Auvelity Drug Information

Major Depressive Disorder

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

Agitation Associated with Dementia Due to Alzheimer’s Disease

AUVELITY is indicated for the treatment of agitation associated with dementia due to Alzheimer’s disease. Limitations of Use: AUVELITY is not indicated as an as needed (“prn”) treatment for agitation associated with dementia due to Alzheimer’s disease.

Important Recommendations

Prior to Initiating and During Treatment with AUVELITY Prior to initiating and during treatment with AUVELITY: assess blood pressure and monitor periodically during treatment . screen patients for a personal or family history of bipolar disorder, mania, or hypomania . screen patients to determine if they are receiving any other medications that contain bupropion or dextromethorphan .

Recommended Dosage for the Treatment of Major Depressive Disorder

The recommended starting dosage ofis AUVELITY (45 mg of dextromethorphan hydrobromide and /105 mg of bupropion hydrochloride) is one tablet once daily in the morning. After 3 daysOn day 4, increase to the maximum recommended dosage of one tablet twice daily, given at least 8 hours apart. Do not exceed two doses within the same day.

Administer AUVELITY orally with or without food . Swallow tablets whole, do not crush, divide, or chew.

Recommended Dosage for Treatment of Agitation Associated with Dementia Due to Alzheimer’s

Disease The recommended titration schedule is as follows: The recommended starting dose is AUVELITY 30 mg/105 mg once daily, in the morning. On day 8, increase to AUVELITY 30 mg/105 mg twice daily, given at least 8 hours apart, based on tolerability. On day 15, after starting AUVELITY, increase to the maximum recommended dosage of 45 mg/105 mg twice daily, given at least 8 hours apart, based on tolerability.

Do not exceed two doses within the same day. Administer AUVELITY orally with or without food. Swallow tablets whole, do not crush, divide, or chew.

Dosage Recommendations in Patients with Renal Impairment For patients with moderate renal

impairment (eGFR 30 to 59 mL/minute/1.73 m²), the dosing recommendations for AUVELITY are as follows: For patients with MDD, the recommended starting and maximum dosage is 45 mg/105 mg once daily in the morning. For patients with Agitation Associated with Dementia due to Alzheimer’s Disease, the recommended starting dosage is 30 mg/105 mg once daily in the morning. On day 8, increase to the maximum recommended dosage of 45 mg/105 mg once daily in the morning, based on tolerability.

Dosage Recommendations for

Concomitant Use with Strong CYP2D6 Inhibitors When AUVELITY is co-administered with strong CYP2D6 inhibitors, the dosing recommendations for AUVELITY are as follows: For MDD, the recommended starting and maximum dosage is 45 mg/105 mg once daily in the morning. For Agitation Associated with Dementia due to Alzheimer’s Disease, the recommended starting dosage is 30 mg/105 mg once daily in the morning. On day 8, increase to the maximum recommended dosage of 45 mg/105 mg once daily in the morning, based on tolerability.

Dosage Recommendations for Known

CYP2D6 Poor Metabolizers (PMs) For patients who are known CYP2D6 poor metabolizers, the dosing recommendations are as follows: For MDD, the recommended starting and maximum dosage is 45 mg/105 mg once daily in the morning. For Agitation Associated with Dementia due to Alzheimer’s Disease, the recommended starting dosage is 30 mg/105 mg once daily in the morning. On day 8, increase to the maximum recommended dosage of 45 mg/105 mg once daily in the morning, based on tolerability.

Switching a Patient to or from a Monoamine Oxidase Inhibitor (MAOI) Antidepressant

At least 14 days must elapse between discontinuation of an MAOI intended to treat depression and initiation of therapy with AUVELITY. Conversely, at least 14 days must be allowed after stopping AUVELITY before starting an MAOI antidepressant .

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. AUVELITY has been evaluated for safety in 2,550 adult patients who participated in multiple-dose clinical trials for major depressive disorder, agitation associated with dementia due to Alzheimers disease, or another indication. Among them, 918 patients were treated with AUVELITY for at least 6 months, and 251 patients were treated with AUVELITY for at least 1 year.

Major Depressive Disorder The data below are based on the 6-week, placebo-controlled study in which either AUVELITY (n=162) or placebo (n=164) was administered twice daily to patients with MDD (Study 1). Demographics of the patients who participated in this study are summarized in Clinical Studies. Adverse Reactions Leading to Discontinuation In the 6-week placebo-controlled study, 4% of patients treated with AUVELITY and 0% of placebo-treated patients discontinued participation due to adverse reactions. The adverse reaction that led to study discontinuation in 1% of patients treated with AUVELITY was anxiety (2%). Most Common Adverse Reactions In the 6-week placebo-controlled clinical study, the most common (incidence 5% for AUVELITY and more than twice as frequently as placebo) adverse reactions were dizziness (16%), headache (8%), diarrhea (7%), somnolence (7%), dry mouth (6%), sexual dysfunction (6%), and hyperhidrosis (5%). Table 2 shows the incidence of adverse reactions that occurred in 2% of patients treated with AUVELITY and more frequently than in patients treated with placebo in Study 1. Table 2: Adverse Reactions Occurring in ≥2% of Adult Patients with MDD Treated with AUVELITY and More Frequently than in Patients Treated with Placebo in a 6-Week Placebo-Controlled Study (Study 1) a Sexual dysfunction includes orgasm abnormal, erectile dysfunction, libido decreased, anorgasmia b Fatigue includes fatigue, lethargy c Paraesthesia includes paraesthesia, hypoaesthesia Adverse Reaction AUVELITY (N=162) % Placebo (N=164) % Dizziness 16 6 Nausea 13 9 Headache 8 4 Diarrhea 7 3 Somnolence 7 3 Dry mouth 6 2 Sexual dysfunction a 6 0 Hyperhidrosis 5 0 Anxiety 4 1 Constipation 4 2 Decreased appetite 4 1 Insomnia 4 2 Arthralgia 3 0 Fatigue b 3 2 Paraesthesia c 3 0 Vision blurred 3 0 Agitation Associated with Dementia Due to Alzheimers Disease The data below are based on the 5-week, placebo-controlled, parallel-group study in which either AUVELITY (n=159) or placebo (n=158) was administered twice daily to patients with agitation associated with dementia due to Alzheimers disease.

Adverse Reactions Leading to Discontinuation In the 5-week placebo-controlled study, 1.3% of patients treated with AUVELITY and 1.3% of placebo-treated patients discontinued participation due to adverse reactions. No individual adverse reaction leading to discontinuation occurred in more than one subject. Most Common Adverse Reactions In the 5-week placebo-controlled clinical study, the most common (incidence 5% for AUVELITY and more than twice as frequently as placebo) adverse reactions consisted of dizziness (9%) and dyspepsia (6%). Table 3 shows the incidence of adverse reactions that occurred in 2% of patients treated with AUVELITY and more frequently than in patients treated with placebo in a 5-week placebo-controlled study (Study 3). Table 3: Adverse Reactions Occurring in ≥2% of Adult Patients with Agitation Associated with Dementia Due to Alzheimer’s Disease Treated with AUVELITY and More Frequently than in Patients Treated with Placebo in a 5-Week Placebo-Controlled Study (Study 3) a Dizziness includes Vertigo, Dizziness postural, Balance disorder. b Somnolence includes Somnolence, Hypersomnia. c Dyspepsia includes Abdominal discomfort, Dyspepsia, Gastritis, Abdominal pain upper, Gastroesophageal reflux disease. d Fatigue includes Asthenia, Lethargy, Fatigue. e Nausea includes Nausea, Vomiting. f Psychotic symptom includes Catatonia, Delusion, Hallucination, Hallucination visual. g Confusional State includes Confusional state, Delirium, Disorientation. h Bacterial infection includes Abscess limb, Staphylococcal infection, Urinary tract infection.

Adverse Reaction AUVELITY (N=159) % Placebo (N=158) % Dizziness a 9 3 Somnolence b 8 4 Dyspepsiac 6 1 Fatigue d 6 3 Nausea e 5 3 Dry Mouth 4 3 Headache 4 3 Constipation 3 0 Psychotic symptom f 3 0 Confusional state g 3 1 Cough 3 1 Bacterial infection h 3 1

Postmarketing Experience

The following adverse reactions have been identified with the use of theAUVELITY and its individual components of AUVELITY, dextromethorphan and bupropion, during postmarketing use. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. AUVELITY: Feeling abnormal, tinnitus, and tremor.

Dextromethorphan Drowsiness, dizziness, nervousness or restlessness, nausea, vomiting, and stomach pain. Bupropion Body (General) : Arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity. These symptoms may resemble serum sickness.

Cardiovascular: Complete atrioventricular block, extrasystoles, hypotension, hypertension (in some cases severe), phlebitis, pulmonary embolism, and Brugada pattern/syndrome. Digestive: Colitis, esophagitis, gastrointestinal hemorrhage, gum hemorrhage, hepatitis, intestinal perforation, pancreatitis, and stomach ulcer. Endocrine: Hyperglycemia, hypoglycemia, hyponatremia, and syndrome of inappropriate antidiuretic hormone secretion.

Hemic and Lymphatic: Anemia, leukocytosis, leukopenia, lymphadenopathy, pancytopenia, and thrombocytopenia. Altered PT and/or INR, infrequently associated with hemorrhagic or thrombotic complications, were observed when bupropion was coadministered with warfarin. Metabolic and Nutritional: Glycosuria.

Musculoskeletal: Muscle rigidity/fever/rhabdomyolysis and muscle weakness. Nervous System: Abnormal electroencephalogram (EEG), aggression, agitation, akinesia, aphasia, coma, completed suicide, delirium, delusions, depression, dysarthria, euphoria, extrapyramidal syndrome (dyskinesia, dystonia, hypokinesia, parkinsonism), hallucinations, homicidal ideation, hostility, increased libido, manic reaction, neuralgia, neuropathy, panic, paranoid ideation, psychosis, restlessness, suicide ideation, suicide attempt, unmasking tardive dyskinesia, aseptic meningitis, and tremor. Respiratory: Pneumonia.

Skin and subcutaneous tissue disorders: Alopecia, angioedema, exfoliative dermatitis, hirsutism, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms (DRESS). Special Senses: Deafness, increased intraocular pressure, mydriasis, and tinnitus. Urogenital : Abnormal ejaculation, cystitis, dyspareunia, dysuria, gynecomastia, menopause, painful erection, salpingitis, urinary incontinence, urinary retention, and vaginitis.

Drugs Having Clinically Important Interactions with

AUVELITY Table 4: Clinically Important Drug Interactions with AUVELITY Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact Concomitant use of AUVELITY with MAOIs increases the risk of hypertensive crisis and serotonin syndrome. Intervention AUVELITY is contraindicated in patients taking MAOIs (including MAOIs such as linezolid or intravenous methylene blue) or in patients who have taken MAOIs within the preceding 14 days. Allow at least 14 days after stopping AUVELITY before starting an MAOI Serotonergic Drugs Clinical Impact Concomitant use of AUVELITY with other serotonergic drugs increases the risk of serotonin syndrome.

Intervention Monitor for symptoms of serotonin syndrome when AUVELITY is used concomitantly with other drugs that may affect the serotonergic neurotransmitter systems. If serotonin syndrome occurs, consider discontinuation of AUVELITY and/or concomitant serotonergic drug . Drugs that Lower Seizure Threshold Clinical Impact AUVELITY contains bupropion which can cause seizure. Co-administration with other drugs that lower seizure threshold may increase risk of seizure.

Intervention Use caution when administering AUVELITY concomitantly with drugs that lower the seizure threshold . Discontinue AUVELITY and do not restart treatment if the patient experiences a seizure. Strong Inhibitors of CYP2D6 Clinical Impact Concomitant use of AUVELITY with strong CYP2D6 inhibitors increases plasma concentrations of dextromethorphan. Intervention Dosage adjustment is necessary when AUVELITY is co-administered with strong inhibitors of CYP2D6 . Monitor patients for adverse reactions potentially attributable to dextromethorphan, such as somnolence and dizziness.

Strong Inducers of CYP2B6 Clinical Impact Concomitant use of AUVELITY with strong CYP2B6 inducers decreases plasma concentrations of dextromethorphan and bupropion and may decrease efficacy of AUVELITY . Intervention Avoid co-administration of AUVELITY with strong inducers of CYP2B6. Consider alternatives to strong CYP2B6 inducers if needed. Drugs Metabolized by CYP2D6 Clinical Impact CYP2D6 Substrates Coadministration of AUVELITY with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Drugs that Require Metabolic Activation by CYP2D6 Drugs that require metabolic activation by CYP2D6 to be effective could have reduced efficacy when administered concomitantly with AUVELITY. Intervention CYP2D6 Substrates When used concomitantly with AUVELITY, it may be necessary to decrease the dose of CYP2D6 substrates, particularly for drugs with a narrow therapeutic index. Drugs that Require Metabolic Activation by CYP2D6 Patients treated concomitantly with AUVELITY may require increased doses of drugs that require activation by CYP2D6 to be effective.

Digoxin Clinical Impact Coadministration of AUVELITY with digoxin may decrease plasma digoxin levels. Intervention Monitor plasma digoxin levels in patients treated concomitantly with AUVELITY and digoxin . Dopaminergic Drugs Clinical Impact CNS toxicity was reported when bupropion was co-administered with levodopa or amantadine. Adverse reactions include restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness.

Intervention Use caution when administering AUVELITY concomitantly with dopaminergic drugs. Alcohol Clinical Impact AUVELITY contains bupropion which can increase adverse neuropsychiatric events or reduce alcohol tolerance. Intervention Consumption of alcohol should be minimized or avoided during treatment with AUVELITY.

Drug-Laboratory Test Interactions False-positive urine immunoassay screening tests for amphetamines have been

reported in patients taking bupropion. This is due to lack of specificity of some screening tests. False positive test results may result even following discontinuation of bupropion therapy.

Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish bupropion from amphetamines.

Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants, including AUVELITY, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Antidepressants at 1-866-961-2388 or online at: https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/. Risk Summary Based on animal studies, AUVELITY may cause fetal harm when administered during pregnancy. AUVELITY is not recommended during pregnancy.

If a female becomes pregnant while being treated with AUVELITY, discontinue treatment and counsel the patient about the potential risk to a fetus . In oral studies conducted in rats and rabbits, a combination of dextromethorphan/quinidine demonstrated developmental toxicity, including fetal malformations (rabbits) and embryolethality, when given to pregnant animals. When bupropion alone was administered to pregnant rats during organogenesis, there was no evidence of fetal malformations at doses up to approximately 21 times the maximum recommended human dose (MRHD) of 210 mg/day. When bupropion alone was given to pregnant rabbits during organogenesis, non-dose–related increases in incidence of fetal malformations, and skeletal variations were observed at doses approximately 2 to 5 times the MRHD and greater.

Decreased fetal weights were seen at bupropion doses approximately 5 times the MRHD and greater. Neurotoxicity findings were observed in juvenile rats treated with a combination of dextromethorphan/quinidine on postnatal day (PND) 7, which corresponds to the third trimester of gestation through the first few months of life and may extend through the first three years of life in humans. Based on these findings, AUVELITY may cause fetal harm when administered to pregnant women (see Data ). The available clinical data on the use of AUVELITY during pregnancy is insufficient to evaluate for a drug-associated risk of major birth malformations, miscarriage, or other adverse maternal or fetal outcomes.

However, there are available data on one of the individual components of AUVELITY, bupropion. Data from epidemiological studies of pregnant women exposed to bupropion in the first trimester have not identified an increased risk of congenital malformations overall (see Data ). There are risks to the mother associated with untreated depression in pregnancy (see Clinical Considerations ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants during pregnancy at the beginning of pregnancy. The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants.

Consider the risks to the mother of untreated depression and potential effects on the fetus when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum. Data Human Data Bupropion Data from the international bupropion Pregnancy Registry (675 first trimester exposures) and a retrospective cohort study using the United Healthcare database (1,213 first trimester exposures) did not show an increased risk for malformations overall. The Registry was not designed or powered to evaluate specific defects but suggested a possible increase in cardiac malformations.

No increased risk for cardiovascular malformations overall has been observed after bupropion exposure during the first trimester. The prospectively observed rate of cardiovascular malformations in pregnancies with exposure to bupropion in the first trimester from the international bupropion Pregnancy Registry was 1.3% (9 cardiovascular malformations/675 first trimester maternal bupropion exposures), which is similar to the background rate of cardiovascular malformations (approximately 1%). Data from the United Healthcare database, which had a limited number of exposed cases with cardiovascular malformations, and a case-control study (11,700 infants with cardiovascular malformations and 20,093 infants with non-cardiovascular malformations) of self-reported antidepressant use, including bupropion (n=728), from the National Birth Defects Prevention Study (NBDPS) did not show an increased risk for cardiovascular malformations overall after bupropion exposure during the first trimester. Study findings on bupropion exposure during the first trimester and risk for left ventricular outflow tract obstruction (LVOTO) or ventricular septal defect (VSD) are inconsistent and do not allow conclusions regarding a possible association.

The United Healthcare database lacked sufficient power to evaluate the LVOTO association. NBDPS found slightly increased risk for LVOTO after partially accounting for underlying maternal conditions (n = 14; adjusted odds ratio = 1.18; 95% CI: 0.58, 2.43), and the Slone Epidemiology case control study did not find increased risk for LVOTO. The Slone Epidemiology Study found an increased risk for VSD following first trimester maternal bupropion exposure (n = 17; adjusted OR = 2.5; 95% CI: 1.3, 5.0) but did not find increased risk for any other cardiovascular malformations studied (including LVOTO as above). The NBDPS and United Healthcare database study did not find an association between first trimester maternal bupropion exposure and VSD. For the findings of LVOTO and VSD, the studies were limited by the small number of exposed cases, inconsistent findings among studies, and the potential for chance findings from multiple comparisons in case control studies. Animal Data In studies conducted in pregnant mice, dextromethorphan-bupropion was administered orally during the period of organogenesis at doses of 0-0, 26-57, 34-75, and 68-150 mg/kg/day, respectively.

Administration of dextromethorphan-bupropion did not affect body weight, weight gain, food consumption, or pregnancy at any dose level and did not produce gross pathologic findings or placental or fetal findings at any dose level. The no-effect level for reproductive organ findings in mice was 68-150 mg/kg in both sexes, which is approximately 3.7/3.5 times the MRHD for AUVELITY on a mg/m 2 basis. When dextromethorphan/quinidine was administered orally (0/0, 5/100, 15/100, and 50/100 mg/kg/day) to pregnant rats during the period of organogenesis, embryo-fetal deaths were observed at the highest dose tested and reduced skeletal ossification was observed at all doses.

Oral administration to pregnant rabbits during organogenesis in two separate studies (0/0, 5/60, 15/60, and 30/60 mg/kg/day; 0/0, 5/100, 15/100, and 50/100 mg/kg/day) resulted in an increased incidence of fetal malformations at all but the lowest dose tested. When dextromethorphan/quinidine was orally administered to female rats during pregnancy and lactation in two separate studies (0/0, 5/100, 15/100, and 30/100 mg/kg/day; 0/0, 5/100, 15/100, and 50/100 mg/kg/day), pup survival and pup weight were decreased at all doses, and developmental delay was observed in offspring at the mid and high doses. A no-effect dose for adverse developmental effects was not identified.

When dextromethorphan/quinidine was orally administered (0/0, 5/50, 15/50, 25/50 mg/kg) to male and female rats on postnatal day (PND) 7, the highest dose resulted in neuronal death in brain (thalamus and medulla oblongata). PND 7 in rat corresponds to the third trimester of gestation through the first several months of life but may extend to approximately three years of age in humans. In studies conducted in pregnant rats and rabbits, bupropion alone was administered orally during the period of organogenesis at doses of up to 450 and 150 mg/kg/day, respectively (approximately 21 and 14 times the MRHD, respectively, on a mg/m 2 basis). There was no evidence of fetal malformations in rats. When given to pregnant rabbits during organogenesis, non-dose–related increases in incidence of fetal malformations and skeletal variations were observed at the lowest dose tested (25 mg/kg/day, approximately 2 times the MRHD on a mg/m 2 basis) and greater.

Decreased fetal weights were observed at doses of 50 mg/kg/day (approximately 5 times the MRHD on a mg/m 2 basis) and greater. No maternal toxicity was evident at doses of 50 mg/kg/day or less. In a pre- and postnatal development study, bupropion administered orally to pregnant rats at doses of up to 150 mg/kg/day (approximately 7 times the MRHD on a mg/m 2 basis) from embryonic implantation through lactation had no effect on pup growth or development.

Pediatric Use The safety and effectiveness of AUVELITY have not been established in pediatric patients. AUVELITY contains bupropion. Antidepressants, including bupropion, increase the risk of suicidal thoughts and behaviors in pediatric patients .

is contraindicated in patients: with a seizure disorder . with a current or prior diagnosis of bulimia or anorexia nervosa as a higher incidence of seizures was observed in such patients treated with the immediate-release formulation of bupropion . undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs . taking, or within 14 days of stopping, MAOIs due to the risk of serious and possibly fatal drug interactions, including hypertensive crisis and serotonin syndrome . Starting AUVELITY in a patient treated with reversible MAOIs such as linezolid or intravenous methylene blue is contraindicated. with known hypersensitivity to bupropion, dextromethorphan, or other components of AUVELITY. Anaphylactoid/anaphylactic reactions and Stevens-Johnson syndrome have been reported with bupropion. Arthralgia, myalgia, fever with rash, and other serum sickness-like symptoms suggestive of delayed hypersensitivity have also been reported with bupropion . Seizure disorder. Current or prior diagnosis of bulimia or anorexia nervosa.

Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. Use with an MAOI or within 14 days of stopping treatment with AUVELITY. Do not use AUVELITY within 14 days of discontinuing an MAOI. Known hypersensitivity to bupropion, dextromethorphan, or other components of AUVELITY.

Human Experience 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. Dextromethorphan 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. Bupropion 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. Overdosage Management 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 Help Line (1-800-222-1222) or a medical toxicologist for overdosage management recommendations for AUVELITY.