AUVELITY

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE AUVELITY is indicated for the treatment of major depressive disorder (MDD) in adults. 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 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION Prior to initiating treatment with AUVELITY: assess blood pressure; screen patients for history of bipolar disorder, mania, or hypomania; and determine if patients are receiving any other medications that contain bupropion or dextromethorphan. ( 2.1 ) Starting dosage is one tablet once daily in the morning. After 3 days, increase to the maximum recommended dosage of one tablet twice daily, separated by at least 8 hours. Do not exceed two doses within the same day. ( 2.2 ) Swallow tablets whole, do not crush, divide, or chew. ( 2.2 ) Moderate renal impairment: One tablet by mouth once daily in the morning. ( 2.3 , 8.6 ) CYP2D6 poor metabolizers: One tablet by mouth once daily in the morning. ( 2.5 , 8.8 , 12.3 ) 2.1 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 [see Warnings and Precautions ( 5.3 )] . screen patients for a personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions ( 5.4 )] . screen patients to determine if they are receiving any other medications that contain bupropion or dextromethorphan [see Warnings and Precautions ( 5.2 , 5.5 , 5.8 )] . 2.2 Recommended Dosage for the 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 [see Clinical Pharmacology ( 12.3 )] . Swallow tablets whole, do not crush, divide, or chew. 2.3 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 m 2 ) is one tablet once daily in the morning [see Use in Specific Populations ( 8.6 ), Clinical Pharmacology ( 12.3 )] . 2.4 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 [see Drug Interactions ( 7.1 ), Clinical Pharmacology ( 12.3 )] . 2.5 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 [see Use in Specific Populations ( 8.8 ), Clinical Pharmacology ( 12.3 )] . 2.6 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 [see Contraindications ( 4 ), Drug Interactions ( 7.1 )] . Warnings and cautions 5 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 ) 5.1 Suicidal 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 tho