Advanced prostate cancer can now be treated with relugolix (Orgovyx), the first oral gonadotropin-releasing hormone (GnRH) receptor antagonist. The drug works by binding to pituitary GnRH receptors, decreasing the release of luteinizing hormone and follicle-stimulating hormone, and consequently decreasing testosterone. The therapeutic effect of relugolix should be monitored by periodically measuring serum concentrations of prostate specific antigen.
The safety and efficacy of relugolix was evaluated in a randomized, open-label study in men with advanced prostate cancer. In a 2:1 ratio, patients were assigned to receive relugolix or a standard therapy, leuprolide acetate, by injection. The efficacy outcome measure was a testosterone level low enough to be considered medical castration (less than 50 ng/dL) by day 29 through week 48 of treatment. Those treated with relugolix were more likely than those treated with leuprolide acetate to achieve low testosterone levels by day 29 (99% versus 82%).
Like other androgen deprivation therapy, relugolix carries the risk of prolonging the QT or QTc interval. The drug may also cause embryo-fetal toxicity. The most common adverse effects are hot flushes, musculoskeletal pain, fatigue, constipation, and diarrhea; the most common laboratory abnormalities are decreases in hemoglobin and elevations in glucose, triglycerides, alanine aminotransferase, and aspartate aminotransferase.
Nurses should teach men with female partners of reproductive age to use effective contraception during treatment and for two weeks after the last relugolix dose. Patients should be told to swallow the drug whole, not to crush or chew it. The drug should be taken at the same time every day. Nurses should use a drug database to confirm that the patient is not also taking a P-glycoprotein (P-gp) inhibitor such as amiodarone, carvedilol, erythromycin, ritonavir, or verapamil, because coadministration with these drugs can increase blood levels of relugolix and therefore the risk of adverse effects. If coadministration with P-gp inhibitors cannot be avoided, relugolix should be taken first followed by a waiting period of at least six hours before taking the other drug. Drugs that are P-gp inducers or inducers of the cytochrome P-450 (CYP) isoenzyme CYP3A (for example, phenytoin, fosphenytoin, and rifampin, which induces both) should be avoided, if possible, as they decrease circulating levels of relugolix.
Because of the risk of a prolonged QT interval, the patient should be assessed for electrolyte abnormalities prior to and throughout therapy, and any abnormalities should be corrected. Patients may require electrocardiogram monitoring during therapy.
For complete prescribing information for relugolix, go to http://www.accessdata.fda.gov/drugsatfda_docs/label/2020/214621s000lbl.pdf.