Patient Information Leaflet

EN 0.5 mg tablets, 1 mg tablets, 2 mg tablets, 1 mg/ml oral drops, solution

Please read all of this leaflet carefully before you take 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, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What EN is and what it is used for

EN is a medicine containing delorazepam, an active substance belonging to the class of benzodiazepines, drugs that reduce anxiety and help sleep. Benzodiazepines are usually used for severe disorders that cause significant distress or that interfere with the performance of normal daily activities.
EN is used to treat:

anxiety, tension, and other anxiety-related disorders
insomnia, a condition characterized by difficulty falling asleep or maintaining adequate sleep

2. What you need to know before taking EN

Do not take EN if:

you are allergic to the active substance or to other medicines in the same class (benzodiazepines) or to any of the other ingredients of this medicine (listed in section 6);
you have severe respiratory problems;
you suffer from sleep apnoea syndrome (interruptions in breathing during sleep);
you have taken large amounts of alcohol or medicines acting on the central nervous system such as hypnotics, analgesics (painkillers), or psychotropics (e.g. neuroleptics, antidepressants, lithium);
you have myasthenia gravis, a disease characterised by muscle weakness and fatigue;
you have narrow-angle glaucoma, a condition characterised by increased pressure inside the eye possibly leading to worsening of vision;
you have severe liver problems;
you are pregnant or breastfeeding (see "Pregnancy and breastfeeding").

Warnings and precautions
Talk to your doctor or pharmacist before taking EN if:

you have or have had drug or alcohol dependence;
you have heart problems or suffer from low blood pressure;
you have severe kidney problems;
you have liver problems;
you have had psychiatric disorders;
you suffer from depression;
you have suicidal thoughts;
you have breathing difficulties;
you are elderly, as this medicine may cause dizziness, drowsiness, tiredness, fatigue, muscle weakness, and coordination problems, increasing the risk of falls.

Other information

Mental side effects – contact your doctor if you experience side effects such as agitation, irritability, restlessness, aggression, self-harm, nightmares or hallucinations, changes in behaviour or memory, fainting, or sleepwalking. These side effects are more likely in children and the elderly.
Amnesia (partial or complete memory loss) – during treatment with EN, you may have difficulty remembering recent events or forming new memories (anterograde amnesia), especially a few hours after taking the medicine. To reduce this risk, take EN immediately before going to bed.
Dependence – during treatment with EN, you may develop physical and psychological dependence; this risk increases with higher doses, longer treatment duration, or if you have had psychiatric disorders or drug or alcohol dependence. For this reason, treatment with EN should be as short as possible.
Withdrawal syndrome – if you have developed dependence and stop treatment with EN abruptly or reduce the dose too quickly, withdrawal symptoms may occur, such as headache, muscle pain, anxiety, tension, restlessness, confusion, and irritability. In severe cases, the following may occur: derealisation and depersonalisation (a distorted perception of the external world or of oneself), numbness and tingling in the extremities, increased sensitivity to light, noise, and physical contact, hallucinations, or epileptic seizures. Other symptoms include: depression, sleep disturbances, sweating, persistent ringing in the ears, involuntary movements, vomiting, altered sensation, abdominal or muscle cramps, tremor, muscle pain, agitation, palpitations, increased heart rate, panic attacks, dizziness, increased reflexes, short-term memory loss, and increased body temperature. If you experience any of these symptoms, consult your doctor.
Tolerance – contact your doctor if during treatment with EN you notice a reduction in effectiveness or duration of the sedative/hypnotic effect.
Rebound symptoms – treatment with EN should be discontinued gradually, with a progressive reduction in dose. Abruptly stopping treatment could cause the return or worsening of symptoms (such as insomnia or anxiety) for which treatment was started (see section 3, "If you stop taking EN").

Children and adolescents
In children and adolescents under 18 years of age, EN should only be used under strict medical supervision.

Other medicines and EN
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, as some medicines may interact with EN or increase the risk of adverse events, even serious ones.
In particular, contact your doctor if you are taking:

medicines acting on the central nervous system, such as antipsychotics, sedatives, anxiolytics, hypnotics, anaesthetics, sedating antihistamines, narcotic analgesics;
medicines used to treat depression (antidepressants);
medicines used to treat epilepsy (antiepileptics);
medicines used to treat bronchial asthma (e.g. theophylline, aminophylline); as these medicines may alter the effect of EN.

The concomitant use of EN and opioids (strong analgesics, medicines for addiction treatment, 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 EN 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 dosage recommendations. It may be helpful to inform friends or family members to watch for the signs and symptoms listed above.
Contact your doctor if you experience any of these symptoms.

EN and alcohol
Do not consume alcohol or medicines containing alcohol during treatment with this medicine, as this could worsen certain side effects affecting the nervous system (e.g. sedation, drowsiness).

Pregnancy and breastfeeding
Do not take EN during pregnancy or while breastfeeding.
If you suspect you are pregnant or are planning a pregnancy, consult your doctor before taking this medicine.

Driving and using machines
EN may cause sedation, memory loss, impaired concentration, and muscle function disturbances. Exercise particular caution before driving or operating machinery.

EN drops contain ethanol, sodium, and propylene glycol

Ethanol
This medicine contains 101.56 mg of ethanol (alcohol) per 1 ml, equivalent to 201.3 mg of ethanol (alcohol) in the maximum daily dose (52 drops), which corresponds to 3.4 mg/kg. The volume amount of this medicine is equivalent to 5 mL of beer or 2 mL of wine. The small amount of alcohol in this medicine will not produce significant effects in adults.

Sodium (as sodium saccharin)
This medicine contains less than 1 mmol (23 mg) of sodium per maximum dose (2 mg equal to 52 drops), i.e. essentially 'sodium-free'.

Propylene glycol
This medicine contains 1497.6 mg of propylene glycol per maximum daily dose (2 mg equal to 52 drops), equivalent to 10.7 mg/kg per mL of solution.
If the child is less than 4 weeks old, talk to your doctor or pharmacist before administering this medicine, especially if the child is taking other medicines containing propylene glycol or alcohol.

EN tablets contain: lactose.
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

3. How to take EN

Take this medicine exactly as your doctor has instructed you.
Your doctor will determine the correct dose and duration of treatment based on the severity of your symptoms and your general condition (for example, if you have liver, kidney or lung problems).
If in doubt, consult your doctor.

If you are taking EN for anxiety
The usual dose is:
1 tablet (0.5, 1 or 2 mg), 2–3 times a day;
or
13–26–52 drops, 2–3 times a day.
Your doctor will tell you which tablet strength or how many drops to use.
Treatment duration should not exceed 8–12 weeks.

If you are taking EN for insomnia
The usual dose is:
1 tablet of 0.5, 1 or 2 mg, in the evening before going to bed;
or
13–26–52 drops, in the evening before going to bed.
Your doctor will tell you which tablet strength or how many drops to use.
Treatment duration ranges from a few days up to 2 weeks, and may be extended up to a maximum of 4 weeks.

Method of administration
EN tablets: swallow the tablets orally with a little water.
EN drops: take the drops diluted in a small amount of water as follows:

To open the bottle: press down on the cap and simultaneously unscrew it (Fig. 1).
Let the drops fall into a glass, holding the bottle in a vertical position with the opening facing downwards (Fig. 2). If you experience difficulty in the drops coming out, please turn the bottle upside down again (even more than once, Fig. 3) and perform repeated downward movements until the drops flow again (Fig. 4).
To close the bottle: screw the cap back on until tightly sealed (Fig. 5).

Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5

Sequence of diagrams illustrating the withdrawal of a drug from a vial using a syringe and the

If you take more EN than you should
You may experience drowsiness, fatigue or coordination difficulties, vision problems such as blurred vision, confusion and lethargy. In severe cases, deep sleep, unconsciousness, coordination disturbances, low blood pressure (hypotension), muscle weakness (hypotonia), breathing difficulties or coma may occur. Excessive doses of this medicine may also result in death.
In case of accidental ingestion or overdose of EN, contact your doctor immediately or go to the nearest hospital, as appropriate measures may be required.

If you forget to take EN
Do not take a double dose to make up for the missed dose. Take the forgotten dose as soon as you remember, then continue your treatment as usual.

If you stop taking EN
Do not stop treatment with EN abruptly, as withdrawal symptoms may occur (see section 2, "Other information"). When discontinuation of treatment is necessary, your doctor will gradually reduce the dose.

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
everyone experiences them.
Stop taking EN immediately and contact your doctor if you experience
severe allergic reactions, which may include: swelling (angioedema) of the eyes, face, tongue, or throat, accompanied by breathing difficulties, shortness of breath, skin rash, nausea, vomiting, or a sudden drop in blood pressure (anaphylactic reactions).
Inform your doctor if, during treatment with EN, you notice the following:

Very common side effects (may affect more than 1 in 10 people)

loss of coordination of movements (ataxia).

Common side effects (may affect up to 1 in 10 people)

confusion, reduced alertness, reduced emotional responsiveness;
increased heart rate (tachycardia);
muscle weakness, fatigue, tiredness (asthenia);
drowsiness, sedation.

Uncommon side effects (may affect up to 1 in 100 people)

changes in sexual desire.

Rare side effects (may affect up to 1 in 1,000 people)

extrapyramidal symptoms including tremors, dizziness, headache, speech difficulties, amnesia, coma;
skin rashes such as blotchy or widespread spots, or skin lesions such as blisters;
disinhibition, excessive happiness (euphoria), thoughts or attempts of self-harm;
reduction in the number of platelets (thrombocytopenia), white blood cells (agranulocytosis), or all blood components (pancytopenia);
decrease in blood pressure (hypotension);
vision disturbances such as double vision (diplopia) or blurred vision;
nausea or difficulty passing stools (constipation);
patchy hair loss (alopecia);
involuntary loss of urine (urinary incontinence);
yellowing of the skin or eyes (jaundice), increased bilirubin, increased liver transaminases, increased alkaline phosphatase;
SIADH (syndrome of inappropriate antidiuretic hormone secretion), a condition characterized by excessive release of a hormone called “antidiuretic hormone”;
decrease in body temperature (hypothermia).

Side effects with unknown frequency

changes in appetite;
decreased sodium levels in the blood (hyponatremia);
more or less sudden appearance of skin lesions (skin reactions);
angioedema;
hypersensitivity reactions, anaphylactic/anaphylactoid reactions;
respiratory problems such as respiratory depression, breathlessness (apnea), worsening of nocturnal apnea, or worsening of pre-existing lung diseases;
stomach or intestinal disturbances;
seizures or epileptic fits, balance disorders, decreased attention or concentration, disorientation;
anxiety, agitation, sleep disturbances.

Other side effects (see section 2, “Other information”)
Some side effects that have occurred with other benzodiazepines might also occur during treatment with EN:

insomnia and anxiety (rebound symptoms);
dependence and withdrawal syndrome;
anterograde amnesia;
mental side effects.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, contact 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 EN

Keep this medicine out of the sight and reach of children.
EN tablets: this medicine requires no special storage conditions.
EN oral drops, solution: this medicine requires no special storage conditions.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What EN contains
The active substance is: delorazepam.
EN 0.5 mg tablets
One 0.5 mg tablet contains: 0.5 mg of delorazepam.
Other components: maize starch, gelatin, lactose, magnesium stearate, talc.
EN 1 mg tablets
One 1 mg tablet contains: 1 mg of delorazepam.
Other components: maize starch, colouring agent E 127, gelatin, lactose, magnesium stearate, talc.
EN 2 mg tablets
One 2 mg tablet contains: 2 mg of delorazepam.
Other components: maize starch, colouring agent E 110, gelatin, lactose, magnesium stearate, talc.
EN 1 mg/ml oral drops, solution
One drop of EN contains: 38.5 mcg of delorazepam; 13 drops contain: 0.5 mg of delorazepam.
Other components: purified water, ethanol, Glicasol N, glycerol, propylene glycol, sodium saccharin.

Description of the appearance of EN and contents of the pack
EN tablets are available in a carton containing 20 tablets.
EN oral drops, solution are available in a 20 ml bottle with dropper, equipped with child-resistant closure.

Marketing Authorization Holder
Mylan Italia S.r.l., Via Vittor Pisani 20, 20124 Milan
Manufacturer
AbbVie S.r.l. - S.R.148 Pontina Km 52 s.n.c. - 04011 Campoverde di Aprilia (LT)
Package leaflet: information for the patient

EN 0.5 mg/1 ml solution for injection, 2 mg/1 ml solution for injection, 5 mg/1 ml solution for injection

delorazepam
Please read this leaflet carefully before 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
their symptoms are the same as yours, because it could be harmful.
If you experience any adverse reaction, including those not listed in this
leaflet, contact your doctor or pharmacist. See section 4.
Contents of this leaflet:

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

1. What EN is and what it is used for

EN is a medicine containing delorazepam, an active substance belonging to the class of benzodiazepines, medicines that reduce anxiety and help sleep. Benzodiazepines are usually used for severe disorders causing significant distress or that interfere with the performance of normal daily activities.
EN is used to treat:

anxiety, tension, and other anxiety-related disorders
sleep disorders;
epilepsy, a condition characterized by sudden loss of consciousness and violent involuntary muscle movements.

Furthermore, EN may be used exclusively by medical personnel or healthcare professionals:

for preparation prior to endoscopic examinations;
before surgical procedures.

2. What you should know before taking EN

Do not take EN if:

you are allergic to the active substance, to other medicines belonging to the same class (benzodiazepines), or to any of the other ingredients of this medicine (listed in section 6);
you have severe respiratory problems;
you suffer from sleep apnoea syndrome (interruptions in breathing during sleep);
you have taken high doses of alcohol or medicines acting on the central nervous system such as hypnotics, analgesics (painkillers), or psychotropic medicines (e.g. neuroleptics, antidepressants, lithium);
you have myasthenia gravis, a disease characterized by muscle weakness and fatigue;
you have narrow-angle glaucoma, a condition characterized by increased pressure inside the eye with possible worsening of vision;
you have severe liver problems;
you are pregnant or breastfeeding (see "Pregnancy and breastfeeding").

EN must not be used for preparation for endoscopic examinations or prior to surgical procedures in patients who have taken sedative or narcotic medicines within the previous 24 hours.

Warnings and precautions

Talk to your doctor or pharmacist before taking EN if:

you have or have had drug or alcohol dependence;
you have heart or blood vessel problems or suffer from low blood pressure;
you have severe kidney problems;
you have liver problems;
you have had psychiatric disorders;
you suffer from depression;
you have suicidal thoughts;
you have breathing difficulties;
you have brain disorders, for example hardening of the walls of brain blood vessels (arteriosclerosis);
you are elderly, as this medicine may cause dizziness, drowsiness, tiredness, fatigue, muscle weakness, and coordination problems, increasing the risk of falls.

Other information

Mental side effects – contact your doctor if you experience side effects such as agitation, irritability, restlessness, aggression, self-harm, nightmares or hallucinations, changes in behaviour or memory, fainting, or sleepwalking. These side effects are more likely in children and elderly patients.
Amnesia (partial or complete memory loss) – during treatment with EN, you may have difficulty remembering recent events or storing new information (anterograde amnesia), especially a few hours after taking the medicine. To reduce this risk, take EN immediately before going to bed.
Dependence – during treatment with EN, you may develop physical and psychological dependence; this risk increases with higher doses and longer treatment duration, or if you have had psychiatric disorders or drug or alcohol dependence. For this reason, treatment with EN should be as short as possible.
Withdrawal syndrome – if you have developed dependence and suddenly stop taking EN or reduce the dose too quickly, withdrawal symptoms may occur, such as headache, muscle pain, anxiety, tension, restlessness, confusion, and irritability. In severe cases, the following may occur: derealization and depersonalization (a distorted perception of the external world or of oneself), numbness and tingling in the extremities, increased sensitivity to light, noise, and physical contact, hallucinations, or epileptic seizures. Other symptoms include: depression, sleep disturbances, sweating, persistent ringing in the ears, involuntary movements, vomiting, altered sensation, abdominal or muscle cramps, tremor, muscle pain, agitation, sensation of a pounding heart, increased heart rate, panic attacks, dizziness, increased reflexes, short-term memory loss, and increased body temperature. If you experience these symptoms, contact your doctor.
Tolerance – contact your doctor if during treatment with EN you notice a reduction in effectiveness or duration of the sedative/hypnotic effect.
Rebound symptoms – treatment with EN should be discontinued gradually, with a progressive reduction in dose. Abruptly stopping treatment may cause the return or worsening of symptoms (e.g. insomnia or anxiety) for which treatment was started (see section 3, "If you stop taking EN").

Additional warnings on the parenteral use of this medicine are provided in the section
“Information intended exclusively for doctors or healthcare professionals” at the end of this
package leaflet.

Children and adolescents
In children and adolescents under 18 years of age, EN should be used only under strict medical supervision. EN may be used if necessary, as it does not contain benzyl alcohol.

Other medicines and EN
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, as some medicines may interact with EN or increase the risk of adverse events, even serious ones.

In particular, contact your doctor if you are taking:

medicines acting on the central nervous system, such as antipsychotics, sedatives, anxiolytics, hypnotics, anaesthetics, sedative antihistamines, narcotic analgesics;
medicines used for depression (antidepressants);
medicines used for epilepsy (antiepileptics);
medicines used to treat bronchial asthma (e.g. theophylline, aminophylline); as these medicines may alter the effect of EN.

Concomitant use of EN and opioids (strong analgesics, medicines for addiction treatment, 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 EN 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 signs and symptoms listed above.

Contact your doctor if you experience such symptoms.

EN and alcohol
Do not consume alcohol or medicines containing alcohol during treatment with this medicine, as this could worsen certain side effects on the nervous system (e.g. sedation, drowsiness).

Pregnancy and breastfeeding
Do not take EN during pregnancy or while breastfeeding.
If you suspect you are pregnant or are planning a pregnancy, consult your doctor before taking this medicine.

Driving and using machines
EN may cause sedation, memory loss, impaired concentration, and altered muscle function. After taking EN, wait at least 12 hours before driving or operating machinery.

EN contains potassium, sodium, ethanol, and propylene glycol

Potassium
This medicine contains less than 1 mmol (39 mg) of potassium per dose, i.e. essentially 'potassium-free';

Sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially 'sodium-free';

Ethanol
EN injectable solution 0.5 mg/mL and 2 mg/mL
This medicine contains 186.6 mg of alcohol (ethanol) in each 1 mL vial, equivalent to 3.1 mg/kg. The volume amount of this medicine is equivalent to less than 5 mL of beer and 2 mL of wine. The small amount of alcohol in this medicine will not produce significant effects in adults.

EN injectable solution 5 mg/mL
This medicine contains 210 mg of alcohol (ethanol) in each 1 mL vial, equivalent to 3.5 mg/kg. The volume amount of this medicine is equivalent to less than 6 mL of beer and 3 mL of wine. The small amount of alcohol in this medicine will not produce significant effects in adults.

Propylene glycol
This medicine contains 312 mg of propylene glycol per vial, equivalent to 4.5 mg/kg per mL of solution.
If the child is less than 4 weeks old, talk to your doctor or pharmacist before administering this medicine, especially if the child is taking other medicines containing propylene glycol or alcohol.

3. How to take EN

If you are taking EN for anxiety or sleep disorders
Always take this medicine exactly as your doctor has instructed you. Your doctor will determine the correct dose and duration of treatment based on the severity of your symptoms and your general condition (for example, if you have liver, kidney or lung problems). If you have any doubts, consult your doctor.
The usual dose is: 0.02–0.05 mg per kg of body weight per day.
Usually, treatment with EN does not exceed 4 weeks in the case of insomnia, and 8–12 weeks in the case of anxiety.

Method of administration
EN may be administered:

into a muscle, via injection;
into a vein, via injection or intravenous infusion (e.g. with physiological saline or glucose solution). Intravenous administration must be performed exclusively in a hospital setting and by medical personnel (see the section at the end of this leaflet).

If you are taking EN for preparation for endoscopic examinations or prior to surgical procedures
Your doctor will administer EN via injection into a muscle or into a vein, before the endoscopic examination or surgical procedure.
Additional “Information intended exclusively for doctors or healthcare professionals”
is available at the end of this package leaflet.

If you take more EN than you should
You may experience drowsiness, fatigue or coordination difficulties, vision problems (e.g. blurred vision), confusion and lethargy. In severe cases, deep sleep, unconsciousness, coordination disturbances, low blood pressure (hypotension), muscle weakness (hypotonia), breathing difficulties or coma may occur. Excessive doses of this medicine may also result in death.
In case of accidental ingestion/overdose of EN, contact your doctor immediately or go to the nearest hospital, as appropriate measures may be necessary.

If you forget to take EN
Do not take a double dose to make up for the forgotten dose. Take the missed dose as soon as you remember, then continue your treatment as normal.

If you stop taking EN
Do not stop treatment with EN abruptly, as withdrawal symptoms may occur (see section 2, “Other information”). When discontinuation of therapy is necessary, your doctor will gradually reduce the dose.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Stop taking EN immediately and contact your doctor if you experience severe allergic reactions, such as: swelling (angioedema) of the eyes, face, tongue, or throat, accompanied by breathing difficulties, shortness of breath, skin rash possibly with nausea and vomiting, sudden drop in blood pressure (anaphylactic reactions).

Inform your doctor if, during treatment with EN, you notice the following:

Very common side effects (may affect more than 1 in 10 people)

loss of coordination of movements (ataxia).

Common side effects (may affect up to 1 in 10 people)

confusion, reduced alertness, reduced emotions;
increased heart rate (tachycardia);
muscle weakness, fatigue, tiredness (asthenia);
drowsiness, sedation.

Uncommon side effects (may affect up to 1 in 100 people)

changes in sexual desire.

Rare side effects (may affect up to 1 in 1,000 people)

extrapyramidal symptoms including tremors, dizziness, headache, speech difficulties, amnesia, coma;
skin eruptions such as patchy and widespread spots or lesions such as blisters;
disinhibition, excessive happiness (euphoria), suicidal thoughts or attempts;
reduced number of platelets (thrombocytopenia), white blood cells (agranulocytosis), or all blood components (pancytopenia);
decreased blood pressure (hypotension);
vision disturbances such as double vision (diplopia) or blurred vision;
nausea or difficulty evacuating (constipation);
patchy hair loss (alopecia);
involuntary loss of urine (urinary incontinence);
yellowing of the skin or eyes (jaundice), increased bilirubin, increased liver transaminases, increased alkaline phosphatase;
SIADH (syndrome of inappropriate antidiuretic hormone secretion), a condition characterized by excessive release of a hormone called "antidiuretic hormone";
decreased body temperature (hypothermia).

Side effects with unknown frequency

changes in appetite;
decreased sodium levels in the blood (hyponatremia);
more or less sudden appearance of skin lesions (skin reactions);
angioedema;
hypersensitivity reactions, anaphylactic/anaphylactoid reactions;
breathing problems such as respiratory depression, breathlessness (apnea), worsening of nocturnal apneas, or worsening of pre-existing lung diseases;
stomach or intestinal problems;
seizures or epileptic fits, balance disorders, reduced attention or concentration, disorientation;
anxiety, agitation, sleep disturbances;
autonomic manifestations.

Other side effects (see section 2, “Other information”)
Some side effects that have occurred with other benzodiazepines may also occur during treatment with EN:

insomnia and anxiety (rebound symptoms);
dependence and withdrawal syndrome;
anterograde amnesia;
mental side effects;
hiccups.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please contact 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 EN

Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage conditions.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of that month.
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 EN contains
The active substance is: delorazepam.
One vial containing 0.5 – 2 – 5 mg contains: 0.5 – 2 – 5 mg of delorazepam.
The other components are: water for injections, ethanol, propylene glycol,
monobasic potassium phosphate, dibasic sodium phosphate.

Description of the appearance of EN and packaging contents
EN is available in packs of 3 vials of 1 ml each, containing 0.5 – 2 – 5 mg of delorazepam.

Marketing Authorization Holder
Mylan Italia S.r.l., Via Vittor Pisani 20, 20124 Milano
Manufacturer
Alfasigma SpA - Via Enrico Fermi 1 - 65020 Alanno (PE)

To use EN for preparation for endoscopic examinations or prior to surgical procedures,
follow the instructions provided below.

If using EN for preparation for endoscopic examinations (premedication)

Diagnostic endoscopic examination
Intramuscular route: 1 vial of 2 mg one hour before the examination;
Intravenous route: 0.02 mg per kg of body weight, 10 minutes before the examination, administered by slow intravenous injection (over 3–5 minutes).

Method of administration
Dilute 1 vial of 2 mg with 9 ml of water for injections or physiological solution (resulting in a solution containing 0.2 mg/ml) and administer 0.1 ml per kg of body weight.

Operative endoscopic examination
Intramuscular route: 1 vial of 5 mg one hour before the examination;
Intravenous route: 0.05 mg per kg of body weight, 10 minutes before the examination, administered by slow intravenous injection (over 3–5 minutes).

Method of administration
Dilute 1 vial of 5 mg with 19 ml of water for injections or physiological solution (resulting in a solution containing 0.25 mg/ml) and administer 0.2 ml per kg of body weight.

If using EN before surgical procedures (preanesthesia)
Intramuscular route: 1 vial of 0.5–2 mg administered intramuscularly alone or in combination with atropine, one hour before surgery.

Special warnings for parenteral administration

EN must not be used for preparation for endoscopic examinations or prior to surgical procedures in patients who have taken sedative or narcotic drugs within the previous 24 hours.
EN injectable solution can be used in paediatrics because it does not contain benzyl alcohol.
EN administered by intravenous infusion does not cause opalescence of the solution and no precipitation of the drug is observed on the walls of the infusion bottle.
Intravenous injection must be performed slowly and into a large-calibre vessel (preferably into a vein at the elbow crease). Excessively rapid injection or use of a vessel with too small a lumen may result in risk of vein inflammation (thrombophlebitis).
Intra-arterial injection must be absolutely avoided due to the risk of necrosis.
In elderly patients and in those with cardiovascular instability, parenteral administration of EN injectable solution, particularly by intravenous route, must be used with caution.
Outpatients treated with EN injectable solution by parenteral route, and particularly by intravenous route, must be carefully monitored for at least one hour after injection and, if possible, should not be discharged unless accompanied. They should also be informed not to drive a vehicle during the day (or at least for the 12 hours following administration).
In patients with organic brain disorders (especially arteriosclerotic) or with cardiorespiratory insufficiency, parenteral administration should be avoided for outpatient treatments. However, in a hospital setting, such patients may be treated parenterally; in case of intravenous injection, doses should be reduced and the injection administered slowly.
Parenteral administration of EN injectable solution generally does not cause significant changes in arterial pressure, pulse, or respiration. However, slight reductions in blood pressure have been reported, rarely exceeding 20 mm Hg for systolic values and 10 mm Hg for diastolic values.
Very rare reports of impaired respiratory function have been observed; these manifestations were generally short-lived and occurred mainly after intravenous injection, particularly in arteriosclerotic patients or in patients who already had respiratory insufficiency. In most of these cases, patients had received excessively high doses or the injection had been administered too rapidly. Therefore, measures to support circulation or respiration should be available.
Hypotonia and hypothermia have been observed in neonates whose mothers received the highest recommended doses during delivery for the treatment of preeclamptic toxemia and eclampsia.