HALCION TRIAZOLAM 0.250MG 30 TABLETS

Description

Pharmacokinetic properties: Triazolam is a hypnotic with a short plasma half-life of 1.5 to 5.5 hours. Studies in healthy volunteers at recommended doses four times a day for 7 days revealed that there was no evidence of alterations in systemic bioavailability in the rate of elimination or accumulation.

Peak plasma levels (range 1 to 6 ng/ml) are reached 2 hours after oral administration.

Triazolam and its metabolites, mainly as glucuronide conjugates which are inactive, are excreted primarily in the urine. Only small amounts of intact triazolam appear in the urine. The two conjugated primary metabolites appear in 79.9% of urinary excretion. Urinary excretion appears to be biphasic in relation to the time course. In in vitro studies, even extremely high concentrations of triazolam do not displace bilirubin bound to serum albumin.

Pharmacodynamics: In sleep laboratory studies, HALCION® significantly decreased sleep latency, increased sleep duration, and decreased the number of nocturnal awakenings.

After two weeks of consecutive nocturnal administration, the effects of the drug on the total time awake is diminished and the values ​​recorded in the last third of the night approach baseline levels. On the first and/or second night after discontinuation of the drug, total sleep time, percentage of time spent sleeping, and rate of falling asleep frequently were significantly less than on the nights before the drug. This effect is often called “rebound” insomnia.

The type and duration of hypnotic effects and the profile of undesirable effects during benzodiazepine administration may be influenced by the biological half-life of the administered drug and any active metabolites formed.
When half-lives are long, the drug or its metabolites may accumulate during periods of nocturnal administration and be associated with impairment of cognitive and motor functions during waking hours, the possibility of interaction with other psychoactive drugs or alcohol will be increased. . In contrast, if half-lives are short, drugs and metabolites will be cleared before the next dose is ingested and effects related to excessive sedation or CNS depression should be minimal or absent. However, during nocturnal use for a long period of pharmacodynamic tolerance or adaptation of some hypnotic benzodiazepine effects may develop.

If the drug has a short elimination half-life, it is possible that a relative deficiency of the drug or its active metabolites (e.g., relative to the receptor site) may occur at some point between each nocturnal administration.

This sequence of events may be taken into account for two reported clinical findings that occurred after two weeks of nocturnal administration of rapidly eliminating benzodiazepine hypnotics.

• Increased wakefulness during the last third of the night.

• The presence of anxiety during the day after 10 days of continuous treatment.