Dextromethorphan-Bupropion

Dextromethorphan-Bupropion is a combination medication used for the treatment of Major Depressive Disorders.  

• Dextromethorphan-Bupropion is available under the following different brand names: Auvelity.

Common side effects of Dextromethorphan-Bupropion include:

• increased urination, 
• vaginal itching, 
• pain during sexual intercourse, 
• pain or discomfort when urinating, 
• abnormal vaginal discharge, 
• pelvic pain, 
• increased urge to urinate, 
• blood in your urine, 
• back pain, 
• nausea, 
• vomiting, and 
• fever

Serious side effects of Dextromethorphan-Bupropion include:

• hives, 
• difficulty breathing, 
• swelling of the face, lips, tongue, or throat, 
• nausea, 
• vomiting, 
• abdominal pain, 
• feeling unwell, 
• shortness of breath, 
• fever, 
• chills, 
• pain and swelling in legs, arms, or spine, 
• sores or ulcers of the legs or feet, 
• leg pain or tenderness, 
• low blood pressure,  
• abnormal lab results (creatinine levels), 
• confusion, 
• fast heartbeat, 
• shakiness, 
• anxiety, 
• lightheadedness, 
• hunger, 
• dizziness, 
• irritability, 
• sweating, 
• pain or tenderness, swelling, redness in the genital or perineal area, 
• vaginal itching, 
• pain during sexual intercourse, 
• pain or discomfort when urinating, and
• abnormal vaginal discharge

Rare side effects of Dextromethorphan-Bupropion include:

• None 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out. 

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet, extended-release

• 45 mg/105 mg

Major Depressive Disorders

Adult dosage

• 1 tablet orally every day in the morning for 3 days, then increase to 1 tablet twice daily given at least 8 hours apart
• Maximum recommended dose: 1 tablet twice daily; do not exceed 2 doses/24 hr

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Dextromethorphan-Bupropion has severe interactions with the following drugs:
  • eliglustat
  • isocarboxazid
  • phenelzine
  • pimozide
  • procarbazine
  • rasagiline
  • safinamide
  • selegiline
  • selegiline
  • selegiline transdermal
  • tranylcypromine
• Dextromethorphan-Bupropion has serious interactions with at least 52 other drugs.
• Dextromethorphan-Bupropion has moderate interactions with at least 165 other drugs.
• Dextromethorphan-Bupropion has minor interactions with at least 40 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Seizure disorders
• Current or prior diagnosis of bulimia or anorexia nervosa (higher incidence of seizures with immediate-release bupropion)
• Abrupt discontinuance of alcohol, benzodiazepine, barbiturates, or antiepileptic drugs
• Taking, or within 14 days of stopping, MAOIs; starting Dextromethorphan-Bupropion in patients treated with reversible MAOIs (eg, linezolid, IV methylene blue)
• Known hypersensitivity to bupropion, dextromethorphan, or other components

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Dextromethorphan-Bupropion?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Dextromethorphan-Bupropion?”

Cautions

• Serotonin syndrome reported; if concomitant use of this medication with other serotonergic drugs clinically warranted, inform patients of increased risk for serotonin syndrome and monitor for symptoms; discontinue treatment and/or concomitant serotonergic drug immediately if above symptoms occur, and initiate supportive symptomatic treatment
• Bupropion may elevate blood pressure; the risk of hypertension increased if coadministered with MAOIs or other drugs that increase dopaminergic or noradrenergic activity
• Caution with angle-closure glaucoma; pupillary dilation that occurs following the use of many antidepressant drugs, including bupropion, may trigger an angle-closure attack in patients with anatomically narrow angles who do not have a patent iridectomy
• May cause dizziness; take precautions to reduce falls and caution patients regarding operating hazardous machinery, including motor vehicles, until they are reasonably certain that therapy does not affect them adversely
• May cause fetal harm; use alternate treatment for females planning to become pregnant
• Suicidality
  • In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (aged below 24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses; this increase was not seen in patients aged above 24 years
  • Closely monitor all antidepressant-treated patients for clinical worsening and for the emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, as well as at times of dosage changes
  • Counsel family members or caregivers of patients to monitor for changes in behavior and to alert healthcare provider; consider changing therapeutic regimen, including possibly discontinuing therapy, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors
• Psychosis/neuropsychiatric reactions
  • Bupropion: Depressed patients treated with bupropion have had a variety of neuropsychiatric signs and symptoms, including delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion; symptoms may abate with dose reduction and/or treatment withdrawal
  • Dextromethorphan: Overdose can cause toxic psychosis, stupor, coma, and hyperexcitability
  • Antidepressants can precipitate manic, mixed, or hypomanic manic episodes; risk increased in patients who have bipolar disorder or have risk factors for bipolar disorder
  • Screen patients for bipolar disorder and use other bupropion- or dextromethorphan-containing products before initiating
• Seizures
  • Bupropion can cause seizure; risk of seizure with bupropion is dose-related; use contraindicated in patients with seizures
  • If concomitant use of this medication with other bupropion-containing products is clinically warranted, inform patients of the risk; discontinue therapy, and do not restart treatment if the patient experiences a seizure
• Drug interaction overview
  • Bupropion (and metabolites): CYP2D6 inhibitor; CYP2B6 substrate
  • Dextromethorphan: CYP2D6 substrate (major)
  • MAOIs
  • Contraindicated
    • Coadministration (or within 14 days) increases the risk of hypertensive crisis and serotonin syndrome
  • Serotonin syndrome
    • Monitor for symptoms of serotonin syndrome
    • Coadministration with other serotonergic drugs (eg, SSRIs, TCAs) increases the risk of serotonin syndrome, a potentially life-threatening condition with changes that include altered mental status, hypertension, restlessness, myoclonus, hyperthermia, hyperreflexia, diaphoresis, shivering, and tremor
  • Drugs that lower the seizure threshold
    • Caution
      • Bupropion can cause seizure; coadministration with other drugs that lower seizure threshold may increase the risk
      • If a seizure occurs, discontinue Dextromethorphan-Bupropion and do not restart
  • Strong CYP2D6 inhibitor
    • Modify (decrease) Dextromethorphan-Bupropion dose
    • Strong CYP2D6 inhibitors increase dextromethorphan plasma concentrations, which may result in somnolence and dizziness
  • Strong CYP2B5 inducers
    • Avoid
      • Strong CYP2B6 inducers decrease plasma concentrations of bupropion
  • CYP2D6 substrates
    • May need to modify the dose of CYP2D6 substrate
    • Bupropion may increase the systemic exposure of CYP2D6 substrates; dose modification of CYP2D6 substrates with narrow therapeutic indexes may be necessary
    • Conversely, drugs requiring metabolic activation by CYP2D6 may have reduced efficacy and require an increased dose
  • Digoxin
    • Monitor digoxin levels
    • Coadministration may decrease plasma digoxin levels
    • Digoxin exposure was decreased when a single oral dose of 0.5-mg digoxin was administered 24 hr after a single oral dose of extended-release 150 mg bupropion in healthy volunteers
  • Dopaminergic drugs
  • Caution
    • Coadministration of levodopa or amantadine with bupropion may cause CNS toxicity, including restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness
  • Alcohol
    • Avoid alcohol during treatment
    • Bupropion can increase adverse neuropsychiatric events or reduce alcohol tolerance

Pregnancy and Lactation

• Not recommended during pregnancy
• Based on animal studies, may cause fetal harm when administered during pregnancy
• Encourage patients to register for the National Pregnancy Registry for Antidepressants at 1-866-961-2388 or online at womensmentalhealth.org/research/pregnancyregistry/antidepressants/
• Clinical considerations
  • 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
  • Women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants
  • Consider maternal risks of untreated depression and potential effects on the fetus when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum
• Lactation
• Owing to the potential for neurotoxicity, advise patients that breastfeeding is not recommended during treatment and for 5 days after the final dose
  • Dextromethorphan
    • Neurotoxicity was observed in juvenile rats treated with dextromethorphan/quinidine on postnatal day 7, which corresponds to the third trimester of gestation through the first few months of life and may extend through the first 3 years of human life
    • Unknown if dextromethorphan is present in human milk; data are not available regarding effects on the breastfed infant or on milk production
  • Bupropion
    • There are no data on the effects of bupropion or its metabolites on milk production
    • Data from postmarketing reports are limited; use in lactating patients has not identified a clear association of adverse reactions in the breastfed infant