MAOI and initiating bupropionselegiline transdermalContraindicated (1)selegiline transdermal and bupropion both increase dopaminergic effects. Contraindicated. Bupropion inhibits reuptake of dopamine and norepinephrine (NE), and MAOIs decrease metabolism of dopamine and NE; coadministration increases risk for hypertensive reactions; allow at least 14 days between discontinuation of MAOI and initiating bupropionsertralineMonitor Closely (2)bupropion will increase the level or effect of sertraline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. sertraline increases levels of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Sertraline may inhibit hydroxylation of bupropion to its major active metabolite hydroxybupropion.solriamfetolMonitor Closely (1)bupropion and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.sorafenibMonitor Closely (1)sorafenib, bupropion. decreasing metabolism. Use Caution/Monitor. Incr levels of bupropion, but decr levels of active metabolites. .sparsentanMonitor Closely (1)sparsentan will decrease the level or effect of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Sparsentan (a CYP2B6 inducer) decreases exposure of CYP2B6 substrates and reduces efficacy related to these substrates.stiripentolMonitor Closely (1)stiripentol, bupropion. affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP2B6 inhibitor and inducer. Monitor CYP2B6 substrates coadministered with stiripentol for increased or decreased effects. CYP2B6 substrates may require dosage adjustment.sufentanil SLMonitor Closely (1)sufentanil SL, bupropion. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.tamoxifenMonitor Closely (2)bupropion decreases effects of tamoxifen by decreasing metabolism. Use Caution/Monitor. Inhibition of CYP2D6 metabolism to tamoxifen's active metabolite, endoxifen. bupropion will decrease the level or effect of tamoxifen by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Inhibition of CYP2D6 decreases metabolism of tamoxifen to active metabolite, endoxifentamsulosinMonitor Closely (1)bupropion increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.tapentadolMonitor Closely (1)bupropion and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.tedizolidSerious - Use Alternative (1)tedizolid, bupropion. Either increases levels of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. both increase serotonin levels; increased risk of serotonin syndrome.telotristat ethylMonitor Closely (1)telotristat ethyl will decrease the level or effect of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Consider increasing dosage of interacting drug, if necessarytemocillinMonitor Closely (1)temocillin increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.theophyllineSerious - Use Alternative (1)theophylline increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.thioridazineSerious - Use Alternative (1)bupropion will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.Minor (1)thioridazine increases toxicity of bupropion by unspecified interaction mechanism. Minor/Significance Unknown. May lower seizure threshold; keep bupropion dose as low as possible.ticarcillinMonitor Closely (1)ticarcillin increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.timololMonitor Closely (1)bupropion will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.tolterodineMonitor Closely (1)bupropion will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.tramadolMonitor Closely (1)bupropion will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.tranylcypromineContraindicated (1)tranylcypromine and bupropion both increase dopaminergic effects. Contraindicated. Bupropion inhibits reuptake of dopamine and norepinephrine (NE), and MAOIs decrease metabolism of dopamine and NE; coadministration increases risk for hypertensive reactions; allow at least 14 days between discontinuation of MAOI and initiating bupropiontrazodoneSerious - Use Alternative (1)trazodone increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.trifluoperazineMonitor Closely (1)bupropion will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Minor (1)trifluoperazine increases toxicity of bupropion by unspecified interaction mechanism. Minor/Significance Unknown. May lower seizure threshold; keep bupropion dose as low as possible.trimipramineMonitor Closely (2)trimipramine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible. bupropion will increase the level or effect of trimipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.tropisetronMinor (1)bupropion will increase the level or effect of tropisetron by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.valbenazineMonitor Closely (1)bupropion will increase the level or effect of valbenazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Consider reducing valbenazine dose based on tolerability if coadministered with a strong CYP2D6 inhibitor.venlafaxineMonitor Closely (1)bupropion will increase the level or effect of venlafaxine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)venlafaxine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.vortioxetineSerious - Use Alternative (1)bupropion, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug. >10% Nausea (32.5%) Constipation (19.2%) Headache (17.6%) Vomiting (10.7%) 1-10% Dizziness (9.9%) Insomnia (9.2%) Dry mouth (8.1%) Diarrhea (7.1%) Anxiety (4.2%) Hot flash (4.2%) Fatigue (4%) Tremor (4%) Upper abdominal pain (3.5%) Viral gastroenteritis (3.5%) Influenza (3.4%) Tinnitus (3.3%) Urinary tract infection (3.3%) Hypertension (3.2%) Abdominal pain (2.8%) Hyperhidrosis (2.6%) Irritability (2.6%) Increased blood pressure (2.4%) Dysgeusia (2.4%) Rash (2.4%) Muscle strain (2.2%) Palpitations (2.1%) Frequency Not Defined Tachycardia Myocardial infarction Vertigo Motion sickness Lower abdominal pain Eructation Lip swelling Hematochezia Hernia Feeling jittery Thirst Feeling hot Asthenia Cholecystitis Pneumonia Staphylococcal infection Kidney infection Increased creatinine clearance Increased hepatic enzymes Decreased hematocrit Dehydration Intervertebral disc protrusion Jaw pain Disturbance in attention Lethargy Intention tremor Balance disorder Memory impairment Amnesia Mental impairment Presyncope Abnormal dreams Nervousness Dissociation (feeling spacy) Tension Agitation Mood swings Vaginal hemorrhage Irregular menstruation Erectile dysfunction Vulvovaginal dryness Alopecia Postmarketing Reports Loss of consciousness, malaise Black Box Warnings Not approved for treatment of major depressive disorder or psychiatric disorders Antidepressants like bupropion increase the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials but were not seen in patients ≥24 years and a lower risk was seen in patients ≥65 years; patients of all ages should be monitored closely for suicidal thoughts and behaviors Serious neuropsychiatric reactions reported in patients taking bupropion for smoking cessation that occurred during therapy or while discontinuing therapy; patients should be monitored for neuropsychiatric reactionsContraindications Uncontrolled hypertension Seizure disorder or a history of seizures Use of other bupropion-containing products Bulimia or anorexia nervosa, which may increase risk of seizures Long-term opioid or opiate agonists use or acute opiate withdrawal Patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs Within 14 days of monoamine oxidase inhibitor therapy Hypersensitivity Pregnancy Cautions Monitor patients for suicidal ideation or behavior and for unusual changes in behavior (see black box warning) Discontinue therapy and do not restart if seizure occurs while on therapy; use caution when prescribing to patients with predisposing risk factors for seizures Not for administration to patients receiving long-term opioids, owing to naltrexone component (opioid antagonist); discontinue therapy if long-term opiate therapy required Following therapy, patients may be more sensitive to opioids, even at lower doses A patient should not attempt to overcome naltrexone opioid blockade by administering large amounts of exogenous opioids; may lead to fatal overdose Opioid-dependent patients, including those being treated for alcohol dependence, should be opioid-free (including tramadol) before therapy is initiated; opioid-free interval of a minimum of 7-10 days is recommended for patients previously dependent on short-acting opioids; patients transitioning from buprenorphine or methadone may need as long as 2 weeks Blood pressure and pulse should be measured prior to starting therapy and should be monitored at regular intervals, particularly among patients with controlled hypertension prior to treatment Discontinue therapy if symptoms or signs of acute hepatitis occur Screen patients for a history of bipolar disorder and the presence of risk factors for bipolar disorder; therapy was not studied in patients receiving antidepressant medications patients with a history of bipolar disorder or recent hospitalization foor psychiatric illness were excluded from clinical trials Angle-closure attack may occur in patients with anatomically narrow angles that do not have a patent iridectomy Measure blood glucose levels prior to and during therapy; patients who develop hypoglycemia after initiating Contrave therapy should adjust antidiabetic drug regimen Use caution in patients with history of tumor or infection of the brain or spine Initiation of therapy in patients receiving linezolid or intravenous (IV) methylene blue Use caution in hepatic impairment May precipitate a manic, mixed, or hypomanic episode; risk higher in patients with bipolar disorders or have risk factors for bipolar disorder, including family history of bipolar disorder, suicide, or depression; not FDA approved for bipolar depression 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 Pregnancy Weight loss offers no benefit to a pregnant patient and may cause fetal harm; when a pregnancy is recognized, advise pregnant patient of risk to fetus, and discontinue therapy; available pharmacovigilance data and data from clinical trials with individual components of combination drug use in pregnant patients have not demonstrated a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes Bupropion Data from epidemiological studies of pregnant patients exposed to bupropion in first trimester have not identified an increased risk of congenital malformations overall When bupropion was administered to pregnant rats during organogenesis, there was no evidence of fetal malformations at doses up to approximately 20 times maximum recommended human dose (MRHD) of 360 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 twice the MRHD and greater; decreased fetal weights were seen at doses 5 times MRHD and greater Naltrexone Limited case report data of pregnant patients exposed to naltrexone in first trimester have not identified an increased risk of congenital malformations overall; daily oral administration of naltrexone during period of organogenesis has been shown to increase incidence of early fetal loss in rats and rabbits at doses ≥15 times and ≥60 times MRHD of 32 mg/day respectively There was no evidence of fetal malformations in rats and rabbits at doses up to approximately 100 and 200 times the MHRD, respectively Appropriate weight gain based on pre-pregnancy weight is currently recommended for all pregnant patients, including those who are already overweight or obese, due to obligatory weight gain that occurs in maternal tissues during pregnancy Lactation Data from published literature report the presence of bupropion and its metabolites in human milk Limited data from postmarketing reports with bupropion use during lactation have not identified a clear association of adverse effects on a breastfed infant Naltrexone and its major metabolite, 6 β-naltrexol, are present in human milk; there are no data on bupropion, naltrexone, or their metabolites on milk production; the developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from drug combination or from mother’s underlying conditionPregnancy 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 Bupropion: Increases dopamine