LORMETAZEPAM KOEHLER 0.2 mg/mL Injectable Solution and Perfusion Solution, Generic

Introduction

PACKAGE LEAFLET

Package Leaflet: Information for the Patient

Lormetazepam Koehler 0.2 mg/ml Solution for Injection and Infusion EFG

Lormetazepam

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the pack

1. What Lormetazepam Koehler is and what it is used for
2. What you need to know before you are given Lormetazepam Koehler
3. How Lormetazepam Koehler is given
4. Possible side effects
5. Storing Lormetazepam Koehler
6. Contents of the pack and other information

1. What Lormetazepam Koehler is and what it is used for

Lormetazepam, the active substance of Lormetazepam Koehler, is a sedative, anxiolytic, and sleep-inducing medication that belongs to the group of benzodiazepines.

Adults:

Lormetazepam Koehler is indicated

• for the symptomatic treatment of acute episodes of tension, excitement, and anxiety during surgical and diagnostic interventions, as well as in intensive care
• for the induction of anesthesia

Pediatric population:

In children aged 2 years and older and in adolescents, Lormetazepam Koehler is only indicated for administration before diagnostic or surgical interventions (anesthesia, intensive care).

2. What you need to know before you are given Lormetazepam Koehler

You will receive Lormetazepam Koehler exclusively from a doctor or under their supervision.

Lormetazepam Koehler must not be given

• if you are allergic to lormetazepam, other benzodiazepines, or any of the other components of this medicine (listed in section 6)
• if you have a known dependence or have a personal history of dependence on alcohol and other medications or drugs
• if you have acute intoxication with alcohol, sleep-inducing medications (hypnotics), pain-relieving medications (analgesics), or psychotropic medications (neuroleptics, antidepressants, lithium)
• if you have a specific type of muscle weakness (myasthenia gravis)
• if your respiratory function is interrupted during sleep (sleep apnea syndrome)
• if you have chronic and severe respiratory difficulty and/or shortness of breath (severe respiratory impairment)
• if you have severe liver impairment (severe hepatic disorder).

Warnings and precautions

Talk to your doctor before receiving Lormetazepam Koehler if you have

• muscle coordination and movement disorders (spinal or cerebellar ataxia)
• renal function limitations (renal impairment).

For more information on the possible occurrence of tolerance, dependence, amnesia, psychiatric or paradoxical reactions, or side effects in case of repeated administration, consult your doctor.

Children and elderly patients

Lormetazepam Koehler must not be given to children aged 2 years or older or to adolescents, unless it is administered before diagnostic or surgical interventions (anesthesia, intensive care).

Lormetazepam Koehler will be administered initially at the lowest possible dose (see posology) to children and adolescents under 18 years of age, as well as to elderly patients or those in poor general condition, particularly those with psycho-organic disorders, circulatory failure, or respiratory failure.

Before continuing with the injection, it is necessary to wait, if necessary, until the reaction of each patient is observed.

Using Lormetazepam Koehler with other medications

Tell your doctor if you are taking or have recently taken or may need to take any other medication, including those purchased without a prescription.

The administration of Lormetazepam Koehler together with other central-acting medications (such as psychotropic medications, sleep-inducing medications, pain-relieving medications, narcotics, and antihistamines) may potentiate the effects of these medications in a reciprocal manner.

Lormetazepam Koehler may potentiate the effects of muscle relaxants.

The nature and degree of interaction cannot be predicted with certainty if you receive continuous treatment with other medications, such as those that lower blood pressure (antihypertensives), beta-blockers, digitalis glycosides, medications for bronchial asthma (methylxanthines), oral contraceptives, and certain antibiotics.

Therefore, caution will be exercised when administering Lormetazepam Koehler together with these medications. Additionally, when concomitant treatment with Lormetazepam Koehler and certain antibiotics is applied, the efficacy of lormetazepam may vary.

Remember that this precaution should also be applied when recent treatment with these medications has been followed.

The concomitant use of Lormetazepam Koehler and opioids (potent analgesics, substitution therapy medications, and some cough medications) increases the risk of drowsiness, difficulty breathing (respiratory depression), coma, and can be potentially fatal. For this reason, concomitant use should only be considered when other treatment options are not possible.

However, if your doctor prescribes Lormetazepam Koehler together with opioids, the dose and duration of concomitant treatment will be limited by your doctor.

Tell your doctor about all opioid medications you are taking. Contact your doctor if you experience any of the aforementioned symptoms.

Using Lormetazepam Koehler with food and beverages and alcohol

Do not drink alcohol during treatment with Lormetazepam Koehler because it could potentiate the efficacy of lormetazepam in an unpredictable manner with alcohol.

Pregnancy and breastfeeding

During pregnancy, Lormetazepam Koehler should only be administered exceptionally and for medically justified reasons, as experience with the administration of lormetazepam during pregnancy is still limited.

If you are pregnant, consult your doctor before starting this treatment.

If Lormetazepam Koehler is administered repeatedly during pregnancy, the baby may experience physical dependence and withdrawal symptoms after birth.

If Lormetazepam Koehler is administered for medically justified reasons in the late phase of pregnancy or during childbirth and delivery, effects on the newborn, such as decreased body temperature (hypothermia), respiratory difficulties (respiratory failure), decreased muscle tone, and difficulties with breastfeeding, may occur.

Apparently, the risk of malformation, when therapeutic doses of benzodiazepines are administered in the early stages of human pregnancy, is low, but according to some studies, the risk of cleft palate increases. Cases of congenital anomalies and mental retardation with benzodiazepine overdoses and poisonings have been described.

Lormetazepam Koehler passes into human breast milk. Therefore, breastfeeding should be interrupted temporarily or definitively if Lormetazepam Koehler is administered repeatedly or in high doses.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medication.

Driving and using machines

If you receive treatment with Lormetazepam Koehler, you will not be able to drive vehicles or operate machinery.

Lormetazepam Koehler affects your reaction ability and decisively influences your ability to drive vehicles or operate machinery, even if you receive a therapeutic dose.

Therefore, you should not drive vehicles or operate machinery or perform other hazardous activities during the first days of treatment.

If lormetazepam is administered to prepare for an outpatient diagnostic intervention (before a medical examination), the patient will only be discharged if accompanied; the patient should not drive any vehicle.

3. How Lormetazepam Koehler is given

Lormetazepam Koehler will be prescribed and administered by a doctor or under their supervision.

At the end of this leaflet, in the relevant sections, information is provided for doctors and healthcare professionals.

Ask your doctor if you notice an overly potent or weak effect of Lormetazepam Koehler.

Higher levels of the medication were observed in patients with mild or moderate liver impairment. Caution is recommended when treating patients with liver impairment.

If you are given more Lormetazepam Koehler than you should

This medication will be administered by healthcare professionals. If an overdose or accidental administration occurs, contact your doctor or consult the Toxicology Information Service, Telephone (91) 562.04.20.

Additional questions:

If you have any further questions about this medication, ask your doctor or pharmacist.

At the end of this leaflet, in the relevant sections, information is provided for doctors and healthcare professionals.

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

The following adverse reactions have been observed:

• suicidal thoughts or plans
• angioedema (rapid swelling of the skin and mucous membranes, which can cause blockage of the airway), difficulty breathing
• heart palpitations (tachycardia)
• hallucinations, delusional ideas, inappropriate behavior
• dependence (use of this medication can cause physical or mental dependence on lormetazepam)
• irritability, aggression, agitation, restlessness
• memory loss or tendency to forget (amnesia), confusion
• obnubilation of consciousness, weakness
• depressive mood, emotional disorders, anxiety, acute psychosis
• thrombosis, venous inflammation
• coordination disorders (balance) (ataxia), increased risk of falls, muscle weakness
• decreased alertness, concentration disorders, and prolonged reaction times, slow thinking
• speech problems
• vomiting, nausea
• constipation, stomach pain
• urination difficulties
• headache
• fatigue, dizziness, drowsiness
• withdrawal symptoms (sleep problems), nightmares
• vision problems
• dry mouth
• loss of taste (dysgeusia)
• skin problems such as rash, itching
• excessive sweating (hyperhidrosis)
• swelling and pain at the injection site (extravasation symptoms)

If you experience any side effects, tell your doctor so that they can treat you.

Reporting side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report them directly through the national reporting system:

Spanish Medication Monitoring System for Human Use: http://www.notificaram.es

By reporting side effects, you can help provide more information on the safety of this medication.

At the end of this leaflet, in the relevant sections, information is provided for doctors and healthcare professionals.

5. Storing Lormetazepam Koehler

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

Do not use this medication after the expiration date stated on the label and carton after EXP. The expiration date is the last day of the month indicated.

Do not store above 25°C.

Do not freeze.

Do not use this medication if you notice the solution is cloudy or if it has been frozen.

Medications should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medications that are no longer needed. This will help protect the environment.

6. Container Content and Additional Information

Composition of Lormetazepam Koehler

• The active ingredient is lormetazepam.
• A 10 ml ampoule contains 2 mg of lormetazepam, equivalent to 0.2 mg of lormetazepam per ml.
• The other components are macrogol-15-hydroxystearate and water for injectable preparations.

Addition to perfusion solutions:

Lormetazepam Koehler can be added to a 5% glucose solution, a 0.9% sodium chloride physiological solution, or a Ringer's solution, respectively.

The resulting perfusion solutions remain stable at room temperature for up to 24 hours.

Appearance of the Product and Container Content

Lormetazepam Koehler is a clear to slightly opalescent aqueous solution, colorless to pale yellow, contained in transparent glass ampoules with a volume of 10 ml.

Lormetazepam Koehler is available in boxes of 5, 25, 50, and 100 (clinical packaging) ampoules.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Dr. Franz Köhler Chemie GmbH

Werner-von Siemens-Strasse 14 - 28

D - 64625 Bensheim

GERMANY

Manufacturer

Dr. Franz Köhler Chemie GmbH

Werner-von Siemens-Strasse 14 – 28

D – 64625 Bensheim

GERMANY

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

Cardiolink S.L.

Córcega 270, 3º 2ª

08008 Barcelona/Spain

Tel. +34 93 237 38 50

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Austria Sedalor 2 mg/10 ml Injektions- /Infusionslösung

Spain Lormetazepam Koehler 0.2 mg/ml solution for injection and perfusion EFG

Malta Sedalor 2 mg/10 ml solution for injection or for infusion

Cyprus Sedalor 2 mg/10 ml ενέσιμο διύλυμα/διύλυμα για έγχυση

Date of the last revision of this leaflet: May 2019.

The following information is part of the patient leaflet and is intended exclusively for doctors and healthcare professionals:

For more information onthis medicinal product, see also the summary of product characteristics.

Dosing Guide and Recommendations

The dosage and duration of treatment will be adjusted according to the individual patient's response and the nature and severity of the disease.

In general, the minimum effective dose will be administered for the shortest possible period.

The following dosage is recommended:

• Premedication before interventions under general anesthesia

On the days prior, the night before, and/or on the day of the intervention:

• Sedation before surgical interventions under general anesthesia

• Sedation (induction of sleep) during diagnostic interventions

• Treatment of acute episodes of tension, excitement, and anxiety and

basic sedation before interventions under local anesthesia

Before anesthesia:

And, in addition, during the intervention, depending on the desired depth of sedation:

• Treatment of acute episodes of tension, excitement, and anxiety

during diagnostic interventions

• Basic sedation in intensive care

Up to a sedation depth of RASS 0/−1 and, if necessary, up to RASS −3.

Special Populations

Elderly patients:

Administer and dose with caution, especially if there is cardiac or respiratory failure (cardiorespiratory insufficiency). Often, elimination is delayed in elderly patients, so the effect of benzodiazepines may be enhanced.

Patients in poor general condition:

Patients in poor general condition, especially those with psycho-organic disorders, circulatory or respiratory insufficiency:

Pediatric Population (see also section 4.1)

Children from 2 to 10 years of age (see also section 1 of this leaflet "What is Lormetazepam Koehler and what is it used for"):

Considering each age group, administer the injectable solution slowly in a large-caliber vein (no more than 5 ml/min). Respect the recommended dosage and pay close attention to respiration, blood pressure, and heart rate.

The daily dose in children should not exceed 3.5 mg (see also "Maintenance of effect" below).

Children and adolescents from 10 to 18 years of age receive the adult dosage.

The dosage recommendations for children under 10 years of age are based on very limited clinical experience in this age group.

Maintenance of effect

Lormetazepam Koehler can be administered repeatedly. In general, however, daily doses should not exceed 5 mg of lormetazepam for adults, 4 mg for patients at risk, and 3.5 mg for children and adolescents.

Method of administration

Administer the injectable solution slowly (approx. 5 ml/min) in a large-caliber vein. During administration pay close attention to respiration, blood pressure, and heart rate.

Lormetazepam Koehler can be administered undiluted and also together with the aforementioned perfusion solutions (see below).

• Instructions for administration by injection without dilution:

Lormetazepam Koehler is administered undiluted.

Lormetazepam Koehler can only be administered intravenously. It must not be injected intramuscularly. Intraarterial application should be avoided. In case of accidental intraarterial injection of Lormetazepam Koehler, flush the affected artery with 50 ml of physiological saline solution through the needle. Then, remove the needle and cover the puncture site with a compressive dressing.

Before opening the ampoule, clean the neck of the ampoule with medicinal alcohol (in spray or swab form).

Discard broken ampoules after administering the medication.

Lormetazepam Koehler does not contain antimicrobial preservatives. Therefore, the contents of the ampoule must be transferred, under aseptic conditions, to a sterile syringe immediately after opening.

The administration of Lormetazepam Koehler will be started immediately. The contents of each Lormetazepam Koehler ampoule will only be administered once to a patient.

After administration, the remaining solution will be discarded.

• Instructions for administration after addition to perfusion solutions:

Lormetazepam Koehler can be added to a 5% glucose solution, a 0.9% sodium chloride physiological solution, or a Ringer's solution, respectively.

The application of other medications or perfusions in the same line as lormetazepam will be carried out through a three-way valve or a Y-connection immediately next to the perfusion tube.

Before opening the ampoule, clean the neck of the ampoule with medicinal alcohol (in spray or swab form).

Lormetazepam Koehler does not contain antimicrobial preservatives. Therefore, the contents of the ampoule must be transferred, under aseptic conditions, to a sterile perfusion system immediately after opening.

When perfusing Lormetazepam Koehler, use a burette, a drip chamber, a syringe pump, or a volumetric pump to control the perfusion rate.

During the perfusion of Lormetazepam Koehler, maintain the aseptic conditions of the medication and the infusion apparatus.

The contents of each Lormetazepam Koehler ampoule, syringe, or perfusion system will only be administered once to a patient.

After completing the perfusion or changing the perfusion system, any remaining Lormetazepam Koehler will be discarded.

Duration of administration:

The designated initial dose of Lormetazepam Koehler will be administered over 2 minutes to achieve the desired effect. The choice of maintenance dose depends on the required effect and the patient's cooperation.

If there is no compelling reason, Lormetazepam Koehler should not be administered for more than one week. Thus, the duration of administration and treatment depend on medical needs and will be determined by the responsible doctor.

Guide for Overdose

As with other benzodiazepines, an overdose of lormetazepam should not be life-threatening, unless it is combined with other central nervous system depressants (including alcohol).

Benzodiazepine overdose usually manifests as a variable depression of the central nervous system, ranging from drowsiness, mental confusion, lethargy, visual disturbances, and dystonia to ataxia, loss of consciousness, central respiratory and circulatory depression, and coma. Other symptoms include: decreased consciousness, paradoxical reactions, agitation, and hallucinations.

Treatment of overdose is primarily symptomatic:

Patients with mild symptoms of intoxication will be monitored for respiratory and circulatory function during sleep. In severe cases, additional measures will be taken, such as gastric lavage, stabilization of cardiovascular functions, and monitoring in an intensive care unit.

If necessary, the specific benzodiazepine antagonist flumazenil can be used to treat overdose in a hospitalized patient. Before administration, the flumazenil datasheet will be consulted.

Given its high binding to plasma proteins and its high volume of distribution, forced diuresis and hemodialysis are of little use in isolated lormetazepam intoxications.

Possible Adverse Reactions, Warnings, and Precautions, and Guide for Repeated Administration

Tolerance

The hypnotic effects of lormetazepam may decrease after repeated administration for several weeks.

Dependence

Lormetazepam, like other benzodiazepines, carries a risk of primary dependence, both physical and psychological. The risk of dependence exists even if it is applied daily for a few weeks. This is the case not only with abuse of higher doses but also with therapeutic doses.

The abrupt interruption of treatment with lormetazepam, after daily administration, may be associated with withdrawal symptoms, such as headache, muscle pain, extreme anxiety, tension, agitation, confusion, and irritability, sleep disturbances, and derealization.

In more severe cases, derealization, depersonalization, hyperacusis, paresthesia, and hypersensitivity to light, noise, and physical contact, hallucinations, or epileptic seizures may occur.

These symptoms may appear: tremors and sweating that intensify to produce physical (convulsive) and psychological reactions (e.g., withdrawal delirium).

Amnesia

Benzodiazepines sometimes induce anterograde amnesia. This condition occurs (almost always, a few hours) after administration of the product. The patient does not always remember what they were doing. To reduce this risk of anterograde amnesia, which depends on the dose, sufficient uninterrupted sleep of 7-8 hours should be ensured for the patient.

Psychiatric Reactions

Sometimes, during benzodiazepine treatment, a pre-existing depression is unmasked and emerges. This reaction could precipitate suicide in such patients. Among patients whose anxiety state overlaps with depression, treatment with benzodiazepines, even if not used primarily as anxiolytics, may cause such severe manifestations of depression that, once the anxiety has been alleviated, suicidal tendencies may be revealed. The doctor will take the corresponding precautions.

Reactions of the type of restlessness, agitation, irritability, aggression, delusional ideas, rage, nightmares, hallucinations, psychosis, inappropriate behavior, and other adverse behavioral effects occur, as is known, with the use of benzodiazepines.

Paradoxical Reactions

The possibility of paradoxical reactions, such as increased aggression, acute excitement states, anxiety, suicidal intent, muscle spasms, sleep disturbances, such as dyskinesia and dysphasia, should be taken into account.

In the face of these reactions, the doctor will discontinue the administration of Lormetazepam Koehler.

Psychiatric and paradoxical reactions occur more frequently in children and elderly patients.

Repeated Administration:

When exceptional repeated administration of Lormetazepam Koehler is required, the benefit of treatment must be weighed against the risk of physical and psychological dependence.

In principle, injections, and especially perfusions, will be administered in large-caliber veins. In general, injection and perfusion in a small vein will be avoided to minimize the risk of venous irritation, which increases as the diameter of the vein decreases.

In isolated cases, allergic reactions (exanthema) occur on the skin and in other areas.

Patients with respiratory tract obstruction and brain damage may suffer from respiratory depression.

Ordinarily, the patient should be monitored for 6 to 12 hours after administering Lormetazepam Koehler.

Occasionally, especially when high doses of lormetazepam are administered or repeated treatment is applied, reversible alterations may appear, such as slowed or unintelligible speech (articulation disorders), motor disorders, unsteady gait, visual disturbances/visual anomalies (diplopia), and nystagmus.

The risk of adverse effects is higher among elderly patients. These patients should be warned of the risk of falls due to the muscle relaxant effect of lormetazepam.