FDA Approves Auvelity (dextromethorphan/bupropion) for Major Depressive Disorder and Agitation in Alzheimer's

Auvelity is a combination of dextromethorphan, an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist, and bupropion, an aminoketone and CYP450 2D6 inhibitor. The precise mechanism in MDD and agitation associated with dementia due to Alzheimer's disease is unknown.

Auvelity is indicated for the treatment of major depressive disorder (MDD) in adults and for the treatment of agitation associated with dementia due to Alzheimer's disease in adults. Limitations of Use: Auvelity is not indicated as an as-needed ("prn") treatment for agitation associated with dementia due to Alzheimer's disease.

Prior to initiating treatment, assess blood pressure, screen for history of bipolar disorder/mania/hypomania, and determine if patient is receiving other medications containing bupropion or dextromethorphan. For MDD: starting dose is 45 mg/105 mg once daily in the morning; increase to 45 mg/105 mg twice daily (at least 8 hours apart) on day 4. For agitation associated with Alzheimer's disease: start with 30 mg/105 mg once daily; on day 8 increase to 30 mg/105 mg twice daily; on day 15 increase to 45 mg/105 mg twice daily based on tolerability. Swallow tablets whole; do not crush, divide, or chew. For moderate renal impairment (eGFR 30-59 mL/min/1.73 m²) or CYP2D6 poor metabolizers: maximum recommended dosage is 45 mg/105 mg once daily for both indications. For concomitant use with strong CYP2D6 inhibitors: maximum recommended dosage is 45 mg/105 mg once daily.

Trial data not available in label.

Not reported in label.

Auvelity offers a novel combination therapy for MDD and agitation associated with Alzheimer's disease. It is not for as-needed use in agitation. Dosing adjustments are required in renal impairment, CYP2D6 poor metabolizers, and with strong CYP2D6 inhibitors.