Package leaflet: Information for the patient

Lorazepam TZF, 2 mg/mL, solution for injection
Lorazepam TZF, 4 mg/mL, solution for injection
Lorazepamum
Please read carefully all the information in this leaflet before using the medicine, as it contains
important information for the patient.

Keep this leaflet, so that you can read it again if necessary.
If you have any doubts, please consult your doctor or nurse.
This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
If any side effects occur, including any not listed in this leaflet, inform your doctor or nurse. See section 4.

Leaflet contents

What Lorazepam TZF is and what it is used for
Important information before using Lorazepam TZF
How to use Lorazepam TZF
Possible side effects
How to store Lorazepam TZF
Contents of the pack and other information

1. What Lorazepam TZF is and what it is used for

Lorazepam TZF is a tranquilizer and anxiolytic medicine belonging to a group of active substances known as benzodiazepines.
Indications for use

Premedication—as a sedative (basic sedation) before surgical and diagnostic procedures and chemotherapy, or during these procedures, to reduce anxiety, tension, and to suppress memory of the event.
Initial treatment of severe neurotic anxiety and intense phobias (preferably administered intravenously).
Short-term adjunctive treatment of severe anxiety disorders and agitation in psychoses and depression, when primary treatment with neuroleptics and (or) antidepressants does not provide, or has not yet provided, sufficient control of these symptoms.
Treatment of status epilepticus in adults, adolescents, children, and infants from 1 month of age due to various types of focal or generalized seizures. Lorazepam TZF is effective in treating generalized seizures (tonic-clonic, "grand mal"), generalized absence seizures ("petit mal"), or states of impaired consciousness in the form of spike-wave stupor, focal motor or psychomotor seizures, as well as combinations such as generalized seizures with focal onset. Initial treatment with Lorazepam TZF leads to prolonged cessation of epileptic seizures.
Lorazepam is not intended for long-term treatment of epilepsy. After cessation of epileptic seizures, other anticonvulsant medicines should be introduced, as decided by the physician. In the treatment of status epilepticus caused by acute, reversible metabolic disturbances (e.g., hypoglycemia, hypocalcemia, hyponatremia, etc.), immediate efforts to correct the underlying condition should be particularly emphasized.

2. Important information before using Lorazepam TZF

When not to use Lorazepam TZF

if the patient is allergic to lorazepam, other benzodiazepines, or any of the other ingredients of this medicine (listed in section 6);
if the patient suffers from sleep apnoea syndrome (transient breathing cessation during sleep);
if the patient has significant breathing difficulties;
if the patient has muscle weakness and easy fatigability (myasthenia);
if the patient has severe liver failure (significant impairment of liver function);
when used concomitantly with scopolamine, as this combination leads to increased sedation, hallucinations, and irrational behaviour.

Lorazepam TZF must not be administered intra-arterially. This may lead to arterial spasm and, consequently, interruption of blood flow, which could result in gangrene and necessitate amputation.
Children and adolescents
Lorazepam TZF in the form of injection solution is contraindicated in children under 12 years of age, except for the control of status epilepticus and only under rare, specific indications, based on a specialist’s decision (paediatric neurologist, psychiatrist) and under their supervision. In the case of status epilepticus, Lorazepam TZF must not be used in newborns.
Children may be particularly sensitive to one or more of the other ingredients of Lorazepam TZF (see section "Lorazepam TZF contains propylene glycol and macrogol 400").
Warnings and precautions
Before starting treatment with Lorazepam TZF, discuss this with your doctor or pharmacist.
Particular caution is required in patients with pathological muscle weakness (myasthenia), movement coordination disorders (spinal or cerebellar ataxia), acute alcohol intoxication, or drugs acting depressively on the central nervous system (e.g. sleeping tablets or painkillers, neuroleptics, antidepressants, lithium).
This medicine should be used with special caution in elderly and severely ill patients, as well as in individuals with low respiratory reserve or central respiratory disturbances or circulatory regulation disorders due to the risk of cardiac arrest or respiratory failure.
Caution is advised in patients with a history of alcohol, drug, or other substance abuse or dependence. Long-term use of benzodiazepines may lead to dependence.
The use of Lorazepam TZF is not recommended in patients with impaired kidney function or significant liver dysfunction. In patients with significant liver dysfunction, drugs such as Lorazepam TZF may cause degenerative brain disease (encephalopathy) (see section "When not to use Lorazepam TZF").
If the patient has a specific form of glaucoma, i.e. an eye disease with increased intraocular pressure, this should be reported to the doctor.
Lorazepam TZF is not indicated as primary therapy for psychotic or depressive disorders and must not be used as the sole antidepressant treatment. If basic treatment with antidepressants or neuroleptics does not eliminate coexisting anxiety or insomnia, sedative medicines such as Lorazepam TZF may be used temporarily. In patients with depression, benzodiazepines may reduce inhibitions and provoke suicidal tendencies; they should not be used without appropriate antidepressant therapy. Anxiety may be a symptom of various other conditions. It is often a manifestation of physical or mental illness and may be treated with other specific therapies.
If the patient suffers from Lennox-Gastaut syndrome (a type of epilepsy), caution is required, as benzodiazepines may provoke epileptic seizures in such patients.
The use of Lorazepam TZF in patients with strong sedation, particularly during anaesthesia, in patients with obstructive lung diseases, in the elderly, and in debilitated individuals may lead to respiratory disturbances. Therefore, necessary equipment ensuring airway patency and supporting respiration/ventilation must be available.
Special caution is required when administering lorazepam to a patient in status epilepticus, especially if the patient has received other drugs acting depressively on the central nervous system or is severely ill. Breathing problems, partial or complete respiratory arrest, may occur. Appropriate ventilation and resuscitation equipment must be available.
After receiving an injection, patients should return home accompanied by another person. They should remain under observation for 24 hours after the injection. For 24 to 48 hours after the injection, patients should refrain from any activities requiring special alertness.
Cases of blood morphology changes or increased liver enzyme activity in serum have been reported during benzodiazepine use. Therefore, in cases of repeated administration, periodic monitoring of blood morphology and liver function is recommended.
Paradoxical reactions have been reported occasionally during benzodiazepine use (see section 4). Such reactions are especially expected in children and the elderly. If paradoxical reactions occur, treatment with lorazepam should be discontinued.
The use of benzodiazepines, including Lorazepam TZF, may lead to respiratory depression potentially resulting in death.
Severe allergic reactions have been reported during benzodiazepine use. Cases of angioedema (skin and/or mucous membrane swelling) involving the tongue, larynx, or vocal cords have occurred after the first or subsequent doses of benzodiazepines. Some patients taking benzodiazepines experienced additional symptoms such as shortness of breath, throat swelling, or nausea and vomiting. Some patients required immediate treatment. If angioedema involves the tongue, larynx, or vocal cords, airway obstruction may occur, which can be fatal. Lorazepam TZF must not be re-administered if angioedema occurs.
In cases of prolonged use, kidney function monitoring is recommended.
Lorazepam TZF has addictive properties. There is a risk of developing psychological and physical dependence, even after daily use of Lorazepam TZF for only a few weeks. This applies not only to misuse of particularly high doses but also to therapeutic dose ranges. The risk of dependence is further increased in patients with a history of alcoholism or prescription drug abuse, as well as in patients with significant personality disorders. Benzodiazepines should always be prescribed only for short periods (e.g. 2 to 4 weeks). Treatment should continue only in cases of urgent indications and after careful consideration of therapeutic benefits versus the risks of habituation and dependence. Long-term use of Lorazepam TZF is not recommended.
Lorazepam TZF and other medicines
Inform your doctor or nurse about all medicines currently or recently taken, as well as any medicines you plan to take.
Concomitant use of Lorazepam TZF with other medicines acting depressively on the central nervous system and with alcohol may mutually enhance the depressive effect on the central nervous system, e.g.:

medicines used in the treatment of mental disorders (neuroleptics, antidepressants)
sleeping pills, sedatives, anaesthetics
blood pressure-lowering medicines (beta-blockers)
certain painkillers used in substitution therapy and antitussives (opioids)
antiallergic sedatives (antihistamines)
medicines used in epilepsy treatment (antiepileptics).

Concomitant use of Lorazepam TZF and opioids (strong painkillers, medicines used in substitution therapy, and certain antitussives) increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. Therefore, concomitant use of these medicines should only be considered if no alternative treatment options are available.
If your doctor prescribes Lorazepam TZF together with opioids, the dose and duration of concurrent treatment should be limited.
Inform your doctor about all opioid-containing medicines you are taking and strictly follow the dosage recommended by your doctor. It may be helpful to inform friends or family members to monitor you for the above-mentioned objective and subjective symptoms. If such symptoms occur, contact your doctor.
Enhanced effects of muscle relaxants and painkillers may occur.
Concomitant use of scopolamine with Lorazepam TZF intensifies sedative effects, hallucinations, and inappropriate behaviour. Combined use of these medicines is contraindicated.
Concomitant use of Lorazepam TZF and clozapine may result in strong sedation, excessive salivation, and movement disorders.
Concomitant use of Lorazepam TZF and haloperidol has been associated with severe adverse reactions (respiratory arrest, bradycardia, cardiac arrest, coma, and even death).
Concomitant use of Lorazepam TZF and valproic acid may increase lorazepam blood levels. When valproic acid is used concomitantly, the dose of Lorazepam TZF should be reduced by approximately half.
Concomitant administration of Lorazepam TZF and probenecid may lead to a faster onset or prolonged action of lorazepam. When probenecid is used concomitantly, the dose of Lorazepam TZF should be reduced by half.
The use of theophylline or aminophylline may reduce the sedative effect of Lorazepam TZF.
An increased dose of Lorazepam TZF may be necessary in women taking oral contraceptives due to accelerated elimination of Lorazepam TZF.
Inform your doctor if the patient is taking disulfiram (a medicine used in the treatment of chronic alcoholism) or metronidazole (an antibiotic). Patients taking these medicines have impaired alcohol and aldehyde dehydrogenase enzyme systems and are predisposed to accumulation of propylene glycol and associated potential adverse effects.
Lorazepam TZF and alcohol
Avoid concomitant consumption of alcoholic beverages, as alcohol may unpredictably alter and intensify the effect of Lorazepam TZF.
Alcoholic beverages should be avoided for at least 24 to 48 hours after administration of Lorazepam TZF due to additive effects on central nervous system depression.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult her doctor or pharmacist before using this medicine.
Pregnancy
Lorazepam TZF should be used only in exceptional cases with significant indications, as therapeutic experience with lorazepam use during this period is insufficient.
If the patient becomes pregnant while using Lorazepam TZF, she must immediately inform her treating doctor so that a decision on discontinuation of treatment can be made.
Prolonged use of Lorazepam TZF by a pregnant woman may cause withdrawal symptoms in the newborn. If Lorazepam TZF is administered towards the end of pregnancy or during labour, the infant may experience reduced activity, decreased muscle tone, lowered body temperature (hypothermia), and/or arterial blood pressure (hypotension), respiratory depression, apnoea, and feeding difficulties (floppy infant syndrome).
Breastfeeding
The medicine passes into breast milk in small amounts. Lorazepam TZF should not be used during breastfeeding. If the patient is breastfeeding, she should contact her doctor, who will decide whether to discontinue breastfeeding or discontinue use of Lorazepam TZF.
Driving and operating machinery
If the patient is using Lorazepam TZF, they must not operate dangerous machinery, drive a vehicle, or perform work requiring high concentration until they are certain they do not experience drowsiness or dizziness due to Lorazepam TZF.
Patients who have received Lorazepam TZF should not drive motor vehicles, operate dangerous machinery, or engage in activities requiring maximum concentration for 24 to 48 hours. Impairment of performance may persist longer in very elderly or very young individuals, when other medicines are used concomitantly, or due to the patient’s general condition.
Lorazepam TZF contains propylene glycol and macrogol 400.
Lorazepam TZF 2 mg/mL contains 845 mg of propylene glycol and 203 mg of macrogol 400 in each mL.
Lorazepam TZF 4 mg/mL contains 843 mg of propylene glycol and 203 mg of macrogol 400 in each mL.
In children under 5 years of age, patients with liver or kidney disease, or pregnant or breastfeeding women, consult a doctor or pharmacist before using the medicine, as excipients may cause adverse effects. The doctor may adjust the dose if the patient or child is taking other medicines containing propylene glycol or alcohol.
This medicine should only be used when prescribed by a doctor. The doctor may order additional tests during treatment with this medicine.
There have been reports of macrogol 400 toxicity (e.g. acute necrosis of renal tubules) during use of Lorazepam TZF, including when doses exceeded recommended levels.

3. How to use Lorazepam TZF

This medicine will be administered to the patient by healthcare professionals as an intramuscular or intravenous injection, or, if necessary, via an infusion line.
Dosage and administration instructions are provided in the section "Information intended exclusively for healthcare professionals".
This medicine should always be used according to the recommendations of a doctor or pharmacist. If in doubt, consult a doctor or pharmacist.
The doctor will determine the dose and duration of treatment based on the patient's condition and individual needs.

Administration of a higher than recommended dose of Lorazepam TZF
If too high a dose has been administered, contact a doctor, hospital, or a poison control center immediately.

Symptoms: Benzodiazepine overdose typically results in central nervous system depression of varying severity, ranging from drowsiness to coma. Mild overdose symptoms may include drowsiness, confusion, and lethargy. In severe cases, symptoms such as ataxia (unsteady gait), hypotonia (muscle weakness), low blood pressure, breathing difficulties, sometimes coma, and in very rare cases, death may occur. When Lorazepam TZF is used concomitantly with other central nervous system depressants, the risk of multiple drug intoxication increases, and the risk of death should be considered.

Treatment: In case of overdose, general supportive measures should be primarily applied. Vital functions will be closely monitored, and assisted ventilation will be provided if necessary. Arterial hypotension can be treated with plasma volume expanders or noradrenaline. In cases of severe intoxication with coma or respiratory depression, flumazenil, a benzodiazepine antidote, may be useful. Hemodialysis has low efficacy in Lorazepam TZF intoxication but may be beneficial in mixed overdoses.

Missed dose of Lorazepam TZF
Do not administer a double dose to make up for a missed dose.

Discontinuation of Lorazepam TZF
Never stop treatment abruptly. If treatment is suddenly discontinued after high-dose use or prolonged administration, withdrawal symptoms described in section 4 may occur. To avoid such symptoms, the dose should be gradually reduced.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Possible adverse effects usually occur at the beginning of treatment. They usually become less
severe or subside during continued treatment or after dose reduction.
If any of the following serious adverse effects occur, treatment with Lorazepam TZF must be stopped
immediately. You must contact your doctor immediately and (or) seek immediate medical help.

paradoxical reactions such as anxiety, excitement, motor restlessness, aggressive behaviour
(hostility, aggression, anger), sleep disturbances/insomnia, sexual arousal, hallucinations.
suicidal thoughts/suicide attempts.
hypersensitivity reactions, anaphylactic/anaphylactoid reactions, skin and (or) mucosal swelling (angioedema).
skin allergic reactions.
respiratory depression (severity dependent on dose), breathing pauses (apnoea), worsening of sleep apnoea (temporary cessation of breathing during sleep).

Adverse effects that may occur during treatment with Lorazepam TZF, together with frequency categories:

Very common: may affect more than 1 in 10 treated patients

sedation, feeling of fatigue, drowsiness

Common: may affect up to 1 in 10 treated patients

unsteady movements and gait (ataxia), dizziness, confusion, depression, emergence of depression
muscle weakness

Uncommon: may affect up to 1 in 100 treated patients

changes in libido, impotence, diminished orgasm
nausea, vomiting, change in appetite

Rare: may affect up to 1 in 1,000 treated patients

low blood pressure (hypotension)

Unknown: frequency cannot be estimated from available data

blood count abnormalities (thrombocytopenia, agranulocytosis, pancytopenia)
syndrome of inappropriate antidiuretic hormone secretion (SIADH)
low sodium levels (hyponatremia)
disinhibition, euphoria
movement coordination disorders (extrapyramidal symptoms)
tremors
vestibular dizziness
visual disturbances (blurred vision, double vision)
dysarthria/slurred speech
headache
seizures
memory loss
coma
hyper- and hypotensive circulatory reactions
respiratory depression (severity dependent on dose)
worsening of obstructive lung disease (airway narrowing)
constipation
increased bilirubin levels, increased liver enzyme activity (aminotransferases, alkaline phosphatase)
hair loss (alopecia)
decreased body temperature (hypothermia)

Additionally, after intramuscular injection, the following symptoms may occur: pain, burning sensation and
redness.
After intravenous administration, local phlebitis, pain and redness may occur.

Dependence / Abuse
After discontinuation of treatment, especially abrupt discontinuation, withdrawal symptoms (e.g., sleep disturbances) may occur.
Withdrawal symptoms may vary in severity – from mild dysphoria (a state of unease) and sleep disturbances
to severe clinical symptoms including generalized seizures, tremors, abdominal cramps and muscle spasms,
vomiting and sweating. The risk of withdrawal symptoms increases with duration of treatment. These effects can usually be avoided by gradually reducing the dose.
There have been reports of tolerance development (increased dose due to adaptation) to the sedative effect of benzodiazepines.
Lorazepam TZF may lead to abuse. Patients with a history of abuse of prescription drugs or alcohol are particularly at risk.

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to gather more information on the safety of the medicine.

5. How to store Lorazepam TZF

Keep this medicine out of the sight and reach of children.
Store in a refrigerator (2°C–8°C). Keep in the original packaging to protect from light.
Chemical and physical stability of the product has been demonstrated for at least 24 hours after opening, under temperatures of 2–8°C and 25°C. From a microbiological standpoint, the product should be used immediately. If the solution is not used immediately, the responsibility for the storage conditions and duration after opening lies with the user.
Do not use this medicine after the expiry date stated on the carton and ampoule after "EXP". The expiry date refers to the last day of the specified month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the package and other information

What Lorazepam TZF contains:
The active substance is lorazepam.
Lorazepam TZF, 2 mg/mL, solution for injection
Each mL contains 2 mg of lorazepam.
Lorazepam TZF, 4 mg/mL, solution for injection
Each mL contains 4 mg of lorazepam.
The other ingredients are macrogol 400 and propylene glycol.

What Lorazepam TZF looks like and contents of the pack
A colourless solution. The pH of the solution is 3.5 ÷ 7.5.
Packaging
10 ampoules in a cardboard box

Marketing Authorisation Holder and Manufacturer
Tarchomin Pharmaceutical Works "Polfa" Joint Stock Company
A. Fleminga Street 2
03-176 Warsaw, Poland
Telephone number: (22) 811 18 14

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Poland: Lorazepam TZF
Portugal: Lorazepam TZF
Lithuania: Lorazepam Polfa Tarchomin 2 mg/mL injekcinis tirpalas
Lorazepam Polfa Tarchomin 4 mg/mL injekcinis tirpalas
Latvia: Lorafen 2 mg/mL šķīdums injekcijām
Lorafen 4 mg/mL šķīdums injekcijām

Information intended exclusively for medical professionals

Dosage and method of administration

Dosage

Premedication

To achieve optimal premedication effects, the dose should be adjusted according to the patient's body weight.
The usual intravenous dose is 0.044 mg per kg of body weight. The drug should be administered
15 to 20 minutes before the procedure. This intravenous dose is sufficient for most adults,
and it should not be exceeded in patients over 50 years of age. In these patients, a starting dose of 2 mg is usually sufficient. In certain cases, a higher dose of up to 0.05 mg/kg body weight may be given, with a maximum total dose of 4 mg.
For intramuscular injection, the usual dose is 0.05 mg per kg of body weight, up to a maximum of 4 mg, administered at least 2 hours before the scheduled procedure.

In elderly and debilitated patients, as well as in patients with severe respiratory or cardiovascular disorders, a lower dose should be selected. In elderly and debilitated patients, the initial dose should be reduced by approximately 50%, and subsequent doses should be adjusted according to individual needs and tolerance (see "Warnings and precautions").

Psychiatry

For acute anxiety attacks, the recommended initial dose is 0.05 mg/kg body weight, administered either intravenously or intramuscularly. Intravenous administration is preferred. If necessary, the dose may be repeated after 2 hours. After acute symptoms have subsided, tablets may be used instead of injections.

Status epilepticus

The usual initial dose in patients over 18 years of age is 4 mg of Lorazepam TZF administered by slow intravenous injection (2 mg/min). If seizures persist or recur within the next 10 to 15 minutes, the same dose may be re-administered. If no improvement occurs within the following 10 to 15 minutes after re-administration, alternative measures should be initiated.

Elderly patients may respond to lower doses, and half the adult dose may be sufficient.

Infants from 1 month of age, children, and adolescents should receive an initial dose of 0.1 mg/kg body weight. The maximum dose is 4 mg per administration. If seizures persist or recur within the next 10 to 15 minutes, the same dose may be re-administered, but no more than two doses should be given.

Due to the potential risk of toxicity related to the accumulation of excipients, the maximum dose of Lorazepam TZF should not be repeated within 24 hours in children under 5 years of age (see section "Lorazepam TZF contains propylene glycol and macrogol 400").

Use in children and adolescents

Lorazepam is not recommended for use in children under 12 years of age, except for the treatment of status epilepticus, in rare special indications, following a decision and under the supervision of a specialist (paediatric neurologist, psychiatrist). Lorazepam should not be used in neonates in the case of status epilepticus (see also section 2).

Patients with renal or hepatic impairment

In patients with mild to moderate hepatic or renal dysfunction, the lowest effective dose should be used, as prolonged duration of action may be expected in such cases.

Duration of treatment

Treatment duration should be as short as possible. Prolonged use of Lorazepam TZF may lead to the development of physical and psychological dependence.

Treatment should not be discontinued abruptly; the dose should be gradually reduced.

Method of administration

Lorazepam TZF may be administered intramuscularly without dilution. The solution should be injected deeply intramuscularly. Because the injection solution is slightly viscous, administration may be facilitated by diluting the contents of the ampoule with an equal volume of a compatible diluent (see below).

For intravenous injection, Lorazepam TZF should be diluted before use in a 1:1 ratio with physiological saline, water for injections, or glucose solution. Compatible diluents are: water for injections, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution. After dilution, the solution should be administered by slow intravenous injection or, if necessary, via an infusion line. Accidental intra-arterial injection must be strictly avoided (see section "Warnings and precautions"). The injection rate should not exceed 2 mg of lorazepam per minute.

Do not use the solution if particulate matter is present or if there is a change in the solution's colour.

Instructions for opening the ampoule

The ampoules are equipped with an OPC (one point cut) system and should be opened only according to the following instructions:

Hold the lower part of the ampoule in one hand, with the coloured dot facing the person opening it.
With the other hand, grasp the upper part of the ampoule, place the thumb over the coloured dot, and press down.

Instructions for preparing the dilution

Withdraw the required amount of injection solution from the ampoule into a syringe, followed by the appropriate volume of diluent. Then pull back the syringe plunger slightly and gently rotate the syringe contents back and forth until the solution is uniformly mixed. Do not shake vigorously, as this may cause air bubbles to form in the injection solution.

Pharmaceutical incompatibilities

Not applicable.

This medicinal product must not be mixed with other medicinal products except those mentioned in the section "Method of administration". It is recommended that each additional medicinal product be administered in a separate syringe.

Lorazepam tzf