indication

For palliative treatment of advanced prostate cancer.

pharmacology

Used in the palliative treatment of advanced prostate cancer. Abarelix is a luteinizing hormone agonist that results in suppression of testicular or follicular steroidogenesis.

mechanism of action

Abarelix binds to the gonadotropin releasing hormone receptor and acts as a potent inhibitor of gonadotropin secretion.

toxicity

The maximum tolerated dose of abarelix has not been determined. The maximum dose used in clinical studies was 150 mg. There have been no reports of accidental overdose with abarelix.

biotransformation

In vitro hepatocyte (rat, monkey, human) studies and in vivo studies in rats and monkeys showed that the major metabolites of abarelix were formed via hydrolysis of peptide bonds. No significant oxidative or conjugated metabolites of abarelix were found either in vitro or in vivo. There is no evidence of cytochrome P-450 involvement in the metabolism of abarelix.

absorption

Following IM administration of 100 mg, abarelix is absorbed slowly with a mean peak concentration of 43.4 ng/mL observed approximately 3 days after the injection.

half life

13.2 ± 3.2 days

drug interactions

Tacrolimus: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Thiothixene: May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.

Toremifene: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.

Trimipramine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Voriconazole: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Vorinostat: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Ziprasidone: Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Zuclopenthixol: Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).