Pharmacology - Brotizolam (Lendormin)

[Jatelka]

OK, so this is less complete than I'd like, but I'm starting to struggle with the benzodiazepines that aren't available in English-speaking countries.

Brotizolam is 2-Bromo-4-(2-chlorphenyl)-9-methyl-6H thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)benzodiazepine. It has the chemical formula C15H10BRCLN4S and the molecular weight 393.7.

Pharmacokinetics

Bioavailability after an oral dose is approximately 70%. Time to peak plasma concentrations is 1 hour. It is 90% bound to plasma proteins. It is metabolized by the liver to N-desmethyl-brotizolam (terminal half-life 4-19.5 hours), and others. Elimination half-life is 5.6 hours (range: 2.6 to 6.9 hours, but up to 13 hours in patients with liver failure). 22.5% of the dose is excreted by the kidneys, and excretion in bile also occurs. Brotizolam is also excreted in breast milk (in animal studies) and has been demonstrated to cross the placenta.

Indications

The short-term treatment of insomnia. The usual therapeutic dose is 0.25-0.5mg at night (0.125mg is recommended as the starting dose in elderly or debilitated patients). The dose should also be reduced in liver and renal failure.

Contraindications

All the usual: Hypersensitivity, severe respiratory and liver disease, closed angle-glaucoma, pregnancy and lactation.

Adverse Effects

In post marketing studies up to 50% of people experienced transient adverse effects, which were more likely at higher doses. Very common (greater than 25%) were somnolence, confusion and ataxia. Common (up to 25%) were headache, depression, slurred speech, poor concentration, changes in libido, GI upset and hypersalivation. Uncommon (1-9%): Jaundice, dermatitis/urticaria, low blood counts, psychosis and paradoxical excitation. Rarely (less than 1%): Hypo/Hypertension, bradycardian and tachycardia.

As with all benzodiazepines a physical tolerance develops with as little as 14 days of continuous use. Brotizolam should not be discontinued suddenly.