DEGARELIX

GENERAL DRUG CLASSIFICATION: Anti-cancer

CHEMICAL NAME: 4S)-N-{4-[(2S)-2-{[(1R)-2-[4-(carbamoylamino)phenyl]-1-{[(1S)-1-

{[(2S)-1-[(2S)-2-{[(1R)-1-carbamoylethyl]carbamoyl}pyrrolidin-1-yl]-
1-oxo-6-[(propan-2-yl)amino]hexan-2-yl]carbamoyl}-3-
methylbutyl]carbamoyl}ethyl]carbamoyl}-2-[(2S)-2-[(2R)-2-[(2R)-3-
(4-chlorophenyl)-2-[(2R)-2-acetamido-3-(naphthalen-2-
yl)propanamido]propanamido]-3-(pyridin-3-yl)propanamido]-3-
hydroxypropanamido]ethyl]phenyl}-2,6-dioxo-1,3-diazinane-4-
carboxamide [1]

GENERIC NAME: Dagarelix acetate [2]

BRAND NAME: Firmagon [2]

INDICATIONS: Degaralix is used for the management of advanced prostate cancer. [1]

PHARMACOKINETICS: Absorption: Degarelix forms a depot at the site of injection after

subcutaneous administration from which the drug slowly released into
circulation. After a single bolus dose of 2mg/kg, peak plasma
concentrations of degarelix occured within 6 hours at a concentration
of 330 ng/mL. Ki = 0.082 ng/mL and 93% of receptors were fully
suppressed; MRT = 4.5 days. [1]

Distribution Central compartment: 8.88 - 11.4 L; Peripheral

compartment: 40.9 L [1]

Metabolism 70% - 80% of degarelix is subject to peptide hydrolysis

during its passage through the hepatobiliary system and then fecally
eliminated. No active or inactive metabolites or involvement of
CYP450 isozymes.[1]

Excretion: Fecal (70% to 80%) and renal (20%-30% of unchanged

drug) [1]
PHARMACODYNAMICS: Degarelix is a synthetic derivative of GnRH decapeptide, the ligand of
the GnRH receptor. Gonadotropin and androgen production result from
the binding of endogenous GnRH to the GnRH receptor. Degarelix
antagonizes the GnRH receptor which in turn blocks the release of LH
and FSH from the pituitary. LF and FSH decreases in a concentration-
dependent manner. The reduction in LH leads to a decrease in
testosterone release from the testes.[1]

DRUG INTERACTIONS: Abexinostat - The risk or severity of QTc prolongation can be

increased when Degarelix is combined with Abexinostat.[1]

Acebutolol - The risk or severity of QTc prolongation can be increased

 when Degarelix is combined with Acebutolol. [1]

Aceprometazine - The risk or severity of QTc prolongation can be

increased when Degarelix is combined with Aceprometazine. [1]

LABORATORY Affects pituitary and gonadal function test. [1]

INTERFERENCES:
[1]
REFERENCES: Degarelix. DrugBank. https://www.drugbank.ca/drugs/DB06699.
Accessed November 22, 2018.
[2]
Cleveland Clinic Cancer. Degarelix. Dexamethasone - Drug
Information - Chemocare. http://chemocare.com/chemotherapy/drug-
info/degarelix.aspx. Accessed November 22, 2018.