Apalutamide, sold under the brand name Erleada among others, is a nonsteroidal antiandrogen (NSAA) medication used for the treatment of prostate cancer.

[2][10] Side effects of apalutamide when added to castration include fatigue, nausea, abdominal pain, diarrhea, high blood pressure, rash, falls, bone fractures, and an underactive thyroid.

[2][16][17][18] It is also a promising potential treatment for metastatic castration-resistant prostate cancer (mCRPC), which the NSAA enzalutamide and the androgen synthesis inhibitor abiraterone acetate are used to treat.

[2] Apalutamide has been found to be well tolerated in clinical trials,[19][16] with the most common side effects reported when added to surgical or medical castration including fatigue, nausea, abdominal pain, and diarrhea.

[2][10][9] Apalutamide is an expected teratogen and has a theoretical risk of birth defects in male infants if taken by women during pregnancy.

[2] When used as a monotherapy (i.e., without surgical or medical castration) in men, NSAAs are known to produce additional, estrogenic side effects like breast tenderness, gynecomastia, and feminization in general by increasing estradiol levels.

[2] Case reports of rare interstitial lung disease with apalutamide exist similarly to with first-generation NSAAs however.

[2] In terms of effects of apalutamide on other drugs, the exposure of substrates of CYP3A4, CYP2C19, CYP2C9, UDP-glucuronosyltransferase, P-glycoprotein, ABCG2, or OATP1B1 may be reduced to varying extents.

[2] Apalutamide acts as a selective competitive silent antagonist of the androgen receptor (AR), via the ligand-binding domain, and hence is an antiandrogen.

[10][14][11][16] It is similar both structurally and pharmacologically to the second-generation NSAA enzalutamide,[19][25] but shows some advantages, including higher antiandrogenic activity as well as several-fold reduced central nervous system distribution.

[18][17] The acquired F876L mutation of the AR identified in advanced prostate cancer cells has been found to confer resistance to both enzalutamide and apalutamide.

[28] Apalutamide may be effective in a subset of prostate cancer patients with acquired resistance to abiraterone acetate.

[41] Apalutamide was approved by the Food and Drug Administration in the United States, under the brand name Erleada, for the treatment of non-metastatic castration-resistant prostate cancer in February 2018.