bupropion (Rx)

>10%

Headache (25-34%)

Dry mouth (17-28%)

Nausea (1-18%)

Weight loss (15-20%)

Insomnia (11-20%)

Agitation (2-32%)

Dizziness (6-22%)

Pharyngitis (3-13%)

1-10%

Constipation (5-10%)

Infection (8-9%)

Abdominal pain (2-9%)

Anxiety (5-7%)

Diarrhea (5-7%)

Tinnitus (3-6%)

Tremor (3-6%)

Nervousness (3-5%)

Anorexia (3-5%)

Palpitation (2-6%)

Myalgia (2-6%)

Sweating (2-5%)

Rash (1-5%)

Sinusitis (1-5%)

Weight gain (4%)

Chest pain (3-4%)

Urinary frequency (2%)

Vaginal hemorrhage (2%)

Pruritus (2-4%)

Vomiting (2-4%)

Arthralgia (1-4%)

Flushing (1-4%)

Migraine (1-4%)

Decreased memory (<3%)

Irritability (2-3%)

Somnolence (2-3%)

Dysphagia (<2%)

Arthritis (2%)

Paresthesia (1-2%)

Fever (1-2%)

Twitch (1-2%)

Seizures (0.4% [<450 mg/day], >3% [>450 mg/day]; may be increased risk with concomitant ECT)

Frequency Not Defined

Confusion

Cystitis

Erythema

Ataxia

Coma

EEG abnormality

Euphoria

Gastric reflux

Postmarketing reports

Hyperglycemia

Hypoglycemia

Hyponatremia

Syndrome of inappropriate antidiuretic hormone secretion

Nervous system: Abnormal electroencephalogram (EEG), aggression, akinesia, aphasia, completed suicide, delirium, delusions, dysarthria, extrapyramidal syndrome (dyskinesia, dystonia, hypokinesia, parkinsonism), hallucinations, increased libido, manic reaction, neuralgia, neuropathy, paranoid ideation, restlessness, suicide attempt, and unmasking tardive dyskinesia

Contraindications

Hypersensitivity to bupropion or other ingredients

History of anorexia/bulimia; patients undergoing abrupt discontinuation of ethanol or sedatives including anticonvulsants, barbiturates, or benzodiazepines

Coadministration of any other medications that contain bupropion, because seizures are dose dependent

Aplenzin contraindications

• Seizure disorder or conditions that increase seizure risk (arteriovenous malformation, severe head injury, CNS tumor, CNS infection, severe stroke, anorexia nervosa or bulimia (current or prior diagnosis)

Coadministration with MAOIs

• Coadministration may cause serotonin syndrome
• Do not use concomitantly or initiate bupropion within 14 days of stopping an MAOI
• Conversely, at least 14 days should be allowed after stopping bupropion before starting an MAOI antidepressant
• Starting bupropion in a patient who is being treated with linezolid or IV methylene blue is contraindicated because of an increased risk of serotonin syndrome
• If linezolid or IV methylene blue must be administered, discontinue bupropion immediately and monitor for CNS toxicity; may resume 24 hr after last linezolid or methylene blue dose or after 2 weeks of monitoring, whichever comes first

Cautions

Caution in severe hepatic cirrhosis (do not exceed 150 mg every other day), mild-moderate hepatic impairment, head trauma and prior seizure history, CNS tumor, concomitant meds lowering seizure threshold

Observe patients for neuropsychiatric symptoms, such as changes in behavior, hostility, agitation, depressed mood, and suicide-related events, including ideation, behavior, and attempted suicide (see Black Box Warnings); therapy may cause delusions, hallucinations, psychosis, paranoia, confusion, and concentration disturbance; symptoms may abate with dose reduction

Healthcare provider should evaluate severity of adverse events and extent to which patient is benefiting from treatment, and consider options including continued treatment under closer monitoring, or discontinuing treatment; in many postmarketing cases, resolution of symptoms after discontinuation of bupropion reported; however, symptoms persisted in some cases; ongoing monitoring and supportive care should be provided until symptoms resolve

Potential risk of hepatotoxicity

Assess blood pressure before initiating treatment with sustained release formulation, and monitor periodically during treatment; risk of hypertension is increased if sustained release formulation is used concomitantly with MAOIs or other drugs that increase dopaminergic or noradrenergic activity; use caution in patients with cardiovascular disease

May cause weight loss; use caution if weight loss not desirable

May cause CNS depression and impair ability to operate heavy machinery

Extended-release: Do not administer less than 8 hr apart

Seizure risk is dose-related; can minimize risk by limiting daily dose to 522 mg and gradually increasing dose; discontinue permanently in patients who experience seizures

May cause sexual dysfunction

Screen patients for bipolar disorder and monitor for these symptoms; may precipitate manic, hypomanic or mixed episodes in patients with bipolar disorder

Instruct patients to contact a healthcare professional if neuropsychiatric reactions occur

Perform thorough cardiovascular assessment to identify risk factors of sudden cardiac death in pediatric ADHD patients

Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy; use caution

False-positive urine immunoassay screening tests for amphetamines have been reported; confirmatory test (eg, gas chromatography, mass spectrometry) will distinguish bupropion from amphetamines

Some patients who stopped smoking reported to have experienced symptoms of nicotine withdrawal, including depressed mood; depression, rarely including suicidal ideation, reported in smokers undergoing a smoking cessation attempt without medication; however, some of these adverse events occurred in patients taking bupropion who continued to smoke

Neuropsychiatric adverse events reported in patients without and with pre-existing psychiatric disease; some patients experienced worsening of their psychiatric illnesses; observe patients for occurrence of neuropsychiatric adverse events; patient should stop therapy and contact healthcare provider immediately if agitation, depressed mood, or changes in behavior or thinking that are not typical for patient are observed, or if patient develops suicidal ideation or suicidal behavior; symptoms may persist after discontinuation of therapy; in some cases; monitoring and supportive care should be provided until symptoms resolve

Bupropion hydrobromide extended-release tablets are intended for oral use only; inhalation of crushed tablets or injection of dissolved bupropion reported; seizures and/or cases of death reported when administered intranasally or by parenteral injection

Abuse warning

• XL and SR tablets are intended for oral use only
• Inhaling crushed tablets or injecting dissolved tablets has been reported to cause seizures and/or death

Pregnancy

There is an independent pregnancy exposure registry that monitors pregnancy outcomes in women exposed to any antidepressants during pregnancy; healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-4056185 or visiting online at https://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants

Data from epidemiological studies of pregnant women exposed to bupropion in first trimester have not identified an increased risk of congenital malformations overall; there are risks to the mother associated with untreated depression in pregnancy

A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants during pregnancy at 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 risks to the mother of untreated depression and potential effects on tfetus when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum

Animal data

• When bupropion was administered to pregnant rats during organogenesis, there was no evidence of fetal malformations at doses up to approximately 10 times maximum recommended human dose (MRHD) of 450 mg/day; when given to pregnant rabbits during organogenesis, non-dose–related increases in incidence of fetal malformations and skeletal variations were observed at doses approximately equal to the MRHD and greater; decreased fetal weights were seen at doses twice the MRHD and greater

Lactation

Data from published literature report presence of drug and its metabolites in human milk; there are no data on effects of bupropion or metabolites on milk production; limited data from postmarketing reports have not identified a clear association of adverse reactions in the breastfed infant; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from therapy or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Not well understood; structurally unrelated to SSRIs, TCAs, MAOIs; does not inhibit the activity of monoamine oxidase or the reuptake of serotonin

Norepinephrine dopamine reuptake inhibitor; may act through dopaminergic or noradrenergic pathways

Absorption

Peak serum time: 2 hr (immediate-release); 3 hr (extended-release)

Distribution

Protein bound: 84%

Vd: 20-47 L/kg

Metabolism

Hepatic, via CYP2B6

Metabolites: Hydroxybupropion (50% potency of parent compound)

Elimination

Half-life: 8-24 hr (immediate-release); 21 +/- 7 hr (extended-release)

Excretion: Urine (87%); feces (10%)

Oral Administration

Swallow extended/sustained-release tablets whole; do not chew, crush, or split; this may lead to adverse effects including seizures