PATIENT LEAFLET: INFORMATION FOR THE USER

Read this leaflet carefully before you start taking this medicine

Keep this leaflet. You may need to read it again.
If you have any doubts, consult your doctor or pharmacist.
This medicine has been prescribed for you. Do not give it to others, even if they have the same symptoms as you, because 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 BROMAZEPAM DOC Generici is and what it is used for
What you need to know before taking BROMAZEPAM DOC Generici
How to take BROMAZEPAM DOC Generici
Possible side effects
How to store BROMAZEPAM DOC Generici
Contents of the pack and other information

BROMAZEPAM DOC Generici 1.5 mg tablets
BROMAZEPAM DOC Generici 3 mg tablets
BROMAZEPAM DOC Generici 2.5 mg/ml oral drops, solution
Generic Medicine

1. WHAT BROMAZEPAM DOC Generici IS AND WHAT IT IS USED FOR

BROMAZEPAM DOC Generici contains bromazepam, a benzodiazepine with anxiolytic action.
BROMAZEPAM DOC Generici is indicated for:
anxiety, tension and other somatic or psychiatric manifestations associated with anxiety disorders;
insomnia.
Benzodiazepines are indicated only when the condition is severe, disabling and causing the patient severe distress.

2. WHAT YOU NEED TO KNOW BEFORE TAKING BROMAZEPAM DOC Generici

Do not take BROMAZEPAM DOC Generici
if you are allergic to bromazepam, to other similar medicines (benzodiazepines), or to any of the
other components of this medicine (listed in section 6).
Bromazepam must not be administered to patients with severe respiratory insufficiency, severe
hepatic insufficiency (benzodiazepines are not indicated for the treatment of patients with severe
liver impairment as they may cause encephalopathy), myasthenia gravis, or sleep apnoea syndrome.

Warnings and precautions
Talk to your doctor or pharmacist before taking BROMAZEPAM DOC Generici.

Amnesia
Benzodiazepines may cause anterograde amnesia. This occurs more frequently several hours after
drug intake; therefore, to reduce the risk, patients should ensure they can have several uninterrupted
hours of sleep. The amnesic effects may be associated with inappropriate behaviour (see section 4).

Psychiatric and paradoxical reactions
Reactions such as restlessness, agitation, irritability, aggression, delirium, rage, nightmares,
hallucinations, psychosis, inappropriate behaviour, and other behavioural disturbances are known to
occur with benzodiazepine use. If this occurs, the medicine should be discontinued.
Such reactions are more common in children and elderly patients.

Duration of treatment
The duration of treatment should be as short as possible (see section 3) and should not exceed eight to twelve weeks, including a gradual withdrawal period. Extending therapy beyond this period should not occur without re-evaluation of the clinical situation.
It may be helpful to inform the patient at the beginning of treatment that it will be of limited duration and to clearly explain how the dosage should be progressively reduced. It is also important that the patient is aware of the possibility of rebound phenomena, thereby minimizing anxiety about such symptoms should they occur during discontinuation of the medicine.
There is evidence to suggest that, in the case of benzodiazepines with a short duration of action, withdrawal symptoms may become apparent within the dosing interval between doses, particularly at high dosages.
When using long-acting benzodiazepines, it is important to warn patients that switching to a short-acting benzodiazepine is not advisable, as withdrawal symptoms may occur.

Concomitant use of alcohol/CNS depressants
Concomitant use of BROMAZEPAM DOC Generici with alcohol and/or other CNS depressants should be avoided. There is a possibility that such concomitant use may enhance the clinical effects of BROMAZEPAM DOC Generici, including profound sedation, respiratory depression, and/or clinically significant cardiovascular depression (see “Use of BROMAZEPAM DOC Generici with food and beverages” and “Use with other medicines”).
Patients should be regularly monitored at the beginning of treatment in order to minimize dosage and/or frequency of administration and to prevent overdose due to accumulation.

Tolerance
A certain loss of efficacy to the hypnotic effects of benzodiazepines may develop after repeated use for several weeks.

Children
Benzodiazepines should not be given to children without careful assessment of the actual need for treatment; the duration of treatment should be as short as possible.

Specific patient groups
Elderly patients should take a reduced dose (see section 3).
A lower dose is also recommended for patients with chronic respiratory insufficiency due to the risk of respiratory depression.
Benzodiazepines are not indicated for the treatment of patients with severe hepatic insufficiency as they may 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 depression (suicide may be precipitated in such patients).
Therefore, BROMAZEPAM DOC Generici should be used with caution, and the prescribed dose should be limited, in patients presenting signs and symptoms of depressive disorders or suicidal tendencies.
Benzodiazepines should be used with extreme caution in patients with a history of drug or alcohol abuse (see “Use of BROMAZEPAM DOC Generici with food and beverages” and “Use with other medicines”).

Dependence
The use of 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.
Once physical dependence has developed, abrupt discontinuation of treatment will be accompanied by withdrawal symptoms. These may include headache, diarrhoea, muscle pain, extreme anxiety, tension, restlessness, confusion, and irritability. In severe cases, the following symptoms may occur: derealization, depersonalization, hyperacusis, numbness and tingling of extremities, hypersensitivity to light, noise, and physical contact, hallucinations, or epileptic seizures.

Rebound insomnia and anxiety: Upon discontinuation of treatment, a transient syndrome may occur in which the symptoms that led to benzodiazepine treatment recur in an aggravated form. It 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 of dosage is recommended.

Other medicines and BROMAZEPAM DOC Generici
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
BROMAZEPAM DOC Generici should be used with caution when combined with other CNS depressants. The central depressive effect may be enhanced when used concomitantly with antipsychotics (neuroleptics), anxiolytics/sedatives, certain antidepressants, narcotic analgesics, opioids, antiepileptics, anaesthetics, and sedative antihistamines.

The concomitant use of BROMAZEPAM DOC Generici and opioids (strong painkillers, medicines for addiction therapy, and some cough medicines) increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. For this reason, concomitant use should only be considered when no other treatment options are available.
However, if your doctor prescribes BROMAZEPAM DOC Generici together with opioids, the dose and duration of concomitant treatment must be limited by the doctor.
Inform your doctor about all opioid medicines you are taking and carefully follow the doctor’s recommendations regarding dosage. It may be helpful to inform friends or family members to watch for the above-mentioned signs and symptoms.
Contact your doctor if you experience such symptoms.
Particular caution should be exercised with medicines that depress respiratory function, such as opioids (analgesics, cough suppressants, substitution treatments), especially in elderly individuals.

Pharmacokinetic interactions
Pharmacokinetic interactions may occur when BROMAZEPAM DOC Generici is administered with substances that inhibit the hepatic enzyme CYP3A4, thereby increasing plasma levels of BROMAZEPAM DOC Generici.
Co-administration of BROMAZEPAM DOC Generici with strong CYP3A4 inhibitors (e.g., azole antifungals, protease inhibitors, or certain macrolides) should be done with caution, and a substantial reduction in dose should be considered. In the case of narcotic analgesics, increased euphoria may occur, leading to an increased risk of psychological dependence.

BROMAZEPAM DOC Generici with alcohol:
Benzodiazepines produce an additive effect when co-administered with alcohol or other CNS depressants. Concomitant use with alcohol is not recommended.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using any medicine.
Although specific clinical data for bromazepam are not available, a large body of cohort study data indicates that exposure to benzodiazepines during the first trimester is not associated with an increased risk of major malformations. However, some recent case-control epidemiological studies have reported an increased risk of oral clefts. The data suggest that the risk of having a newborn with oral cleft after maternal exposure to benzodiazepines is less than 2/1000 compared to an expected frequency of approximately 1/1000 in the general population.
Treatment with high doses of benzodiazepines during the second and/or third trimester of pregnancy has been associated with reduced fetal movement and variability in fetal heart rate.
When treatment is administered for medical reasons during late pregnancy, even at low doses, the "floppy infant syndrome" may be observed, characterized by axial hypotonia and sucking difficulties leading to poor weight gain. These signs are reversible but may last from 1 to 3 weeks, depending on the half-life of the product. At high doses, neonatal respiratory depression, apnoea, and hypothermia may occur. Additionally, neonatal withdrawal symptoms may be observed a few days after birth, including hyperexcitability, agitation, and tremor, even in the absence of the "floppy infant syndrome."
Given these data, the use of BROMAZEPAM DOC Generici during pregnancy may be considered only if therapeutic indications and dosage are strictly adhered to.
If treatment with BROMAZEPAM DOC Generici is necessary during late pregnancy, high doses should be avoided, and the newborn should be monitored for withdrawal symptoms and/or "floppy infant syndrome."
Since BROMAZEPAM DOC Generici is excreted in breast milk, breastfeeding is not recommended during treatment.

Driving and using machines:
Sedation, amnesia, impaired concentration, and impaired muscle function may negatively affect the ability to drive and operate machinery. If sleep duration has been insufficient, the likelihood of altered alertness may be increased (see “Use of BROMAZEPAM DOC Generici with food and beverages” and “Use of BROMAZEPAM DOC Generici with other medicines”). This effect is enhanced in patients who have consumed alcohol.

BROMAZEPAM DOC Generici tablets contain lactose:
If your doctor has diagnosed you with an intolerance to certain sugars, consult them before taking this medicine.

BROMAZEPAM DOC Generici drops contain sodium:
This medicine contains less than 1 mmol (23 mg) of sodium per maximum daily dose (30 drops three times daily), i.e., essentially 'sodium-free'.

BROMAZEPAM DOC Generici drops contain propylene glycol:
This medicine contains 1182 mg of propylene glycol per 30-drop dose (equivalent to 3 mg of bromazepam).

If the child is under 5 years of age, talk to your doctor or pharmacist before administering this medicine, especially if the child is taking other medicines containing propylene glycol or alcohol.
If you are pregnant or breastfeeding, do not take this medicine unless otherwise recommended by your doctor. Your doctor may perform additional monitoring during treatment.
If you have liver or kidney disease, do not take this medicine unless otherwise recommended by your doctor. Your doctor may perform additional monitoring during treatment.

3. HOW TO USE BROMAZEPAM DOC Generici

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
The recommended dose, due to individual variability in response, ranges between 1.5 and 3 mg, 2–3 times daily (1–2 tablets of 1.5 mg 2–3 times a day or 1 tablet of 3 mg 2–3 times a day, or 15–30 drops 2–3 times a day).

Anxiety
Treatment should be as short as possible. The patient should be regularly reassessed, and the need for continued treatment should be carefully evaluated, particularly if the patient is symptom-free. Overall duration of treatment should generally not exceed 8–12 weeks, including a period of gradual withdrawal. In certain cases, extension beyond the maximum treatment period may be necessary; in such cases, this should not occur without re-evaluation of the patient's condition.

Insomnia
Treatment should be as short as possible. Duration of treatment generally varies from a few days to two weeks, up to a maximum of four weeks, including a period of gradual withdrawal.
In certain cases, extension beyond the maximum treatment period may be necessary; in such cases, this should not occur without re-evaluation of the patient's condition.
Treatment should be initiated with the lowest recommended dose.
The maximum dose should not be exceeded.
In elderly patients or patients with impaired liver function: dosage must be carefully determined by the doctor, who will consider whether a reduction of the above-mentioned doses is necessary.

If you feel that the effect of BROMAZEPAM DOC Generici is too strong or too weak, consult your doctor or pharmacist.

If you take more BROMAZEPAM DOC Generici than you should:
Symptoms
Benzodiazepines commonly cause drowsiness, ataxia, dysarthria, and nystagmus. Overdose with BROMAZEPAM DOC Generici rarely poses a life-threatening risk if the drug is taken alone, but may lead to dysarthria, areflexia, apnea, hypotension, cardiorespiratory depression, and coma. Coma, if it occurs, usually lasts for a few hours but may be prolonged and may recur cyclically, particularly in elderly patients. Respiratory depressant effects of benzodiazepines are more severe in patients with respiratory disorders.
Benzodiazepines increase the effects of other central nervous system depressants, including alcohol.

Treatment
Monitor vital signs and institute supportive measures as indicated by the patient's clinical condition. In particular, patients may require symptomatic treatment for cardiorespiratory or central nervous system effects.
Further absorption can be prevented using an appropriate method, such as administration of activated charcoal within 1–2 hours. If activated charcoal is used in unconscious patients, airway protection is mandatory. Gastric lavage may be considered in cases of ingestion of multiple substances, but not as a routine measure.
If CNS depression is severe, consider the use of flumazenil (Anexate), a benzodiazepine antagonist. This should be administered only under close monitoring. It has a short half-life (approximately one hour), therefore patients who have received flumazenil must be monitored after its effects have worn off. Flumazenil must be used with extreme caution in the presence of drugs that lower the seizure threshold (e.g., tricyclic antidepressants). For further information on the correct use of this drug, refer to the prescribing information for flumazenil (Anexate).

If you forget to take BROMAZEPAM DOC Generici:
Continue treatment as prescribed and do not take a double dose to make up for the forgotten dose.

If you stop taking BROMAZEPAM DOC Generici:
Do not stop treatment with BROMAZEPAM DOC Generici unless instructed by your doctor (see “Before taking BROMAZEPAM DOC Generici”).

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, this medicine can cause adverse reactions, although not everybody gets them.
The following adverse reactions have been reported during treatment with bromazepam, with the following frequencies:
Very common (≥ 1/10),
Common (≥ 1/100, < 1/10),
Uncommon (≥ 1/1000, < 1/100),
Rare (≥ 1/10,000, < 1/1000),
Very rare (< 1/10,000),
Not known (frequency cannot be estimated from the available data).

MedDRA Classification by System Organ Class | Frequency | Adverse Reactions
--- | --- | ---
Immune system disorders | Not known | Hypersensitivity, anaphylactic shock, angioedema
Psychiatric disorders | Not known | Confusional state, emotional disturbance, changes in libido, drug dependence, drug abuse, withdrawal syndrome
| | Depression
| | Paradoxical reactions such as restlessness, agitation, irritability, aggression, delirium, anger, nightmares, hallucinations, psychosis, inappropriate behaviour
| | Anterograde amnesia, memory impairment
Nervous system disorders | Not known | Somnolence, headache, dizziness, decreased alertness, ataxia
Eye disorders | Not known | Diplopia
Cardiac disorders | Not known | Cardiac failure including cardiac arrest
Respiratory, thoracic and mediastinal disorders | Not known | Respiratory depression
Gastrointestinal disorders | Not known | Nausea, vomiting, constipation
Skin and subcutaneous tissue disorders | Not known | Rash, pruritus, urticaria
Musculoskeletal and connective tissue disorders | Not known | Muscle weakness
Renal and urinary disorders | Not known | Urinary retention
General disorders and administration site conditions | Not known | Fatigue
Injury, poisoning and procedural complications | Not known | Falls, fractures

These adverse reactions occur mainly at the beginning of therapy and usually disappear with repeated administration.
See “Do not take BROMAZEPAM DOC Generici if”

The risk of falls and fractures is higher in patients taking sedatives concomitantly (including alcoholic beverages) and in elderly patients.

Amnesia
Anterograde amnesia may occur even at therapeutic doses; the risk increases with higher doses.
Amnesic effects may be associated with behavioural changes (see section 4.4 “Special warnings and precautions for use”).

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

Dependence
The 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 (see section 4.4 “Special warnings and precautions for use”). Psychological dependence may also occur. Abuse of benzodiazepines has been reported.

Following the instructions provided in this leaflet reduces the risk of adverse reactions.

Reporting of suspected adverse reactions.
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. You can also report adverse reactions directly via the national reporting system at the following website: www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversawww.agenziafarmaco.gov.it/it/responsabili. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. HOW TO STORE BROMAZEPAM DOC Generici

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp.".
The expiry date refers to the last day of that month.
The expiry date refers to the product in its original, unopened packaging, correctly stored.
No special storage instructions are required.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. CONTENTS OF THE PACKAGE AND OTHER INFORMATION

What BROMAZEPAM DOC Generici contains
BROMAZEPAM DOC Generici 1.5 mg tablets
The active substance is: bromazepam 1.5 mg.
The other components are: microcrystalline cellulose, lactose, talc, magnesium stearate.

BROMAZEPAM DOC Generici 3 mg tablets
The active substance is: bromazepam 3 mg.
The other components are: microcrystalline cellulose, lactose, talc, magnesium stearate, E172.

BROMAZEPAM DOC Generici 2.5 mg/ml oral drops, solution
The active substance (in 1 ml of solution) is: bromazepam 2.5 mg.
The other components are: saccharin, disodium edetate (Sequestrene Na2), mixed fruit flavours, purified water, propylene glycol (E 1520).

Description of the appearance of BROMAZEPAM DOC Generici and the contents of the pack
BROMAZEPAM DOC Generici 1.5 mg tablets
Blister pack containing 20 tablets of 1.5 mg.

BROMAZEPAM DOC Generici 3 mg tablets
Blister pack containing 20 tablets of 3 mg.

BROMAZEPAM DOC Generici 2.5 mg/ml oral drops
Bottle containing 20 ml of solution at a concentration of 2.5 mg/ml.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
DOC Generici S.r.l. - Via Turati, 40 - 20121 Milan, Italy

Manufacturers:
Tablets: Doppel Farmaceutici srl - Via Volturno 48 – Quinto de’ Stampi – Rozzano (MI);
ABC Farmaceutici S.p.A. – Cantone Moretti 29 – San Bernardo – Ivrea (TO).

Oral drops, solution: Doppel Farmaceutici srl - Via Martiri delle Foibe, 1 – 29016 Cortemaggiore (PC);
ABC Farmaceutici S.p.A. – Cantone Moretti 29 – San Bernardo – Ivrea (TO).

Bromazepam Doc Generici