Package leaflet: Information for the user

Lorxagen 1 mg tablets, 2.5 mg tablets

Lorazepam
Generic medicine
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 other people, even if their symptoms are the same as yours, as 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 Lorxagen is and what it is used for
What you need to know before taking Lorxagen
How to take Lorxagen
Possible side effects
How to store Lorxagen
Contents of the pack and other information

1. What Lorxagen is and what it is used for

LORXAGEN contains the active substance Lorazepam. Lorazepam belongs to a group of medicines called benzodiazepines and acts on the central nervous system by reducing anxiety (anxiolytic effect), promoting sleep closely comparable to normal sleep (hypnotic effect), improving mood, and reducing the intensity of emotional responses to psychological stress (tranquilizing effect).
Lorxagen is used for the short-term treatment of the following conditions when they are severe and cause distress in everyday life:

Anxiety and emotional tension states associated with anxiety
Insomnia

2. What you should know before taking Lorxagen

Do not take Lorxagen

if you are allergic to lorazepam, to benzodiazepines, or to any of the other ingredients of this medicine (listed in section 6);
if you suffer from a disease causing severe muscle weakness and easy fatigue (myasthenia gravis);
if you have serious breathing problems (respiratory failure);
if you have serious liver problems (hepatic insufficiency);
if you suffer from episodes of breathing interruption for several seconds during sleep (sleep apnea);
if you suffer from increased pressure inside the eye (narrow-angle glaucoma);
if you are or think you may be pregnant (see section “Pregnancy and breastfeeding”).

Warnings and precautions
The duration of treatment with Lorxagen should be as short as possible. It is recommended not to
exceed 4 weeks for the treatment of insomnia and 8–12 weeks for the treatment of anxiety. The
recommended duration of treatment includes also the period required for gradual dose reduction.
See section 3 “How to take Lorxagen”.
Talk to your doctor or pharmacist before taking Lorxagen if you think any of the following
conditions apply to you (also see section 4 “Possible side effects”):

you have or have ever had breathing problems, because this medicine may reduce your spontaneous ability to breathe. Breathing problems may also be associated with the following conditions:
- you suffer from heart problems (heart failure);
- you suffer from low blood pressure;
- you suffer from general breathing problems, chronic inability to breathe adequately and regularly, either during exertion or at rest;
- you suffer from episodes of breathing interruption for several seconds during sleep (sleep apnea). If you have any of these conditions and need to start treatment with Lorxagen, your doctor will monitor you regularly;
you suffer or have ever suffered from allergic reactions to benzodiazepines. This medicine may cause severe and rapidly occurring allergic reactions (anaphylactic reactions) or swelling of the face, tongue, and throat with difficulty swallowing and breathing (angioedema). Sometimes, these reactions can be fatal. If one or more of these symptoms occur, go immediately to the nearest emergency room. In such cases, your doctor will advise you to stop taking lorazepam-containing medicines and to continue treatment of your condition with other medicines;
you have or have ever had problems with alcohol, drug, or medicine abuse and dependence, because Lorxagen may also cause dependence (see section “Development of dependence”);
you suffer or have ever suffered from depression, because Lorxagen may worsen your condition and increase suicidal tendencies;
you suffer or have ever suffered from difficulties in relating to other people or to various life situations, even if you have not always been aware of these difficulties. Lorxagen is not recommended as the main treatment for this condition;
you have or have ever had liver problems (hepatic insufficiency), because this medicine could worsen your condition. Your doctor will recommend the most appropriate dosage for your condition;
you have or have ever had kidney problems (renal insufficiency). Your doctor will recommend the most appropriate dosage for your condition.

Memory disturbances
After taking Lorxagen, you may have difficulty remembering what happened after taking the
medicine. Therefore, it is advisable that you are able to sleep for 7–8 hours after taking this
medicine.
Paradoxical reactions
Lorxagen may cause mental reactions and effects opposite to those expected (paradoxical effects)
(see section 4 “Possible side effects”). These effects are more frequent in children and elderly people.
If you experience these effects, consult your doctor, who will advise you on the correct way to
discontinue taking this medicine.
Development of tolerance and dependence, withdrawal reactions, and drug abuse
A reduction in effectiveness (tolerance) of this medicine may occur after continuous use. This medicine is recommended for short-term treatment only.
Treatment with this medicine also increases sensitivity to the effects of alcohol and other medicines that affect brain function. Therefore, talk to your doctor if you are taking alcohol or medicines of this type.
The use of benzodiazepines, including Lorxagen, may lead to dependence. The risk of dependence increases with higher doses and prolonged use. The risk of dependence is also higher if you have a history of alcohol or drug abuse, or if you have significant personality disorders.
Talk to your doctor if:

you have taken or are currently taking illegal substances;
you regularly consume alcohol or have frequently consumed large amounts of alcohol in the past;
you have had or currently have a desire to take large quantities of medicines;
you have personality disorders, e.g. difficulties in interacting with other people or difficulties in certain life situations, even if you were not aware of these problems.

In principle, benzodiazepines should only be used for short periods and discontinued gradually. Before starting treatment, you and your doctor should agree on how long you will take the medicine.
If you abruptly stop taking the medicine or rapidly reduce the dosage, withdrawal reactions may occur. Do not stop this medicine abruptly. Consult your doctor on how to discontinue treatment.
Some withdrawal reactions may be life-threatening.
Withdrawal symptoms may range from mild depression and insomnia to a more severe syndrome with muscle and abdominal cramps, vomiting, sweating, tremors, and seizures. More severe withdrawal signs and symptoms, including life-threatening reactions, may include delirium tremens, depression, hallucinations, mania, psychosis, seizures, and suicide. Seizures/epileptic fits may occur more frequently in patients with pre-existing seizure disorders or in patients taking other medicines that lower the seizure threshold, such as antidepressants.
Other withdrawal reactions may include: headache, anxiety, restlessness, tension, confusion and irritability, depressed mood, dizziness, feelings of detachment or alienation from oneself and the external world, excessive increase in noise perception, tinnitus, tingling and numbness of limbs, sensitivity to light, noise, and physical contact / changes in perception, involuntary movements, stomach pain, loss of appetite, diarrhea, panic attacks, muscle pain, states of excitement, increased perception of heartbeat (palpitations), rapid heartbeat (tachycardia), sensation of loss of balance, exaggerated reflexes, inability to recall recent events, and increased body temperature.
The symptoms for which this medicine was prescribed may also reappear briefly (rebound phenomena).
Do not give Lorxagen to family members or friends. Store this medicine safely so that it cannot cause harm to others.
If you are elderly and/or suffer from specific health conditions
If you are elderly and/or your general health condition is very weak, or if you suffer from significant brain diseases (especially cerebral arteriosclerosis), you are more sensitive to the effects of Lorxagen.
If you suffer from low blood pressure, this medicine may increase episodes of blood pressure drop.
Therefore, it is recommended to use the lowest possible dose of this medicine or to avoid its use altogether.
If you have severe liver problems
If you suffer from severe liver problems, with or without cerebral symptoms such as mental confusion, altered level of consciousness, or coma, Lorxagen must not be used because it could worsen your condition (see also section 2 “Do not take Lorxagen”).
Children and adolescents
The efficacy and safety of Lorxagen in children under 12 years of age are unknown. Your doctor will decide whether Lorxagen can be administered to children based on their condition. The duration of treatment should be as short as possible.
Other medicines and Lorxagen
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The concomitant use of Lorxagen and opioids (strong painkillers, substitution therapy medicines, 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 possible.
However, if your doctor prescribes Lorxagen together with opioids, the dose and duration of concomitant therapy must be limited by your doctor.
Inform your doctor about all opioid medicines you are taking and carefully follow your doctor’s recommendations regarding dosage. It may be helpful to inform friends or relatives so they are aware of the above-mentioned signs and symptoms. Contact your doctor if such symptoms occur.
Inform your doctor or pharmacist if you are taking any of the following medicines together with Lorxagen, as caution is required:

medicines that strongly reduce all brain functions, such as:
- sedatives and sleep-inducing medicines (barbiturates, hypnotics/sedatives);
- medicines for treating certain mental illnesses (antipsychotics);
- medicines for treating anxiety (anxiolytics);
- medicines for treating acute or chronic severe pain (narcotic analgesics, opioids);
- medicines used to treat epileptic seizures (antiepileptics);
- anaesthetics;
- medicines used to counteract allergic reactions (sedating antihistamines). Lorxagen, when administered together with anaesthetic medicines, may cause euphoria, increasing the likelihood of developing psychological dependence;
clozapine (a medicine used for thought disorders), because taking it together with Lorxagen may cause marked sedation, increased salivation, and loss of movement coordination;
valproate (a medicine used for epileptic seizures), because it may enhance the effects of Lorxagen. In this case, your doctor may decide to halve the dose of Lorxagen;
probenecid (a medicine used for gout), because it may enhance the effects of Lorxagen. In this case, your doctor may decide to halve the dose of Lorxagen;
theophylline and aminophylline (medicines used for bronchial asthma), because they may reduce the effects of Lorxagen;
loxapine (a medicine used for thought disorders), because taking it together with Lorxagen may cause a state characterized by excessive passivity and inertia towards events and people (e.g. immobility and mutism), marked reduction in breathing rate, and low blood pressure;
baclofen (a medicine used as a muscle relaxant);
caffeine (a substance mainly found in coffee, but also in many energy drinks), because it may reduce the effects of Lorxagen.

Lorxagen and alcohol
Do not drink alcohol while taking Lorxagen, because alcohol increases drowsiness and reduced consciousness caused by this medicine.
This may also severely impair your ability to drive or operate machinery (see section “Driving and using machines”).
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 taking this medicine.
Pregnancy
This medicine must not be taken during pregnancy, especially during the first 3 months, because it may cause congenital malformations in the fetus.

If, for serious reasons, you take this medicine at high doses during the last 3 months of pregnancy, during the period preceding childbirth (labour), or during delivery, the newborn may show the following symptoms:
- excessive reduction in motor activity;
- poor muscle tone;
- moderate reduction in breathing rate;
- low body temperature;
- breathing interruption for several seconds (apnea);
- feeding difficulties;
- reduced cold resistance and consequent metabolic disturbances;
- yellow/yellowish skin and mucous membranes (jaundice).
If you take this medicine for a prolonged period during the late stages of pregnancy, the newborn may develop physical dependence or withdrawal symptoms shortly after birth (see section “Development of dependence”).

Breastfeeding
This medicine passes into breast milk. Your doctor will decide whether you can take Lorxagen during breastfeeding.
If you breastfeed while taking this medicine, the newborn may experience drowsiness and reduced ability to feed.
Driving and using machines
Do not drive or operate machinery if you experience drowsiness or dizziness during treatment with Lorxagen. Lorxagen may also cause amnesia, impaired concentration, and muscle function disturbances. Your alertness may be impaired, especially if you have not slept long enough after taking Lorxagen.
Lorxagen contains lactose
This medicine contains lactose, a type of sugar. If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.
Lorxagen contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially “sodium-free”.

3. How to take Lorxagen

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor.

The dose and duration of treatment must be adjusted according to your individual condition. Your doctor will advise you on the appropriate dose, the number of daily administrations, and the duration of treatment with Lorxagen, so that you take the lowest possible dose for the shortest possible time. Do not alter or exceed the prescribed dose. To discontinue treatment, the dose must be gradually reduced under medical supervision. This reduces the risk of withdrawal reactions, which in some cases may be life-threatening (see section 2).

If you need to increase the dose of this medicine, your doctor will advise you on how to do so gradually to avoid unwanted effects. When increasing the dose of Lorxagen, the evening dose should first be increased, followed if necessary by an increase in the morning dose.

Lorxagen must be taken orally.

Treatment of anxiety
The recommended treatment duration should not exceed 8–12 weeks. This period includes the time needed to gradually reduce the dose of Lorxagen before stopping. Your doctor will decide whether treatment may continue beyond the maximum recommended period.

It is recommended not to exceed the maximum daily dose.
The recommended dose is 2 or 3 tablets of 1 mg per day. In severe cases, the recommended dose is 3 or 4 tablets of 2.5 mg per day.

Treatment of insomnia
The recommended treatment duration ranges from a few days to a maximum of 4 weeks. This period includes the time needed to gradually reduce the dose of Lorxagen before stopping. Your doctor will decide whether treatment may continue beyond the maximum recommended period. It is recommended not to exceed the maximum daily dose.

The recommended dose is 1 or 2 tablets of 1 mg, taken at bedtime.
In cases of persistent insomnia, the recommended dose is 1 or 2 tablets of 2.5 mg, taken at bedtime.

If you are elderly and/or in very poor general health
The recommended starting dose is 1 mg or 2 mg per day, divided into several doses.

If you have kidney or liver problems (renal or hepatic impairment)
Your doctor will determine the most appropriate dose for you and will monitor you frequently.

Preparation of patients awaiting surgery
Major surgery: the recommended dose is 2 mg–4 mg of Lorxagen, taken the evening before surgery.
Minor surgery: the recommended dose is 2 mg–4 mg, taken 1–2 hours before surgery.

Duration of treatment
The duration of treatment is determined by your doctor. You will be prescribed the lowest effective dose for the shortest possible time, as there is a risk of becoming dependent on this medicine. Your doctor will regularly review your treatment.

It is necessary to stop taking this medicine or to reduce the dose gradually and under medical supervision to prevent withdrawal reactions (see section 2).

If you take more Lorxagen than you should
It is important that you never take more medicine than prescribed. Generally, there are no life-threatening risks if you accidentally take a higher dose than prescribed, unless you also consume alcohol or other medicines at the same time.

Symptoms
In mild cases, symptoms may include:

blurred vision, drowsiness, disorientation, and reduced sensory function;
slurred speech;
confusion;
prolonged sleep and reduced response to normal stimuli;
inability to completely empty the bladder;
changes in sexual desire.

In more severe cases, such as when large quantities are taken with suicidal intent or when this medicine is taken together with alcoholic beverages or other medicines that reduce consciousness and major brain functions, symptoms may include:

loss of motor coordination;
reduced muscle tone;
low blood pressure;
excessive drowsiness;
paradoxical reactions opposite to the expected effects of this medicine (paradoxical symptoms);
reduced function of the central nervous system;
reduced heart function;
reduced breathing;
coma;
death.

Treatment
Contact your doctor immediately or go to the nearest emergency department if you take more Lorxagen than prescribed. If you are conscious, vomiting will be induced within one hour of taking the medicine; if you are unconscious, gastric lavage will be performed. If these measures are insufficient, activated charcoal may be administered to reduce absorption of Lorxagen, or flumazenil, a medicine that counteracts the effects of Lorxagen.

If you forget to take Lorxagen
If you forget to take a dose, take it as soon as you remember, but ensure that you can rest immediately afterwards for a sufficiently long period (7–8 hours). Do not take a double dose to make up for a missed dose. If you think you have missed more than one dose, consult your doctor.

If you stop taking Lorxagen
Do not stop taking this medicine suddenly unless you suspect a serious side effect, as doses must be gradually reduced. Your doctor will advise you on how to discontinue treatment. If you think you are experiencing a serious side effect, contact your doctor immediately. If you stop taking Lorxagen or suddenly reduce the dose, temporary withdrawal symptoms or rebound symptoms may occur (see section 2).

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 everybody will experience them.
Normally, side effects occur at the beginning of treatment and generally decrease in intensity or disappear with continuation of treatment or by reducing the dose.
Contact your doctor immediately if you experience any of the following side effects, because treatment with Lorxagen must be discontinued:

paradoxical reactions (opposite to the expected effects) (see section 2 "Paradoxical disorders"), such as:
- depression or unmasking of pre-existing depression
- restlessness
- agitation
- irritability
- aggression
- feelings of disappointment
- anger
- nightmares
- hallucinations
- difficulty interpreting reality correctly and disturbances in thinking
- changes in behaviour
drowsiness, even during the day
dizziness
loss of ability to coordinate movements
sleep disturbances, insomnia
confusion
changes in sexual desire
anxiety states
feelings of hostility
general state of excitement
sexual excitement
reduced ability to reach the peak of sexual excitement (orgasm)
fatigue
impotence

Contact your doctor immediately if you experience any of the following side effects, as they may be serious:

severe allergic reaction (anaphylactic shock)
swelling of the face, tongue and throat leading to difficulty swallowing and breathing
difficulty remembering events occurring after taking the medicine (anterograde amnesia). This may also be accompanied by changes in behaviour (see section 2 "Memory disorders")
drug abuse and physical dependence on drugs (see section 2 "Development of tolerance and dependence, withdrawal reactions and drug abuse")
drug withdrawal symptoms (see section 2 "Development of tolerance and dependence, withdrawal reactions and drug abuse")
rebound symptoms (see section 2 "Development of tolerance and dependence, withdrawal reactions and drug abuse")
coma
suicidal thoughts, suicide attempts
excessive use of Lorxagen (abuse) or of similar medicines (benzodiazepines)
severe decrease in white blood cell count, which may increase susceptibility to infections.

Contact your doctor if you experience any of the following side effects:
Common side effects (may affect up to 1 in 10 people):

muscle weakness

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

nausea

Side effects with unknown frequency (frequency cannot be estimated from the available data):

reduction in all blood cells
decrease in the number of blood platelets
hypersensitivity reactions
condition characterized by excessive secretion of antidiuretic hormone, causing water retention in the body and reduced sodium levels in the blood
changes in appetite
decreased sodium levels in the blood
disinhibition
disorientation
euphoria
reduced ability to experience emotions
disturbance of nervous centres controlling instinctive movements. This may cause: tremors, vertigo, difficulty in articulating speech (extrapyramidal symptoms)
seizures/epileptic fits
amnesia
reduced attention and/or reduced concentration ability
reduced level of alertness
changes in skin colour, blood pressure, heart rate, salivation, and other nervous functions not under voluntary control, as manifestations that may accompany an epileptic seizure
balance disorders
sensation of instability
headache
visual disturbances such as double vision or blurred vision
disturbances in eye function
lowering of body temperature
reduced blood pressure
respiratory depression
temporary suspension of breathing for several seconds (apnoea)
worsening of pre-existing sleep apnoea
worsening of chronic lung diseases with breathing difficulties
stomach and intestinal problems
constipation
allergic skin reactions
patchy hair loss (alopecia)
yellow/yellowish discoloration of the skin and mucous membranes (jaundice)
inability to completely empty the bladder (urinary retention)
increased levels in the blood of bilirubin, transaminases and alkaline phosphatase (substances produced by the liver).

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 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 Lorxagen

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after "Exp.".
The expiry date refers to the last day of that month.
Do not store above 25°C.
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 Lorxagen contains
One 1 mg Lorxagen tablet contains 1 mg of lorazepam.
One 2.5 mg Lorxagen tablet contains 2.5 mg of lorazepam.
The other components are: maize starch, microcrystalline cellulose, sodium starch glycolate type A,
magnesium stearate, Ludipress (granules of monohydrate lactose, povidone and crospovidone).

Description of the appearance of Lorxagen and pack contents
The tablets are available in PVC/aluminum blisters in packs of 20 tablets.

Marketing Authorization Holder
Genetic SpA - Via della Monica, 26 - Castel San Giorgio (SA)

Manufacturer
Genetic S.p.A. – Contrada Canfora – Fisciano (SA)

This leaflet was last updated on