AUVELITY is indicated for the treatment of major depressive disorder (MDD) in adults.

AUVELITY extended-release tablets contain 45 mg dextromethorphan hydrobromide and 105 mg bupropion hydrochloride. The tablets are beige and round with “45/105” debossed on one side.

AUVELITY is contraindicated in patients:

The following adverse reactions are discussed in more detail in other sections of the labeling:

There is limited clinical study experience regarding human overdosage with AUVELITY. Overdosage information is based on experience with the individual components, dextromethorphan and bupropion. Metabolism of the dextromethorphan component of AUVELITY is inhibited by the bupropion component, such that overdose due to AUVELITY might be more severe or more persistent compared to overdose of dextromethorphan alone.

Symptoms of dextromethorphan overdose include nausea, vomiting, stupor, coma, respiratory depression, seizures, tachycardia, hyperexcitability, and toxic psychosis. Other adverse effects include ataxia, nystagmus, dystonia, blurred vision, and changes in muscle reflexes. Dextromethorphan may cause serotonin syndrome, and this risk is increased by overdose, particularly if taken with other serotonergic agents, SSRIs or tricyclic antidepressants.

Overdoses of up to 30 grams or more of bupropion (approximately 143 times the maximum recommended dose of AUVELITY) have been reported. Seizure was reported in approximately one-third of all cases. Other serious reactions reported with overdoses of bupropion alone included hallucinations, loss of consciousness, mental status changes, sinus tachycardia, ECG changes such as conduction disturbances (including QRS prolongation) or arrhythmias, clonus, myoclonus, and hyperreflexia. Fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure have been reported mainly when bupropion was part of multiple drug overdoses.

Although most patients recovered without sequelae, deaths associated with overdoses of bupropion alone have been reported in patients ingesting large doses of the drug. Multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest prior to death were reported in these patients.

Treatment of dextromethorphan overdosage should be directed at symptomatic and supportive measures.

There are no known antidotes for bupropion. In case of an overdose, provide supportive care, including close medical supervision and monitoring. Consider the possibility of multiple drug overdose. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. Induction of emesis is not recommended.

Consider contacting a Poison Center (1-800-222-1222) or a medical toxicologist for overdosage management recommendations for AUVELITY.

AUVELITY is a combination of dextromethorphan hydrobromide, an uncompetitive NMDA receptor antagonist and sigma-1 receptor agonist, and bupropion hydrochloride, an aminoketone and CYP450 2D6 inhibitor.

The chemical name of dextromethorphan hydrobromide is morphinan, 3- methoxy-17-methyl-, (9α, 13α, 14α), hydrobromide monohydrate. Dextromethorphan hydrobromide has the empirical formula C

Dextromethorphan hydrobromide powder is white or almost white, crystalline, and sparingly soluble in water.

The chemical name of bupropion hydrochloride is:(±)-1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1­propanone hydrochloride. Bupropion hydrochloride has the empirical formula C

Bupropion hydrochloride powder is white and highly soluble in water.

AUVELITY is for oral administration and is available as round bilayer tablets. Each tablet contains 45 mg dextromethorphan hydrobromide (equivalent to 32.98 mg dextromethorphan base) in an immediate-release formulation and 105 mg bupropion hydrochloride (equivalent to 91.14 mg bupropion base) in an extended-release formulation. Each tablet contains the following inactive ingredients: carbomer homopolymer, colloidal silicon dioxide, crospovidone, glyceryl monocaprylocaprate, l-cysteine hydrochloride monohydrate, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol, red iron oxide, sodium lauryl sulfate, stearic acid, talc, titanium dioxide, and yellow iron oxide.

The efficacy of AUVELITY for the treatment of MDD in adults was demonstrated in a placebo-controlled clinical study (Study 1,

In Study 1, adult patients (18 to 65 years of age) who met the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for MDD were randomized to receive AUVELITY (45 mg of dextromethorphan hydrobromide and 105 mg of bupropion hydrochloride) twice daily (N=156) or placebo twice daily (N=162) for 6 weeks. Patients in Study 1 had a median age of 41 years and were 67% female, 55% Caucasian, 35% Black, and 5% Asian.

The primary outcome measure was the change from baseline to Week 6 in the total score of the Montgomery-Asberg Depression Rating Scale (MADRS). The MADRS is a clinician-rated scale used to assess the severity of depressive symptoms. Patients are rated on 10 items to assess feelings of sadness, inner tension, reduced sleep or appetite, difficulty concentrating, lassitude, lack of interest, pessimism, and suicidality. Scores on the MADRS range from 0 to 60, with higher scores indicating more severe depression. AUVELITY was statistically significantly superior to placebo in improvement of depressive symptoms as measured by decrease in MADRS total score at Week 6 (see

The change from baseline in MADRS total score by week in Study 1 is displayed in Figure 3. The change in MADRS total score from baseline to Week 1 and from baseline to Week 2 were pre-specified secondary efficacy endpoints. The difference between AUVELITY and placebo in change from baseline in MADRS total score was statistically significant at Week 1 and at Week 2.

SE = Standard Error

Examination of demographic subgroups by age, sex, and race did not suggest differences in response.

In Study 2, patients with MDD were randomized to receive AUVELITY or bupropion hydrochloride sustained-release tablets 105 mg twice daily for 6 weeks. The primary outcome measure was calculated by assessing the change from baseline in total MADRS score at each on-site visit from Week 1 to Week 6 and then taking the average of those scores. The results of the study demonstrated that dextromethorphan contributes to the antidepressant properties of AUVELITY.

AUVELITY (dextromethorphan hydrobromide and bupropion hydrochloride) extended-release tablets are beige, film-coated, round, bilayer tablets with “45/105” debossed on one side. AUVELITY is supplied in the following package configuration:

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Advise patients and caregivers to look for the emergence of suicidal ideation and behavior, especially early during treatment and when the dose is adjusted up or down, and instruct them to report such symptoms to the healthcare provider

Advise patients that both immediate and delayed hypersensitivity reactions to AUVELITY could occur. Instruct patients to seek medical attention immediately if they experience symptoms indicative of hypersensitivity, such as skin rash, pruritus, hives, chest pain, edema, shortness of breath, arthralgia, myalgia, or fever after taking AUVELITY

Advise patients that AUVELITY can cause seizure and that excessive use or abrupt discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedatives/hypnotics can increase the risk. Advise patients to minimize or avoid use of alcohol. Instruct patients to use AUVELITY as directed and to discontinue, and not restart, AUVELITY if they experience a seizure while on treatment

Advise patients that AUVELITY can cause increased blood pressure and hypertension and that the risk is increased if used with some other medications such as MAOIs and drugs that increase dopaminergic or noradrenergic activity

Advise patients to observe for signs of activation of mania/hypomania and instruct them to report such symptoms to the healthcare provider

Inform patients that changes in mood including delusions, hallucinations, psychosis, concentration disturbances, paranoia, and confusion have occurred with use of bupropion, a component of AUVELITY. Instruct patients to notify a healthcare provider if they experience such symptoms

Patients should be advised that taking AUVELITY can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle-closure glaucoma

Advise patients that AUVELITY may cause dizziness. Inform patients to take precautions to reduce the risk of falls, particularly for patients with motor impairment affecting gait or a history of falls. Caution patients about operating hazardous machinery, including motor vehicles, until they know how they will be affected by AUVELITY

Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of AUVELITY with SSRIs or tricyclic antidepressants. Instruct patients to contact their health care provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome

Advise pregnant females and females of reproductive potential of the potential risk to a fetus

Advise patients not to breastfeed during treatment with AUVELITY and for 5 days after the final dose

Advise patients not to take more than two tablets in the same day and to allow at least an 8-hour interval between doses

Inform patients that AUVELITY increases the risk of drug interactions. Instruct patients to inform their healthcare provider about all the medications that they are taking before taking AUVELITY. Before taking any new medications, patients should tell their healthcare provider that they are taking AUVELITY.

Advise patients that AUVELITY can increase adverse neuropsychiatric reactions or reduce alcohol tolerance and to avoid or limit use of alcohol during treatment with AUVELITY

Inform patients that AUVELITY contains bupropion which is an active ingredient in medications for other uses. Advise patients to inform their healthcare provider of all the medications that they are taking, including other bupropion-containing products

Inform patients that AUVELITY contains dextromethorphan which is an active ingredient in medications for other uses. Advise patients to inform their healthcare provider of all the medications that they are taking, including other dextromethorphan-containing products

Distributed by:

Axsome Therapeutics, Inc.

AXSOME THERAPEUTICS and AUVELITY are trademarks or registered trademarks of Axsome Therapeutics, Inc. in the United States and other countries.

For patent information: www.axsome.com/IP

©2025 Axsome Therapeutics, Inc. All rights reserved.

AUV-USPI-003.000-20251119

(dextromethorphan HBr and bupropion HCl)

extended-release tablets

(dextromethorphan HBr and bupropion HCl)

extended-release tablets

(dextromethorphan HBr and bupropion HCl)

extended-release tablets

(dextromethorphan HBr and bupropion HCl)

extended-release tablets 45mg/105mg

Dispense with Medication Guide

(dextromethorphan HBr and bupropion HCl)

extended-release tablets

(dextromethorphan HBr and bupropion HCl)

extended-release tablets 45mg/105mg

Dispense with Medication Guide