AUVELITY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AUVELITY (AUVELITY).
AUVELITY (dextromethorphan HBr and bupropion HCl) is an NMDA receptor antagonist (via dextromethorphan) and a norepinephrine-dopamine reuptake inhibitor (via bupropion). Dextromethorphan also modulates sigma-1 receptor activity.
| Metabolism | Dextromethorphan is metabolized primarily by CYP2D6 to dextrorphan. Bupropion is extensively metabolized by CYP2B6 to hydroxybupropion, and to a lesser extent by CYP2C19, CYP2C9, and CYP3A4. |
| Excretion | Renal 81% (dextromethorphan and metabolites: 78% as unchanged drug and 3% as dextrorphan conjugates), fecal 9% (dextromethorphan and metabolites), biliary <1% |
| Half-life | Dextromethorphan: 13.5 hours (terminal half-life; prolonged due to CYP2D6 inhibition by bupropion, allowing sustained NMDA antagonism; bupropion: 13.7 hours) |
| Protein binding | Dextromethorphan: 60-70% bound to albumin; bupropion: 84% bound to albumin (highly protein bound; clinical significance minimal) |
| Volume of Distribution | Dextromethorphan: 5.3-6.4 L/kg (large Vd indicating extensive tissue distribution, crossing blood-brain barrier); bupropion: 20-25 L/kg (very large Vd due to lipophilicity and tissue binding) |
| Bioavailability | Oral: Dextromethorphan bioavailability is low (~3-5%) due to extensive first-pass metabolism; bupropion bioavailability is ~20% due to first-pass effect. Auvelity formulation (dextromethorphan + bupropion) increases dextromethorphan bioavailability via CYP2D6 inhibition |
| Onset of Action | Oral: Not rapidly achieved; therapeutic effects (antidepressant) may require 2-4 weeks of daily dosing; single-dose receptor occupancy maximal at 6-8 hours |
| Duration of Action | 24 hours (once-daily dosing; steady-state achieved within 7 days; clinical effect sustained over 24 hours due to long half-life of active component) |
45 mg orally once daily, given as dextromethorphan hydrobromide 45 mg and bupropion hydrochloride 105 mg combination tablet.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | eGFR 30-59 mL/min/1.73m2: 45 mg once daily; eGFR 15-29 mL/min/1.73m2: not recommended; eGFR <15 mL/min/1.73m2: contraindicated. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: not recommended; Child-Pugh Class C: contraindicated. |
| Pediatric use | Not approved for use in pediatric patients. Safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required. Monitor for increased sensitivity to anticholinergic effects (bupropion) and dissociative effects (dextromethorphan). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AUVELITY (AUVELITY).
| Breastfeeding | Excreted in human milk; M/P ratio not determined. Potential for serious adverse reactions in nursing infant, including serotonin syndrome. Decision to discontinue nursing or drug based on importance to mother. Use caution. |
| Teratogenic Risk | First trimester: No adequate studies; animal studies show no teratogenic effects at clinically relevant doses. Second and third trimesters: No reported fetal abnormalities; potential risk of neonatal serotonin syndrome if used near term due to SSRI component (dextromethorphan/bupropion). Avoid in third trimester unless benefit outweighs risk. |
■ FDA Black Box Warning
WARNING: SUICIDAL THOUGHTS AND BEHAVIORS; AND NEUROPSYCHIATRIC REACTIONS. Antidepressants increased the risk of suicidal thoughts and behaviors in children, adolescents, and young adults. Bupropion is associated with neuropsychiatric reactions including mania, psychosis, and suicidal ideation in patients with bipolar disorder. Close monitoring is required.
| Serious Effects |
["Concomitant use with MAOIs or within 14 days of MAOI discontinuation","Concomitant use with other bupropion-containing products","Seizure disorder or history of seizures","Current or prior diagnosis of bulimia or anorexia nervosa","Known hypersensitivity to bupropion or dextromethorphan","Concomitant use with linezolid or intravenous methylene blue"]
| Precautions | ["Suicidality risk: Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients. Monitor closely.","Neuropsychiatric reactions: Mania, psychosis, and suicidal ideation, especially in bipolar patients.","Seizure risk: Dose-related; avoid in patients with seizure disorders or conditions lowering seizure threshold.","Increased blood pressure: Monitor blood pressure, especially in patients with hypertension.","Angle-closure glaucoma: May cause mydriasis; avoid in untreated narrow-angle glaucoma.","Serotonin syndrome: Risk when coadministered with other serotonergic drugs.","Anticholinergic effects: Dextromethorphan has anticholinergic properties; use caution with other anticholinergics."] |
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| Fetal Monitoring | Monitor for signs of serotonin toxicity in mother (agitation, hyperthermia, clonus). Assess fetal growth if prolonged use. Monitor neonate for respiratory depression, feeding difficulties, and serotonin syndrome after delivery if used late in pregnancy. |
| Fertility Effects | No human data on fertility; animal studies showed no impairment at doses up to 1.6 times MRHD. Potential for reduced fertility due to hyperprolactinemia from dopamine reuptake inhibition (bupropion component). |
| Food/Dietary | No specific food interactions have been reported. However, grapefruit juice may increase dextromethorphan levels via CYP3A4 inhibition, though clinical significance is unclear; caution advised. Avoid excessive caffeine intake as bupropion may increase caffeine levels and risk of seizures. |
| Clinical Pearls | Auvelity (dextromethorphan/bupropion) is a rapid-acting oral antidepressant approved for major depressive disorder. Onset of benefit may be seen within 1 week. It combines dextromethorphan (NMDA receptor antagonist/σ1 agonist) with bupropion (CYP2D6 inhibitor) to increase dextromethorphan exposure. Bupropion component also provides norepinephrine-dopamine reuptake inhibition. Avoid in patients with seizure disorders, eating disorders, or abrupt discontinuation of alcohol/benzodiazepines. Monitor for hypertension, suicidality, and serotonin syndrome. CYP2D6 poor metabolizers may have higher dextromethorphan levels; consider dose adjustment. |
| Patient Advice | Take one tablet once daily for 3 days, then increase to one tablet twice daily (at least 8 hours apart). · Swallow tablets whole; do not crush, chew, or divide. · Do not take with other bupropion-containing products or MAOIs. · May cause dizziness, headache, or insomnia; avoid driving until you know how it affects you. · Report new or worsening depression, suicidal thoughts, or unusual changes in mood or behavior. · Avoid alcohol while taking this medication. · If you miss a dose, skip it and take the next dose at the scheduled time; do not double up. · Do not stop abruptly without consulting your healthcare provider. |