Drug Interactions between elacestrant and Nuedexta

GENERALLY AVOID: Coadministration with potent CYP450 2D6 inhibitors (e.g., quinidine, terbinafine) may significantly increase the plasma concentrations of dextromethorphan in patients who are extensive metabolizers of this isoenzyme (approximately 93% of Caucasians and more than 98% of Asians and individuals of African descent). The proposed mechanism is inhibition of the CYP450 2D6-mediated O-demethylation of dextromethorphan. Studies in humans have shown an increase in systemic exposure of dextromethorphan of up to 43-fold when given concurrently with quinidine. Increased plasma concentrations increase the risk of dextromethorphan-related adverse effects (e.g., agitation, confusion, tremor, insomnia, diarrhea, and respiratory depression) and serotonin syndrome. However, this interaction has also been used clinically, with dextromethorphan in combination with quinidine indicated by some authorities for the treatment of pseudobulbar affect. Data evaluating the impact of this interaction in patients who are poor metabolizers of CYP450 2D6 are limited; most studies include extensive metabolizers of this isoenzyme. It is expected that poor metabolizers would have elevated dextromethorphan levels without concurrent quinidine

MANAGEMENT: The combination of dextromethorphan with potent CYP450 2D6 inhibitors should be generally avoided. Some manufacturers consider the concomitant use of dextromethorphan and selective serotonin reuptake inhibitors contraindicated. If use is considered necessary, the patient should be monitored for signs of dextromethorphan adverse effects (e.g., agitation, confusion, tremor, insomnia, diarrhea, and respiratory depression) and serotonin syndrome, and advised to notify their health care professional if these adverse effects develop or worsen. Dose reduction of dextromethorphan may also be required.

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.

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.