Lormetazepam

Structural formula
	Simplified structural formula - 1: 1 mixture of two enantiomers
General
Non-proprietary name	Lormetazepam
other names	( RS ) -7-chloro-5- (2-chlorophenyl) -3-hydroxy-1-methyl-2,3-dihydro-1 H -1,4-benzodiazepin-2-one ( IUPAC ) ; Lormetazepamum ( Latin ) ;
Molecular formula	C 16 H 12 Cl 2 N 2 O 2
External identifiers / databases
EC number	212-700-5
ECHA InfoCard	100,011,546
PubChem	13314
ChemSpider	12750
DrugBank	DB13872
Wikidata	Q186257
Drug information
ATC code	N05 CD06
Drug class	Benzodiazepine; Hypnotic;
properties
Molar mass	335.19 g · mol -1
Physical state	firmly
Melting point	205-207 ° C
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 319-360-362
	P: ?
Toxicological data	1790 mg kg −1 ( LD 50 , mouse , oral ) ; 6250 mg kg −1 ( LD 50 , rat , ip ) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Lormetazepam is a drug in the benzodiazepine family . Like all members of his family, Lormetazepam acts as an anxiolytic , hypnotic , tranquilizer , anticonvulsant and muscle relaxant , but it is mainly used as a hypnotic . Like all drugs from the benzodiazepine group, it has a high potential for dependence , i. This means that after a few weeks of use in therapeutic doses, dependency can occur.

pharmacology

The therapeutic dosage for the treatment of difficulty falling asleep and staying asleep as well as for the treatment of acute anxiety is 0.5 mg to 2 mg as a single dose per 24 hours, taken 30 minutes before bedtime. In premedication before surgical or diagnostic interventions up to 2 mg as a single dose 60 minutes before the intervention.

Maximum plasma levels are reached after approx. 1.5 hours, the elimination half-life in the human organism averages 12 hours. In the elderly, this time can increase up to 20 hours. So Lormetazepam one of the medium-acting benzodiazepines with sufficiently rapid flooding and is therefore suitable for short-term use also for the symptomatic treatment of sleep disorders .

The bioavailability after oral administration is approx. 80%, the substance is subject to a first-pass effect in the liver. Lormetazepam is 90% water-soluble from the human organism by glucuronidation in the liver and excreted in the urine. A metabolism into active metabolites takes place to a lesser extent and pharmacologically irrelevant to lorazepam. Lormetazepam (like oxazepam and lorazepam ) is not metabolized by the enzyme cytochrome P450 . Therefore, unlike almost all other benzodiazepines, no interactions with inhibitors or inducers of this enzyme are to be expected.

Clinical information

Application areas (indications)

Lormetazepam is used in oral administration, for example as tablets or capsules , in particular for the short-term treatment of sleep disorders. For the treatment of acute tension, excitement and anxiety and for induction of anesthesia , the active ingredient is also available in ampoules of 2 mg for intravenous injection. Lormetazepam is also used in anesthesiology for pre- and post-treatment during surgical or diagnostic interventions.

Contraindications (contraindications)

In addition to a known hypersensitivity to the active ingredient, myasthenia gravis , dependence on alcohol, drugs or drugs as well as acute poisoning with alcohol, other sleeping pills, painkillers or psychotropic drugs are absolute contraindications and therefore exclude the use of lormetazepam. Lormetazepam may only be used with special caution and after weighing up the risk-benefit ratio in patients with spinal and cerebellar ataxias , sleep apnea syndromes , severe respiratory failure, or severe liver or kidney failure .

Interactions

The simultaneous use of lormetazepam with other central depressant drugs, in particular neuroleptics , other tranquilizers or sleeping pills , antidepressants , opioid analgesics , anesthetics , and antihistamines , but also the simultaneous consumption of lormetazepam with alcohol, can lead to a mutual intensification of the effects . Because of the muscle relaxant effects of lormetazepam, the effects of other muscle relaxants may be increased. In addition, the effect of drugs for long-term use of cardiovascular and respiratory problems, especially beta blockers , cardiac glycosides and theophylline , as well as the safety of antibiotics and the “ birth control pill ” can be influenced.

Side effects

The most common side effects observed during treatment with lormetazepam include headache (frequency> 10%), dizziness and light-headedness (3%), persistent fatigue, incoordination, difficulty concentrating (2%), prolonged reaction times (1%), confusion, muscle weakness and depression Upset.

Dependency

Like all benzodiazepines, Lormetazepam has a potential for dependence. Even with daily intake for a few weeks, even in the therapeutic dose range, there is a risk of developing addiction.

Suddenly discontinuing lormetazepam after a long period of regular use can lead to withdrawal symptoms. These include in particular sleep disorders, increased dreaming, fear, states of tension, excitement, inner restlessness, tremors and sweating up to threatening physical and mental reactions such as seizures and psychoses.

Central nervous system

The side effects of lormetazepam that are characteristic of benzodiazepines include the muscle weakness caused by central muscle relaxation and the associated unsteadiness of movement and gait as well as the risk of falling. Reversible disorders such as slow or unclear speech, visual disturbances and nystagmus can also occur , particularly with high doses and with long-term treatment . Like other benzodiazepines, Lormetazepam can cause anterograde amnesia , so that later the patient may not remember any actions taken after taking medication. In addition, so-called paradoxical reactions such as increased aggressiveness, acute states of excitement, anxiety, suicidal thoughts , muscle spasms as well as difficulty falling asleep and staying asleep can occur. Particularly in patients with anxiety and depression, the risk of suicide can be increased after use with lormetazepam.

Skin and immune system

Approximately 2% of patients associated itching with the intake of lormetazepam. Allergic skin reactions, including rashes, have been observed in isolated cases.

breathing

Patients with airway obstruction and brain damage may be at risk of respiratory depression after taking lormetazepam.

Trade names

Ergocalm (D), Loramet (CH), Loretam (D), Noctamid (D, CH), Sedalam (ampoules of 2 mg) (D) and numerous generic drugs (D)

Stereochemistry

Lormetazepam contains a stereocenter and consists of two enantiomers. This is a racemate , i.e. a 1: 1 mixture of ( R ) - and ( S ) -form:

Enantiomers of Lormetazepam
CAS number: 113679-56-4	CAS number: 113679-54-2

literature

Otto Benkert, Florian Holsboer, Gerhard Founder: Manual of Psychopharmacotherapy . 1st edition. Springer, Berlin 2007, ISBN 978-3-540-20475-6 , doi : 10.1007 / 978-3-540-68748-1 .

Individual evidence

^ Entry on Lormetazepam. In: Römpp Online . Georg Thieme Verlag, accessed on June 1, 2014.
↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of lormetazepam in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), which was retrieved on July 7, 2020, is reproduced from a self-classification by the distributor .
↑ ^a ^b Entry on lormetazepam in the ChemIDplus database of the United States National Library of Medicine (NLM) .
↑ ^a ^b ^c ^d ^e ^f ^g ^h Federal Institute for Drugs and Medical Devices (BfArM): Sample text for the specialist information on Lormetazepam. ( RTF ; 76 kB) Retrieved May 15, 2010 .
↑ A. Doenicke, R. Dorow, U. Täuber: The pharmacokinetics of lormetazepam following cimetidine. In: Anaesthesiologist. 40 (12), Dec 1991, pp. 675-679. PMID 1685875 .
↑ Rote Liste Service GmbH (Ed.): Rote Liste 2017 - drug directory for Germany (including EU approvals and certain medical devices) . Rote Liste Service GmbH, Frankfurt / Main, 2017, edition 57, ISBN 978-3-946057-10-9 , p. 196.

[RÖMPP_Online-1] Entry on Lormetazepam. In: Römpp Online . Georg Thieme Verlag, accessed on June 1, 2014.

[2] Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of lormetazepam in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), which was retrieved on July 7, 2020, is reproduced from a self-classification by the distributor .

[ChemIDplus-3] Entry on lormetazepam in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[FI-4] ↑ ^a ^b ^c ^d ^e ^f ^g ^h Federal Institute for Drugs and Medical Devices (BfArM): Sample text for the specialist information on Lormetazepam. ( RTF ; 76 kB) Retrieved May 15, 2010 .

[5] A. Doenicke, R. Dorow, U. Täuber: The pharmacokinetics of lormetazepam following cimetidine. In: Anaesthesiologist. 40 (12), Dec 1991, pp. 675-679. PMID 1685875 .

[Rote_Liste-6] Rote Liste Service GmbH (Ed.): Rote Liste 2017 - drug directory for Germany (including EU approvals and certain medical devices) . Rote Liste Service GmbH, Frankfurt / Main, 2017, edition 57, ISBN 978-3-946057-10-9 , p. 196.