Relugolix

Brand Names: Orgovyx

Drug Class: Gonadotropin Releasing Hormone Receptor Antagonist

Overview

11 DESCRIPTION Relugolix is a nonpeptide small molecule, GnRH receptor antagonist. The chemical name is N-(4-{1-[(2,6-difluorophenyl)methyl]-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl}phenyl)-N'-methoxyurea. The molecular weight is 623.63 daltons and the molecular formula is C 29 H 27 F 2 N 7 O 5 S.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Relugolix is a nonpeptide GnRH receptor antagonist that competitively binds to pituitary GnRH receptors, thereby, reducing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and consequently testosterone. 12.2 Pharmacodynamics Pituitary and Gonadal Hormones Relugolix reduced LH, FSH ( Figure 1 ), and testosterone concentrations after oral administration of the recommended loading dose of 360 mg and a 120 mg dose once daily. Out of 622 patients, 56% had testosterone concentrations at castrate levels ( 280 ng/dL) or baseline at 90 days was 55% [see Clinical Studies ( 14 )] .

Indications

  • 1 INDICATIONS AND USAGE ORGOVYX is indicated for the treatment of adult patients with advanced prostate cancer. ORGOVYX is a gonadotropin-releasing hormone (GnRH) receptor antagonist indicated for the treatment of adult patients with advanced prostate cancer ( 1 ).

Common Doses

  • 360 mg
  • 120 mg
  • 240 mg

Dosage

2 DOSAGE AND ADMINISTRATION Recommended Dosage: A loading dose of 360 mg on the first day of treatment followed by 120 mg taken orally once daily, at approximately the same time each day ( 2.1 ). ORGOVYX can be taken with or without food ( 2.1 , 12.3 ). Instruct patients to swallow tablets whole and not to crush or chew tablets ( 2.1 ). 2.1 Recommended Dosage Initiate treatment of ORGOVYX with a loading dose of 360 mg on the first day and continue treatment with a 120 mg dose taken orally once daily at approximately the same time each day.

Contraindications

  • 4 CONTRAINDICATIONS ORGOVYX is contraindicated in patients with severe hypersensitivity to relugolix or to any of the product components. Known severe hypersensitivity to relugolix or to any of the product components ( 4 ).

Side Effects

  • 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: QT/QTc Interval Prolongation [see Warnings and Precautions ( 5.1 )] . The most common adverse reactions (≥ 10%) and laboratory abnormalities (≥ 15%) were hot flush, glucose increased, triglycerides increased, musculoskeletal pain, hemoglobin decreased, alanine aminotransferase (ALT) increased, fatigue, aspartate aminotransferase (AST) increased, constipation, and diarrhea ( 6.1 ).

Interactions

  • 7 DRUG INTERACTIONS P-gp Inhibitors: Avoid co-administration. If unavoidable, take ORGOVYX first, separate dosing by at least 6 hours, and monitor patients more frequently for adverse reactions ( 2.2 , 7.1 ). Combined P-gp and Strong CYP3A Inducers: Avoid co-administration. If unavoidable, increase the ORGOVYX dose to 240 mg once daily ( 2.3 , 7.1 ). 7.1 Effect of Other Drugs on ORGOVYX P-gp Inhibitors Relugolix is a P-gp substrate. Co-administration of ORGOVYX with an oral P-gp inhibitor increases relugolix exposure [see Clinical Pharmacology ( 12.