Lorazepam Almus: detailed information

PACKAGE LEAFLET: INFORMATION FOR THE USER

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

Generic medicine
Please read all of this leaflet carefully before taking this medicine.

Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor or pharmacist.
This medicine has been prescribed for you personally. Do not pass it on to others, even if their symptoms appear to be the same as yours, as it could be harmful.
If any of the side effects worsens, or if you notice any side effects not listed in this leaflet, inform your doctor or pharmacist.

Contents of this leaflet:

What Lorazepam Almus is and what it is used for
Before you take Lorazepam Almus
How to take Lorazepam Almus
Possible side effects
How to store Lorazepam Almus
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 anxiety states or nervous tension, nervous insomnia, and anxious depression.
Benzodiazepines are indicated only when the disorder is severe, disabling, or causes the patient severe distress.

2. BEFORE TAKING 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 severe myasthenia gravis
if you suffer from severe respiratory insufficiency (e.g. severe chronic obstructive pulmonary disease)
if you suffer from sleep apnoea syndrome
if you suffer from narrow-angle glaucoma
if you suffer from severe hepatic insufficiency
if you have acute intoxication due to alcohol, hypnotic, analgesic, or psychotropic medicines (neuroleptics, antidepressants, lithium)
if you are pregnant or breastfeeding

Take special care with Lorazepam Almus
If your doctor has diagnosed you with intolerance to certain sugars, contact him before taking this medicine.
The use of benzodiazepines, including Lorazepam Almus, may lead to potentially fatal respiratory depression.
Severe anaphylactic/anaphylactoid reactions have been reported with the use of benzodiazepines. Cases of angioedema affecting 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 experienced additional symptoms such as dyspnea, throat closure, or nausea and vomiting. Some patients required emergency treatment. If angioedema affects the tongue, glottis, or larynx, airway obstruction may occur, which could be fatal.
Patients who develop angioedema after treatment with benzodiazepines must not be re-treated with the drug.
Tolerance. After repeated use for several weeks, a certain loss of efficacy of the hypnotic effects of benzodiazepines may develop.
Dependence. The use of lorazepam and other benzodiazepines may lead to the development of physical and psychological dependence on these drugs. The risk of dependence increases with dose and duration of treatment; it is higher in patients with a history of drug or alcohol abuse. Therefore, benzodiazepines should be used with extreme caution in patients with a history of alcohol or drug abuse.
The possibility of dependence is reduced when Lorazepam Almus is used at the appropriate dose for short-term treatment.
Withdrawal symptoms. Once physical dependence has developed, abrupt discontinuation of treatment will be accompanied by withdrawal symptoms. These may include headache, 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 limbs, hypersensitivity to light, noise, and physical contact, hallucinations, and epileptic seizures.
Other symptoms include: depression, insomnia, sweating, persistent tinnitus, involuntary movements, vomiting, paresthesia, perceptual disturbances, 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 appear within the dosing interval, particularly with high doses. This is unlikely to occur with lorazepam because its elimination half-life is approximately 12–16 hours. However, withdrawal symptoms may occur when switching to lorazepam after prolonged and/or high-dose use of benzodiazepines with significantly longer duration of action.
Rebound insomnia and anxiety. Upon discontinuation of treatment, a transient syndrome may occur in which the symptoms that led to benzodiazepine treatment reappear in a worsened form. This may 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 reduction in dosage is recommended.
It is also important that the patient be informed about the possibility of rebound phenomena, in order to minimize the anxious reaction that the appearance of such symptoms might trigger when lorazepam is discontinued.
Amnesia. Benzodiazepines may induce anterograde amnesia. This occurs most frequently several hours after ingestion of the drug; therefore, to reduce the risk, it must be ensured 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, aggressiveness, delirium, delusion, rage, anger, nightmares, hallucinations, psychosis, inappropriate behavior, and other behavioral changes may occur with the use of benzodiazepines. If this occurs, the use of the medicine must be discontinued.
These reactions are more likely to occur in elderly patients and in patients with organic brain syndrome.
At present, it cannot be excluded that in patients with acute endogenous psychosis, especially severe depressive states, symptoms may be worsened by the use of lorazepam. Therefore, benzodiazepines are not recommended for the primary treatment of psychotic disorders. The presence of depression must always be ruled out, particularly in early or morning sleep disturbances, since symptoms may be otherwise masked and risks associated with the underlying disease (e.g. suicidal tendencies) are always present.
Specific patient groups
Paediatric patients: Lorazepam should not be administered to patients under 18 years of age without careful assessment of the actual need for treatment; treatment duration should be as short as possible.
Elderly patients: The use of benzodiazepines may be associated with an increased risk of falls due to adverse effects such as ataxia, muscle weakness, dizziness, drowsiness, fatigue, and tiredness; therefore, elderly patients should be treated with caution.
Elderly patients should take a reduced dose or should not be treated at all.
Patients with chronic respiratory insufficiency: a lower dose is recommended in patients with chronic respiratory insufficiency due to the risk of respiratory depression (see also “Do not take Lorazepam Almus”).
Patients with severe hepatic insufficiency: caution is recommended in patients with severe hepatic insufficiency and/or encephalopathy, as lorazepam, like all benzodiazepines, may precipitate hepatic encephalopathy.
Patients with renal insufficiency: lorazepam should be administered with caution in patients with severe renal insufficiency.
Patients with psychosis: benzodiazepines are not recommended for the primary treatment of psychotic disorders. 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 should be applied to patients with heart failure and low blood pressure, who should undergo regular monitoring during treatment with Lorazepam Almus (as recommended with other benzodiazepines and psychotropic agents).
In patients in whom gastrointestinal or cardiovascular disorders coexist with anxiety, it should be noted that Lorazepam Almus has not shown significant benefits in treating the gastrointestinal or cardiovascular components.
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. Extending therapy beyond these periods should not occur without re-evaluation of the clinical situation. It is useful to inform the patient at the start of treatment that it is of limited duration and to clearly explain how the dose should be progressively reduced.
Taking Lorazepam with other medicines
Inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including those without a prescription.
In particular, take care in the following cases:

Medicines that depress the Central Nervous System: The central depressive effect may be increased when used concomitantly with medicines that depress the Central Nervous System such as antipsychotics (neuroleptics), hypnotics, anxiolytics/tranquilizers/sedatives, antidepressants, narcotic analgesics, antiepileptics, anesthetics, and sedative antihistamines. Narcotic analgesics may cause increased euphoria leading to increased psychological dependence.
Cytochrome P450 inhibitors: Compounds that inhibit certain liver enzymes (especially cytochrome P450) may increase the activity of benzodiazepines. To a lesser extent, this also applies to benzodiazepines metabolized solely by conjugation.
Clozapine: Concomitant use of clozapine and lorazepam may produce marked sedation, excessive salivation, and ataxia.
Valproate: Concurrent administration of lorazepam with valproate may lead to increased plasma concentrations and reduced elimination of lorazepam. The dose of Lorazepam Almus must be reduced by 50% when co-administered with valproate.
Probenecid: Concurrent administration of lorazepam with probenecid may result in a faster onset or prolonged effect of lorazepam due to increased half-life or reduced total elimination. The dose of Lorazepam Almus must be reduced by 50% when co-administered with probenecid.
Theophylline and aminophylline: Administration of theophylline or aminophylline may reduce the effects of benzodiazepines.
Loxapine: Cases of excessive stupor, significantly reduced respiratory rate, and, in one case, hypotension have been reported when lorazepam was administered concomitantly with loxapine.

Taking Lorazepam Almus with food and drinks
Alcohol: Concomitant intake of the medicine with alcohol must be avoided. The sedative effect may be increased when the medicine is taken together with alcohol, which 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, childbirth, or breastfeeding.
If you are of childbearing age, you should contact your doctor, both if you plan to become pregnant and if you suspect you are pregnant, regarding discontinuation of the medicine.
If, for serious medical reasons, the product is administered during the last stage of pregnancy or during labor at high doses, 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 medicine may occur.
Furthermore, newborns born to mothers who have chronically taken benzodiazepines during late pregnancy may develop physical dependence and may be at risk of developing withdrawal symptoms in the postnatal period.
It appears that in newborns, lorazepam conjugation occurs slowly, with its glucuronide detectable in 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 must not be administered to breastfeeding mothers.
Driving and using machines
Do not drive and do not use tools or machinery because sedation, amnesia, altered concentration, and impaired muscle function may negatively affect your ability to drive or use machinery.
Reactions may vary depending on the time of ingestion, individual sensitivity, and dose. This occurs particularly with high doses in combination with alcohol.
If sleep duration has been insufficient, the likelihood of impaired vigilance may be increased.
Important information about some excipients of Lorazepam Almus
The tablets contain lactose. Patients with rare hereditary problems of 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 directed by your doctor. If you have any doubts, consult your doctor or pharmacist.

Route of administration
Oral use

How much Lorazepam Almus to take
For optimal results, the dose, frequency of administration, and duration of treatment must be individually adjusted according to your response.
The lowest effective dose should be prescribed for the shortest possible time.
Since the risk of withdrawal or rebound symptoms is higher after abrupt discontinuation of treatment, a gradual reduction of the dosage is recommended.

Anxiety
Treatment should be as short-term as possible.
You should be regularly re-evaluated, and the need for continued treatment should be carefully assessed, especially if you are symptom-free. Overall treatment duration should generally not exceed 8–12 weeks, including the period of gradual withdrawal.
In certain cases, extension beyond the maximum treatment period may be necessary; in such cases, this should not occur without a re-evaluation of your condition.
Generally, a daily dosage of 2–3 mg is recommended for mild cases and 7.5–10 mg for severe cases. It is advisable to take the highest dose in the evening, before bedtime.
For elderly patients, dosage must be carefully determined by the doctor, who should consider reducing the above-mentioned doses. In general, for elderly or debilitated patients, an initial dosage of 1–2 mg per day in divided doses is recommended, to be adjusted according to need and tolerability.
Patients with impaired hepatic and/or renal function should take a reduced dose.

Insomnia
Treatment should be as short-term as possible. Generally, treatment duration ranges from a few days to 2 weeks, up to a maximum of 4 weeks, including the period of gradual withdrawal.
In certain cases, extension beyond the maximum treatment period may be necessary; if so, this should not occur without careful re-evaluation of your condition.
Generally, a daily dosage of 1–2 mg is recommended for mild cases and 2.5–5 mg for severe cases, administered at bedtime.
For elderly patients, dosage must be carefully determined by the doctor, who should consider reducing the above-mentioned doses. In general, for elderly or debilitated patients, an initial dosage of 1–2 mg per day in divided doses is recommended, to be adjusted according to need and tolerability.
Patients with impaired hepatic and/or renal function should take a reduced dose.
As pre-surgical therapy, a dosage of 2–4 mg of lorazepam is recommended the evening before and/or 1–2 hours before surgery.
Treatment should be initiated with the lowest recommended dose.
The maximum dose must not be exceeded.
Daily doses and duration of treatment must be determined at the physician's discretion.

When to take Lorazepam Almus
Lorazepam Almus may be administered at any time, regardless 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 life-threatening risk unless it is taken concomitantly with other central nervous system depressants (including alcohol).
Overdose of benzodiazepines typically manifests as varying degrees of central nervous system depression, ranging from drowsiness to coma. Symptoms of mild intoxication include drowsiness, fatigue, ataxia, visual disturbances, mental clouding, confusion, and lethargy. Oral administration of higher doses may lead to symptoms ranging from deep sleep to unconsciousness, ataxia, hypotonia, hypotension, respiratory depression, rarely coma, and very rarely death.
In managing overdose of any drug, the possibility of simultaneous ingestion of other substances must be considered.
Following an oral overdose of benzodiazepines, vomiting should be induced (within one hour) if the patient is conscious, or gastric lavage should be performed with protection of the airway if the patient is unconscious.
If no improvement is observed after gastric emptying, activated charcoal should be administered to reduce absorption.
Special attention must be paid to respiratory and cardiovascular functions during emergency treatment.
In case of hypotension, peripheral-acting vasopressors (e.g., noradrenergic agents) and volume expanders should be used. Assisted ventilation is required in case of respiratory impairment, which may also be caused by peripheral muscular relaxation.
In cases of mixed intoxication, hemodialysis and peritoneal dialysis may be useful. However, these methods are not efficient in cases of lorazepam monointoxication, as lorazepam is poorly dialyzable, whereas its inactive metabolite, the glucuronide, is highly dialyzable.
Flumazenil, a benzodiazepine antagonist, may be used as an antidote in hospitalized patients, in addition to appropriate supportive treatment of benzodiazepine overdose, but not as a substitute. Flumazenil has an elimination half-life of 40 to 80 minutes. Patients must be closely monitored due to its short duration of action; repeated doses of flumazenil may be necessary. The antagonism caused by flumazenil on the effects of benzodiazepines may increase the risk of neurological disturbances (e.g., seizures), particularly in patients with epilepsy, those on long-term benzodiazepine therapy, and in cases of overdose with cyclic antidepressants.
Opioid antagonists are contraindicated.

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

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

4. POSSIBLE ADVERSE EFFECTS

Like all medicines, Lorazepam Almus can cause adverse effects, although not everyone experiences
them.
Adverse effects, if they occur, are usually observed at the beginning of treatment and generally
decrease in intensity or disappear as therapy progresses, or by reducing the dosage.
The following frequency descriptions have been used to estimate the incidence of side effects:
Very common – in more than 1 out of 10 patients treated
Common – in less than 1 out of 10, but in more than 1 out of 100 patients treated
Uncommon – in less than 1 out of 100, but in more than 1 out of 1000 patients treated
Rare – in less than 1 out of 1000, but in more than 1 out of 10,000 patients treated
Very rare – in less than 1 out of 10,000 patients treated
Not known (frequency cannot be estimated from the available data)

The following adverse 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, blunting of emotions.
Rare: disinhibition, euphoria, suicidal ideation/suicide attempts.
Frequency not known: anxiety, agitation, sleep disturbances.

Nervous system disorders
Very common: ataxia.
Common: drowsiness, sedation.
Rare: extrapyramidal symptoms: tremors, dizziness, headache, dysarthria/difficulty in articulating
speech, amnesia, coma.
Frequency not known: seizures/epileptic fits, disturbances of balance, 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
pulmonary obstructive disease, and autonomic manifestations.
(*) The extent of respiratory depression with benzodiazepines is dose-dependent; more severe
depression occurs at higher doses.

Gastrointestinal disorders
Rare: nausea, constipation.
Frequency not known: various gastrointestinal disturbances.

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.

General disorders and administration site conditions
Common: fatigue, asthenia.
Rare: hypothermia.

In cases of relative overdose, more significant symptoms may rarely occur, which usually resolve
spontaneously within a few days or upon dose adjustment: ataxia, dysarthria, urinary retention,
dizziness, tremors, skin rashes, altered libido.
The incidence of sedation and unsteadiness increases with age.

Adverse reactions of the benzodiazepine class

Dependence
Use of benzodiazepines (even at therapeutic doses) may lead to the development of physical
dependence: discontinuation of treatment may result in rebound or withdrawal phenomena.
Psychological dependence may also occur. Abuse of benzodiazepines has been reported.
Once physical dependence has developed, abrupt discontinuation of treatment may be accompanied
by withdrawal symptoms. These may include extreme anxiety, tension, restlessness, confusion,
irritability, headache, and muscle pain. In severe cases, the following symptoms may occur:
derealization, depersonalization, hallucinations, paresthesia of limbs, hypersensitivity to light, noise
and physical contact, hyperacusis, and epileptic seizures. There is evidence that, when using
short-acting benzodiazepines, withdrawal symptoms may appear between doses, especially at high
doses. This is unlikely to occur with lorazepam, as 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
an aggravated form following benzodiazepine treatment. Since the risk of rebound/withdrawal
phenomena is higher after abrupt discontinuation, it is recommended to gradually reduce the dose.
Patients should be informed about the possibility of rebound phenomena to minimize anxiety caused
by such symptoms, which may appear when benzodiazepines are discontinued.

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

Amnesia
Anterograde amnesia may occur even at therapeutic doses; the risk increases at higher doses.
Amnesic effects may be associated with behavioral disturbances.

Additionally, other rare adverse reactions reported with benzodiazepines include: increased
bilirubin, jaundice, increased liver transaminases, increased alkaline phosphatase, thrombocytopenia,
agranulocytosis, pancytopenia, SIADH (syndrome of inappropriate antidiuretic hormone secretion).

If any of the adverse effects worsens, or if you notice any adverse effect not listed in this leaflet, inform
your doctor or pharmacist.
Following the instructions in this leaflet reduces the risk of adverse effects.
It is important to inform your doctor or pharmacist about any adverse effect, even if not described in this leaflet.

5. HOW TO STORE LORAZEPAM ALMUS

Expiry and storage
Expiry: see the expiry date stated on the packaging.
The expiry date refers to the product in its original, unopened packaging, properly stored.
Warning: do not use the medicine after the expiry date stated on the packaging.
Store the medicine at a temperature not exceeding 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 substance is lorazepam.
Lorazepam Almus 1 mg:
The excipients are: Tablet core: monohydrate lactose, microcrystalline cellulose, potassium polacrilin,
magnesium stearate. Film coating: hypromellose, macrogol 6000, titanium dioxide, talc.
Lorazepam Almus 2.5 mg:
The excipients are: Tablet core: monohydrate lactose, microcrystalline cellulose, potassium polacrilin,
magnesium stearate. Film coating: hypromellose, macrogol 6000, titanium dioxide, talc.

Pharmaceutical form and contents
Lorazepam Almus 1 mg: film-coated tablets
Box containing 20 tablets

Lorazepam Almus 2.5 mg: film-coated tablets
Box containing 20 divisible tablets

Marketing Authorization Holder
ALMUS S.r.l. – Via Cesarea 11/10 – 16121 Genoa

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)