Control - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf Life and Storage

Active ingredients: Lorazepam

Control 1 mg tablets
Control 2.5 mg tablets

Indications Why is Control used? What is it for?

Control contains the active substance lorazepam which belongs to a group of medicines called benzodiazepines.

Benzodiazepines are indicated only when the disorder is severe, disabling or subjecting the subject to severe discomfort and only for short-term treatment.

This medicine is prescribed to treat:

  • anxiety and symptoms related to anxiety;
  • insomnia.

Contraindications When Control should not be used

Do not take Control

  • if you are allergic to lorazepam, benzodiazepines or any of the other ingredients of this medicine (listed in section 6);
  • if your muscles are always very weak or tired (myasthenia gravis);
  • if you have severe breathing problems (severe respiratory failure);
  • if you have trouble breathing during sleep (sleep apnea syndrome);
  • if you have severe liver problems (severe liver failure);
  • if you have an eye condition characterized by high eye pressure and visual impairment (narrow angle glaucoma);
  • if you are pregnant, intend to become or suspect a pregnancy;
  • if you are breast-feeding.

Precautions for use What you need to know before you take Control

Talk to your doctor or pharmacist before taking Control if:

  • have a predisposition to addiction (history of drug and / or alcohol abuse) or personality disorders;
  • you are elderly, debilitated or have vascular lesions (atherosclerosis) because the effects of benzodiazepines, such as the lorazepam contained in this medicine, may increase the risk of falls due to the inability to make coordinated movements (ataxia), muscle weakness, sense of instability, drowsiness, fatigue;
  • have breathing problems (chronic respiratory failure, COPD - Chronic Obstructive Pulmonary Disease or sleep apnea syndrome), or have heart problems (heart failure) or have low (arterial) blood pressure;
  • have liver or kidney problems or severe brain disease (hepatic encephalopathy);
  • suffer from depression, as this medicine can increase thoughts of suicide;
  • have suffered from depression, as it may come back during treatment with this medicine.

Interactions Which drugs or foods may change the effect of Control

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Do not take Control with the following medicines unless prescribed by your doctor:

  • other medicines that affect the central nervous system such as neuroleptics (used to treat psychiatric disorders), hypnotics (used to treat insomnia), anxiolytics / sedatives or barbiturates (used to treat anxiety), antidepressants (used to treat depression ), antiepileptics such as phenobarbital or hydantoin (used to treat epilepsy), anesthetics (used for anesthesia), because they can increase the effects of this medicine; taking these substances together with lorazepam should be avoided.
  • antihistamines (used to treat allergies), as they can increase the effects of this medicine;
  • narcotic analgesics (used for pain relief), which can cause euphoria and increase the risk of addiction;
  • clozapine (used to treat schizophrenia), because it can cause severe sedation, excessive saliva production and an inability to make coordinated movements (ataxia);
  • valproate (used to treat epilepsy), because it increases the amount of Control in your blood. If you need to take it at the same time, your doctor will reduce the dose of lorazepam you need to take;
  • probenecid (used to treat gout), as it may increase the effects of this medicine. In case of need to take it at the same time, your doctor will reduce the dose of lorazepam you have to take;
  • cisapride (used to treat gastroesophageal reflux), as it may increase the effects of this medicine;
  • lofexidine (used to control opioid withdrawal symptoms), as it may increase the effects of this medicine;
  • nabilone (used to treat nausea and vomiting in chemotherapy), as it may increase the effects of this medicine;
  • disulfiram (used to treat alcoholism), as it may increase the effects of this medicine;
  • muscle relaxants, such as baclofen or tizanidine, (used to reduce muscle spasms that cause pain), as they can increase the effects of this medicine;
  • sodium oxybate (used to treat narcolepsy), as its effect may be increased by the simultaneous intake of lorazepam;
  • theophylline or aminophylline (used to treat asthma), as they reduce the effects of this medicine;
  • loxapine (mainly used in the treatment of schizophrenia), because together with Control it may cause excessive loss of cognitive function (stupor), reduced number of breaths and lowered blood pressure (hypotension).

Compounds affecting liver enzymes (particularly cytochrome P450) may also increase benzodiazepine activity; however, unlike many other benzodiazepines, pharmacokinetic interactions between the P-450 and Control system have not been demonstrated.

Control with food, drink and alcohol

This medicine should not be taken with alcohol because the sedative effect may be enhanced. Caffeine, on the other hand, may reduce the sedative and anxiolytic effects of lorazepam.

Warnings It is important to know that:

Children

In children this medicine should not be used unless strictly necessary and under the supervision of a doctor. The duration of treatment is determined by the doctor and should be as short as possible.

Pregnancy, breastfeeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

Benzodiazepines, including the lorazepam contained in this medicine, can cause damage (malformations) to your baby if taken during the first trimester of pregnancy. If you take this medicine during late pregnancy or during labor, your baby may have lower body temperature (hypothermia), muscle weakness (hypotonia) and difficulty breathing (moderate respiratory depression) or have difficulty breathing (moderate respiratory depression) once born. a yellowish discoloration of the skin and eyes due to increased bilirubin (neonatal jaundice). If you have taken this medicine regularly during the late pregnancy, your baby may develop withdrawal symptoms after birth.

Feeding time

Do not take this medicine if you are breastfeeding. The lorazepam contained in this medicine passes into breast milk and the infant may cause sedation and inability to suckle milk from the breast.

Fertility

If you are a woman of childbearing potential, you should contact your doctor, both if you intend to become pregnant and if you suspect that you are pregnant, regarding discontinuation of the medicine.

Driving and using machines

This medicine can make you feel profound relaxation (sedation), memory loss (amnesia), it can affect your ability to concentrate and control your muscles and cause you dizziness and disturbed vision. All of these effects may impair your ability to drive or use machines. Avoid driving even if your sleep time is insufficient (less than 7-8 hours of uninterrupted sleep) because you are likely to be less alert.

Control contains lactose

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

Dose, Method and Time of Administration How to use Control: Posology

Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.

The dose, frequency of use and duration of therapy will be determined by your doctor according to your disease.

Your doctor will prescribe the therapy for the shortest time possible, if necessary he will increase the dose during the therapy gradually, to avoid the onset of side effects, and will make you stop the treatment in an equally gradual way to avoid withdrawal symptoms.

Treatment of anxiety:

Treatment should be as short as possible. Your doctor will check your condition regularly.

The recommended dose is 1 tablet of 1 mg, or ½-1 tablet of 2.5 mg, 1-3 times a day.

The duration of treatment should generally not exceed 8 - 12 weeks, including a gradual withdrawal period. In certain cases, the doctor may decide to extend the treatment, after evaluating your health condition.

Treatment of insomnia:

The duration of treatment should be as short as possible.

The recommended dose is 1 - 2.5 mg.

It is recommended to take the medicine in the evening, before going to bed.

Treatment should be started with the lowest recommended dose. The maximum dose should not be exceeded.

The duration of treatment generally ranges from a few days to 2 weeks, up to a maximum of 4 weeks, including a gradual withdrawal period. In certain cases, the doctor may decide to extend the treatment, after evaluating your health condition.

Method of recruitment:

The tablets can be taken at any time of the day with or without meals.

The evening dose should be increased before the day dose.

Use in elderly or debilitated people

In the elderly and in debilitated patients, the doctor will evaluate the administration of a reduced dose.

Use in people with kidney or liver problems

In patients with severe kidney or liver problems (renal or hepatic insufficiency) the doctor will consider administering a reduced dose.

If you stop using Control

  • At the end of treatment with this medicine, your doctor will decide if you need to continue therapy.
  • The dose and frequency of taking this medicine should be slowly reduced before stopping treatment. This allows the body to get used to the lack of the medicine, and reduces the risk of unpleasant effects when the treatment is stopped. Your doctor will tell you how.
  • Do not stop treatment abruptly, otherwise the symptoms you were being treated for may reappear even more intense than before (insomnia and rebound anxiety). Upon discontinuation of treatment you may experience withdrawal symptoms such as headache, muscle pain, anxiety, tension, restlessness, confusion, irritability, depressed and nervous mood (dysphoria), dizziness, nausea, diarrhea and loss of appetite. The following symptoms may occur severe: loss of sense of reality (derealization), altered perception of self (depersonalization), hypersensitivity to sounds (hyperacusis), numbness or tingling sensation in the hands and feet, hypersensitivity to light, noise and contact physical, hallucinations up to delirium, seizures or convulsions (violent and involuntary contractions of the muscles). Other symptoms are: depression, insomnia, sweating, ringing in the ears (tinnitus), involuntary movements, vomiting, widespread tingling (paraesthesia), altered perceptions (perceptual changes), pain in the abdomen and muscles (abdominal and muscle cramps), tremor, muscle pain (myalgia), agitation, feeling heart rate (palpitations), rapid heart rate (tachycardia), panic attacks, balance disturbances (dizziness), marked muscle reflexes (hyper-reflexia), short-term memory loss, increased body temperature (hyperthermia) ).
  • Insomnia or anxiety that required treatment with this medicine may also come back in a more severe form (rebound phenomena with mood changes, anxiety, restlessness or sleep disturbances). If you suffer from these symptoms ask your doctor for advice.
  • If you suffer from epilepsy or seizures or are taking medicines for depression (antidepressants), be careful, as you have an increased risk of having seizures when you stop taking this medicine.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Overdose What to do if you have taken too much Control

If you take more than the prescribed dose of Control, notify your doctor immediately or go to the nearest hospital. Take this leaflet and the pack of this medicine with you even if it is empty.

Some of the symptoms of overdosing can be: numbness of thinking and senses (drowsiness), mental confusion and continuous sleep (lethargy). In severe cases (especially when taking lorazepam together with other CNS depressant drugs or alcohol) the symptoms may be: inability to coordinate movements (ataxia), decreased muscle contraction (hypotonia), lowering blood pressure (hypotension), blockage of the activity of the brain centers that control breathing (respiratory depression) and can rarely lead to coma and very rarely to death.

Side Effects What are the side effects of Control

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If any of the following serious side effects appear, tell your doctor immediately:

  • restlessness, agitation, irritability, aggression, disappointment, anger, insomnia, nightmares, hallucinations, psychosis, sexual arousal and behavioral changes.

If the dose is not correct, an excessive state of "calm" (sedation) and excessive relaxation of the muscles can be obtained, resulting in the following side effects:

  • drowsiness, loss of emotions, decreased alertness, confusion, fatigue, headache, dizziness, muscle weakness, inability to make coordinated movements (ataxia), double vision (diplopia).

These are effects that appear more frequently at the beginning of the treatment and that tend to disappear with the continuation of the therapy.

Side effects can be:

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

  • sleepiness during the day and excessive calm (sedation).

Common (may affect up to 1 in 10 people)

  • tremors, dizziness;
  • muscle weakness, loss of energy (asthenia), fatigue.

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

  • confusion, depression and unmasking of a pre-existing depressive state, loss of emotions, disinhibition, euphoria, changes in appetite, sleep disturbances, change in libido, decreased orgasm;
  • headache, decreased alertness, difficulty in speech articulation (dysarthria), recent memory loss (transient anterograde amnesia) or memory impairment;
  • visual disturbances, double vision (diplopia), blurred vision);
  • low blood pressure (hypotension);
  • breathing problems (respiratory depression, apnea, worsening of sleep apnea, worsening of obstructive pulmonary disease);
  • nausea, constipation, altered salivation;
  • increased bilirubin, yellowing of the skin and eyes (jaundice), increase in some liver enzymes (transaminases and alkaline phosphatase);
  • allergic skin reactions (allergic dermatitis), hair loss (alopecia);
  • decreased sexual potency in men (impotence).

Very rare (may affect up to 1 in 10,000 people)

  • alteration in the number of some cells present in the blood (thrombocytopenia, leukopenia, agranulocytosis, pancytopenia);
  • generalized allergic reactions (hypersensitivity including anaphylaxis and anaphylactoid reactions);
  • hormonal disease called SIADH (syndrome of inappropriate antidiuretic hormone secretion);
  • decrease in the amount of sodium in the blood (hyponatraemia);
  • extrapyramidal symptoms, coma;
  • excessive decrease in body temperature (hypothermia).

Not known (frequency cannot be estimated from the available data)

  • addiction, withdrawal syndrome, suicide attempts.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

You can also report side effects directly via the website: http://www.agenziafarmaco.gov.it/it/responsabili.

By reporting side effects you can help provide more information on the safety of this medicine

Expiry and Retention

Store below 25 ° C.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after "EXP". The expiry date refers to the last day of that month.

Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

Other_information "> Other information

What does Control

Control 1 mg tablets

  • The active ingredient is lorazepam. Each tablet contains 1 mg of lorazepam.
  • The other ingredients are microcrystalline cellulose, lactose monohydrate, maize starch, magnesium stearate, amberlite IRP 88.

Control 2.5 mg tablets

  • The active ingredient is lorazepam. Each tablet contains 2.5 mg of lorazepam.
  • The other ingredients are microcrystalline cellulose, lactose monohydrate, maize starch, magnesium stearate, amberlite IRP 88.

Description of what Control looks like and contents of the package

Control 1 mg tablets are presented in a pack containing two PVC / Aluminum blisters of 15 tablets each. Pack of 30 tablets.

Control 2.5 mg tablets are presented in a pack containing two PVC / Aluminum blisters of 10 tablets each. Pack of 20 tablets.

Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.

More information on Control can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT - 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION - 03.0 PHARMACEUTICAL FORM - 04.0 CLINICAL PARTICULARS - 04.1 Therapeutic indications - 04.2 Posology and method of administration - 04.3 Contraindications - 04.4 Special warnings and appropriate precautions for use - 04.5 Interactions with other medicinal products and other forms of interaction - 04.6 Pregnancy and lactation - 04.7 Effects on the ability to drive and use machines - 04.8 Undesirable effects - 04.9 Overdose - 05.0 PHARMACOLOGICAL PROPERTIES - 05.1 "Pharmacodynamic properties - 05.2 Pharmacokinetic properties" - 05.3 Preclinical safety data - 06.0 PHARMACEUTICAL PARTICULARS - 06.1 Excipients - 06.2 Incompatibility "- 06.3 Shelf life" - 06.4 Special precautions for storage - 06.5 Nature of the primary packaging and contents of the package - 06.6 Instructions for use and handling - 07.0 AUTHORIZATION HOLDER ALL "PLACING ON THE MARKET - 08.0 MARKETING AUTHORIZATION NUMBER - 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION - 10.0 DATE OF REVISION OF THE TEXT - 11.0 FOR RADIO DRUGS, COMPLETE DATA ON INTERNAL RADIATION DOSIMETRY - 12.0 INSTRUCTIONS FOR RADIOPHONES ON EXTEMPORARY PREPARATION AND QUALITY CONTROL -

01.0 NAME OF THE MEDICINAL PRODUCT -

CONTROL TABLETS

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -

Control 1 mg tablets

One tablet contains: 1 mg lorazepam

Control 2.5 mg tablets

One tablet contains: 2.5 mg lorazepam

Excipients with known effects: lactose monohydrate.

For the full list of excipients, see section 6.1

03.0 PHARMACEUTICAL FORM -

Tablet.

04.0 CLINICAL INFORMATION -

04.1 Therapeutic indications -

Anxiety, tension and other somatic or psychiatric manifestations associated with anxiety syndrome. Insomnia.

Benzodiazepines are indicated only when the disorder is severe, disabling and subjecting the subject to severe discomfort and only for short-term treatment.

04.2 Posology and method of administration -

Control is administered orally.

For best results the dose, frequency of administration and duration of therapy should be individually adjusted according to the patient's response. The lowest effective dose should be prescribed for the shortest time possible.

Since the risk of withdrawal or rebound symptoms is greater after abrupt discontinuation of treatment, a gradual decrease in dosage is suggested (see section 4.4).

Any dose increase should be done gradually to avoid adverse reactions. The evening dose should be increased before the day dose.

Anxiety

Treatment should be as short as possible.

As an indication, we recommend:

Anxiety disorders: 1 tablet of 1 mg, 1-3 times a day.

Or: ½-1 tablet of 2.5 mg, 1-3 times a day.

In the treatment of elderly or debilitated patients, the posology must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above to be adapted according to the needs and tolerability.

In patients with impaired hepatic and / or renal function the posology must be carefully established by the physician who will have to evaluate a possible reduction of the dosages indicated above to be adapted according to the patient's response.

The patient should be re-evaluated regularly and the need for continued treatment should be carefully considered, particularly if the patient is symptom-free. The overall duration of treatment should generally not exceed 8-12 weeks, including a gradual withdrawal period.

In certain cases, extension beyond the maximum treatment period may be necessary, in which case this should not be done without reassessment of the patient's condition.

Insomnia

Treatment should be as short as possible.

As an indication it is recommended

Insomnia: 1 to 2.5 mg in the evening, before bedtime.

In the treatment of elderly or debilitated patients the posology must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above.

Patients with impaired hepatic and / or renal function should take a reduced dose.

Treatment should be started with the lowest indicated dose.

The maximum dose should not be exceeded.

The duration of treatment generally ranges from a few days to 2 weeks, up to a maximum of 4 weeks, including a gradual withdrawal period.

In certain cases, extension beyond the maximum treatment period may be necessary; if so, this should not be done without reassessment of the patient's condition.

Treatment should be started with the lowest recommended dose.

The maximum dose should not be exceeded.

Control can be administered at any time regardless of meals. Daily doses and duration of treatment should be determined by the physician.

04.3 Contraindications -

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1;

• myasthenia gravis;

• hypersensitivity to benzodiazepines;

• severe respiratory failure;

• sleep apnea syndrome;

• severe hepatic insufficiency;

• narrow angle glaucoma;

• during pregnancy and breastfeeding.

04.4 Special warnings and appropriate precautions for use -

Lorazepam should be used with caution in patients with impaired respiratory function (e.g. in patients with COPD or sleep apnea syndrome).

Tolerance

Some loss of efficacy to the hypnotic effects of benzodiazepines may develop after repeated use for a few weeks.

Patients should be advised that tolerance for alcohol and other CNS depressants may decrease in conjunction with benzodiazepine treatment, and therefore these substances should be avoided or reduced.

Addiction-Withdrawal-Sudden Treatment Discontinuation Syndrome

The use of benzodiazepines can lead to the development of physical and mental dependence on these drugs. The risk of dependence increases with dose and duration of treatment; it is greater in patients with a history of drug, medication, alcohol or alcohol abuse. marked personality disorders.

The possibility of dependence is reduced when Control is used in the appropriate dose with short-term treatment, while it increases with the use of higher doses and for longer periods. In general, benzodiazepines should only be prescribed for short periods (2-4 weeks). Continuous long-term use is not recommended.

Once the physical dependence has developed, the abrupt termination of treatment will be accompanied by withdrawal symptoms. These can consist of headache, body aches, extreme anxiety, tension, restlessness, confusion, irritability, rebound phenomena, dysphoria, dizziness, nausea, diarrhea and loss of appetite. In severe cases the following symptoms may occur: derealization, depersonalization, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations / delirium, seizures or convulsions.

Seizures / seizures may occur more commonly in patients with pre-existing seizure disorders or who use other drugs that lower the seizure threshold such as antidepressants.

Other symptoms are: depression, insomnia, sweating, persistent tinnitus, involuntary movements, vomiting, paraesthesia, perceptual changes, abdominal and muscle cramps, tremor, myalgia, agitation, palpitations, tachycardia, panic attacks, dizziness, hyper-reflexia, loss of short-term memory, hyperthermia.

Rebound insomnia and anxiety: A transient syndrome in which symptoms leading to benzodiazepine treatment recur in an aggravated form may occur upon discontinuation of treatment. It may be accompanied by other reactions, including mood changes, anxiety, restlessness or disturbances. of sleep.

Withdrawal symptoms, especially the more serious ones, are more common in those patients who have received excessive doses for a long period of time, but they can also occur after discontinuation of benzodiazepines taken continuously at therapeutic doses, especially if the withdrawal occurs in a manner abrupt.

Since the risk of withdrawal or rebound symptoms is greater after abrupt discontinuation of treatment, a gradual decrease in dosage is suggested.

The patient should be advised to consult their physician both before increasing or decreasing the dose of the drug, and before stopping it.

There is evidence of development of tolerance to the sedative effects of benzodiazepines.

Control may have potential for abuse especially in patients with a history of drug and / or alcohol abuse.

Duration of treatment

The duration of treatment should be as short as possible (see section 4.2) depending on the indication, but should not exceed 4 weeks for insomnia and 8 to 12 weeks for anxiety, including a gradual withdrawal period. Extension of therapy beyond these periods should not occur without re-evaluation of the clinical situation.

It may be helpful to inform the patient when treatment is started that it will be of limited duration and to explain precisely how the dosage should be progressively decreased.

Furthermore, it is important that the patient is informed of the possibility of rebound phenomena, thus minimizing anxiety about such symptoms should they occur when the drug is discontinued.

Amnesia

Benzodiazepines can induce anterograde amnesia. This occurs most often several hours after ingestion of the drug and, therefore, to reduce the risk it should be ensured that patients can have 7-8 hours of uninterrupted sleep (see section 4.8).

Psychiatric and paradoxical reactions

When using benzodiazepines it is known that reactions such as restlessness, agitation, irritability, aggression, disappointment, anger, nightmares, hallucinations, psychosis, altered behavior can occur. Should this occur, the use of the medicinal product should be discontinued.

Such reactions are more frequent in children and the elderly.

Anxiety and insomnia can be symptoms of various other conditions. Therefore it should be taken into consideration that such disorders could be due to underlying physical or psychiatric pathologies.

Specific groups of patients

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

Due to the highly variable reactivity to psychotropic drugs, elderly or debilitated patients and those with organic brain changes (especially atherosclerotic) must be treated with low doses or must not be treated at all (see section 4.2). Benzodiazepines may be associated with an increased risk of falls due to adverse reactions such as ataxia, muscle weakness, dizziness, somnolence, fatigue, so it is recommended to treat elderly patients with particular caution.

Also a lower dose is suggested for patients with chronic respiratory failure due to the risk of respiratory depression. The same prudential measures should be taken for patients with heart failure and low blood pressure who should be regularly monitored during Control therapy (as recommended with other benzodiazepines and other psychopharmacological agents). Although arterial hypotension is a rare event, benzodiazepines should be taken with caution in patients in whom sudden drops in blood pressure could have cardiovascular or cerebrovascular complications.

Control should not be used in patients with severe hepatic insufficiency and / or encephalopathy as, like all benzodiazepines, it can precipitate hepatic 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 (they may have a disinhibiting effect and lead to suicidal tendencies in such patients).

Benzodiazepines should be used with extreme caution in patients with a history of drug or alcohol abuse.

Some patients may experience dyscrasia, and others may have increased liver enzymes.

In case of prolonged treatment or when cyclical repetitions of therapy are necessary, it is advisable to check the blood picture and liver and / or renal function.

In patients with renal or hepatic insufficiency the dosage should be carefully adjusted according to the patient's response.

Important information about some of the excipients

Control contains lactose: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

04.5 Interactions with other medicinal products and other forms of interaction -

The association with other psychotropic drugs requires particular attention and vigilance on the part of the physician to avoid unexpected undesirable effects from interaction.

Concomitant intake with alcohol should be avoided as the sedative effect may be enhanced. This adversely affects the ability to drive or use machines.

Association with CNS depressants: the central depressive effect may be enhanced in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics / sedatives, antidepressants, narcotic analgesics, antiepileptics, anesthetics and sedative antihistamines. increase in euphoria leading to an increase in psychic dependence.

The concomitant use of clozapine and Control can produce marked sedation, excessive salivation, ataxia.

Co-administration of Control with valproate may result in increased plasma concentrations and reduced elimination of Control. Valproate may inhibit the glucuronidation of lorazepam (the latter may consequently have increased serum concentrations, and increased risk of somnolence); the dose of lorazepam should be reduced by approximately 50% when co-administered with valproate.

Concomitant therapy of lorazepam with probenecid may result in faster initiation or prolongation of the effects of lorazepam due to its increased half-life and reduced clearance. In this case the lorazepam dose will need to be reduced by approximately 50%. .

Other substances may also enhance the sedative effect of benzodiazepines: cisapride, lofexidine, nabilone, disulfiram and muscle relaxants - baclofen and tizanidine.

Avoid concomitant use with sodium oxybate, as its effect may be enhanced.

Administration of theophylline or aminophylline may reduce the effects of benzodiazepines, including Control.

Compounds that inhibit certain liver enzymes (especially cytochrome P450) may increase the activity of benzodiazepines.

To a lesser extent, this also applies to benzodiazepines which are metabolized only by conjugation.

The cytochrome P-450 system has not been shown to be involved in the metabolism of Control and, unlike many benzodiazepines, pharmacokinetic interactions involving the P-450 system have not been observed with Control.

Cases of excessive stupor, significant reduction in respiratory rate and, in one case, hypotension have been reported when the Control was administered concomitantly with loxapine.

No interferences in laboratory tests have been reported or identified with the use of lorazepam.

Concomitant use of phenobarbital may have additive effects on the central nervous system; there should be special precautions when adjusting the starting dose.

Side effects may be more evident in association with barbiturates and hydantoin.

Caffeine

It can reduce the sedative and anxiolytic effects of lorazepam.

04.6 Pregnancy and breastfeeding -

Pregnancy

Control should not be used during pregnancy. Taking benzodiazepines during pregnancy can cause fetal harm. An increased risk of congenital malformations associated with the use of anxiolytic agents (chlordiazepoxide, diazepam, meprobamate) during the first trimester of pregnancy has been suggested in several studies; therefore, always avoid the administration of benzodiazepines during the first trimester of pregnancy. The possibility of pregnancy should be considered before a woman of childbearing age starts benzodiazepine therapy. If Control has already been prescribed to a woman of childbearing potential, she should be advised to inform her doctor if she is planning to become pregnant, or if she suspects that she is pregnant, to plan for it to be phased out.

If, for serious medical reasons, lorazepam is administered during the last period of pregnancy, or during labor at high doses, effects on the newborn such as hypothermia, hypotonia and moderate respiratory depression, due to the pharmacological action of the drug, may occur. Additionally, infants born to mothers who have chronically taken benzodiazepines during late pregnancy may develop physical dependence and may be at some risk of developing withdrawal symptoms in the postnatal period.

In neonates, Control conjugation appears to occur slowly as its glucuronide is detectable in the urine for more than 7 days. Control glucuronidation can competitively inhibit bilirubin conjugation, leading to hyperbilirubinemia in the neonate.

Feeding time

Since benzodiazepines are excreted in breast milk, they should not be given to breastfeeding mothers.

Sedation and inability to take breast milk occurred during lactation in infants whose mothers were taking benzodiazepines.

Fertility

If the drug is prescribed to a woman of childbearing potential, the patient should be advised of the need to inform her doctor, both if she intends to become pregnant and if she suspects she is pregnant, regarding discontinuation of the drug.

04.7 Effects on ability to drive and use machines -

Control affects the ability to drive and use machines.

Sedation, amnesia, impaired concentration, dizziness, visual disturbances and the muscle relaxant effect may adversely affect the ability to drive or use machines. If sleep duration was insufficient, the likelihood of alertness is altered may be increased (see section 4.5).

04.8 Undesirable effects -

If the dosage is not adapted to individual needs, secondary effects may appear due to excessive sedation and muscle relaxation, such as: drowsiness, dulling of emotions, reduced alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia, double vision . These phenomena occur mainly at the beginning of therapy and usually disappear with subsequent administrations.

Adverse reactions are listed by frequency:

Very common (≥1 / 10); Common (≥1 / 100,

Disorders of the blood and lymphatic system

Very rare: thrombocytopenia, leukopenia, agranulocytosis, pancytopenia.

Disorders of the immune system

Very rare: hypersensitivity including anaphylaxis and anaphylactoid reactions.

Endocrine pathologies

Very rare: SIADH (syndrome of inappropriate antidiuretic hormone secretion), hyponatremia.

Psychiatric disorders

Rare: confusion, depression and unmasking of a pre-existing depressive state, loss of emotions, disinhibition, euphoria, changes in appetite, sleep disturbances, change in libido, decreased orgasm.

Not known: dependence, withdrawal syndrome (see section 4.4 Special warnings and precautions for use), suicidal thoughts / suicide attempts.

Nervous system disorders

Very common: daytime sleepiness, sedation.

Common: tremors and dizziness.

Rare: headache, decreased alertness, dysarthria / speech difficulties, transient anterograde amnesia or memory disturbances.

Very rare: extrapyramidal symptoms, coma (see section 4.9 Overdose).

Eye disorders

Rare: visual disturbances (including diplopia and blurred vision).

Vascular pathologies

Rare: hypotension (see section 4.4 Special warnings and precautions for use).

Respiratory, thoracic and mediastinal disorders

Rare: respiratory depression, apnea, worsening of sleep apnea, worsening of obstructive pulmonary disease.

Gastrointestinal disorders

Rare: nausea, constipation, changes in salivation.

Hepatobiliary disorders

Rare: increased bilirubin, jaundice, increased liver transaminases, increased alkaline phosphatase.

Skin and subcutaneous tissue disorders

Rare: allergic skin reactions, allergic dermatitis, alopecia.

Musculoskeletal and connective tissue disorders

Common: muscle weakness.

Diseases of the reproductive system and breast

Rare: impotence.

General disorders and administration site conditions

Common: asthenia, fatigue.

Very rare: hypothermia.

Paradoxical reactions such as restlessness, agitation, irritability, aggression, disappointment, anger, insomnia, nightmares, hallucinations, psychosis, sexual arousal, behavioral changes have been reported.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address: www.agenziafarmaco.gov.it/it/responsabili.

04.9 Overdose -

As with other benzodiazepines, an overdose is not expected to be life threatening unless concomitant other CNS depressants (including alcohol) are taken.

Overdosage of benzodiazepines usually results in varying degrees of CNS depression ranging from clouding to coma. In mild cases, symptoms include drowsiness, mental confusion, and lethargy. In severe cases, and especially when other CNS depressant drugs or alcohol are taken concomitantly, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, rarely coma and very rarely death.

In the treatment of overdose of any drug, the possibility that other substances have been taken at the same time should be considered.

Following an overdose of oral benzodiazepines, vomiting should be induced (within 1 hour) if the patient is conscious or gastric lavage with respiratory protection undertaken if the patient is unconscious. If no improvement is observed with stomach emptying, activated charcoal should be given to reduce absorption. Special attention should be paid to respiratory and cardiovascular functions in emergency therapy.

Flumazenil can be useful as an antidote.

05.0 PHARMACOLOGICAL PROPERTIES -

05.1 "Pharmacodynamic properties -

Pharmacotherapeutic group: anxiolytics / benzodiazepine derivatives.

ATC code: N05BA06.

The active ingredient of Control, lorazepam, is a benzodiazepine derivative that has qualitatively similar but more intense actions than chlordiazepoxide and diazepam, both as an anxiolytic and as an anticonvulsant, thus allowing its use at significantly reduced doses.

Mechanism of action

The exact mechanism of action of benzodiazepines has not yet been elucidated; however, benzodiazepines appear to act through various mechanisms. Benzodiazepines presumably exert their effects through binding to specific receptors at different sites within the central nervous system, enhancing the effects of synaptic or presynaptic inhibition mediated by g-aminobutyric acid, or by directly influencing the mechanisms that generate the action potential.

05.2 "Pharmacokinetic properties -

Absorption

Lorazepam is rapidly absorbed from the digestive system.

Distribution

After 1-2 hours it is present in the serum, with a bioavailability of about 90%. Peak plasma concentrations are reached after approximately two hours following oral administration and remain elevated for approximately 4 hours and then gradually decrease over 24 hours.

Biotransformation

Lorazepam is about 85% bound to plasma proteins and does not require biotransformation processes to make it active. It is readily transformed into a water-soluble form in the liver to an inactive glucuronide.

Elimination

Approximately 99% renally eliminated.

The elimination time is slow: urinary excretion at 96 hours is 66%.

The elimination half-life is 14 ± 5 ​​hours.

The volume of distribution is 1.3 l / kg.

05.3 Preclinical safety data -

LD50 - os - mouse> 3000 mg / kg; rat> 5000 mg / kg; dog> 2000 mg / kg. The subacute and chronic toxicity tests in the various animal species have made it possible to highlight that the active principle is well tolerated at doses extremely higher than those used in human therapy.

Lorazepam does not interfere with embryonic development or reproductive processes.

Numerous trials conducted in rabbits, rats and mice exclude teratogenic effects of lorazepam.

06.0 PHARMACEUTICAL INFORMATION -

06.1 Excipients -

Microcrystalline cellulose, lactose monohydrate, corn starch, magnesium stearate, amberlite IRP 88.

06.2 Incompatibility "-

Not relevant.

06.3 Period of validity "-

2 years.

06.4 Special precautions for storage -

Store below 25 ° C.

06.5 Nature of the immediate packaging and contents of the package -

Control 1 mg: PVC / Aluminum blister of 15 tablets

pack of 30 tablets

Control 2.5 mg: PVC / Aluminum blister of 10 tablets

pack of 20 tablets

06.6 Instructions for use and handling -

No special instructions for disposal.

07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -

Pharmaceutical Laboratory SIT S.r.l. - via Cavour, 70 - 27035 Mede (PV)

08.0 MARKETING AUTHORIZATION NUMBER -

Control 1 mg AIC 022959011

Control 2.5 mg AIC 022959023

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -

Date of first authorization: 24 October 1974

Date of most recent renewal: 11 August 2016

10.0 DATE OF REVISION OF THE TEXT -

December 14, 2016

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY -

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL -

none:  veterinary hypertension test