Auvelity

Auvelity is a prescription medicine used to treat the symptoms of major depressive disorder in adults.

Auvelity may be used alone or with other medications.

Auvelity belongs to a class of drugs called dopamine/norepinephrine reuptake inhibitors; NMDA antagonists.

It is not known if Auvelity is safe and effective in children.

SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and emergence of suicidal thoughts and behaviors. Auvelity is not approved for use in pediatric patients.

Auvelity may cause serious side effects including:

• hives,
• difficulty breathing,
• swelling of your face, lips, tongue, or throat,
• thoughts of self-harm,
• new or worsening depression or anxiety,
• agitation,
• restlessness,
• difficulty sleeping (insomnia),
• aggression,
• panic attacks,
• new or worsening irritability,
• impulsive behavior,
• unusual changes in behavior or mood,
• seizures,
• high blood pressure,
• greatly increased energy,
• racing thoughts,
• unusual grand ideas,
• talking more or faster,
• severe trouble sleeping,
• reckless behavior,
• excessive happiness or irritability,
• changes in your vision,
• swelling or redness of your eye,
• dizziness,
• hallucinations,
• confusion,
• coma,
• fast heartbeat,
• blood pressure changes,
• sweating,
• flushing,
• high body temperature,
• shaking (tremors),
• stiff muscles,
• muscle twitching,
• loss of coordination,
• nausea,
• vomiting, and
• diarrhea

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of Auvelity include:

• dizziness,
• headache,
• diarrhea,
• sleepiness,
• dry mouth,
• sexual function problems, and
• excessive sweating  

Tell the doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Auvelity. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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 Treatment Of Major Depressive Disorder

• The recommended starting dosage of Auvelity (45 mg of dextromethorphan hydrobromide and 105 mg of bupropion hydrochloride) is one tablet once daily in the morning. After 3 days, 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.

Dosage Recommendations In Patients With Renal Impairment

• The recommended dosage of Auvelity for patients with moderate renal impairment (eGFR 30 to 59 mL/minute/1.73 m²) is one tablet once daily in the morning.

Dosage Recommendations For Concomitant Use With Strong CYP2D6 Inhibitors

• The recommended dosage of Auvelity when co-administered with strong CYP2D6 inhibitors is one tablet once daily in the morning.

Dosage Recommendations For Known CYP2D6 Poor Metabolizers (PMs)

• The recommended dosage for patients known to be poor CYP2D6 metabolizers is one tablet once daily in the morning.

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.

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.

Drug Abuse And Dependence

Controlled Substance

• Auvelity contains dextromethorphan and bupropion which are not controlled substances.

Abuse

• Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects.
• Auvelity has not been systematically studied in animals or humans for its potential for abuse, tolerance, or physical dependence. However, Auvelity is a combination product containing dextromethorphan and bupropion, and cases of dextromethorphan abuse have been reported.
• While clinical studies with Auvelity did not reveal drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this experience the extent to which Auvelity will be misused, diverted, and/or abused once marketed. Therefore, patients with a history of drug abuse should be observed closely for signs of Auvelity misuse or abuse (e.g., development of tolerance, increases in dose, drug-seeking behavior).
• Auvelity is intended for oral use only. Seizures and/or cases of death have been reported when bupropion has been administered intranasally or by parenteral injection.

Dextromethorphan

• Dextromethorphan has not been systematically studied in animals or humans for its potential for abuse, tolerance, or physical dependence. Cases of dextromethorphan abuse have been reported, predominantly in adolescents.

Bupropion

• Controlled clinical trials conducted in normal volunteers, in subjects with a history of multiple drug abuse, and in depressed subjects showed some increase in motor activity and agitation/excitement, often typical of central stimulant activity.
• In a population of individuals experienced with drugs of abuse, a single oral dose of 400 mg of bupropion (approximately 1.9 times the maximum recommended daily dosage of Auvelity) produced mild amphetamine-like activity as compared with placebo on the Morphine-Benzedrine Subscale of the Addiction Research Center Inventories (ARCI) and a score intermediate between placebo and amphetamine on the Liking Scale of the ARCI. These scales measure general feelings of euphoria and drug liking which are often associated with abuse potential.
• Findings in clinical trials, however, are not known to reliably predict the abuse potential of drugs. Nonetheless, evidence from single-dose studies does suggest that the recommended daily dosage of bupropion when administered in divided doses is not likely to be significantly reinforcing to people who abuse amphetamines or CNS stimulants. However, higher doses (which could not be tested because of the risk of seizure) might be modestly attractive to those who abuse CNS stimulant drugs.

Drugs Having Clinically Important Interactions With Auvelity

Table 3: Clinically Important Drug Interactions with Auvelity

• 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.
• 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/.
• Advise patients not to breastfeed during treatment with Auvelity and for 5 days after the final dose.
• Data from published literature report the presence of bupropion and its metabolites in human milk. There are no data on the effects of bupropion or its metabolites on milk production. Limited data from postmarketing reports of bupropion use in lactating patients have not identified a clear association of adverse reactions in the breastfed infant.

Do not take Auvelity if you:

• have or had a seizure disorder
• have or had an eating disorder such as anorexia nervosa or bulimia
• have recently suddenly stopped drinking alcohol or use medicines called benzodiazepines, barbiturates, or antiseizure medicines, and you have recently suddenly stopped taking them.
• take a monoamine oxidase inhibitor (MAOI)
• have stopped taking an MAOI in the last 14 days
• are being treated with the antibiotic linezolid or intravenous methylene blue
• are allergic to dextromethorphan, bupropion, or any of the ingredients in Auvelity. See the end of this Medication Guide for a complete list of ingredients in Auvelity.

Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI or one of these medicines, including the antibiotic linezolid or intravenous methylene blue.

Do not start Auvelity if you stopped taking an MAOI in the last 14 days.

Do not start taking an MAOI for at least 14 days after you stop treatment with Auvelity.

Before taking Auvelity, tell your healthcare provider about all your medical conditions, including if you:

• have or had seizures or convulsions
• have had a head injury
• have had a heart attack or have heart problems
• have a tumor in your nervous system (brain or spine)
• have had a stroke
• have low blood sugar
• have low sodium levels in your blood
• have liver problems
• have kidney problems
• drink a lot of alcohol
• abuse prescription medicines or street drugs
• have diabetes and take oral diabetes medicines or use insulin to control your blood sugar
• have high blood pressure
• have history of falls
• have or had bipolar disorder, or have a family history of bipolar disorder, suicide, or depression
• have high pressure in the eye (glaucoma)
• are pregnant or plan to become pregnant. Auvelity may harm your unborn baby if you take Auvelity during pregnancy. Auvelity is not recommended during pregnancy.
  • Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with Auvelity. Your healthcare provider will prescribe another treatment for females who plan to become pregnant.
  • There is a pregnancy registry for females who are exposed to Auvelity during pregnancy. The purpose of the registry is to collect information about the health of females exposed to Auvelity and their baby. If you become pregnant during treatment with Auvelity, talk to your healthcare provider about registering with the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visit online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/.
• are breastfeeding or plan to breastfeed. One of the ingredients in Auvelity, bupropion, passes into your breast milk. Do not breastfeed during treatment with Auvelity and for 5 days after the final dose.