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, indicated for the treatment of major depressive disorder (MDD) in adults ( 1.1 ) the treatment of agitation associated with dementia due to Alzheimer’s disease ( 1.2 ) Limitations of Use: AUVELITY is not indicated as an as needed (“prn”) treatment for agitation associated with dementia due to Alzheimer’s disease (1.2).
1.1Major Depressive Disorder
AUVELITY is indicated for the treatment of major depressive disorder (MDD) in adults.
1.2Agitation 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 [see Clinical Studies Section 14.2 ].
Contraindications
AUVELITY is contraindicated in patients: with a seizure disorder [see Warnings and Precautions ( 5.2 )] . 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 [see Warnings and Precautions ( 5.2 )] . undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see Warnings and Precautions ( 5.2 ), Drug Interactions ( 7.1 )] . 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 [see Dosage and Administration ( 2.7 ), Warnings and Precautions ( 5.8 ), Drug Interactions ( 7.1 )] .
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 [see Adverse Reactions ( 6.2 )] .
Two medicines in one question?
Name two or more medicines and Osler runs an interaction check. A severe interaction is stated at the very top of the answer.
Seizure disorder. ( 4 ) Current or prior diagnosis of bulimia or anorexia nervosa. ( 4 ) Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. ( 4 ) Use with an MAOI or within 14 days of stopping treatment with AUVELITY. Do not use AUVELITY within 14 days of discontinuing an MAOI. ( 4 ) Known hypersensitivity to bupropion, dextromethorphan, or other components of AUVELITY. ( 4 )
Warnings and precautions
Seizure: Risk is dose-related. Discontinue if seizure occurs. ( 4 , 5.2 ) Increased Blood Pressure and Hypertension: AUVELITY can increase blood pressure and cause hypertension. Assess blood pressure before initiating treatment and monitor periodically during treatment. ( 5.3 ) Activation of Mania or Hypomania: Screen patients for bipolar disorder. ( 5.4 ) Psychosis and Other Neuropsychiatric Reactions: Instruct patients to contact a healthcare provider if such reactions occur.
( 5.5 ) Angle-Closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants. ( 5.6 ) Dizziness: AUVELITY may cause dizziness. Take precautions to reduce falls and use caution when operating machinery. ( 5.7 ) Serotonin Syndrome: Use of AUVELITY with selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants increases the risk.
Discontinue if occurs. ( 5.8 , 7.1 ) Embryo-fetal Toxicity: May cause fetal harm. Advise pregnant females of the potential risk to a fetus. Discontinue treatment in pregnant females and use alternative treatment for females who are planning to become pregnant. ( 5.9 , 8.1 , 8.3 ) Hyponatremia: Can occur in association with SIADH. ( 5.10 )
5.1Suicidal Thoughts and Behaviors in Adolescents and Young Adults
In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied.
There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 1. Table 1: Risk Differences of the Number of Patients of Suicidal Thoughts and Behavior in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric* and Adult Patients *AUVELITY is not approved for use in pediatric patients.
Age Range Drug-Placebo Difference in Number of Patients of Suicidal Thoughts or Behaviors per 1000 Patients Treated Increases Compared to Placebo <18 years old 14 additional patients 18-24 years old 5 additional patients Decreases Compared to Placebo 25-64 years old 1 fewer patient ≥65 years old 6 fewer patients It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term use, i.e., beyond four months.
However, there is substantial evidence from placebo-controlled maintenance studies in adults with MDD that antidepressants delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors. Monitor all antidepressant-treated patients for any indication for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at times of dosage changes.
Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing AUVELITY, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.
5.2Seizure Bupropion,
a component of AUVELITY, can cause seizure. The risk of seizure with bupropion is dose-related. When a bupropion hydrochloride (HCl) sustained-release tablet was dosed up to 300 mg per day (approximately 1.5 times the maximum recommended daily dosage of AUVELITY), the incidence of seizure was approximately 0.1% (1/1,000) and increased to approximately 0.4% (4/1,000) at the maximum recommended dosage for the sustained-release tablet of 400 mg per day (approximately 2 times the maximum recommended daily dosage of AUVELITY).
The risk of seizures is also related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold. Consider these risks before initiating treatment with AUVELITY. AUVELITY is contraindicated in patients with a seizure disorder, current or prior diagnosis of anorexia nervosa or bulimia, or undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see Contraindications ( 4 ), Drug Interactions ( 7.1 )] .
The following conditions can also increase the risk of seizure: severe head injury; arteriovenous malformation; CNS tumor or CNS infection; severe stroke; concomitant use of other medications that lower the seizure threshold (e.g., other bupropion products, antipsychotics, tricyclic antidepressants, theophylline, and systemic corticosteroids); metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, and hypoxia); use of illicit drugs (e.g., cocaine); or abuse or misuse of prescription drugs such as CNS stimulants.
Additional predisposing conditions include diabetes mellitus treated with oral hypoglycemic drugs or insulin; use of anorectic drugs; and excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates. Because the risk of seizure with bupropion is dose-related, screen patients for use of other bupropion-containing products prior to initiating AUVELITY [see Dosage and Administration ( 2.1 )] . If concomitant use of AUVELITY with other bupropion-containing products is clinically warranted, inform patients of the risk.
Discontinue AUVELITY and do not restart treatment if the patient experiences a seizure.
5.3Increased Blood Pressure and Hypertension
AUVELITY contains bupropion, which can cause elevated blood pressure and hypertension. The risk of hypertension is increased if AUVELITY is used concomitantly with MAOIs or other drugs that increase dopaminergic or noradrenergic activity [see Contraindications ( 4 ), Drug Interactions ( 7.1 )] . Data from a comparative trial of a sustained-release tablet formulation of bupropion HCl, nicotine transdermal system (NTS), the combination of sustained-release bupropion plus NTS, and placebo as an aid to smoking cessation suggest a higher incidence of hypertension in patients treated with the combination of sustained-release bupropion and NTS.
In this trial, 6.1% of subjects treated with the combination of sustained-release bupropion and NTS had hypertension compared with 2.5%, 1.6%, and 3.1% of subjects treated with sustained-release bupropion, NTS, and placebo, respectively. The majority of these subjects had evidence of pre-existing hypertension. Three subjects (1.2%) treated with the combination of sustained-release bupropion and NTS and 1 subject (0.4%) treated with NTS had study medication discontinued due to hypertension compared with none of the subjects treated with sustained-release bupropion or placebo.
Monitor blood pressure in patients who receive the combination of bupropion and nicotine replacement. In a clinical trial of an immediate-release bupropion tablet formulation in MDD subjects with stable congestive heart failure (N=36), bupropion was associated with an exacerbation of pre-existing hypertension in 2 subjects, leading to discontinuation of bupropion treatment. There are no controlled trials assessing the safety of bupropion in patients with a recent history of myocardial infarction or unstable cardiac disease.
Assess blood pressure prior to initiating treatment, and periodically monitor blood pressure during treatment with AUVELITY [see Dosage and Administration ( 2.1 )] .
5.4Activation of Mania or Hypomania
Antidepressant treatment can precipitate a manic, mixed, or hypomanic manic episode. The risk appears to be increased in pat
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Interactions
Strong CYP2D6 inhibitors: For patients with MDD or agitation associated with dementia due to Alzheimer’s disease, maximum recommended dosage is one tablet of 45 mg dextromethorphan hydrobromide/105 mg bupropion hydrochloride by mouth once daily in the morning. ( 2.5 , 7.1 ) Strong CYP2B6 inducers: Avoid use. ( 7.1 ) CYP2D6 Substrates: Increases the exposures of drugs that are substrates of CYP2D6. ( 7.1 ) Digoxin: May decrease plasma digoxin levels.
Monitor digoxin levels. ( 7.1 ) Drugs that lower seizure threshold: Coadministration may increase risk of seizure. ( 7.1 ) Dopaminergic drugs: Central Nervous System (CNS) toxicity can occur with concomitant use. ( 7.1 ) Drug-laboratory test interactions: AUVELITY can cause false-positive urine test results for amphetamines. ( 7.2 )
7.1Drugs 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 [see Dosage and Administration ( 2.7 ), Contraindications ( 4 ), Warnings and Precautions ( 5.3 , 5.8 )] 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 [see Dosage and Administration ( 2.1 ), Warnings and Precautions ( 5.8 )] . 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 [see Warnings and Precautions ( 5.2 )] .
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 [see Dosage and Administration ( 2.5 )] . 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 [see Clinical Pharmacology ( 12.3 )] . 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 [see Clinical Pharmacology ( 12.3 )] . 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.
7.2Drug-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.
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Pregnancy and breastfeeding
8.1Pregnancy 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 [see Warnings and Precautions ( 5.9 )] . 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 [OR] = 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 ge
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Adverse reactions
The following adverse reactions are discussed in more detail in other sections of the labeling: Suicidal Thoughts and Behaviors in Adolescents and Young Adults [see Warnings and Precautions ( 5.1 )] Seizure [see Warnings and Precautions ( 5.2 )] Increased Blood Pressure and Hypertension [see Warnings and Precautions ( 5.3 )] Activation of Mania or Hypomania [see Warnings and Precautions ( 5.4 )] Psychosis and Other Neuropsychiatric Reactions [see Warnings and Precautions ( 5.5 )] Angle-closure Glaucoma [see Warnings and Precautions ( 5.6 )] Dizziness [see Warnings and Precautions ( 5.7 )] Serotonin Syndrome [see Warnings and Precautions ( 5.8 )] Embryo-fetal Toxicity [see Warnings and Precautions ( 5.9 )] Hyponatremia [see Warnings and Precautions ( 5.10 )] MDD: Most common adverse reactions (≥5% and more than twice as frequently as placebo): dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and hyperhidrosis.
(6.1) Agitation associated with dementia due to Alzheimer’s disease: Most common adverse reactions (≥5% and more than twice as frequently as placebo): dizziness and dyspepsia. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Axsome Therapeutics at 1-800-484-1672 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical 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 [see Clinical Studies (Section 14.1 )].
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. [see Clinical Studies (Section 14.2 )] 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
6.2Postmarketing 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.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
