Daily Medication Pearl: Dextromethorphan and Bupropion (Auvelity)

Medication Pearl of the Day: Dextromethorphan and Bupropion (Auvelity)

Indication: Auvelity is a combination of dextromethorphan, an uncompetitive N-methyl D-aspartate (NDMA) receptor antagonist and sigma-1 receptor agonist, and bupropion, an aminoketone and CYP450 2D6 inhibitor, indicated for the treatment of major depressive disorder (MDD) in adults.

Insight:

• Dosing: Starting dose is 1 tablet once daily in the morning. After 3 days, increase to the maximum recommended dosage of 1 tablet twice daily, separated by at least 8 hours. Do not exceed 2 doses within the same day.
• Dosage forms: Extended-release tablets 45 mg/105 mg dextromethorphan/bupropion.
• Adverse events: Most common adverse reactions (≥5% and more than twice as frequently as placebo) are dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and hyperhidrosis.
• Mechanism of action: Dextromethorphan is an uncompetitive antagonist of the NMDA receptor (an ionotropic glutamate receptor) and a sigma-1 receptor agonist. The mechanism of dextromethorphan in the treatment of MDD is unclear. The mechanism of action of bupropion in the treatment of MDD is unclear; however, it may be related to noradrenergic and/or dopaminergic mechanisms. Bupropion increases plasma levels of dextromethorphan by competitively inhibiting cytochrome P450 2D6, which catalyzes a major biotransformation pathway for dextromethorphan. Bupropion is a relatively weak inhibitor of the neuronal reuptake of norepinephrine and dopamine and does not inhibit monoamine oxidase or the reuptake of serotonin.

Reference: auvelity-prescribing-information.pdf (axsome.com)