Lormetazepam Koehler 0.2 mg/ml solution for injection and infusion EFG

Package Leaflet: Information for the user

Introduction

PACKAGE LEAFLET

Package leaflet: Information for the patient

Lormetazepam Koehler 0.2 mg/ml solution for injection and infusion EFG

Lormetazepam

Read the entire 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 questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents

1. What Lormetazepam Koehler is and what it is used for
2. What you need to know before receiving Lormetazepam Koehler
3. How Lormetazepam Koehler is administered
4. Possible side effects
5. How to store 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 in Lormetazepam Koehler, is a sedative, anxiolytic, and sleep-inducing medicine belonging to the benzodiazepine group.

Adults:

Lormetazepam Koehler is indicated

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

Paediatric population:

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

2. What you need to know before receiving Lormetazepam Koehler

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

Lormetazepam Koehler must not be administered

• if you are allergic to lormetazepam, to other benzodiazepines, or to any of the other components of this medicine (listed in section 6)
• if you have a known dependence or a personal history of alcohol, drug, or medication dependence
• if you have acute intoxication due to alcohol, hypnotic drugs (sleep-inducing medications), pain-relieving drugs (analgesics), or psychotropic drugs (neuroleptics, antidepressants, lithium)
• if you suffer from a specific type of muscle weakness (myasthenia gravis)
• if your breathing stops 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 failure (severe hepatic disorder).

Warnings and precautions

Talk to your doctor before receiving Lormetazepam Koehler if you have

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

For further information regarding possible development of tolerance, dependence, amnesia, paradoxical or psychiatric reactions, or adverse effects with repeated administration, consult your doctor.

Children and elderly patients

Lormetazepam Koehler must not be administered to children aged 2 years and older or adolescents, except prior to diagnostic procedures (clinical examination) or surgical interventions (anesthesia, intensive care).

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

Before continuing the injection, wait if necessary until the patient's reaction has been observed.

Use of Lormetazepam Koehler with other medicines

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription.

The administration of Lormetazepam Koehler together with other centrally acting drugs (such as psychotropic drugs, hypnotics, analgesics, narcotics, and antihistamines) may mutually enhance the effects of these medicines.

Lormetazepam Koehler may enhance the effects of muscle-relaxing drugs (muscle relaxants).

The nature and extent of interaction cannot be predicted with certainty when you are undergoing continuous treatment with other medicines such as antihypertensives, beta-blockers, digitalis glycosides, medications for bronchial asthma (methylxanthines), oral contraceptives, and certain antibiotics.

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

Remember that this precaution also applies when recent treatment with these medicines has been carried out.

The concomitant use of Lormetazepam Koehler and opioids (potent analgesics, substitution therapy medications, and some cough medicines) increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be potentially fatal. For this reason, concomitant use should only be considered when no other treatment options are available.

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

Inform your doctor about all opioid medications you are taking. Contact your doctor if you experience any of the symptoms mentioned above.

Use of Lormetazepam Koehler with food, beverages, and alcohol

Do not consume alcohol during treatment with Lormetazepam Koehler, as alcohol may enhance the effect of lormetazepam in an unpredictable manner.

Pregnancy and breastfeeding

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

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

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

If Lormetazepam Koehler is administered for justified medical reasons during the late stages of pregnancy or during labor and delivery, effects in the newborn may occur, such as decreased body temperature (hypothermia), breathing difficulties (respiratory failure), reduced muscle tone, and feeding difficulties.

The risk of malformations following therapeutic doses of benzodiazepines during early pregnancy appears to be low; however, according to some studies, the risk of cleft palate may increase. Cases of congenital abnormalities and mental retardation have been reported with benzodiazepine overdose and intoxication.

Lormetazepam Koehler passes into human breast milk. Therefore, breastfeeding should be temporarily or permanently discontinued if Lormetazepam Koehler is administered repeatedly or at high doses.

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

Driving and use of machines

If you are being treated with Lormetazepam Koehler, you must not drive or operate machinery.

Lormetazepam Koehler impairs your reaction ability and significantly affects your capacity to drive or operate machinery, even when taking a therapeutic dose.

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

If lormetazepam is administered to prepare for an outpatient diagnostic procedure (before a medical examination), the patient may only be discharged if accompanied; the patient must not drive any type of vehicle.

3. How Lormetazepam Koehler is administered

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

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

Consult your physician if you notice an effect that is too strong or too weak from Lormetazepam Koehler.

Higher drug levels have been observed in patients with mild or moderate hepatic impairment. Caution is recommended when treating patients with hepatic impairment.

If you receive more Lormetazepam Koehler than you should

This medicine will be administered by healthcare professionals. In case of overdose or accidental administration, contact your physician or consult the Toxicology Information Service, Telephone (91) 562.04.20.

Additional questions:

If you have any further questions about this medicine, ask your physician or pharmacist.

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

4. Possible adverse effects

Like all medicines, this medicine may cause adverse 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 may cause airway obstruction), difficulty breathing
• heart palpitations (tachycardia)
• hallucinations, delusional ideas, inappropriate behavior
• dependence (use of this medicine may lead to physical or mental dependence on lormetazepam)
• irritability, aggressiveness, agitation, restlessness
• memory loss or tendency to forget (amnesia), confusion
• clouding of consciousness, weakness
• depressive mood, emotional disturbances, anxiety, acute psychosis
• thrombosis, venous inflammation
• coordination disorders (balance) (ataxia), increased risk of falls, muscle weakness
• reduced alertness, concentration difficulties and prolonged reaction times, slowed thinking
• speech problems
• vomiting, nausea
• constipation, stomach pain
• difficulty urinating
• headache
• fatigue, dizziness, numbness
• withdrawal symptoms (sleep disturbances), nightmares
• vision problems
• dry mouth
• loss of taste sensation (dysgeusia)
• skin problems such as rash, itching
• excessive sweating (hyperhidrosis)
• swelling and pain at the injection site (extravasation symptoms)

If you experience any side effect, inform your doctor so that it can be treated.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system:

Spanish System for Pharmacovigilance of Human Medicines: http://www.notificaram.es

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

Information for physicians and healthcare professionals is provided at the end of this leaflet, in the corresponding sections.

5. Storage of Lormetazepam Koehler

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 label and the carton after EXP. The expiry date refers to the last day of the month indicated.

Do not store above 25°C.

Do not freeze.

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer require. This will help protect the environment.

6. Contents of the pack and other information

Composition of Lormetazepam Koehler

• The active substance is lormetazepam.
• One 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 injections.

Addition to infusion solutions:

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

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

Appearance of the product and contents of the pack

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

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

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation 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

Further information on this medicinal product is available upon request to the local representative of the Marketing Authorisation Holder:

Cardiolink S.L.

Córcega 270, 3º 2ª

08008 Barcelona/Spain

Tel. +34 93 237 38 50

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

Austria Sedalor 2 mg/10 ml Injection/Infusion Solution

Spain Lormetazepam Koehler 0.2 mg/ml injectable and infusion solution EFG

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

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

Date of the most recent review of this leaflet: May 2019.

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

For more information on this medicinal product, please also consult the Summary of Product Characteristics.

Dosage guide and recommendations

Dosage and duration of treatment should be adjusted according to each patient's response, as well as the nature and severity of the condition.

In general, the lowest effective dose for the shortest possible duration should be administered.

The following dosage is recommended:

• Premedication prior to procedures under general anaesthesia

In the days preceding, on the night before and/or on the day of the procedure:

Recommended dose of lormetazepam	Equivalent dose of Lormetazepam Koehler
0.4 – 1 mg lormetazepam	2 – 5 ml

• Preoperative sedation before surgical procedures under general anesthesia

Recommended dose of lormetazepam	Equivalent dose of Lormetazepam Koehler
0.4 – 2 mg of lormetazepam, equivalent to 0.006 – 0.03 mg/kg body weight	2 – 10 ml

• Sedation (induction of sleep) during diagnostic procedures

Recommended dose of lormetazepam	Equivalent dose of Lormetazepam Koehler
1 – 2 mg of lormetazepam, equivalent to 0.015 – 0.03 mg/kg of body weight	5 – 10 ml

• Symptomatic treatment of acute episodes of tension, excitement, and anxiety, and
  basic sedation prior to procedures under local anesthesia

Before anesthesia:

Recommended dose of lormetazepam	Equivalent dose of Lormetazepam Koehler
0.4 – 1 mg of lormetazepam, equivalent to 0.006 – 0.015 mg/kg body weight	2 – 5 ml

And, during the procedure, depending on the desired depth of sedation:

Recommended dose of lormetazepam	Equivalent dose of Lormetazepam Koehler
up to a total dose of 2 mg of lormetazepam	up to 10 ml

• Symptomatic treatment of acute episodes of tension, excitement, and anxiety during diagnostic procedures

Recommended dose of lormetazepam	Equivalent dose of Lormetazepam Koehler
0.6 – 1 mg of lormetazepam, equivalent to 0.009 – 0.015 mg/kg body weight	3 – 5 ml

• Basic sedation in intensive care

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

Recommended dose of lormetazepam	Equivalent dose of Lormetazepam Koehler
0.2 – 0.4 mg of lormetazepam	1 – 2 ml

Special populations

Elderly patients:

Administer and dose with caution, especially if cardiac or respiratory function is impaired (cardiorespiratory insufficiency). Elimination is often delayed in elderly patients, which may potentiate the effect of benzodiazepines.

Patients in poor general condition:

Patients in poor general condition, especially those with psychosomatic disorders, circulatory or respiratory insufficiency:

Recommended dose of lormetazepam	Equivalent dose of Lormetazepam Koehler
0.2 – 1 mg of lormetazepam, equivalent to 0.003 – 0.015 mg/kg body weight	1 – 5 ml

Pediatric population (see also section 4.1)

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

Recommended dose of lormetazepam	Equivalent dose of Lormetazepam Koehler
0.1 – 0.8 mg of lormetazepam, equivalent to 0.0015 – 0.012 mg/kg body weight	0.5 – 4 ml

Considering each age group, slowly administer the injectable solution into a large-bore vein (no more than 5 ml/min). Adhere strictly to the recommended dosage regimen and carefully and continuously monitor respiration, blood pressure, and heart rate.

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

Children and adolescents aged 10 to 18 years receive the adult dosage.

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

Maintenance of effect

Lormetazepam Koehler may be administered repeatedly. However, daily doses should generally not exceed 5 mg of lormetazepam for adults, 4 mg for at-risk patients, and 3.5 mg for children and adolescents.

Method of administration

Administer the injectable solution slowly (approximately 5 ml/min) into a large-bore vein. During administration, carefully and continuously monitor respiration, blood pressure, and heart rate.

Lormetazepam Koehler may be administered undiluted and may also be given together with the perfusion solutions mentioned below (see further).

• Instructions for undiluted injection administration:

Lormetazepam Koehler is administered undiluted.

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

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

Discard broken ampoules after administering the medication.

Lormetazepam Koehler does not contain antimicrobial preservatives. Therefore, immediately after opening the ampoule, transfer its contents under aseptic conditions into a sterile syringe.

Administration of Lormetazepam Koehler must begin immediately. The contents of each Lormetazepam Koehler ampoule must be administered only once to a single patient.

Any remaining solution must be discarded after administration.

• Instructions for administration after addition to perfusion solutions:

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

Administration of other medications or infusions through the same line as lormetazepam must be performed using a three-way stopcock or Y-connector placed immediately adjacent to the infusion tubing.

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

Lormetazepam Koehler does not contain antimicrobial preservatives. Therefore, immediately after opening the ampoule, transfer its contents under aseptic conditions into a sterile infusion system.

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

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

The contents of each Lormetazepam Koehler ampoule, syringe, or infusion system must be administered only once to a single patient.

After completion of the infusion or changing the infusion system, any remaining Lormetazepam Koehler must be discarded.

Duration of administration:

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

Unless there is a strong medical justification, Lormetazepam Koehler should not be administered for longer than one week. Thus, the duration of administration and treatment depends on medical needs and will be determined by the responsible physician.

Overdose management

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

Benzodiazepine overdose typically manifests, depending on the dose administered, as variable central nervous system depression 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 level of consciousness, paradoxical reactions, agitation, and hallucinations.

Treatment of overdose is primarily symptomatic:

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

If necessary, the specific benzodiazepine antagonist flumazenil may be used to treat an admitted patient with overdose. The flumazenil product information must be consulted before administration.

Due to its high plasma protein binding and large volume of distribution, forced diuresis and hemodialysis are of little benefit in isolated lormetazepam intoxications.

Possible adverse reactions, warnings and precautions, and guidance for repeated administration

Tolerance

The hypnotic effects of lormetazepam may diminish after repeated administration over several weeks.

Dependence

Lormetazepam, like other benzodiazepines, carries a risk of primary dependence, both physical and psychological. The risk of dependence exists even when administered daily for only a few weeks. This occurs not only with abuse of high doses but also with therapeutic doses.

Abrupt discontinuation of lormetazepam treatment after daily administration may be associated with withdrawal symptoms such as headache, muscle pain, extreme anxiety, tension, agitation, confusion, irritability, sleep disturbances, and dream-like mentation.

In more severe cases, derealization, depersonalization, hyperacusis, numbness and tingling in the extremities, hypersensitivity to light, noise, and physical contact, hallucinations, or epileptic seizures may occur.

These symptoms may include tremor and sweating, which may intensify into dangerous physical (e.g., convulsive seizures) and psychological reactions such as symptomatic psychosis (e.g., withdrawal delirium).

Amnesia

Benzodiazepines may occasionally induce anterograde amnesia. This condition occurs (usually within a few hours) after administration of the drug. The patient may not always remember what they were doing. To reduce the risk of dose-dependent anterograde amnesia, ensure the patient has an uninterrupted sleep period of sufficient duration (7–8 hours).

Psychiatric reactions

During benzodiazepine treatment, a pre-existing depression may sometimes emerge or become unmasked. This reaction could precipitate suicide in such patients. In patients whose anxiety state overlays depression, treatment with benzodiazepines—even when not primarily used as anxiolytics—may lead to severe manifestations of depression, including suicidal tendencies becoming evident once anxiety is reduced. The physician should therefore take appropriate precautions.

Reactions such as restlessness, agitation, irritability, aggressiveness, delusional thoughts, rage, nightmares, hallucinations, psychosis, inappropriate behavior, and other adverse behavioral effects are known to occur with benzodiazepine use.

Paradoxical reactions

The possibility of paradoxical reactions such as increased aggression, acute excitement states, anxiety, suicidal ideation, muscle spasms, sleep disturbances such as discoimesis and disfilaxia, must be considered.

In the event of such reactions, the physician must discontinue administration of Lormetazepam Koehler.

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

Repeated administration:

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

In principle, injections and particularly infusions should be administered into large-bore veins. Injections and infusions into small veins should generally be avoided to minimize the risk of venous irritation, which increases as vein diameter decreases.

Allergic reactions (e.g., rash) may occur occasionally in the skin and other sites.

Patients with respiratory tract obstruction or cerebral damage may experience respiratory depression.

Patients should usually be monitored for 6 to 12 hours after administration of Lormetazepam Koehler.

Occasionally, especially when high doses of lormetazepam are administered or repeated treatment is given, reversible disturbances such as delayed or slurred speech (speech articulation disorders), motor disturbances, unsteady gait, visual disturbances/visual abnormalities (diplopia), and nystagmus may occur.

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