SUMMARY  

• Apalutamide is metabolized primarily by CYP2C8 and CYP3A4 to form N-desmethyl apalutamide. Co-administration of a strong CYP2C8 or CYP3A4 inhibitor is predicted to increase the steady-state exposure of apalutamide based on predicted active unbound fraction changes. No initial dose adjustment is necessary however, consider reduction of the ERLEADA dose based on tolerability.^1,2
• Apalutamideis a strong inducer of CYP3A4 and CYP2C19, and a weak inducer of CYP2C9 in humans. Concomitant use of ERLEADA with medications that are primarily metabolized by CYP3A4, CYP2C19, or CYP2C9 can result in lower exposure to these medications. Substitution for these medications is recommended when possible or evaluate for loss of activity if medication is continued.^1,3
• Apalutamide was shown to be a weak inducer of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transporting polypeptide 1B1 (OATP1B1) clinically. Induction of CYP3A4 by apalutamide suggests that UDP-glucuronosyl transferase (UGT) may also be induced via activation of nuclear pregnane X receptor. Concomitant use of ERLEADA with medications that are substrates of P-gp, BCRP, OATP1B1, or UGT can result in lower exposure and/or loss of efficacy of these medications. Use caution if substrates of P-gp, BCRP, OATP1B1, or UGT must be
  co-administered with ERLEADA and evaluate for loss of efficacy if medication is continued.^1,3

DRUG INTERACTIONS

For up-to-date drug interaction, pharmacokinetic, and pharmacodynamic clinical data pertaining to specific medicinal agents, please review the local labeling of ERLEADA and/or contact the manufacturers of these agents for additional information.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on
04 September 2024.