation.
In certain cases, an extension beyond the maximum treatment period may be necessary; if so, this should not occur without a careful reassessment of your condition.
In general, a daily dosage of 1-2 mg is recommended for mild forms and 2.5-5 mg for severe forms, administered at bedtime.
In the treatment of elderly patients, the dosage must be carefully established by the doctor, who will have to assess a possible reduction of the dosages mentioned above. In general, in elderly or debilitated patients, an initial dosage of 1-2 mg per day in divided doses is recommended, to be adjusted according to needs and tolerability.
Patients with impaired liver and/or kidney function should take a reduced dose.
As pre-surgical therapy, a dosage of 2-4 mg of lorazepam the evening before and/or 1-2 hours before the operation is recommended.
Treatment should be started with the recommended lowest dose.
The maximum dose should not be exceeded.
Daily doses and the duration of treatment should be established at the doctor's discretion.

When to take Lorazepam Almus
Lorazepam Almus can be administered at any time, independently of meals.

If you take more Lorazepam Almus than you should
If you or someone else has taken an excessive amount of Lorazepam Almus, contact your doctor or pharmacist immediately.
As with other benzodiazepines, an overdose of lorazepam should not pose a risk to life unless there is concomitant intake of other Central Nervous System depressants (including alcohol).
Benzodiazepine overdose usually manifests with varying degrees of Central Nervous System depression ranging from obtundation to coma. Symptoms of mild intoxication are drowsiness, fatigue, ataxia, visual disturbances, obtundation, mental confusion and lethargy. Oral administration of higher doses can lead to symptoms ranging from deep sleep to unconsciousness, ataxia, hypotension, respiratory depression, rarely coma and very rarely death.
In the treatment of drug overdose, the possibility of simultaneous intake of other substances must be considered.
Following an overdose of benzodiazepines by oral route, vomiting should be induced (within one hour) if the patient is conscious or gastric lavage with protection of the airways should be performed if the patient is unconscious.
If no improvement is observed with gastric emptying, activated charcoal should be administered to reduce absorption.
Special attention must be paid to respiratory and cardiovascular functions in emergency therapy.
In case of hypotension, drugs for peripheral circulation such as noradrenergic and volemic agents should be used. Assisted ventilation is required in case of respiratory impairment, which may 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 case of mono-intoxication with lorazepam because it is poorly dialyzable while its inactive metabolite, glucuronide, is highly dialyzable.
Flumazenil, a benzodiazepine antagonist, can be used as an antidote in hospitalized patients, in addition to appropriate treatment of a benzodiazepine overdose, not as a substitute. Flumazenil has an elimination half-life ranging from 40 to 80 minutes. Patients must be kept under close observation due to its short duration of action; additional doses of flumazenil may be necessary. The antagonism caused by flumazenil to the effects of benzodiazepines can increase the risk of neurological disorders (seizures), especially in patients with epilepsy, in those who have been using benzodiazepines for a long time and in case of overdose with tricyclic antidepressants.
Morphine antagonists are contraindicated.

If you forget to take Lorazepam Almus
Do not take a double dose to make up for a missed dose.

If you stop taking Lorazepam Almus
If you have any doubts about the use of Lorazepam Almus, consult your doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS

Like all medicines, Lorazepam Almus can cause side effects, although not everyone will experience them.
If they occur, side effects are usually observed at the beginning of treatment
and generally decrease in intensity or disappear as therapy progresses, or
by reducing the dosage.
To estimate the frequency of side effects, the following descriptions of frequency have been used:
Very common – in more than 1 in 10 patients treated
Common – in less than 1 in 10, but in more than 1 in 100 patients treated
Uncommon – in less than 1 in 100, but in more than 1 in 1000 patients treated
Rare – in less than 1 in 1000, but in more than 1 in 10000 patients treated
Very rare – in less than 1 in 10000 patients treated
Not known (frequency cannot be estimated based on available data)
The following side effects have been observed during treatment with Lorazepam Almus:
Blood and lymphatic system disorders
Rare: thrombocytopenia, agranulocytosis, pancytopenia.
Immune system disorders
Frequency not known: hypersensitivity reactions, anaphylactic/anaphylactoid reactions, angioedema.
Endocrine disorders
Rare: SIADH (syndrome of inappropriate antidiuretic hormone secretion).
Metabolism and nutrition disorders
Frequency not known: changes in appetite, hyponatremia.
Psychiatric disorders
Common: confusion, reduced alertness, blunted emotions.
Rare: disinhibition, euphoria, suicidal ideation/suicide attempts.
Frequency not known: anxiety, agitation, sleep disorders.
Nervous system disorders
Very common: ataxia.
Common: drowsiness, sedation
Rare: extrapyramidal symptoms: tremors, dizziness, headache, dysarthria/difficulty in articulation of
speech, amnesia, coma.
Frequency not known: convulsions/seizures, balance disorders, impaired
attention/concentration, disorientation.
Eye disorders
Rare: diplopia, blurred vision.
Cardiac disorders
Common: tachycardia.
Vascular disorders
Rare: hypotension.
Respiratory, thoracic and mediastinal disorders
Frequency not known: respiratory depression (*), apnea, worsening of nocturnal apnea,
worsening of obstructive pulmonary disease and autonomic manifestations.
(*) The extent of respiratory depression with benzodiazepine use is dosage-dependent; a
more severe depression occurs with higher doses.
Gastrointestinal disorders
Rare: nausea, constipation.
Frequency not known: various gastrointestinal disorders.
Hepatobiliary disorders
Rare: increased bilirubin, jaundice, increased liver transaminases, increased alkaline phosphatase.
Skin and subcutaneous tissue disorders
Rare: skin rashes, alopecia.
Frequency not known: skin reactions.
Musculoskeletal and connective tissue disorders
Common: muscle weakness.
Renal and urinary disorders
Rare: urinary incontinence.
Reproductive system and breast disorders
Uncommon: changes in libido.
Systemic disorders and administration site conditions
Common: fatigue, asthenia.
Rare: hypothermia.
In case of relative overdose, more significant symptoms may rarely be observed, which normally
disappear spontaneously within a few days or with dosage adjustment: ataxia, dysarthria,
urinary retention, dizziness, tremors, skin rashes, altered libido.
The incidence of sedation and instability increases with age.

Adverse reactions of the benzodiazepine class

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. Psychological dependence can occur. Abuse of benzodiazepines has been reported.
Once physical dependence has developed, abrupt discontinuation 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, the following symptoms may appear:
derealization, depersonalization, hallucinations, paresthesia of the limbs,
hypersensitivity to light, noise and physical contact, hyperacusis and seizures. There is evidence
to suggest that, in the case of benzodiazepines with a short duration of action, withdrawal symptoms may become
manifest between doses, especially at high doses. This is unlikely to occur with lorazepam, because its elimination half-life is approximately
14 hours.

Rebound insomnia and anxiety
Upon discontinuation of treatment, a transient syndrome such as insomnia may occur, which recurs
in a more severe form following treatment with benzodiazepines. Because, after abrupt
discontinuation of treatment, the risk of rebound/withdrawal phenomena is higher, it is recommended
to gradually reduce the dose. The patient should be informed of the possibility of rebound phenomena, in order to minimize the anxiety caused by these symptoms, which may appear when
benzodiazepines are discontinued.

Depression
During the use of benzodiazepines, a pre-existing depressive state may be unmasked.
Benzodiazepines and benzodiazepine-like compounds can cause reactions such as: restlessness,
irritability, aggression, delirium, anger, nightmares, hallucinations, psychosis, behavioral changes.
These reactions can be quite severe. They are more likely in children and the elderly.

Amnesia
Anterograde amnesia can occur even at therapeutic doses, the risk increases at higher doses.
Amnesic effects may be associated with behavioral changes.
In addition, rarely other adverse reactions have been reported with benzodiazepines including:
increased bilirubin, jaundice, increased liver transaminases, increased alkaline phosphatase,
thrombocytopenia, agranulocytosis, pancytopenia, SIADH (syndrome of inappropriate
antidiuretic hormone secretion).
If any of these side effects worsen, or if you notice any other effect

It is important to inform your doctor or pharmacist of the appearance of any side effect

5. HOW TO STORE LORAZEPAM ALMUS

Expiry date and storage
Expiry date: see the expiry date printed on the packaging.
The expiry date refers to the product in intact packaging, correctly stored.
Warning: do not use the medicine after the expiry date printed on the packaging.
Store the medicine at a temperature below 25°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 the medicine out of the reach and sight of children.

6. OTHER INFORMATION

Composition
The active ingredient is lorazepam
Lorazepam Almus 1 mg:
The excipients are: Tablet: lactose monohydrate, microcrystalline cellulose, potassium polacrilin,
magnesium stearate. Film coating: hypromellose, macrogol 6000, titanium dioxide, talc.
Lorazepam Almus 2,5 mg:
The excipients are: Tablet: lactose monohydrate, microcrystalline cellulose, potassium polacrilin,
magnesium stearate. Film coating: hypromellose, macrogol 6000, titanium dioxide, talc.

Pharmaceutical form and content
Lorazepam Almus 1 mg: film-coated tablets
Pack of 20 tablets
Lorazepam Almus 2,5 mg: film-coated tablets
Pack of 20 divisible tablets

Marketing Authorisation Holder
ALMUS S.r.l. – Via Cesarea 11/10 – 16121 Genova

Manufacturers responsible for batch release
DOPPEL FARMACEUTICI Srl – Via Volturno, 48 – Quinto de’Stampi – 20089 Rozzano (MI)
ABC Farmaceutici S.p.A. – Canton Moretti, 29 – 10090 San Bernardo d’Ivrea (TO)