Drug Interactions between AccessPak for HIV PEP Expanded with Viracept and elacestrant

GENERALLY AVOID: Coadministration with potent or moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of elacestrant, which is primarily metabolized by the isoenzyme. When elacestrant (172 mg once daily) was administered with itraconazole, a potent CYP450 3A4 inhibitor, elacestrant peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 4.4-fold and 5.3-fold, respectively. Concomitant use of fluconazole, a moderate CYP450 3A4 inhibitor, is predicted to increase elacestrant (345 mg single dose) Cmax and AUC by 1.6-fold and 2.3-fold, respectively. Increased exposure to elacestrant may increase the risk of adverse reactions such as musculoskeletal pain, nausea, dyslipidemia, increased liver enzymes, fatigue, decreased hemoglobin, and vomiting.

MANAGEMENT: Coadministration of elacestrant with potent or moderate CYP450 3A4 inhibitors should be generally avoided. However, if a potent or moderate CYP450 3A4 inhibitor must be used, some authorities recommend the following dose adjustments for elacestrant: For concomitant use with potent CYP450 3A4 inhibitors, the elacestrant dose should be reduced to 86 mg once daily and for concomitant use with moderate CYP450 3A4 inhibitors, the elacestrant dose should be reduced to 172 mg once daily. Patient tolerability should be assessed throughout treatment and a subsequent dose reduction of elacestrant to 86 mg once daily may be considered with moderate CYP450 3A4 inhibitors. If the CYP450 3A4 inhibitor is discontinued, elacestrant should be increased to its prior dose after 5 half- lives of the CYP450 3A4 inhibitor.

MONITOR: Coadministration with elacestrant may increase the plasma concentrations of drugs that are substrates of P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP). When the P-gp substrate digoxin was administered with elacestrant (345 mg single dose), digoxin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.3-fold and 1.1-fold, respectively. The Cmax and AUC of rosuvastatin, a BCRP substrate, increased by 1.5-fold and 1.2-fold, respectively, when administered with the same dose of elacestrant. Adverse reactions associated with P-gp and BCRP substrates may be increased.

MANAGEMENT: Caution is advised if elacestrant is coadministered with substrates of P-gp and/or BCRP, particularly sensitive substrates or those with a narrow therapeutic range. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration and for any dosage adjustments that may be required.