indication

For the treatment of insomnia.

pharmacology

Glutethimide is a hypnotic sedative that was introduced in 1954 as a safe alternative to barbiturates to treat insomnia. Before long, however, it had become clear that glutethimide was just as likely to cause addiction and caused similarly severe withdrawal symptoms.

mechanism of action

Glutethimide seems to be a GABA agonist which helps induced sedation. It also induces CYP 2D6. When taken with codeine, it enables the body to convert higher amounts of the codeine (higher than the average 5 - 10%) to morphine. The general sedative effect also adds to the power of the combination.

toxicity

In adults, death has been reported after 5 g. The usual lethal dose is 10 to 20g, although survival after a dose of 28 g has been reported.

biotransformation

Hepatic. Glutethimide is almost completely metabolized.

absorption

Variable

half life

10-12 hours

route of elimination

glutethimide is inactivated by conjugation and the metabolites are excreted in urine, only 2% of the parent substance is excreted in urine, up to 2% of the dose has been reported to be found in the faeces.

drug interactions

Acenocoumarol: Glutethimide may decrease the anticoagulant effect of acenocoumarol.

Anisindione: Glutethimide may decrease the anticoagulant effect of anisindione.

Dicumarol: Glutethimide may decrease the anticoagulant effect of dicumarol.

Donepezil: Possible antagonism of action

Galantamine: Possible antagonism of action

Rivastigmine: Possible antagonism of action

Triprolidine: The CNS depressants, Triprolidine and Glutethimide, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.

Warfarin: Glutethimide may decrease the serum concentration of warfarin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if glutethimide is initiated, discontinued or dose changed.