Package leaflet: Information for the patient

COMPENDIUM

1.5 mg hard capsules
3 mg hard capsules
2.5 mg/ml oral drops, solution
Bromazepam
Please read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

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 only. Do not give it to others, even if they have the same symptoms as yours, because it may be harmful.
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Compendium is and what it is used for
What you need to know before taking Compendium
How to take Compendium
Possible side effects
How to store Compendium
Contents of the pack and other information

1. What Compendium is and what it is used for

Compendium contains the active substance bromazepam, which belongs to a class of
medicines called "benzodiazepine derivatives".
Compendium is used in adults for the treatment of:

Anxiety, emotional tension and other symptoms associated with anxiety
Insomnia, only when severe and causing significant distress in normal daily life.

2. What you need to know before taking Compendium

Do not take Compendium

if you are allergic to bromazepam or any of the other ingredients of this medicine (listed in section 6)
if you are allergic to benzodiazepines (medicines similar to bromazepam)
if you suffer from severe respiratory insufficiency (severe reduction in respiratory system activity)
if you suffer from severe liver disease
if you suffer from severe myasthenia gravis (a serious muscle disease characterized by weakness and fatigue)
if you suffer from sleep apnoea syndrome (temporary cessation of breathing during sleep)
narrow-angle glaucoma (an eye disease caused by increased pressure of the fluid inside the eye)
if you abuse alcohol
if you abuse medicines:
- hypnotics, calming medicines used to promote sleep
- narcotic analgesics, medicines for treating severe acute or chronic pain
- psychotropic medicines, medicines used for mental disorders and/or depression.

Warnings and precautions
Talk to your doctor or pharmacist before taking Compendium.
In particular, inform your doctor if:

you suffer from depression or anxiety associated with depression, or have suicidal thoughts (attempting to kill yourself), because Compendium may worsen your condition and increase suicidal tendencies
you have previously had problems with drug or alcohol abuse
you suffer from chronic respiratory insufficiency (reduced respiratory system function)
you suffer from renal insufficiency (reduced kidney function)
you suffer from heart failure (reduced heart function); in this case, your doctor will monitor you regularly during treatment with Compendium
you suffer from low blood pressure; in this case, your doctor will monitor you regularly during treatment with Compendium
you suffer from a mental disorder causing altered perception of reality, thought disturbances, or mental confusion (psychosis).

Development of tolerance
After repeated use of this medicine for several weeks, its effectiveness may decrease (tolerance). If after a few weeks you feel that the medicine is not working as well as it did at the beginning of treatment, consult your doctor.
Development of dependence
Taking high doses and/or using bromazepam for prolonged periods may lead to physical and psychological dependence.
This risk is higher if you have previously abused medicines, drugs, or alcohol, as you are more likely to develop habituation and dependence on this medicine.
The risk of dependence is reduced if you take Compendium at the appropriate dose as prescribed by your doctor and for a short duration (see section 3 “How to take Compendium”).
If you are elderly
Take Compendium with caution and under medical supervision if you are elderly.
This medicine may increase the risk of falls due to side effects such as ataxia (reduced motor coordination and gait), muscle weakness, dizziness, drowsiness, fatigue, and tiredness. In addition, elderly patients more frequently experience side effects such as restlessness, agitation, irritability, and aggression (see section “Possible side effects”).
Children and adolescents
Do not give this medicine to children and adolescents (0–18 years) without first consulting a doctor.
Bromazepam, like other medicines similar to bromazepam, should be given to children only when strictly necessary and under direct medical supervision. The doctor will evaluate the use of the medicine based on the child’s condition. In any case, treatment duration will be as short as possible.
Other medicines and Compendium
Inform your doctor or pharmacist if you are currently using, have recently used, or might use any other medicine.
Inform your doctor or pharmacist if you are taking any of the following medicines together with Compendium, as caution is required:

medicines that reduce or block the activity of the central nervous system. Avoid taking Compendium together with the following medicines, as this may increase the risk of side effects such as deep sedation (physical and mental relaxation similar to that caused by anaesthetics) and severe reduction in respiratory and/or heart function:
- medicines used for certain mental illnesses (antipsychotics/neuroleptics)
- calming medicines used to promote sleep (hypnotics)
- medicines causing physical and mental dullness (anxiolytics/sedatives)
- medicines for treating depression (antidepressants)
- medicines for treating severe acute or chronic pain ( opioids , narcotic analgesics, cough sedatives, substitution treatments). The concomitant use of Compendium and opioids increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. The simultaneous use should be considered only if no other treatment options are available. However, if your doctor prescribes Compendium together with opioids, the dose and duration of concomitant therapy will be determined by your doctor. Inform your doctor about all opioid medicines you are taking and strictly follow the recommended dose. It may be helpful to inform friends or family members about the signs and symptoms described above. Contact your doctor if you experience any of these symptoms. Narcotic analgesics may increase feelings of euphoria, leading to increased psychological dependence.
- medicines for treating epilepsy (antiepileptics)
- anaesthetics
- medicines used to treat allergic reactions (sedating antihistamines)
cimetidine (a medicine used in stomach ulcers), as it may increase the effects of Compendium;
theophylline or aminophylline (medicines used for bronchial asthma), as they may reduce the effects of Compendium;
medicines that affect the metabolism of Compendium, as they may increase its effects, for example:
- medicines for treating fungal infections (azole antifungals)
- medicines for treating HIV (protease inhibitors)
- certain antibiotics (macrolides).

Compendium and alcohol
Do not drink alcohol while taking Compendium, as the simultaneous intake of alcohol and Compendium may cause side effects such as sedation and severe reduction in respiratory and/or heart function (see section “Do not take Compendium”).
If you have previously abused alcohol, your doctor will monitor you closely during treatment with Compendium, as you are more likely to develop dependence on this medicine.
Taking alcohol with Compendium may also severely impair your ability to drive vehicles or operate machinery (see section “Driving and use of machinery”).
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Do not take Compendium during pregnancy without first consulting your doctor.
Available data indicate that the use of bromazepam:

during the first 3 months of pregnancy may cause a congenital lip defect in the newborn called "cleft lip" (oral cleft)
during the last 6 months of pregnancy may reduce fetal movements and cause variability in the fetal heart rhythm.

If, for serious health reasons, your doctor decides to prescribe this medicine during the late stages of pregnancy, the newborn may show symptoms of the "floppy infant syndrome" even at low doses, such as:

axial hypotonia (reduced muscle tone)
sucking difficulties leading to poor weight gain. These signs are temporary but may last from 1 to 3 weeks. After high doses and/or prolonged use of Compendium during late pregnancy, the newborn may experience:
respiratory depression
temporary cessation of breathing (apnoea)
lowered body temperature (hypothermia)
symptoms of physical dependence or withdrawal, including increased excitability, agitation, and tremors. These effects may appear several days after birth.

If treatment with Compendium is necessary during the final stages of pregnancy,
your doctor will avoid using high doses and/or prolonged treatment and will monitor the newborn for possible withdrawal symptoms after birth.
Breastfeeding
Bromazepam is excreted in breast milk; therefore, breastfeeding is not recommended during treatment with Compendium.
Driving and use of machinery
Do not drive vehicles or operate machinery if you experience side effects such as sedation (physical and mental relaxation similar to that caused by anaesthetics), amnesia (memory disturbances), impaired concentration, or altered muscle function while being treated with Compendium. These effects may worsen if you consume alcohol together with Compendium (see section “Compendium and alcohol”).
Your alertness may be impaired, especially if you have not had sufficient sleep after taking Compendium.
Compendium hard capsules contain lactose
If your doctor has diagnosed you with an intolerance to certain sugars, consult them before taking this medicine.
Compendium oral drops, solution contains propylene glycol
This medicine contains 1141 mg of propylene glycol per dose, equivalent to 951 mg/ml.

3. How to take Compendium

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Adults
Your doctor will determine the most appropriate dose and frequency for you in order to avoid the possible intake of an excessive dose of this medicine. Generally, your doctor will start with the lowest recommended dose and, if necessary, may gradually increase it.
The average recommended dose is:

Hard capsules: 1–2 capsules of 1.5 mg 2–3 times daily; or 1 capsule of 3 mg 2–3 times daily
Oral drops: 15–30 drops 2–3 times daily.

If you are elderly or suffer from liver disorders or chronic respiratory disorders
If you are elderly or suffer from liver disorders or chronic respiratory disorders, your doctor will evaluate whether to prescribe lower doses than those indicated above.
Duration of treatment
Your doctor will prescribe the shortest possible duration of treatment.
Depending on the condition for which your doctor has prescribed this medicine, the duration of treatment is as follows:

Anxiety: generally, the total duration of treatment does not exceed 8–12 weeks, including a gradual withdrawal period
Insomnia: generally, the duration of treatment ranges from a few days to 2 weeks, up to a maximum of 4 weeks, including a gradual withdrawal period. In certain cases, after reassessing your health status, your doctor may decide to extend the duration of treatment indicated above. During the period of discontinuation of Compendium treatment, your doctor will explain how to gradually reduce the dose of this medicine in order to minimize the risk of withdrawal and rebound symptoms. (See section “If you stop taking Compendium” and “Possible side effects”).

If you take more Compendium than you should
In case of accidental ingestion/overdose of Compendium, contact your doctor immediately or go to the nearest hospital.
Symptoms
If you accidentally take a dose higher than prescribed, there is rarely a life-threatening risk, provided the medicine is taken alone (alcohol increases the depressant effects on the nervous system).
In mild cases, symptoms of accidental overdose of Compendium may include:

Drowsiness
Mental confusion
Lethargy (continuous sleep and reduced response to normal stimuli).
In more severe cases, symptoms may include:
Ataxia (reduced motor coordination and gait instability)
Hypotonia (decreased muscle tone)
Hypotension (low blood pressure)
Respiratory depression and/or reduced heart activity
Coma
Death.

Additionally, you may experience the following symptoms:

Dysarthria (speech disorder)
Nystagmus (oscillating eye movements)
Difficulty speaking
Areflexia (absence of reflexes)
Apnea (temporary cessation of breathing).

Treatment
After evaluating the symptoms, your doctor will provide appropriate supportive therapy (e.g., activated charcoal and/or gastric lavage).
Your doctor may consider using flumazenil (a medicine that acts by blocking the effects of benzodiazepines). If you are taking medicines for depression or suffer from epilepsy, inform your doctor, as flumazenil must be used with extreme caution in these cases.
For further information on the correct use of this medicine, consult your doctor.
If you forget to take Compendium
Do not take a double dose to make up for the forgotten dose.
If you stop taking Compendium

Do not stop treatment with Compendium abruptly without first consulting your doctor.
Your doctor will gradually reduce your dose during the discontinuation phase.
Abruptly stopping this medicine may cause:
Withdrawal symptoms, such as headache, muscle pain, extreme anxiety, tension, restlessness, confusion, and irritability
Rebound symptoms (when the symptoms that led to treatment with bromazepam reappear in a more severe form after stopping treatment), such as mood changes, anxiety, restlessness, or sleep disturbances
Severe symptoms, including: feeling detached or estranged from oneself or the external world, increased sensitivity to sound, numbness and tingling in the arms or legs, hypersensitivity to light, noise, and physical touch, perception of non-existent things (hallucinations), epileptic seizures.
Other symptoms: depression, insomnia, sweating, persistent sensation of tinnitus (ringing in the ears), involuntary body movements, vomiting, paresthesia (tingling sensation), perceptual disturbances, abdominal and muscular cramps, tremor, myalgia (muscle pain), agitation, palpitations (sensation of increased heartbeat), tachycardia (increased heart rate), panic attacks, dizziness, exaggerated reflexes, loss of ability to recall recent events, hyperthermia (elevated body temperature).
These symptoms occur especially if you have developed physical dependence on this medicine (see section “Warnings and precautions”).

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Contact your doctor immediately if, during treatment with Compendium, you experience any of the following serious side effects; your doctor will explain how to stop taking the medicine:

depression
restlessness
agitation
irritability
aggressiveness
delusions
anger
nightmares
perception of things not existing in reality (hallucinations)
behavioural changes
psychosis (mental disorder causing altered perception of reality, thought disturbances, mental confusion). These reactions are more frequent in children and elderly patients, or if you suffer from a brain disorder causing reduced mental function (organic brain syndrome).

Additionally, during treatment with Compendium, as with any medicine, you may experience the following side effects, the frequency of which cannot be determined from the available data:
Effects related to the heart

reduced heart function (heart failure)
heart attack (cardiac arrest).

Effects related to the eyes

double vision (diplopia). This side effect occurs mainly at the beginning of therapy and usually disappears with subsequent doses
blurred vision.

Effects related to the stomach and intestine

nausea and vomiting. These side effects occur mainly at the beginning of therapy and usually disappear with subsequent doses
constipation.

Effects related to various parts of the body

fatigue. This side effect occurs mainly at the beginning of therapy and usually disappears with subsequent doses

Effects related to the body's defence system

allergic reaction and/or severe allergic reaction (anaphylactic/anaphylactoid). The allergic reaction may manifest as swelling affecting the tongue and/or throat, possibly leading to airway obstruction which could be fatal (angioedema), but may also include dyspnoea (difficulty breathing), throat closure, or nausea and vomiting.

Trauma

falls and fractures. The risk of falls and fractures is increased if you are taking other sedative medicines (medicines causing physical and mental dullness) or alcohol at the same time, or if you are elderly.

Effects related to the mind

confusion. This side effect occurs mainly at the beginning of therapy and usually disappears with subsequent doses
emotional disturbances. This side effect occurs mainly at the beginning of therapy and usually disappears with subsequent doses
drug dependence/abuse (see section “Warnings and precautions”)
withdrawal symptoms (see sections “Warnings and precautions” and “If you stop taking Compendium”)
changes in sexual desire
memory disorders/amnesia. These side effects may occur even at recommended doses; the risk increases with higher doses. This effect may be associated with behavioural disturbances. This effect occurs more frequently several hours after taking the medicine; therefore, to reduce the risk, before taking this medicine you must ensure you can have an uninterrupted period of several hours of sleep (see section “How to take Compendium”).

Effects related to the kidneys and urinary tract

inability of the urinary bladder to empty completely (urinary retention)
condition characterised by accumulation of water in the body and reduced sodium levels in the blood (syndrome of inappropriate antidiuretic hormone secretion).

Effects related to the muscles

muscle weakness. This side effect occurs mainly at the beginning of therapy and usually disappears with subsequent doses

Effects related to the nervous system
The following side effects occur mainly at the beginning of therapy and usually disappear with subsequent doses:

drowsiness
reduced alertness
tiredness
headache
dizziness
lightheadedness
reduced motor coordination and gait (ataxia).

Effects related to the respiratory system

respiratory depression
temporary cessation of breathing (apnoea) and worsening of nocturnal apnoea

Effects related to the skin

skin rash
itching
skin redness accompanied by itching (urticaria).

Effects related to the liver

yellowish discoloration of the skin and whites of the eyes (jaundice).

Diagnostic tests

increased blood levels of bilirubin, transaminases and alkaline phosphatase (substances produced by the liver).

Effects related to the blood

thrombocytopenia (reduced platelets in the blood)
agranulocytosis (reduced white blood cells in the blood)
pancytopenia (reduced counts of all blood cells).

Other side effects reported with other medicines belonging to the benzodiazepine class, such as Compendium, and which may therefore also potentially occur with Compendium:
Effects related to various parts of the body

rebound symptoms (when the anxiety and insomnia that led to bromazepam treatment reappear in a more severe form after stopping treatment). These side effects generally occur during the treatment discontinuation phase, especially after abrupt cessation. To reduce these side effects, do not stop treatment abruptly; consult your doctor, who will advise you on how to gradually reduce the dose (see sections “If you stop taking Compendium” and “How to take Compendium”).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at the website
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Compendium

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after "Exp".
The expiry date refers to the last day of that month.
Hard capsules: store below 30 °C.
Oral drops: no special storage conditions required.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist
how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Compendium contains
Compendium 1.5 mg hard capsules

The active substance is: bromazepam (1 hard capsule contains 1.5 mg of bromazepam)
The other components are: lactose (see section “Compendium capsules contain lactose”), maize starch, talc, magnesium stearate, titanium dioxide (E171), yellow iron oxide (E172), gelatin.

Compendium 3 mg hard capsules

The active substance is: bromazepam (1 hard capsule contains 3 mg of bromazepam)
The other components are: lactose (see section “Compendium capsules contain lactose”), maize starch, talc, magnesium stearate, titanium dioxide (E171), indigo carmine (E132), gelatin.

Compendium 2.5 mg/ml oral drops, solution

Active substance: bromazepam (1 ml of solution contains 2.5 mg of bromazepam)
The other components are: sodium saccharin, disodium edetate, blackcurrant flavour, raspberry flavour, purified water, propylene glycol.

Description of Compendium and contents of the pack
Hard capsules
White/yellow 1.5 mg and white/blue 3 mg hard capsules for oral use,
packed in blisters in a carton box containing 30 capsules.
Oral drops
Clear solution contained in a 20 ml dosing bottle with child-resistant closure.

Marketing Authorization Holder
POLIFARMA S.p.A. - Viale dell’Arte, 69 - 00144 ROMA.
Manufacturer
ISTITUTO DE ANGELI S.r.l., Località Prulli 103/C – 50066 Reggello (FI)