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NOCTAMID has a high affinity for specific binding sites in the central nervous system. These benzodiazepine receptors display a close functional relationship to the receptors of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). As a benzodiazepine receptor agonist, NOCTAMID reinforces the GABA-ergic inhibition of the activity of distal neurones. This effect becomes pharmacologically manifest in the form of anxiolytic, anticonvulsive, muscle relaxing and sedative-hypnotic effects.

NOCTAMID shortens sleep latency, reduces the frequency of nocturnal arousals and prolongs sleep duration without contributing to undesired sedation or reduced performance on the day after its use. The anxiolytic and muscle relaxing effects can be exploited pre- and post-operatively.

Pharmacokinetics
Lormetazepam is completely absorbed from the NOCTAMID tablet.

Absorption proceeds with a half-life of 0.5 - 0.9 hours.

Maximum plasma levels of about 6 ng/ml are reached 1.5 hours after ingestion of NOCTAMID 1 mg. Postmaximal decrease of drug plasma levels is in two phases characterised by half-lives of 2 - 2.5 hours and about 10 hours. During absorption and first-pass through the liver about 20 % of the dose are inactivated presystemically. Thus, the absolute bioavailability is about 80 % of the dose.

Lormetazepam is extensively bound to plasma albumin. Independent of the concentration, 8.6 % of total plasma levels are present as free portions. The metabolic clearance rate accounted for 3.6 ml/min/kg. Lormetazepam is almost exclusively metabolized by glucuronidation. Lormetazepam glucuronide does not bind to the benzodiazepine-receptor, is the main metabolite and the only one found in plasma and is almost exclusively excreted with urine. Only less than 6 % of dose were found as N-demethylated lormetazepam glucuronide exclusively in urine. Excretion rate was in one phase, for which a half-life of 13.6 hours was calculated. In urine 86 % of dose were recovered. Renal clearance of lormetazepam glucuronide was about 0.65 ml/min/kg.
The pharmacokinetics of lormetazepam are dose linear within the range of 1 - 3 mg.

No sex differences in pharmacokinetics were found. Small differences in terms of lower metabolic clearance rate, longer half-life of the terminal disposition phase in plasma and higher steady-state drug levels in plasma were found in elderly volunteers as compared to young test subjects. The elimination of lormetazepam glucuronide from plasma was significantly slower in the elderly population (t ½ = 20 hours) than in a group of young subjects (t ½ = 12 hours).

Multiple (daily) dose pharmacokinetics of lormetazepam is predictable from single dose parameters. Steady-state conditions are reached within 3 days at latest and respective steady-state drug plasma levels increased by a factor of 1.3 (young) or 1.6 (elderly).

No drug/drug interactions are expected at the level of protein binding. At the level of phase I biotransformation no interaction was expected and found with cimetidine.

Terminal renal failure did not affect lormetazepam pharmacokinetics. The drug's glucuronide showed a dialysate clearance of 20 ml/min and inactive glucuronide levels decreased with a half-life of about 80 hours due to the forced biliary (instead of renal) elimination.

Liver cirrhosis did not alter the pharmacokinetics of lormetazepam or its glucuronide.

No enterohepatic recirculation of lormetazepam or its glucuronide was found.

Lormetazepam was not detectable in breast milk. By calculation at most 0.35 % of the daily dose of a breast feeding mother could reach the newborn.

Indications
Short-term treatment of insomnia (characterised by difficulty in falling asleep and frequent nocturnal awakenings).

Benzodiazepines are only indicated when the disorder is severe, disabling or subjecting the individual to extreme distress.

Dosage and Administration
Short term treatment of insomnia
The duration of treatment should be as short as possible. Generally it varies from a few days to two weeks with a maximum, including tapering off, of four weeks.

In certain cases extension beyond the maximum treatment period may be necessary; if so, it should not take place without re-evaluation of the patient's situation.

Adults take 1 mg NOCTAMID as a single dose. Patients of advanced age take 0.5 mg NOCTAMID as a single dose. It is possible to double the dose in individual cases. The tablets are taken with some liquid shortly before going to bed.