Dextromethorphan; bupropion is an oral combination product indicated for the treatment of major depressive disorder in adults. Dextromethorphan is a noncompetitive N-methyl D-aspartate (NDMA) receptor antagonist and sigma-1 receptor agonist and bupropion is an antidepressant from the aminoketone class and a CYP2D6 inhibitor. When used together, bupropion inhibits the metabolism of dextromethorphan, increasing serum levels and clinical effect. The combination was demonstrated to be effective in a placebo-controlled trial that included adult patients who met DSM-5 criteria for major depressive disorder (MDD). Patients received 45 mg dextromethorphan/105 mg bupropion orally twice daily or placebo for 6 weeks. The primary outcome measure was change from baseline to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. Study results indicate that dextromethorphan; bupropion was statistically significantly superior to placebo in improvement in depressive symptoms as measured by decrease in total MADRS score at week 6. Of note, the change in MADRS total score from baseline to week 1 and baseline to week 2 were statistically significant. This rapid onset of symptom improvement is different from other antidepressant medications on the market, which often take 4 to 6 weeks to take effect. In a second, 6-week study of adult patients with MDD, 45 mg dextromethorphan/105 mg bupropion orally twice daily was compared to 105 mg bupropion sustained-release orally twice daily. The primary outcome was change from baseline MADRS total score over the 6-week period. Outcomes from the study indicate that dextromethorphan contributes to the antidepressant efficacy of dextromethorphan; bupropion. The most common side effects of dextromethorphan; bupropion include dizziness, drowsiness, headache, dry mouth, diarrhea, sexual dysfunction, and hyperhidrosis. Dosage adjustments are needed for patients with moderate renal impairment or patients who are CYP2D6 poor metabolizers; avoid use in patients with severe hepatic or severe renal impairment. Since bupropion may cause seizure, dextromethorphan; bupropion is contraindicated in patients with a seizure disorder, a current or prior diagnosis of bulimia or anorexia nervosa, and those who are undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic medications. Dextromethorphan; bupropion was FDA approved in August 2022.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
-A MedGuide is available which informs patients about the increased risk of suicidal thoughts and behaviors in children and young adults during early phase treatment with antidepressants.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-May administer with or without food.
-Swallow tablets whole; do not crush, chew, or split.
-When administered twice daily, doses should be given at least 8 hours apart.
-If a dose is missed, skip the dose and take the next dose at the regular time. Do not take extra doses or more than 1 dose at a time.
In a 6-week placebo-controlled study, some of the most common side effects associated with dextromethorphan; bupropion use were dizziness (16% vs 6% with placebo), headache (8% vs 4%), and somnolence or drowsiness (7% vs 3%). Additional adverse effects reported during the study were insomnia (4% with dextromethorphan; bupropion vs 2% with placebo), fatigue or lethargy (3% vs 2%), and paresthesias, including hypoaesthesia, (3% vs 0%). Other neurologic symptoms reported with postmarketing use of dextromethorphan include drowsiness, dizziness, and restlessness or nervousness. Postmarketing adverse effects reported with bupropion include abnormal EEG changes, akinesia, aphasia, coma, dysarthria, extrapyramidal symptoms (such as dyskinesia, dystonia, hypokinesia, and pseudoparkinsonism), unmasking tardive dyskinesia, restlessness, neuropathy, and neuralgia (neuropathic pain).
The most common gastrointestinal adverse effects associated with dextromethorphan; bupropion were nausea (13% vs 9% with placebo), diarrhea (7% vs 3%), xerostomia (6% vs 2%), constipation (4% vs 2%), and decreased appetite or anorexia (4% vs 1%). Postmarketing adverse effects with the use of dextromethorphan include nausea, vomiting, and stomach or abdominal pain. Adverse Effects reported with postmarketing use of bupropion include colitis, esophagitis, GI bleeding, gum hemorrhage, hepatitis, intestinal or GI perforation, pancreatitis, and stomach ulcer.
The most commonly reported psychiatric adverse reaction during a 6-week placebo-controlled trial of dextromethorphan; bupropion was anxiety, affecting 4% of patients on the combination treatment (vs 1% on placebo). The adverse reaction that led to study discontinuation in 1% or more of patients treated with dextromethorphan; bupropion was anxiety (2%). Postmarketing experience with dextromethorphan has resulted in reports of increased nervousness or restlessness. Adverse reactions reported with postmarketing use of bupropion include agitation, aggression, delirium, delusions, euphoria, hallucinations, hostility, panic, paranoia (paranoid ideation), and psychosis. Due to the voluntary nature of postmarketing reports, neither causality nor the incidence can be established.
Monitor all patients treated with an antidepressant for any indication for worsening of depression or the condition being treated and the emergence of suicidal behaviors or suicidal ideation, especially during the initial few months of drug therapy and after dosage changes. In a pooled analysis of placebo controlled trials of antidepressants (n = 4,500 pediatric patients and 77,000 adult patients), there was an increased risk for suicidal thoughts and behaviors in patients 24 years of age and younger receiving an antidepressant versus placebo, with considerable variation in the risk of suicidality among drugs. The difference in the absolute risk of suicidal thoughts and behaviors across different indications was highest in those with major depression. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over 24 years of age; there was a reducton in risk with antidepressant use in patients aged 65 and older. It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term use (i.e., beyond 4 months). In adults with major depression, there is substantial evidence from placebo-controlled studies that antidepressants delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors. Completed suicide, depression, homicidal ideation, suicide ideation, and suicide attempts have been reported with postmarketing use of bupropion. Patients, family members, and caregivers should be advised to monitor any patient taking dextromethorphan; bupropion for worsening of depressive symptoms and emergence of suicidal ideation or actions and report these to their healthcare team immediately.
Use of antidepressants, including bupropion, in patients with depression can precipitate mania or hypomania in predisposed individuals. Manic reaction has been reported with postmarketing use of bupropion. Patients should be screened for a personal or family history of bipolar disorder, mania, or hypomania prior to initiating treatment with dextromethorphan; bupropion. If manic symptoms occur, dextromethorphan; bupropion should be discontinued and the patient should be monitored closely for symptom improvement.
Dextromethorphan; bupropion can increase the risk of seizures due to bupropion effects on seizure threshold. These effects are dose-related and some patients may be more at risk of experiencing seizures with bupropion. The incidence of seizure has been shown to increase from 0.1% with bupropion hydrochloride sustained-release 300 mg/day to 0.4% with bupropion hydrochloride sustained-release 400 mg/day. Obtain detailed medical history of concomitant disease, conditions, and medications before initiation of bupropion therapy. In addition, screen patients for use of other bupropion-containing products and, if possible, avoid coadministration. If concomitant use with other bupropion is clinically warranted, inform patients of the risk of seizures. Dextromethorphan; bupropion should be discontinued and not re-initiated in patients who experience a seizure during treatment.
Sexual dysfunction, including orgasm dysfunction (abnormal orgasm), anorgasmia, impotence (erectile dysfunction), and libido decrease, occurred in 6% of patients receiving dextromethorphan; bupropion in a 6-week, placebo-controlled study. No patients in the placebo arm reported these effects. The following adverse reactions have been reported with postmarketing use of bupropion: abnormal ejaculation, cystitis, dyspareunia, dysuria, gynecomastia, libido increase, menopause, painful erection, salpingitis, urinary incontinence, urinary retention, and vaginitis.
Arthralgia was reported in 3% of patients taking dextromethorphan; bupropion in a 6-week, placebo-controlled study. There were no reports of these effects in the placebo arm. Myalgia, muscle rigidity, rhabdomyolysis, and myasthenia (muscle weakness) have also been reported with postmarketing use of bupropion monotherapy.
One of the most commonly reported adverse reactions in the 6-week clinical study was hyperhidrosis, which occurred in 5% of patients treated with dextromethorphan; bupropion; no patients treated with placebo experienced hyperhidrosis. Postmarketing experience with bupropion monotherapy has included reports of alopecia, angioedema, exfoliative dermatitis, hirsutism, and Stevens-Johnson syndrome. There have also been reports of arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity with postmarketing use of bupropion; these symptoms may resemble serum sickness.
In a 6-week, placebo-controlled trial of dextromethorphan; bupropion, 3% of patients experienced blurred vision compared to no patients in the placebo group. Mydriasis and ocular hypertension (increased intraocular pressure) have also been reported with postmarketing use of bupropion monotherapy.
Dextromethorphan; bupropion can cause elevated blood pressure and hypertension; these effects may be further increased if coadministered with other medications that increase blood pressure. Assess blood pressure prior to starting dextromethorphan; bupropion therapy and periodically during treatment. Other cardiovascular adverse effects that have been reported with postmarketing use of bupropion monotherapy include complete atrioventricular block (AV block), extrasystoles, hypotension, hypertension (in some cases severe), phlebitis, and pulmonary embolism.
While not reported in placebo-controlled clinical trials of dextromethorphan; bupropion, postmarketing reports of hearing loss or deafness have occurred with bupropion monotherapy use. As these reactions are reported voluntarily from a population of unknown size, the true incidence of occurrence is not known.
Hyperglycemia, hypoglycemia, glycosuria, hyponatremia, and syndrome of inappropriate antidiuretic hormone (SIADH) have been reported with postmarketing use of bupropion. Due to the voluntary nature of postmarketing reports, neither causality nor the incidence can be established.
While not reported in clinical trials of the dextromethorphan; bupropion combination, hematologic and lymphatic effects have been reported with postmarketing use of bupropion monotherapy. Anemia, leukocytosis, leukopenia, lymphadenopathy, pancytopenia, and thrombocytopenia have all been reported with postmarketing use of bupropion. Altered PT and/or INR, infrequently associated with hemorrhagic or thrombotic complications, were observed when bupropion was coadministered with warfarin.
While not reported during clinical trials of dextromethorphan; bupropion, postmarketing reports of respiratory infection (specifically pneumonia) have occurred with bupropion monotherapy.
Dextromethorphan is associated with serotonergic effects. Excessive dosage due to higher than recommended doses or substance abuse (e.g., in combination with products containing narcotics or sympathomimetics) may result in additional adverse effects consistent with serotonin syndrome such as, confusion, excitement, nervousness, restlessness, irritability, nausea, vomiting, and dysarthria (slurred speech). In an ISMP safety report, bupropion was noted as 1 of 19 overall drugs and one of the 9 antidepressants having the strongest signals for serotonin syndrome with 18 cases reported over 1 year to the FDA Adverse Event Reporting System (FAERS). Serotonin syndrome rarely happens with single drug therapy, and more commonly is reported with interactions between multiple serotonergic drugs or accidental or intentional drug overdoses. How bupropion might promote serotonergic excess is unclear, as bupropion is a relatively weak inhibitor of the neuronal reuptake of norepinephrine and dopamine, and does not inhibit the reuptake of serotonin. Bupropion does not inhibit monoamine oxidase. The manufacturers have not reported serotonin syndrome as a postmarketing event. Prior to initiating dextromethorphan; bupropion, patients should be screened for any use of other dextromethorphan-containing products. If concomitant use of dextromethorphan; bupropion with other serotonergic medications is necessary, patients should be counseled on the risks of serotonin syndrome and monitored for symptoms, which may include altered mental status, hypertension, restlessness, myoclonus, hyperthermia, hyperreflexia, diaphoresis, shivering, and tremor. Dextromethorphan; bupropion and/or the concomitant serotonergic drug should be discontinued immediately if these symptoms occur, and supportive symptomatic care should be initiated.
Dextromethorphan; bupropion is contraindicated in patients with a history of hypersensitivity to dextromethorphan, hypersensitivity to bupropion, or any inactive ingredients in the formulations. Delayed hypersensitivity reactions, consisting of arthralgia, myalgia, and fever with rash have been reported in association with bupropion and may resemble serum sickness. Anaphylactoid/anaphylactic reactions and Stevens-Johnson syndrome have also been reported with bupropion products.
Dextromethorphan; bupropion is contraindicated in patients with a seizure disorder, a current or prior history of bulimia nervosa, anorexia nervosa, and in patients undergoing abrupt benzodiazepine withdrawal or abrupt withdrawal from alcohol, barbiturates, or antiepileptic drugs, as these patients may be at higher risk of seizures. Other predisposing factors that may increase the risk of seizure include severe head trauma; arteriovenous malformation; CNS infection; CNS tumor (e.g., brain tumor or intracranial mass); severe stroke; metabolic disorder (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, or hypoxemia); diabetes mellitus treated with oral hypoglycemic agents or insulin; alcoholism; substance abuse (e.g., cocaine or prescription abuse of stimulants such as amphetamines); excessive use of benzodiazepines, sedative/hypnotics, or opiates; use of anorectic drugs; or use of concomitant medications that lower seizure threshold (e.g., other bupropion products, antipsychotics, tricyclic antidepressants, theophylline, tramadol, or systemic corticosteroids). The risk of seizures with bupropion use is dose-related. The incidence of seizure has been shown to increase from 0.1% with bupropion hydrochloride sustained-release 300 mg/day to 0.4% with bupropion hydrochloride sustained-release 400 mg/day. Prior to starting dextromethorphan; bupropion, screen patients for use of other bupropion-containing products and, if possible, avoid coadministration. If concomitant use with other bupropion is clinically warranted, inform patients of the risk of seizures. Dextromethorphan; bupropion should be discontinued and not re-initiated in patients who experience a seizure during treatment.
Dextromethorphan; bupropion is contraindicated with concurrent use of MAOI therapy due to the risk of serious and potentially fatal drug interactions, including hypertensive crisis and serotonin syndrome. At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and initiation of dextromethorphan; bupropion. Conversely, allow at least 14 days after stopping dextromethorphan; bupropion before starting an MAOI antidepressant. Starting dextromethorphan; bupropion in a patient being treated with reversible MAOIs, such as linezolid or methylene blue, is also contraindicated. If necessary to initiate treatment with linezolid or intravenous methylene blue, discontinue dextromethorphan; bupropion before starting treatment with the MAOI.
The safety and efficacy of dextromethorphan; bupropion is not established in pediatric patients less than 18 years of age. Antidepressants, including bupropion, increase the risk of suicidal ideation and behaviors in pediatric patients. In a pooled analysis of placebo-controlled trials of antidepressants (n = 4,500 pediatrics and 77,000 adults), there was an increased risk for suicidal thoughts and behaviors in patients 24 years of age and younger receiving an antidepressant versus placebo, with considerable variation in the risk of suicidality among drugs. The difference in absolute risk of suicidal thoughts and behaviors across different indications was highest in those with major depression. It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term use (i.e., beyond 4 months). However, there is substantial evidence from placebo-controlled maintenance studies in adult patients with major depression that depression itself is a risk factor for suicidal thoughts and behaviors and that antidepressant therapy delays recurrence of depression. All patients should be monitored for symptom worsening or suicidality, especially during the initial few months of therapy and after dose changes. Caregivers and/or patients should immediately notify the care team of changes in behavior or suicidal ideation. A change to the treatment regimen or discontinuation of dextromethorphan; bupropion may be necessary in patients with emerging suicidality or worsening depression.
Antidepressant treatment (including the use of bupropion) has been associated with the development of mania or hypomania in susceptible individuals. Patients with bipolar disorder or who have risk factors for bipolar disorder appear to be at increased risk of manic, mixed, or hypomanic episodes. Patients should be adequately screened for bipolar disorder prior to starting dextromethorphan; bupropion, including a detailed personal and family history of bipolar disorder, depression, and suicidal thoughts or actions. Bupropion has also been reported to cause neuropsychiatric reactions, such as delusions, hallucinations, psychosis, concentration disturbance, paranoia, confusion, and other behavioral changes in patients diagnosed with depression. Some patients experiencing the adverse events had bipolar disorder. In most cases, these symptoms resolved after dose reductions or withdrawal of treatment. High doses of dextromethorphan have been associated with psychosis, stupor, coma, and hyperexcitability. Since the risks of adverse neuropsychiatric reactions are dose-related, screen patients for use of other dextromethorphan- or bupropion-containing products prior to starting dextromethorphan; bupropion therapy. If concomitant use with other dextromethorphan- or bupropion-containing products is clinically warranted, closely monitor patients for neuropsychiatric changes, behavioral changes or worsening of a pre-existing psychiatric illness (e.g., schizophrenia, depression, bipolar disorder); instruct patients to contact their care team if such reactions or changes occur.
Dextromethorphan; bupropion has not been evaluated in patients with severe hepatic impairment (Child-Pugh class C). As such, the use of this combination is not recommended in patients with severe hepatic disease. No dose adjustment is required in patients with mild or moderate hepatic impairment (Child-Pugh class A or B).
The use of dextromethorphan; bupropion in patients with severe renal impairment or renal failure has not been studied and should be avoided. A reduction in dose is recommended for patients with moderate renal impairment (eGFR 30 to 59 mL/minute/1.73 m2); no dosage adjustments are needed in patients with mild renal impairment (eGFR 60 mL/minute/1.73 m2 or greater). Caution is advised when using this combination in patients with renal disease due to the potential risk of accumulation; patients should be monitored closely for adverse effects that could indicate increased serum levels due to the accumulation of dextromethorphan; bupropion or metabolites.
Caution is advised when using dextromethorphan; bupropion in patients with hypertension. Bupropion can increase blood pressure and cause hypertension, which may be problematic in patients with a recent history of acute myocardial infarction or unstable cardiac disease, including heart failure. Risk of hypertension is increased if administered concomitantly with other drugs that increase dopaminergic or noradrenergic activity or MAOIs. In a clinical trial of patients with major depression and stable congestive heart failure, treatment with immediate-release bupropion was associated with exacerbation of hypertension in 2 patients, requiring discontinuation of therapy. Bupropion has not been studied in patients with a recent history of myocardial infarction or unstable cardiac disease. Assess blood pressure prior to initiating treatment and periodically throughout the use of dextromethorphan; bupropion.
Patients should be warned to use caution when driving or operating machinery or performing other tasks that require mental alertness until they know how dextromethorphan; bupropion will affect them. Dextromethorphan; bupropion may cause dizziness. Patients at risk of falls, especially those with motor impairment affecting gait, balance issues, or a history of falls, should take extra precaution to avoid injury. Patients should also be encouraged to avoid ethanol intoxication and minimize consumption of alcohol while taking dextromethorphan; bupropion. Patients who consume alcohol while taking bupropion may be at increased risk of neuropsychiatric events or have reduced alcohol tolerance.
Caution is recommended when prescribing dextromethorphan; bupropion to patients with closed-angle glaucoma. Avoid use in patients with untreated anatomically narrowed angles. The pupillary dilation that can occur with antidepressants, including bupropion, may precipitate a closed-angle glaucoma attack in patients with anatomically narrow angles who do not have a patent iridectomy. An acute attack of closed-angle glaucoma is considered a medical emergency because the increased intraocular pressure is rapid and severe, and may quickly result in blindness if left untreated.
Laboratory test interference may occur with dextromethorphan; bupropion use. False-positive urine immunoassay screening tests for amphetamines have been reported in patients taking bupropion. The false-positive result is due to lack of specificity of some screening tests. False-positive test results may result even following discontinuation of bupropion therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish bupropion from amphetamines.
Available clinical data on the use of dextromethorphan; bupropion is insufficient to evaluate any drug-associated risks of major birth malformations, miscarriage, or other adverse maternal or fetal outcomes. Dextromethorphan; bupropion administered to pregnant mice during organogenesis at doses of 26 mg/57 mg, 34 mg/75 mg, and 68 mg/150 mg/kg/day, respectively, did not affect body weight, weight gain, food consumption, or pregnancy and did not produce gross pathologic findings or placental or fetal findings at any dose level. The no-effect level for reproductive organ findings in mice was 68 mg/150 mg/kg in both sexes, which is approximately 3.7 times and 3.5 times, respectively the maximum recommended human dose (MRHD) for dextromethorphan; bupropion on a mg/m2 basis. Data from epidemiological studies including pregnant women exposed to bupropion in the first trimester indicate no increased risk of congenital malformations. In addition, no increased risk of cardiovascular malformations during first trimester exposure to bupropion has been observed. The rate of cardiovascular malformations following 675 exposures to bupropion in the first trimester was 1.3% versus a background rate of about 1%. Data collected from the United Healthcare database and the National Birth Defects Prevention Study (11,700 infants with cardiovascular malformations and 20,093 infants with non-cardiovascular malformations) did not show an overall increased risk from cardiovascular malformations after bupropion exposure during the first trimester. Study findings on bupropion exposure during the first trimester and risk for left ventricular outflow tract obstruction (LVOTO) are inconsistent and do not allow conclusions regarding a possible association. The United Healthcare database lacked sufficient power to evaluate this association; the NBDPS found increased risk for LVOTO, and the Slone Epidemiology case control study did not find increased risk for LVOTO. Study findings on bupropion exposure during the first trimester and risk for ventricular septal defect (VSD) are inconsistent and do not allow conclusions regarding a possible association. The Slone Epidemiology Study found an increased risk for VSD following first trimester maternal bupropion exposure but did not find increased risk for any other cardiovascular malformations studied (including LVOTO). The NBDPS and United Healthcare database study did not find an association between first trimester maternal bupropion exposure and VSD. For the findings of LVOTO and VSD, the studies were limited by the small number of exposed cases, inconsistent findings among studies, and the potential for chance findings from multiple comparisons in case control studies. No clear evidence of teratogenic activity was found in reproductive developmental studies conducted in rats and rabbits. However, in rabbits, slightly increased incidences of fetal malformations and skeletal variations were observed at doses approximately 2 times the MRHD and greater, while decreased fetal weights were seen at doses 5 times the MRHD and greater. Since dextromethorphan acts as a low affinity antagonist to the glutamate receptor subtype N-methyl-D-aspartate (NMDA) in the CNS, there has been some concern about its safe use during pregnancy. Dextromethorphan exhibited adverse developmental effects in avian embryos; however, the avian study data have limited applicability to human gestation. Human surveillance data and retrospective studies have shown dextromethorphan to be relatively safe during the first trimester; a human epidemiologic study and a smaller controlled study have not demonstrated elevated risks of congenital malformations. In one controlled study, there were no cases of neural tube defects, and no differences in number of live births, spontaneous or elective abortions, stillbirths, or major or minor malformations among infants exposed to dextromethorphan during the first trimester and those who were not. The results suggested that use during pregnancy does not pose a risk to the fetus; however, due to the small sample size, an increased risk of rare malformations could not be ruled out. Dextromethorphan; quinidine administered to female rats during organogenesis, pregnancy, and lactation resulted in embryo-fetal deaths at the highest studied dose of 50 mg/100 mg/kg/day and reduced skeletal ossification, pup survival, and pup weight at all studied doses. Developmental delay was observed in offspring at the mid and high doses. An increased incidence of fetal malformations was observed following oral administration of dextromethorphan; quinidine to pregnant rabbits during organogenesis. Due to the lack of data specific to the dextromethorphan; bupropion combination and the risks noted in animal studies, dextromethorphan; bupropion is not recommended during pregnancy. If a female becomes pregnant while taking dextromethorphan; bupropion, treatment should be discontinued and the patient should be counseled about potential risks to the fetus. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to antidepressants, including dextromethorphan; bupropion. Information about the registry can be obtained at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/ or by calling 1-866-961-2388.
Due to the potential for neurotoxicity, breast-feeding should be avoided during dextromethorphan; bupropion treatment and for 5 days after the final dose. Data from published literature report the presence of bupropion and its metabolites in human milk; however, there are no data on the effects of bupropion or its metabolites on milk production. Limited data from postmarketing reports of bupropion use in breast-feeding patients have not identified a clear association of adverse events in the breastfed infant. Peak breast milk concentrations of bupropion and its metabolites are present within 2 to 4 hours after an oral dose. In a lactation study of 10 women, levels of bupropion and its active metabolites were measured in expressed milk. Average daily infant exposure to bupropion and its metabolites (assuming 150 mL/kg daily consumption) was 2% of the maternal weight-adjusted dose. One case report describes a possible seizure in a breast-fed infant during maternal use of extended-release bupropion. In two other cases, no infant-related adverse events were noted during breast-feeding. Postmarketing reports have also described seizures in breast-fed infants, but the relationship of bupropion exposure and these seizures is not clear. It is not known whether dextromethorphan is present in human milk. The effects of dextromethorphan on the breast-fed infant or effects on milk production are also unknown. Neurotoxicity was observed in animal studies of juvenile rats that were treated with a combination of 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 life in humans.
Due to the potential reproductive risk with dextromethorphan; bupropion, use alternative therapy in patients who are planning to become pregnant. Based on animal studies, dextromethorphan; bupropion may cause fetal harm when administered during pregnancy. In addition, the separate effect of dextromethorphan on developmental toxicity at the recommended clinical dose is unclear.
Clinical trials with dextromethorphan; bupropion did not include geriatric patients (65 years and older) and it is not known whether there are any differences in pharmacokinetics or clinical response compared to younger adult patients. Use of dextromethorphan; bupropion is not recommended in patients with severe hepatic or renal impairment and dose reduction is recommended for patients with moderate renal impairment (eGFR 30 to 59 mL/minute/1.73 m2). Geriatric patients may have increased rates of renal or hepatic impairment. Due to the lack of available data and potential for impaired hepatic or renal impairment, consider alternative therapy for geriatric patients. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of antidepressants in residents of long-term care facilities; treatment duration should follow recommendations of pertinent literature and clinical practice guidelines for the condition treated. Monitor treated patients closely for worsening of depression and suicidal behavior or thinking, especially during initiation of therapy and during dose changes. Antidepressants may cause a variety of adverse effects; some side effects can increase the risk of falls. Before discontinuation, many antidepressants may need a taper to avoid a withdrawal syndrome. Bupropion may increase seizure risk and activity in susceptible individuals. At least quarterly, the facility should review the continued need of the antidepressant and document the rationale for continuation. When the drug is being used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt to taper the medication as outlined in the OBRA guidelines, unless a taper is clinically contraindicated.
For the treatment of major depression:
Oral dosage:
Adults: Initially, 45 mg dextromethorphan/105 mg bupropion PO once daily each morning. After 3 days, increase to 45 mg dextromethorphan/105 mg bupropion PO twice a day with doses separated by at least 8 hours. Do not exceed 2 doses within the same day. Max: 90 mg dextromethorphan/210 mg bupropion per day.
Maximum Dosage Limits:
-Adults
90 mg/day PO dextromethorphan; 210 mg/day PO bupropion.
-Geriatric
Safety and efficacy have not been established.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Mild or moderate hepatic impairment (Child-Pugh Class A or Child-Pugh Class B): No dosage adjustments needed.
Severe hepatic impairment (Child-Pugh Class C): Not recommended.
Patients with Renal Impairment Dosing
eGFR 60 mL/minute/1.73 m2 or greater: No dosage adjustment needed.
eGFR 30 to 59 mL/minute/1.73 m2: Dose adjustment to 45 mg dextromethorphan/105 mg bupropion PO once daily.
eGFR 29 mL/minute/1.73 m2 or less: Dextromethorphan; bupropion has not been evaluated in this population. Use is not recommended.
*non-FDA-approved indication
Abiraterone: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy.
Acetaminophen; Caffeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. (Moderate) Concomitant use of dihydrocodeine with bupropion may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of bupropion could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Bupropion is a strong inhibitor of CYP2D6.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Acetaminophen; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6.
Acetaminophen; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Acetazolamide: (Moderate) It should be noted that when anticonvulsants are used for the purpose of treating epilepsy (versus use in mood disorders or neuropathic pain or other non-epilepsy conditions), that bupropion should not be used by patients with a preexisting seizure disorde; this represents a disease-drug interaction, and not a drug-drug interaction per se. Bupropion may be combined with anticonvulsant treatments with caution when an anticonvulsant is used for non-epilepsy conditions. Addiive CNS effects are possible, and the patient may feel dizzy, drowsy or more tired when taking these drugs together.
Acrivastine; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Albuterol; Budesonide: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Alfentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) If concomitant use of alfentanil and bupropion is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Almotriptan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Alosetron: (Moderate) Alosetron, if used with drugs that have anticholinergic effects such as bupropion, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid these drugs in patients taking alosetron.
Amantadine: (Major) Use caution when concurrently administering bupropion and amantadine; if concurrent use is necessary, low initial dosing and slow dosage titration of bupropion should be considered. Both bupropion and amantadine have dopamine agonist effects, and coadministration may result in additive CNS dopaminergic effects. Reported adverse reactions have included neurologic side effects such as restlessness, agitation, gait disturbance, vertigo, and dizziness; some patients have required hospitalization. In reported cases, discontinuation of the drugs resulted in symptom resolution.
Amifampridine: (Major) Carefully consider the need for concomitant treatment with bupropion and amifampridine, as coadministration may increase the risk of seizures. Consider alternatives to bupropion. If use together is medically necessary, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Bupropion is known to have a dose-dependent risk for seizures.
Amitriptyline: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with tricyclic antidepressants. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as tricyclic antidepressants. Use low initial doses of bupropion and increase the dose gradually. Monitor patients for an increase in tricyclic antidepressant-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases; a dose reduction of the tricyclic antidepressant may be necessary. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Tricyclic antidepressants are CYP2D6 substrates and bupropion is a CYP2D6 inhibitor.
Amobarbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery.
Amoxapine: (Major) Concurrent administration of amoxapine with bupropion should be undertaken only with extreme caution due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus may reduce the clearance of amoxapine leading to a potential for increased Cmax, AUC and half-life. Amoxapine appears to be metabolized via CYP2D6. Low initial dosing and gradual dose increases of both drugs should be employed. If bupropion is added to a regimen of a patient already receiving amoxapine, the need to reduce the amoxapine dosage should be considered.
Amphetamine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including amphetamine; dextroamphetamine. Use low initial doses of bupropion and increase the dose gradually.
Amphetamine; Dextroamphetamine Salts: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including amphetamine; dextroamphetamine. Use low initial doses of bupropion and increase the dose gradually.
Amphetamine; Dextroamphetamine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including amphetamine; dextroamphetamine. Use low initial doses of bupropion and increase the dose gradually.
Aripiprazole: (Major) Recommendations for managing aripiprazole and bupropion vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer half of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg. Further dosage reductions may be required in patients who are also receiving a CYP3A inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; bupropion is a strong CYP2D6 inhibitor. (Major) Recommendations for managing aripiprazole and bupropion vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg or for patients known to be poor metabolizers of CYP2D6. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP3A inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; bupropion is a strong CYP2D6 inhibitor.
Armodafinil: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary.
Artemether; Lumefantrine: (Moderate) Use of dextromethorphan with lumefantrine may result in increased dextromethorphan exposure. Lumefantrine inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Asenapine: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery.
Aspirin, ASA; Caffeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6.
Atazanavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with bupropion as there is a potential for elevated cobicistat concentrations. Bupropion is a CYP2D6 inhibitor in vitro, while cobicistat is a substrate of CYP2D6. (Moderate) Use of dextromethorphan with cobicistat may result in increased dextromethorphan exposure. Cobicistat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Atomoxetine: (Major) Dosage reduction of atomoxetine is recommended in patients receiving bupropion due to the potential for increased atomoxetine exposure and related adverse effects. In children and adolescents up to 70 kg receiving bupropion, atomoxetine should be initiated at 0.5 mg/kg/day and only increased to the usual target dose of 1.2 mg/kg/day if symptoms fail to improve after 4 weeks and the initial dose is well-tolerated. In children and adolescents over 70 kg and adults receiving bupropion, atomoxetine should be initiated at 40 mg/day and only increased to the usual target dose of 80 mg/day if symptoms fail to improve after 4 weeks and the initial dose is well-tolerated. Bupropion is a strong CYP2D6 inhibitor; atomoxetine is a CYP2D6 substrate. Coadministration of a strong CYP2D6 inhibitor and atomoxetine in extensive metabolizers of CYP2D6, increased atomoxetine steady-state plasma concentrations by approximately 6 to 8-fold. This increase is similar to exposures observed in poor metabolizers. Concurrent use of a strong CYP2D6 inhibitor with atomoxetine in poor metabolizers is not expected to increase atomoxetine exposure.
Atropine: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Atropine; Difenoxin: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Azelastine; Fluticasone: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Barbiturates: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery.
Beclomethasone: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Contraindicated) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving intravenous methylene blue. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with intravenous methylene blue, bupropion should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits of methylene blue outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of methylene blue. It is not known if administration of methylene blue by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. (Major) Because of the potential risk and severity of serotonin syndrome, coadministration of dextromethorphan and IV methylene blue should be avoided if possible. Methylene blue has been demonstrated to be a potent monoamine oxidase inhibitor (MAOI) and may cause potentially fatal serotonin toxicity (serotonin syndrome) when combined with serotonin reuptake inhibitors (SRIs). Dextromethorphan increases central serotonin effects. If methylene blue is judged to be indicated, all SRIs, including dextromethorphan, must be ceased prior to treatment/procedure/surgery. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Benzphetamine: (Major) The risk of seizures from the use of bupropion may be increased with concomitant use of CNS stimulants and anorectics that may induce seizures, including benzphetamine. Concurrent use is not recommended. Extreme caution and close clinical monitoring is recommended if these agents must be used together.
Benztropine: (Moderate) Additive anticholinergic effects may be seen when benztropine is used concomitantly with other drugs that possess anticholinergic properties, such as bupropion. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Betamethasone: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Bethanechol: (Moderate) Bupropion exhibits moderate anticholinergic properties. Avoid co-use when possible since the effects of bethanechol, a cholinergic agonist, may be diminished. If co-use is necessary, monitor for the intended clinical response.
Brexpiprazole: (Major) Because brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the brexpiprazole dose be reduced to one-half of the usual dose in patients receiving a strong CYP2D6 inhibitor and one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. Bupropion is a strong inhibitor of CYP2D6. If these agents are used in combination, the patient should be carefully monitored for brexpiprazole-related adverse reactions. Additionally, bupropion is associated with a dose-related increase in seizures; antipsychotics may increase this risk. It should be noted that no dosage adjustment is needed in patients taking a strong CYP2D6 inhibitor who are receiving brexpiprazole as adjunct treatment for major depressive disorder because CYP2D6 considerations are already factored into general dosing recommendations.
Brimonidine; Timolol: (Minor) Monitor for an increased incidence of timolol-related adverse effects if bupropion and timolol are used concomitantly. Coadministration of bupropion and timolol may result in increased plasma concentrations of timolol. Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Timolol is a CYP2D6 substrate.
Brompheniramine; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Budesonide: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Budesonide; Formoterol: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Buprenorphine: (Moderate) If concomitant use of buprenorphine and bupropion is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. (Moderate) If concomitant use of buprenorphine and dextromethorphan is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Buprenorphine; Naloxone: (Moderate) If concomitant use of buprenorphine and bupropion is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. (Moderate) If concomitant use of buprenorphine and dextromethorphan is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Bupropion: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of bupropion is necessary. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Bupropion; Naltrexone: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of bupropion is necessary. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Butalbital; Acetaminophen: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery.
Butalbital; Acetaminophen; Caffeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6.
Caffeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy.
Caffeine; Sodium Benzoate: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy.
Calcium, Magnesium, Potassium, Sodium Oxybates: (Major) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as sodium oxybate. The risk of seizures with bupropion is dose related and is also related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold. Consider these risks before initiating treatment If used together, use low initial doses of bupropion and increase the dose gradually.
Cannabidiol: (Moderate) Consider a dose adjustment of bupropion when coadministered with cannabidiol. Coadministration may alter plasma concentrations of bupropion resulting in an increased risk of adverse reactions and/or decreased efficacy. Bupropion is a substrate of CYP2B6; cannabidiol may inhibit and/or induce CYP2B6 at clinically relevant concentrations.
Carbamazepine: (Moderate) Monitor for reduced bupropion efficacy during coadministration of carbamazepine as concurrent use may decrease bupropion exposure. A bupropion dose adjustment may be necessary; do not exceed maximum dose. Avoid concomitant use of combination dextromethorphan; bupropion and carbamazepine. Bupropion is a CYP2B6 substrate and carbamazepine is a strong CYP2B6 inducer. Concomitant use was observed to decrease bupropion overall exposure by 76% and dextromethorphan overall exposure by 64%.
Carbidopa; Levodopa: (Moderate) Use bupropion and levodopa with caution and monitor for CNS toxicity, including restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness, which may result from cumulative dopamine agonist effects.
Carbidopa; Levodopa; Entacapone: (Moderate) Use bupropion and levodopa with caution and monitor for CNS toxicity, including restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness, which may result from cumulative dopamine agonist effects.
Cariprazine: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored.
Carvedilol: (Minor) Monitor for an increased incidence of carvedilol-related adverse effects if bupropion and carvedilol are used concomitantly. Coadministration of bupropion and carvedilol may result in increased plasma concentrations of carvedilol. Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Carvedilol is a CYP2D6 substrate.
Celecoxib; Tramadol: (Moderate) Monitor for reduced efficacy of tramadol, signs of opioid withdrawal, seizures, or serotonin syndrome if coadministration with bupropion is necessary. If bupropion is discontinued, consider a dose reduction of tramadol and frequently monitor for signs of respiratory depression and sedation. Tramadol is a CYP2D6 substrate and bupropion is a CYP2D6 inhibitor. Concomitant use of tramadol with CYP2D6 inhibitors can increase the plasma concentration of tramadol and decrease the plasma concentration of the active metabolite M1. Since M1 is a more potent mu-opioid agonist, decreased M1 exposure could result in decreased therapeutic effects, and may result in signs and symptoms of opioid withdrawal in patients who have developed physical dependence to tramadol. Increased tramadol exposure can result in increased or prolonged therapeutic effects and increased risk for serious adverse events including seizures and serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Cenobamate: (Major) Increase the dosage of bupropion as needed when coadministered with cenobamate due to the potential for reduced efficacy of bupropion. Multiple doses of cenobamate decreased bupropion exposure by 39%. Bupropion is a sensitive substrate of CYP2B6; cenobamate is a weak CYP2B6 inducer.
Cetirizine; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Cevimeline: (Moderate) Cevimeline is partially metabolized by CYP2D6. Inhibitors of this isoenzyme, like bupropion, would be expected to lead to an increase in cevimeline plasma concentrations.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Chlordiazepoxide; Amitriptyline: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with tricyclic antidepressants. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as tricyclic antidepressants. Use low initial doses of bupropion and increase the dose gradually. Monitor patients for an increase in tricyclic antidepressant-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases; a dose reduction of the tricyclic antidepressant may be necessary. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Tricyclic antidepressants are CYP2D6 substrates and bupropion is a CYP2D6 inhibitor.
Chlordiazepoxide; Clidinium: (Moderate) Bupropion exhibits moderate anticholinergic effects. Clinicians should consider this when using antimuscarinics and other medications with anticholinergic activity in combination with bupropion.
Chlorpheniramine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Chlorpheniramine; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Chlorpromazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of chlorpromazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of chlorpromazine may result in QT prolongation, somnolence, anticholinergic effects, or orthostasis.
Ciclesonide: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Citalopram: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Monitor for an increase in the frequency and severity of citalopram-related adverse effects, such as QT prolongation and serotonin syndrome, during concomitant use of bupropion. Concomitant use has been observed to increase the peak and overall exposure of citalopram by 30% and 40%, respectively.
Clobazam: (Moderate) Use of dextromethorphan with clobazam may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Clobazam inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. A dosage reduction of dextromethorphan may be necessary for some patients. During one in vivo study, co-administration of dextromethorphan and clobazam resulted in increased AUC and Cmax of dextromethorphan by 90% and 59%, respectively.
Clomipramine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with tricyclic antidepressants. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as tricyclic antidepressants. Use low initial doses of bupropion and increase the dose gradually. Monitor patients for an increase in tricyclic antidepressant-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases; a dose reduction of the tricyclic antidepressant may be necessary. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Tricyclic antidepressants are CYP2D6 substrates and bupropion is a CYP2D6 inhibitor.
Clopidogrel: (Moderate) Monitor for an increase in bupropion-related adverse reactions during coadministration of clopidogrel as concurrent use may increase bupropion exposure. A bupropion dose adjustment may be necessary. Bupropion is a sensitive substrate of CYP2B6; clopidogrel is a weak CYP2B6 inhibitor.
Clozapine: (Major) Monitor for evidence of clozapine-related adverse reactions and consider a clozapine dose reduction if necessary when coadministered with bupropion. If bupropion is discontinued after dose adjustments are made, monitor for lack of clozapine affect and consider increasing the clozapine dose if necessary. Concurrent use may result in increased clozapine exposure due to inhibition of CYP2D6 metabolism by bupropion. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Elevated plasma concentrations of clozapine may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. Furthermore, bupropion is associated with a dose-related risk of seizures; this risk may be increased by antipsychotics.
Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with bupropion as there is a potential for elevated cobicistat concentrations. Bupropion is a CYP2D6 inhibitor in vitro, while cobicistat is a substrate of CYP2D6. (Moderate) Use of dextromethorphan with cobicistat may result in increased dextromethorphan exposure. Cobicistat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Cocaine: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as cocaine. This is of particular concern in those with excessive cocaine use (i.e., cocaine addition). Patients should be closely monitored if this combination is necessary.
Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6.
Codeine; Guaifenesin: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6. (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Codeine; Phenylephrine; Promethazine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6. (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as promethazine. Use low initial doses of bupropion and increase the dose gradually.
Codeine; Promethazine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If bupropion is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bupropion is a strong inhibitor of CYP2D6. (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as promethazine. Use low initial doses of bupropion and increase the dose gradually.
Corticosteroids: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Cortisone: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Cyclobenzaprine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as cyclobenzaprine. Use low initial doses of bupropion and increase the dose gradually. Monitor patients for signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome.
Dabrafenib: (Major) The concomitant use of dabrafenib and bupropion may lead to decreased bupropion concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents is unavoidable, monitor patients for loss of bupropion efficacy. In vitro, dabrafenib is an inducer of CYP2B6 via activation of the pregnane X receptor and constitutive androstane receptor nuclear receptors. Bupropion is a sensitive CYP2B6 substrate.
Dacomitinib: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of dacomitinib is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and dacomitinib is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Dalfampridine: (Moderate) Due to additive risks for seizure, extreme caution when coadministering bupropion with other drugs that lower seizure threshold (e.g., dalfampridine). Use low initial doses and increase the dose gradually. Monitor for seizure activity. Consider benefits against the risk of seizures. Consider alternatives to bupropion. Additionally, bupropion inhibits OCT2 in vitro, but the clinical relevance is not certain. Concurrent treatment with OCT2 inhibitors, such as bupropion, may cause increased exposure to dalfampridine. Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking OCT2 inhibitors concurrently with dalfampridine should be considered against the risk of seizures in these patients.
Darifenacin: (Moderate) Bupropion, an inhibitor of CYP2D6 may inhibit the metabolism of darifenacin. In addition, bupropion is associated with moderate anticholinergic effects which could be additive when coadministered with darifenacin. Patients should be monitored for increased anticholinergic effects or other adverse effects when these two drugs are coadministered. Dosage adjustments may be necessary. (Minor) Use of dextromethorphan with darifenacin may result in increased dextromethorphan exposure. Darifenacin is a moderate inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Darunavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with bupropion as there is a potential for elevated cobicistat concentrations. Bupropion is a CYP2D6 inhibitor in vitro, while cobicistat is a substrate of CYP2D6. (Moderate) Use of dextromethorphan with cobicistat may result in increased dextromethorphan exposure. Cobicistat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is warranted when cobicistat is administered with bupropion as there is a potential for elevated cobicistat concentrations. Bupropion is a CYP2D6 inhibitor in vitro, while cobicistat is a substrate of CYP2D6. (Moderate) Use of dextromethorphan with cobicistat may result in increased dextromethorphan exposure. Cobicistat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Deflazacort: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Delavirdine: (Moderate) Use of dextromethorphan with delavirdine may result in increased dextromethorphan exposure. Delavirdine inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Desipramine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with tricyclic antidepressants. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as tricyclic antidepressants. Use low initial doses of bupropion and increase the dose gradually. Monitor patients for an increase in tricyclic antidepressant-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases; a dose reduction of the tricyclic antidepressant may be necessary. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Tricyclic antidepressants are CYP2D6 substrates and bupropion is a CYP2D6 inhibitor.
Desloratadine; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Desvenlafaxine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with desvenlafaxine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. In addition, the manufacturer of desvenlafaxine recommends that the dose of CYP2D6 substrates, such as dextromethorphan, be reduced by up to 50% if used with desvenlafaxine 400 mg/day, a CYP2D6 inhibitor.
Deutetrabenazine: (Major) Do not exceed 18 mg/dose or 36 mg/day of deutetrabenazine if must use concurrently with a strong CYP2D6 inhibitor. Bupropion is a strong CYP2D6 inhibitor, and the metabolites of deutetrabenazine, alpha- and beta-HTBZ, are CYP2D6 substrates. The systemic exposure of alpha- and beta-HTBZ may be increased resulting in an increase in deutetrabenazine-related adverse reactions, like QT prolongation and drowsiness.
Dexamethasone: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Dexmethylphenidate: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including methylphenidate. Use low initial doses of bupropion and increase the dose gradually.
Dextroamphetamine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including amphetamine; dextroamphetamine. Use low initial doses of bupropion and increase the dose gradually.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Dextromethorphan; Quinidine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of quinidine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and quinidine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Dicyclomine: (Moderate) Additive anticholinergic effects may be seen when dicyclomine is used concomitantly with other drugs that possess anticholinergic properties, such as bupropion. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Diethylpropion: (Major) Drugs which may lower the seizure threshold, such as diethylpropion, should be used with great caution or avoided in patients taking bupropion. The manufacturer recommends low initial dosing and slow dosage titration of bupropion if this combination must be used concurrently; the patient should be closely monitored.
Digoxin: (Moderate) Monitor plasma digoxin concentrations during concomitant bupropion use. Concomitant use may decrease plasma digoxin concentrations. Digoxin exposure was decreased when a single oral dose of digoxin 0.5 mg was administered 24 hours after a single oral dose of extended-release bupropion 150 mg in healthy volunteers.
Diphenoxylate; Atropine: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Donepezil; Memantine: (Moderate) Dextromethorphan is a NMDA antagonist and may lead to additive adverse effects if combined with memantine, also an NMDA antagonist. It may be prudent to avoid coadministration of dextromethorphan with memantine. If coadministration cannot be avoided, monitor for increased adverse effects such as agitation, dizziness and other CNS events.
Dorzolamide; Timolol: (Minor) Monitor for an increased incidence of timolol-related adverse effects if bupropion and timolol are used concomitantly. Coadministration of bupropion and timolol may result in increased plasma concentrations of timolol. Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Timolol is a CYP2D6 substrate.
Doxepin: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with tricyclic antidepressants. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as tricyclic antidepressants. Use low initial doses of bupropion and increase the dose gradually. Monitor patients for an increase in tricyclic antidepressant-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases; a dose reduction of the tricyclic antidepressant may be necessary. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Tricyclic antidepressants are CYP2D6 substrates and bupropion is a CYP2D6 inhibitor.
Doxercalciferol: (Moderate) CYP450 enzyme inhibitors, like bupropion, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if cytochrome P450 inhibitors are coadministered with doxercalciferol.
Doxorubicin Liposomal: (Major) In vitro, bupropion is a mild CYP2D6 inhibitor and doxorubicin is a major CYP2D6 substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of bupropion and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Doxorubicin: (Major) In vitro, bupropion is a mild CYP2D6 inhibitor and doxorubicin is a major CYP2D6 substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of bupropion and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Dronedarone: (Moderate) Use of dextromethorphan with dronedarone may result in increased dextromethorphan exposure. Dronedarone inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Duloxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with duloxetine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Monitor for increased duloxetine-related adverse effects if coadministered with bupropion. Concurrent use may result in increased duloxetine exposure. Duloxetine is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Coadministration with another strong CYP2D6 inhibitor increased the duloxetine AUC by about 60%.
Dutasteride; Tamsulosin: (Moderate) Use caution if coadministration of bupropion with tamsulosin is necessary, especially at a tamsulosin dose higher than 0.4 mg, as the systemic exposure of tamsulosin may be increased resulting in increased treatment-related adverse reactions including hypotension, dizziness, and vertigo. Tamsulosin is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Concomitant treatment with another strong CYP2D6 inhibitor increased the Cmax and AUC of tamsulosin by a factor of 1.3 and 1.6, respectively.
Efavirenz: (Major) Concurrent use of efavirenz 600 mg/day and bupropion in healthy volunteers resulted in a reduction of the AUC and Cmax of bupropion by approximately 55% and 34%, respectively. The AUC of hydroxybupropion was unchanged and the Cmax of hydroxybupropion was increased by 50%. Healthcare providers are advised to increase the dose of bupropion based on clinical response during concurrent use with efavirenz; however, the maximum recommended dose of bupropion should not be exceeded.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Concurrent use of efavirenz 600 mg/day and bupropion in healthy volunteers resulted in a reduction of the AUC and Cmax of bupropion by approximately 55% and 34%, respectively. The AUC of hydroxybupropion was unchanged and the Cmax of hydroxybupropion was increased by 50%. Healthcare providers are advised to increase the dose of bupropion based on clinical response during concurrent use with efavirenz; however, the maximum recommended dose of bupropion should not be exceeded.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Concurrent use of efavirenz 600 mg/day and bupropion in healthy volunteers resulted in a reduction of the AUC and Cmax of bupropion by approximately 55% and 34%, respectively. The AUC of hydroxybupropion was unchanged and the Cmax of hydroxybupropion was increased by 50%. Healthcare providers are advised to increase the dose of bupropion based on clinical response during concurrent use with efavirenz; however, the maximum recommended dose of bupropion should not be exceeded.
Eletriptan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Eliglustat: (Major) Reduce the dose of eliglustat to 84 mg once daily in patients who are extensive or intermediate CYP2D6 metabolizers (EMs or IMs) and receiving bupropion. Eliglustat is contraindicated in EMs and IMs who are receiving bupropion plus a strong or moderate CYP3A inhibitor. Eliglustat is contraindicated in poor metabolizers (PMs) who are receiving bupropion plus a strong CYP3A inhibitor and should be avoided, if possible, in patients who are receiving bupropion plus a moderate CYP3A inhibitor. Concomitant use may increase eliglustat exposure. Eliglustat is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. A strong CYP2D6 inhibitor is predicted to increase eliglustat overall exposure by 8.4-fold and 2.3-fold in extensive and intermediate metabolizers, respectively. Strong CYP2D6s inhibitors alone are not expected to affect eliglustat concentrations in CYP2D6 poor metabolizers (PMs). (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when cobicistat is administered with bupropion as there is a potential for elevated cobicistat concentrations. Bupropion is a CYP2D6 inhibitor in vitro, while cobicistat is a substrate of CYP2D6. (Moderate) Use of dextromethorphan with cobicistat may result in increased dextromethorphan exposure. Cobicistat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when cobicistat is administered with bupropion as there is a potential for elevated cobicistat concentrations. Bupropion is a CYP2D6 inhibitor in vitro, while cobicistat is a substrate of CYP2D6. (Moderate) Use of dextromethorphan with cobicistat may result in increased dextromethorphan exposure. Cobicistat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Ergotamine; Caffeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy.
Escitalopram: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking bupropion. Bupropion is associated with a dose-related risk of seizures. Alcohol abuse and abrupt discontinuation of alcohol have also been associated with seizures. Neuropsychiatric events and reduced alcohol tolerance have also been described in postmarketing reports.
Ethiodized Oil: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Bupropion should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Fedratinib: (Moderate) Use of dextromethorphan with fedratinib may result in increased dextromethorphan exposure. Fedratinib is a moderate inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Felbamate: (Major) Bupropion should not be used by patients taking anticonvulsants for seizures because it may decrease the seizure threshold. Bupropion may also interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function.
Fenfluramine: (Major) Do not exceed a maximum dose of fenfluramine 20 mg per day if coadministered with bupropion; for patients also receiving stiripentol plus clobazam, do not exceed a maximum dose of fenfluramine 17 mg per day. Concomitant use may increase fenfluramine plasma concentrations and the risk of adverse reactions. Fenfluramine is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Coadministration with another strong CYP2D6 inhibitor increased fenfluramine overall exposure by 81% and decreased norfenfluramine overall exposure by 13%. (Moderate) Use fenfluramine and dextromethorphan with caution due to an increased risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Fentanyl: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering fentanyl with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) If concomitant use of fentanyl and bupropion is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Fexinidazole: (Moderate) Monitor for loss of efficacy of bupropion during coadministration of fexinidazole as concurrent use may decrease bupropion exposure. A bupropion dose adjustment may be necessary; do not exceed maximum dose. Bupropion is a sensitive substrate of CYP2B6; fexinidazole is a CYP2B6 inducer.
Fexofenadine; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Flavoxate: (Moderate) Bupropion exhibits moderate anticholinergic effects. Clinicians should keep this in mind when using antimuscarinics and other medications with anticholinergic activity in combination with bupropion.
Flecainide: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with bupropion is necessary. Flecainide is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Plasma concentrations of flecainide may increase, especially in extensive CYP2D6 metabolizers.
Fludrocortisone: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Flunisolide: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Fluoxetine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of fluoxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and fluoxetine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold. (Moderate) Monitor for increased fluoxetine-related adverse effects if coadministered with bupropion. Concomitant use may increase fluoxetine exposure. Fluoxetine is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor.
Fluphenazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of fluphenazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of fluphenazine may result in extrapyramidal symptoms, somnolence, or other adverse effects.
Fluticasone: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Fluticasone; Salmeterol: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Fluticasone; Vilanterol: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Fluvoxamine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with fluvoxamine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by CYP2D6 should be approached with caution. Many selective serotonin reuptake inhibitors (SSRIs) are CYP2D6 substrates including fluvoxamine. Although clinical evidence of interactions is lacking, plasma concentrations of SSRIs metabolized by CYP2D6 may be increased if bupropion is added. In addition, in vitro studies suggest that fluvoxamine inhibits the hydroxylation of bupropion.
Formoterol; Mometasone: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Fosphenytoin: (Moderate) Monitor for loss of efficacy of bupropion during coadministration of fosphenytoin as concurrent use may decrease bupropion exposure. A bupropion dose adjustment may be necessary; do not exceed maximum dose.
Frovatriptan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with bupropion is necessary; the risk is increased in CYP2D6 poor metabolizers. Based on in vitro data, gefitinib is metabolized to O-desmethyl gefitinib by CYP2D6 and bupropion is a strong CYP2D6 inhibitor. In healthy CYP2D6 poor metabolizers, the concentration of O-desmethyl gefitinib was not measurable and mean exposure to gefitinib was 2-fold higher compared to extensive metabolizers. The impact of CYP2D6 inhibitors on gefitinib pharmacokinetics has not been evaluated; however, the manufacturer recommends precautions based on exposure in patients with poor CYP2D6 metabolism.
Givosiran: (Moderate) If possible, avoid concomitant use of dextromethorphan with givosiran due to the risk of increased dextromethorphan-related adverse reactions. If use is necessary, consider decreasing the dextromethorphan dose. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Dextromethorphan is a sensitive CYP2D6 substrate. Givosiran may moderately reduce hepatic CYP2D6 enzyme activity because of its pharmacological effects on the hepatic heme biosynthesis pathway.
Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Glycopyrrolate; Formoterol: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Grapefruit juice: (Minor) Intake of grapefruit juice or seville orange juice increased dextromethorphan bioavailability in one study. Patients with increased concentrations of dextromethorphan may experience drowsiness or serotonergic side effects (dizziness, nervousness or restlessness, nausea, vomiting, stomach upset) not usually noted with prescribed or nonprescription product doses. Grapefruit juice and seville orange juice contain compounds that can inhibit P-glycoprotein in the intestinal wall, and dextromethorphan absorption may be affected by P-glycoprotein activity. Dextromethorphan is largely metabolized by CYP2D6, so this particular interaction with grapefruit juice may be more relevant in patients who are poor CYP2D6 metabolizers.
Guaifenesin; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Guanfacine: (Moderate) There is one case report that describes a grand mal seizure that occurred in a child of 10 years of age receiving guanfacine and bupropion concurrently. It is not possible, based on this limited report, to determine if guanfacine was a contributor to the event. Causality has not been established.
Haloperidol: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. In addition, bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by the CYP2D6 isoenzyme, such as haloperidol, should be approached with caution. Dosage reductions of haloperidol may be needed. Conversely, if bupropion therapy is discontinued, the antipsychotic dosage may need to be increased in some patients.
Homatropine; Hydrocodone: (Moderate) Additive anticholinergic effects may be seen when homatropine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6.
Hydrocortisone: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Hydromorphone: (Moderate) Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures.
Hyoscyamine: (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Contraindicated) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving intravenous methylene blue. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with intravenous methylene blue, bupropion should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits of methylene blue outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of methylene blue. It is not known if administration of methylene blue by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. (Major) Because of the potential risk and severity of serotonin syndrome, coadministration of dextromethorphan and IV methylene blue should be avoided if possible. Methylene blue has been demonstrated to be a potent monoamine oxidase inhibitor (MAOI) and may cause potentially fatal serotonin toxicity (serotonin syndrome) when combined with serotonin reuptake inhibitors (SRIs). Dextromethorphan increases central serotonin effects. If methylene blue is judged to be indicated, all SRIs, including dextromethorphan, must be ceased prior to treatment/procedure/surgery. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Ibuprofen; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Iloperidone: (Major) Reduce the iloperidone dose by one-half if coadministered with bupropion. If bupropion is discontinued, increase the iloperidone dose to the previous level. Increased iloperidone exposure may occur with concurrent use. Additionally, bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. Iloperidone is a CYP2D6 substrate. Bupropion is a strong inhibitor of CYP2D6. Coadministration of other strong CYP2D6 inhibitors increased mean steady-state peak concentrations of iloperidone and its metabolite P88, by up to 3-fold, and decreased mean steady-state peak concentrations of its metabolite P95 by one-half.
Imatinib: (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Imipramine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with tricyclic antidepressants. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as tricyclic antidepressants. Use low initial doses of bupropion and increase the dose gradually. Monitor patients for an increase in tricyclic antidepressant-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases; a dose reduction of the tricyclic antidepressant may be necessary. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Tricyclic antidepressants are CYP2D6 substrates and bupropion is a CYP2D6 inhibitor.
Indacaterol; Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Iobenguane I 131: (Major) Discontinue bupropion for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart bupropion until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as bupropion, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy.
Iodixanol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Bupropion should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ioflupane I 123: (Major) Hold bupropion for 8 days, or at least 5 medication half-lives, prior to performing dopamine transporter (DAT) imaging with radiolabeled ioflupane. Bupropion binds to the dopamine transporter which may interfere with striatal tracer binding and increase the risk for a false-positive scan.
Iohexol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Bupropion should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iomeprol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Bupropion should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopamidol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Bupropion should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopromide: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Bupropion should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ioversol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Bupropion should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Isavuconazonium: (Moderate) Caution and close monitoring are advised when administering isavuconazonium concurrently with buproprion, as decreased buproprion serum concentrations may result. If decreased bupropion efficacy is noted, it may be necessary to increase the dose (not to exceed the maximum recommended dose). Isavuconazole, the active moiety of isavuconazonium, is an inducer of hepatic isoenzyme CYP2B6; bupropion is metabolized by this enzyme.
Isocarboxazid: (Contraindicated) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotonergic agent and its active metabolites. (Contraindicated) Monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with bupropion or within 14 days of discontinuing treatment with bupropion. Conversely, bupropion should not be initiated within 14 days of stopping an MAOI. There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism, such as MAOIs.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function such as rifampin. Pharmacokinetic studies describe patients who developed subtherapeutic bupropion serum concentrations when enzyme-inducing agents were added. In healthy volunteers, coadministration of bupropion with rifampin reduced the mean AUC of bupropion by 3-fold and the mean half-life from 15.9 hours to 8.2 hours.
Isoniazid, INH; Rifampin: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function such as rifampin. Pharmacokinetic studies describe patients who developed subtherapeutic bupropion serum concentrations when enzyme-inducing agents were added. In healthy volunteers, coadministration of bupropion with rifampin reduced the mean AUC of bupropion by 3-fold and the mean half-life from 15.9 hours to 8.2 hours.
Isosulfan Blue: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Bupropion should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ivosidenib: (Moderate) Monitor for loss of efficacy of bupropion during coadministration of ivosidenib. A bupropion dose increase may be necessary; do not exceed the maximum recommended dose. Bupropion is a sensitive substrate of CYP2B6; ivosidenib may induce CYP2B6 leading to decreased bupropion concentrations.
Lasmiditan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and bupropion. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management. (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Lemborexant: (Moderate) Monitor for loss of efficacy of bupropion during coadministration of lemborexant as concurrent use may decrease bupropion exposure. A bupropion dose adjustment may be necessary; do not exceed maximum dose for the specific product prescribed. Bupropion is a sensitive substrate of CYP2B6; lemborexant is a weak CYP2B6 inducer.
Levodopa: (Moderate) Use bupropion and levodopa with caution and monitor for CNS toxicity, including restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness, which may result from cumulative dopamine agonist effects.
Levomilnacipran: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with levomilnacipran. Dextromethorphan has serotonergic activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Linezolid: (Contraindicated) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving linezolid, an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with linezolid, bupropion should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of linezolid. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
Lisdexamfetamine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including lisdexamfetamine. Use low initial doses of bupropion and increase the dose gradually.
Lofexidine: (Moderate) Monitor for orthostatic hypotension and bradycardia during concurrent use of lofexidine and bupropion. Coadministration may increase lofexidine exposure. Lofexidine is a CYP2D6 substrate; bupropion is a strong CYP2D6 inhibitor. Coadministration with a strong CYP2D6 inhibitor increased the lofexidine AUC by 28%.
Lopinavir; Ritonavir: (Moderate) Concurrent administration of bupropion with ritonavir results in decreased concentrations of bupropion and its active metabolite. According to the manufacturers of bupropion, increased doses of bupropion may be necessary during concurrent therapy; however, the maximum recommended dose of bupropion should not be exceeded. Closely monitor bupropion efficacy if these drugs are given together. Ritonavir induces CYP2B6, which is responsible for bupropion's metabolism. In one study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. In addition, exposure to the active metabolite of bupropion (hydroxybupropion) was decreased by 23%. When given with ritonavir 600 mg twice daily, the AUC and Cmax of bupropion decreased by 66% and 63% respectively and exposure to hydroxybupropion decreased by 78%.
Loratadine; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Lorcaserin: (Moderate) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, bupropion. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with lorcaserin. Both medications have serotonergic activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan, increasing dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased dextromethorphan exposure may result in adverse effects consistent with the serotonin syndrome.
Loxapine: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of bupropion by decreasing its systemic exposure. If used together, monitor patients closely for loss of bupropion efficacy; a bupropion dosage adjustment may be required to obtain the desired therapeutic effect. Do not exceed the maximum recommended dose. Bupropion is a substrate of CYP2B6; in vitro data suggest that lumacaftor may induce this enzyme.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of bupropion by decreasing its systemic exposure. If used together, monitor patients closely for loss of bupropion efficacy; a bupropion dosage adjustment may be required to obtain the desired therapeutic effect. Do not exceed the maximum recommended dose. Bupropion is a substrate of CYP2B6; in vitro data suggest that lumacaftor may induce this enzyme.
Lurasidone: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored.
Maprotiline: (Major) Concurrent administration of maprotiline with bupropion should be undertaken only with extreme caution due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus may reduce the clearance of maprotiline leading to a potential for increased Cmax, AUC and half-life. Maprotiline appears to be metabolized via CYP2D6. Low initial dosing and gradual dose increases of both drugs should be employed. If bupropion is added to a regimen of a patient already receiving maprotiline, the need to reduce the maprotiline dosage should be considered.
Memantine: (Moderate) Dextromethorphan is a NMDA antagonist and may lead to additive adverse effects if combined with memantine, also an NMDA antagonist. It may be prudent to avoid coadministration of dextromethorphan with memantine. If coadministration cannot be avoided, monitor for increased adverse effects such as agitation, dizziness and other CNS events.
Meperidine: (Moderate) Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures.
Methadone: (Moderate) Consider a reduced dose of methadone with frequent monitoring for respiratory depression and sedation if concurrent use of bupropion is necessary. If bupropion is discontinued, methadone plasma concentrations can decrease resulting in reduced efficacy and potential withdrawal syndrome in a patient who has developed physical dependence to methadone. Methadone is a substrate of CYP3A4, CYP2B6, CYP2C19, CYP2C9, and CYP2D6; bupropion is a strong CYP2D6 inhibitor. Concomitant use with bupropion can increase methadone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of methadone.
Methamphetamine: (Major) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as methamphetamine. If used together, use low initial doses of bupropion and increase the dose gradually.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Contraindicated) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving intravenous methylene blue. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with intravenous methylene blue, bupropion should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits of methylene blue outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of methylene blue. It is not known if administration of methylene blue by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. (Major) Because of the potential risk and severity of serotonin syndrome, coadministration of dextromethorphan and IV methylene blue should be avoided if possible. Methylene blue has been demonstrated to be a potent monoamine oxidase inhibitor (MAOI) and may cause potentially fatal serotonin toxicity (serotonin syndrome) when combined with serotonin reuptake inhibitors (SRIs). Dextromethorphan increases central serotonin effects. If methylene blue is judged to be indicated, all SRIs, including dextromethorphan, must be ceased prior to treatment/procedure/surgery. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Methohexital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery.
Methscopolamine: (Moderate) Additive anticholinergic effects may be seen when methscopolamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Methylene Blue: (Contraindicated) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving intravenous methylene blue. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with intravenous methylene blue, bupropion should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits of methylene blue outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of methylene blue. It is not known if administration of methylene blue by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. (Major) Because of the potential risk and severity of serotonin syndrome, coadministration of dextromethorphan and IV methylene blue should be avoided if possible. Methylene blue has been demonstrated to be a potent monoamine oxidase inhibitor (MAOI) and may cause potentially fatal serotonin toxicity (serotonin syndrome) when combined with serotonin reuptake inhibitors (SRIs). Dextromethorphan increases central serotonin effects. If methylene blue is judged to be indicated, all SRIs, including dextromethorphan, must be ceased prior to treatment/procedure/surgery. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Methylphenidate Derivatives: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including methylphenidate. Use low initial doses of bupropion and increase the dose gradually.
Methylphenidate: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including methylphenidate. Use low initial doses of bupropion and increase the dose gradually.
Methylprednisolone: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Metoclopramide: (Major) When metoclopramide is used with a potent CYP2D6 inhibitor for the treatment of gastroesophageal reflux (GERD), dosage reductions of oral metoclopramide are required, with maximum oral dosage not to exceed 30 mg/day (e.g., 5 mg 4 times daily or 10 mg 3 times daily). There is a known increase in metoclopramide exposure and an increased risk for extrapyramidal adverse reactions. Metoclopramide is a substrate of CYP2D6 and bupropion is a strong CYP2D6 inhibitor. The manufacturer recommends avoidance of bupropion when oral metoclopramide is used in patients with diabetic gastroparesis. Healthy patients given 20 mg of metoclopramide and a potent CYP2D6 inhibitor for 8 days had a 40% and 90% increase in metoclopramide Cmax and AUC, respectively, compared to patients who received metoclopramide alone.
Metoprolol: (Moderate) Monitor for metoprolol-related adverse reactions, including bradycardia and hypotension, during coadministration with bupropion. Concomitant use may increase metoprolol serum concentrations which would decrease the cardioselectivity of metoprolol. Metoprolol is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Coadministration with strong CYP2D6 inhibitors has been shown to double metoprolol concentrations.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for metoprolol-related adverse reactions, including bradycardia and hypotension, during coadministration with bupropion. Concomitant use may increase metoprolol serum concentrations which would decrease the cardioselectivity of metoprolol. Metoprolol is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Coadministration with strong CYP2D6 inhibitors has been shown to double metoprolol concentrations.
Mexiletine: (Major) Coadministration of bupropion and mexiletine can increase the exposure of mexiletine. If used together, it may be necessary to decrease the dose of mexiletine and slowly titrate to effect. Mexiletine is primarily metabolized via CYP2D6 and bupropion and its metabolites are inhibitors of CYP2D6.
Midazolam: (Moderate) Bupropion is contraindicated in patients undergoing abrupt withdrawal of benzodiazepines since the risk of seizures associated with bupropion may be increased. Excessive use of benzodiazepines is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion.
Midostaurin: (Moderate) Monitor for loss of efficacy of bupropion during coadministration of midostaurin as concurrent use may decrease bupropion exposure. A bupropion dose adjustment may be necessary; do not exceed maximum dose. Bupropion is a sensitive substrate of CYP2B6; midostaurin is a moderate CYP2B6 inducer.
Mifepristone: (Moderate) Monitor for an increase in bupropion-related adverse reactions during coadministration of mifepristone as concurrent use may increase bupropion exposure. A bupropion dose adjustment may be necessary. Bupropion is a sensitive substrate of CYP2B6; mifepristone is a moderate CYP2B6 inhibitor.
Milnacipran: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with milnacipran. Dextromethorphan has serotonergic activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Mirabegron: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Mirtazapine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with mirtazapine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Mitapivat: (Moderate) Monitor for loss of efficacy of bupropion during coadministration of mitapivat as concurrent use may decrease bupropion exposure. A bupropion dose adjustment may be necessary; do not exceed maximum dose. Bupropion is a sensitive substrate of CYP2B6; mitapivat is a weak CYP2B6 inducer.
Modafinil: (Major) Bupropion is associated with a dose-related risk of seizures. It is unclear whether modafinil lowers the seizure threshold. Seizures have occurred during post-marketing use of modafinil, although the frequency is unknown.
Molindone: (Major) Drugs which may lower the seizure threshold, such as molindone, should be used with great caution or avoided in patients taking bupropion. The manufacturer recommends low initial dosing and slow dosage titration of bupropion if this combination must be used concurrently; the patient should be closely monitored.
Mometasone: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Monoamine oxidase inhibitors: (Contraindicated) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotonergic agent and its active metabolites. (Contraindicated) Monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with bupropion or within 14 days of discontinuing treatment with bupropion. Conversely, bupropion should not be initiated within 14 days of stopping an MAOI. There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism, such as MAOIs.
Morphine: (Moderate) Monitor for seizure activity during concomitant bupropion and morphine use. Bupropion is associated with a dose-related seizure risk and excessive opioid use also increases seizure risk.
Morphine; Naltrexone: (Moderate) Monitor for seizure activity during concomitant bupropion and morphine use. Bupropion is associated with a dose-related seizure risk and excessive opioid use also increases seizure risk.
Naproxen; Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Naratriptan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with bupropion; adjust the nebivolol dose according to blood pressure response. Concomitant use may increase the exposure of nebivolol. Nebivolol is a CYP2D6 substrate and bupropion is a moderate CYP2D6 inhibitor.
Nebivolol; Valsartan: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with bupropion; adjust the nebivolol dose according to blood pressure response. Concomitant use may increase the exposure of nebivolol. Nebivolol is a CYP2D6 substrate and bupropion is a moderate CYP2D6 inhibitor.
Nefazodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with nefazodone. Both drugs have serotonergic activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Nelfinavir: (Minor) In vitro studies suggest that nelfinavir inhibits the hydroxylation of bupropion. The clinical significance of this finding is unknown.
Neostigmine; Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Nicotine: (Moderate) Monitor blood pressure during concomitant bupropion and nicotine use. Clinical trial data suggest a higher incidence of treatment-emergent hypertension during concomitant use.
Niraparib; Abiraterone: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Nirmatrelvir; Ritonavir: (Moderate) Concurrent administration of bupropion with ritonavir results in decreased concentrations of bupropion and its active metabolite. According to the manufacturers of bupropion, increased doses of bupropion may be necessary during concurrent therapy; however, the maximum recommended dose of bupropion should not be exceeded. Closely monitor bupropion efficacy if these drugs are given together. Ritonavir induces CYP2B6, which is responsible for bupropion's metabolism. In one study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. In addition, exposure to the active metabolite of bupropion (hydroxybupropion) was decreased by 23%. When given with ritonavir 600 mg twice daily, the AUC and Cmax of bupropion decreased by 66% and 63% respectively and exposure to hydroxybupropion decreased by 78%.
Nitroglycerin: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Bupropion should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Nortriptyline: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with tricyclic antidepressants. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as tricyclic antidepressants. Use low initial doses of bupropion and increase the dose gradually. Monitor patients for an increase in tricyclic antidepressant-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases; a dose reduction of the tricyclic antidepressant may be necessary. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Tricyclic antidepressants are CYP2D6 substrates and bupropion is a CYP2D6 inhibitor.
Olanzapine: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored.
Olanzapine; Fluoxetine: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of fluoxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and fluoxetine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold. (Moderate) Monitor for increased fluoxetine-related adverse effects if coadministered with bupropion. Concomitant use may increase fluoxetine exposure. Fluoxetine is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor.
Olanzapine; Samidorphan: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored.
Oliceridine: (Moderate) If concomitant use of oliceridine and dextromethorphan is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and bupropion is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and bupropion may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If bupropion is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Olopatadine; Mometasone: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Oritavancin: (Moderate) Administration of oritavancin, a weak inducer of CYP2D6 and CYP3A4, with dextromethorphan resulted in a 31% reduction in the ratio of dextromethorphan to dextrorphan concentrations in the urine. The efficacy of dextromethorphan may be reduced if these drugs are administered concurrently.
Oxcarbazepine: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold.
Oxymorphone: (Moderate) Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures.
Ozanimod: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome.
Paliperidone: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as paliperidone. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored.
Panobinostat: (Major) Avoid coadministrating panobinostat with sensitive CYP2D6 substrates such as dextromethorphan due to increased dextromethorphan exposure. Consider alternatives to dextromethorphan if possible. If concomitant use cannot be avoided, closely monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Panobinostat inhibits CYP2D6. When a single 60-mg dose of dextromethorphan (DM) was administered after 3 doses of panobinostat (20 mg on days 3, 5, and 8), the DM Cmax increased by 20% to 200% and DM exposure (AUC) increased by 20% to 130% (interquartile ranges) vs. when DM was given alone; however, the change in exposure was highly variable among the patients studied.
Paroxetine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with bupropion is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold.
Pazopanib: (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
Peginterferon Alfa-2b: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Pentazocine; Naloxone: (Moderate) Plasma concentrations of opiate agents metabolized by CYP2D6, such as pentazocine, may be increased if bupropion, an inhibitor of the CYP2D6 isoenzyme, is added. Dosage reductions of pentazocine may be needed. Conversely, if bupropion therapy is discontinued, dosages of pentazocine may need to be adjusted upward in some patients.
Pentobarbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery.
Perphenazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of perphenazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of perphenazine may result in extrapyramidal symptoms, somnolence, or other adverse effects.
Perphenazine; Amitriptyline: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of perphenazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of perphenazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with tricyclic antidepressants. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as tricyclic antidepressants. Use low initial doses of bupropion and increase the dose gradually. Monitor patients for an increase in tricyclic antidepressant-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases; a dose reduction of the tricyclic antidepressant may be necessary. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Tricyclic antidepressants are CYP2D6 substrates and bupropion is a CYP2D6 inhibitor.
Phendimetrazine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of phendimetrazine is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary.
Phenelzine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotonergic agent and its active metabolites. (Contraindicated) Monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with bupropion or within 14 days of discontinuing treatment with bupropion. Conversely, bupropion should not be initiated within 14 days of stopping an MAOI. There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism, such as MAOIs.
Phenobarbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. (Moderate) Additive anticholinergic effects may be seen when scopolamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Phentermine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including phentermine. Use low initial doses of bupropion and increase the dose gradually.
Phentermine; Topiramate: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including phentermine. Use low initial doses of bupropion and increase the dose gradually.
Phenytoin: (Moderate) Monitor for loss of efficacy of bupropion during coadministration of phenytoin as concurrent use may decrease bupropion exposure. A bupropion dose adjustment may be necessary; do not exceed maximum dose.
Pimozide: (Contraindicated) Coadministration of pimozide and bupropion is contraindicated due to the potential for increased pimozide exposure. Elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death. The risk of seizure may also be increased as both drugs lower the seizure threshold. Bupropion is a strong CYP2D6 inhibitor; pimozide is a CYP2D6 substrate. Coadministration of pimozide with another strong CYP2D6 inhibitor increased the pimozide AUC by 151%.
Pitolisant: (Major) Initiate pitolisant at 8.9 mg once daily in patients taking bupropion; increase pitolisant after 7 days to a maximum dosage of 17.8 mg once daily. If bupropion is initiated in a patient on a stable dose of pitolisant, reduce the pitolisant dose by half. Pitolisant is a CYP2D6 substrate; bupropion is a strong CYP2D6 inhibitor. Coadministration of strong CYP2D6 inhibitors increases pitolisant exposure by 2.2-fold.
Prednisolone: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Prednisone: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Primidone: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery.
Procarbazine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with procarbazine, an antineoplastic agent with monoamine oxidase inhibitor (MAOI) activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Prochlorperazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of prochlorperazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of prochlorperazine may result in extrapyramidal symptoms, somnolence, or other adverse effects.
Promethazine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as promethazine. Use low initial doses of bupropion and increase the dose gradually.
Promethazine; Dextromethorphan: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as promethazine. Use low initial doses of bupropion and increase the dose gradually.
Promethazine; Phenylephrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as promethazine. Use low initial doses of bupropion and increase the dose gradually.
Propafenone: (Moderate) Monitor for increased propafenone toxicity if coadministered with bupropion; concurrent use may increase propafenone exposure and therefore increase the risk of proarrhythmias. Avoid simultaneous use of propafenone and bupropion with a CYP3A4 inhibitor. Propafenone is a CYP3A4 and CYP2D6 substrate; bupropion is a strong CYP2D6 inhibitor. (Minor) Use of dextromethorphan with propafenone might increase dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. In vitro studies suggest that propafenone inhibits CYP2D6, but clinically relevant interactions have not been reported due to this potential action. Dextromethorphan is a CYP2D6 substrate.
Propantheline: (Moderate) Additive anticholinergic effects may be seen when propantheline is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Propranolol: (Minor) Monitor for an increased incidence of propranolol-related adverse effects if bupropion and propranolol are used concomitantly. Coadministration of bupropion and propranolol may result in increased plasma concentrations of propranolol. Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Propranolol is a CYP2D6 substrate.
Protriptyline: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with tricyclic antidepressants. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as tricyclic antidepressants. Use low initial doses of bupropion and increase the dose gradually. Monitor patients for an increase in tricyclic antidepressant-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases; a dose reduction of the tricyclic antidepressant may be necessary. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Tricyclic antidepressants are CYP2D6 substrates and bupropion is a CYP2D6 inhibitor.
Pseudoephedrine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Pseudoephedrine; Triprolidine: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as pseudoephedrine. Use low initial doses of bupropion and increase the dose gradually.
Quinidine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of quinidine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and quinidine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Quinine: (Moderate) Although clinical drug interaction studies have not been performed, antimalarial doses of quinine (greater than or equal to 600 mg/day in adults) may inhibit the metabolism of CYP2D6 substrates such as dextromethorphan and may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Ranolazine: (Moderate) Bupropion inhibits CYP2D6. Coadministration of bupropion with medications that are metabolized by CYP2D6, like ranolazine, may result in increased ranolazine plasma concentrations if bupropion is added.
Rasagiline: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including rasagiline. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Contraindicated) Monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with bupropion or within 14 days of discontinuing treatment with bupropion. Conversely, bupropion should not be initiated within 14 days of stopping an MAOI. There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism, such as MAOIs. The manufacturer of rasagiline advises against concurrent use with any antidepressant.
Rifampin: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function such as rifampin. Pharmacokinetic studies describe patients who developed subtherapeutic bupropion serum concentrations when enzyme-inducing agents were added. In healthy volunteers, coadministration of bupropion with rifampin reduced the mean AUC of bupropion by 3-fold and the mean half-life from 15.9 hours to 8.2 hours.
Risperidone: (Moderate) Monitor for an increase in risperidone-related adverse effects if concomitant use with bupropion is necessary and reduce risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, an anticipatory dosage decrease may be considered prior to initiation of bupropion. Concomitant use may increase risperidone exposure. Additionally, bupropion is associated with a dose-related increase in seizures; antipsychotics may increase this risk. Risperidone is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Concomitant use with other strong CYP2D6 inhibitors increased risperidone overall exposure by 2.5- to 9-fold.
Ritonavir: (Moderate) Concurrent administration of bupropion with ritonavir results in decreased concentrations of bupropion and its active metabolite. According to the manufacturers of bupropion, increased doses of bupropion may be necessary during concurrent therapy; however, the maximum recommended dose of bupropion should not be exceeded. Closely monitor bupropion efficacy if these drugs are given together. Ritonavir induces CYP2B6, which is responsible for bupropion's metabolism. In one study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. In addition, exposure to the active metabolite of bupropion (hydroxybupropion) was decreased by 23%. When given with ritonavir 600 mg twice daily, the AUC and Cmax of bupropion decreased by 66% and 63% respectively and exposure to hydroxybupropion decreased by 78%.
Rizatriptan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Rolapitant: (Moderate) Rolapitant increases exposure to dextromethorphan. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Rolapitant is a moderate CYP2D6 inhibitor with a prolonged effect; the inhibitory effect of rolapitant is expected to persist beyond 28 days for an unknown duration. During drug interaction studies, exposure (AUC) to dextromethorphan following a single dose of rolapitant increased close to 3-fold on Days 8 and Day 22. The inhibition of CYP2D6 persisted on Day 28 with a 2.3-fold increase in dextromethorphan exposure (AUC), the last time point measured.
Safinamide: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
Scopolamine: (Moderate) Additive anticholinergic effects may be seen when scopolamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Secobarbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery.
Selegiline: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The manufacturer of bupropion contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with bupropion. After stopping treatment with bupropion, a time period equal to 4 to 5 half-lives of bupropion or any active metabolite should elapse before starting therapy with selegiline.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as stimulants including methylphenidate. Use low initial doses of bupropion and increase the dose gradually.
Serotonin-Receptor Agonists: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Sertraline: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with sertraline. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. In addition, sertraline inhibits CYP2D6 and may increase systemic dextromethorphan exposure. Increased dextromethorphan concentrations may result in adverse effects consistent with the serotonin syndrome.
Sodium Oxybate: (Major) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as sodium oxybate. The risk of seizures with bupropion is dose related and is also related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold. Consider these risks before initiating treatment If used together, use low initial doses of bupropion and increase the dose gradually.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for decreased efficacy and/or increased bupropion-related adverse effects if concomitant use of taurursodiol is necessary. A bupropion dose adjustment may be necessary. Concomitant use may alter bupropion exposure. Bupropion is a sensitive substrate of CYP2B6; taurursodiol is a weak CYP2B6 inhibitor and inducer. The net effect on bupropion exposure is unknown.
Solriamfetol: (Moderate) Monitor for dopamine-mediated effects including nausea, vomiting, dizziness, tremor, and changes in moods or behaviors if solriamfetol, a central dopamine and norepinephrine reuptake inhibitor, is administered with other dopaminergic drugs, such as bupropion. Caution is recommended since this combination has not been evaluated.
Sparsentan: (Moderate) Monitor for loss of efficacy of bupropion during coadministration of sparsentan as concurrent use may decrease bupropion exposure. A bupropion dose adjustment may be necessary; do not exceed maximum dose. Bupropion is a sensitive substrate of CYP2B6; sparsentan is a weak CYP2B6 inducer. Concomitant use decreased bupropion overall exposure by 33%.
St. John's Wort, Hypericum perforatum: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with St. John's Wort. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Stiripentol: (Moderate) Consider a dose adjustment of bupropion when coadministered with stiripentol. Coadministration may alter plasma concentrations of bupropion resulting in an increased risk of adverse reactions and/or decreased efficacy. Bupropion is a sensitive CYP2B6 substrate. In vitro data predicts inhibition or induction of CYP2B6 by stiripentol potentially resulting in clinically significant interactions.
Sumatriptan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Sumatriptan; Naproxen: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Tamoxifen: (Moderate) Monitor for decreased efficacy of tamoxifen if coadministration with bupropion is necessary. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. Bupropion is a strong CYP2D6 inhibitor. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors; plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the levels of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established.
Tamsulosin: (Moderate) Use caution if coadministration of bupropion with tamsulosin is necessary, especially at a tamsulosin dose higher than 0.4 mg, as the systemic exposure of tamsulosin may be increased resulting in increased treatment-related adverse reactions including hypotension, dizziness, and vertigo. Tamsulosin is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Concomitant treatment with another strong CYP2D6 inhibitor increased the Cmax and AUC of tamsulosin by a factor of 1.3 and 1.6, respectively.
Tedizolid: (Minor) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with tedizolid. Tedizolid is an antibiotic that is also a weak, reversible, non-selective MAO inhibitor in vitro. In theory, tedizolid has potential to interact with serotonergic agents, but interactions are thought to be unlikely. In clinical interaction studies with a related antibiotic (linezolid), interactions with dextromethorphan were studied, but serotonin syndrome or adverse effects were not reported. No drug-drug interaction precautions with dextromethorphan are specifically mentioned in the tedizolid label. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Terbinafine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Theophylline, Aminophylline: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as aminophylline. The manufacturer recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. In addition, when bupropion is used for smoking cessation, it should be noted that cessation of smoking may result in elevated serum concentrations of some drugs that are hepatically metabolized, such as theophylline or aminophylline, due to lowered induction of hepatic oxidative microsomal enzymes (tobacco smoke induces hepatic enzymes). Downward dosage adjustments of such drugs and more frequent monitoring may be required during smoking cessation. (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as theophylline. The manufacturer recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. In addition, when bupropion is used for smoking cessation, it should be noted that cessation of smoking may result in elevated serum concentrations of some drugs that are hepatically metabolized, such as theophylline or aminophylline, due to lowered induction of hepatic oxidative microsomal enzymes (tobacco smoke induces hepatic enzymes). Downward dosage adjustments of such drugs and more frequent monitoring may be required during smoking cessation.
Thioridazine: (Contraindicated) Bupropion is a strong inhibitor of CYP2D6 and the use of thioridazine with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias resulting from elevated serum concentrations of thioridazine. In addition, bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines, such as thioridazine, on lowering the seizure threshold.
Thiotepa: (Moderate) The concomitant use of thiotepa and bupropion may increase the exposure of bupropion but decrease hydroxybupropion exposure; however, the clinical relevance of this interaction is unknown. Dosage adjustment of bupropion may be necessary based on clinical response. Thiotepa is a CYP2B6 inhibitor in vitro; bupropion is a sensitive substrate of CYP2B6 in vitro.
Thiothixene: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored.
Timolol: (Minor) Monitor for an increased incidence of timolol-related adverse effects if bupropion and timolol are used concomitantly. Coadministration of bupropion and timolol may result in increased plasma concentrations of timolol. Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Timolol is a CYP2D6 substrate.
Tipranavir: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of tipranavir is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and tipranavir is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Tocilizumab: (Minor) Concomitant use of tocilizumab and dextromethorphan may lead to a decrease in the efficacy of dextromethorphan; clinical significance of this interaction is not known or established. Inhibition of IL-6 signaling by tocilizumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping tocilizumab. A 5% decrease in dextromethorphan exposure and a 29% decrease in its metabolite, dextrorphan was noted 1 week after a single tocilizumab infusion. In vitro, tocilizumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Dextromethorphan is a CYP2D6 substrate.
Tolterodine: (Moderate) Bupropion exhibits moderate anticholinergic effects. Clinicians should keep this in mind when using antimuscarinics and other medications with anticholinergic activity in combination with bupropion.
Tramadol: (Moderate) Monitor for reduced efficacy of tramadol, signs of opioid withdrawal, seizures, or serotonin syndrome if coadministration with bupropion is necessary. If bupropion is discontinued, consider a dose reduction of tramadol and frequently monitor for signs of respiratory depression and sedation. Tramadol is a CYP2D6 substrate and bupropion is a CYP2D6 inhibitor. Concomitant use of tramadol with CYP2D6 inhibitors can increase the plasma concentration of tramadol and decrease the plasma concentration of the active metabolite M1. Since M1 is a more potent mu-opioid agonist, decreased M1 exposure could result in decreased therapeutic effects, and may result in signs and symptoms of opioid withdrawal in patients who have developed physical dependence to tramadol. Increased tramadol exposure can result in increased or prolonged therapeutic effects and increased risk for serious adverse events including seizures and serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Tramadol; Acetaminophen: (Moderate) Monitor for reduced efficacy of tramadol, signs of opioid withdrawal, seizures, or serotonin syndrome if coadministration with bupropion is necessary. If bupropion is discontinued, consider a dose reduction of tramadol and frequently monitor for signs of respiratory depression and sedation. Tramadol is a CYP2D6 substrate and bupropion is a CYP2D6 inhibitor. Concomitant use of tramadol with CYP2D6 inhibitors can increase the plasma concentration of tramadol and decrease the plasma concentration of the active metabolite M1. Since M1 is a more potent mu-opioid agonist, decreased M1 exposure could result in decreased therapeutic effects, and may result in signs and symptoms of opioid withdrawal in patients who have developed physical dependence to tramadol. Increased tramadol exposure can result in increased or prolonged therapeutic effects and increased risk for serious adverse events including seizures and serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Tranylcypromine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotonergic agent and its active metabolites. (Contraindicated) Monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with bupropion or within 14 days of discontinuing treatment with bupropion. Conversely, bupropion should not be initiated within 14 days of stopping an MAOI. There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism, such as MAOIs.
Triamcinolone: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Triazolam: (Moderate) Bupropion is contraindicated in patients undergoing abrupt withdrawal of benzodiazepines since the risk of seizures associated with bupropion may be increased. Excessive use of a benzodiazepine is associated with an increased seizure risk upon discontinuation of the drug; seizures may be more likely to occur in these patients during concurrent use of bupropion.
Tricyclic antidepressants: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with tricyclic antidepressants. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as tricyclic antidepressants. Use low initial doses of bupropion and increase the dose gradually. Monitor patients for an increase in tricyclic antidepressant-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases; a dose reduction of the tricyclic antidepressant may be necessary. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Tricyclic antidepressants are CYP2D6 substrates and bupropion is a CYP2D6 inhibitor.
Trifluoperazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of trifluoperazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of trifluoperazine may result in extrapyramidal symptoms, somnolence, or other adverse effects.
Trihexyphenidyl: (Moderate) Additive anticholinergic effects may be seen when trihexyphenidyl is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Trimipramine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with tricyclic antidepressants. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as tricyclic antidepressants. Use low initial doses of bupropion and increase the dose gradually. Monitor patients for an increase in tricyclic antidepressant-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases; a dose reduction of the tricyclic antidepressant may be necessary. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Tricyclic antidepressants are CYP2D6 substrates and bupropion is a CYP2D6 inhibitor.
Trospium: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like trospium and bupropion are used concomitantly. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function and temperature regulation. While CNS-related side effects such as drowsiness and blurred vision are not typically noted with trospium, they may occur in some patients.
Valproic Acid, Divalproex Sodium: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Use with caution when valproic acid and its derivatives (valproate, divalproex) are used for other purposes, as additive CNS reactions may be possible. Pharmacokinetic interactions have not been noted.
Vemurafenib: (Minor) Use of dextromethorphan with vemurafenib increases dextromethorphan exposure. Vemurafenib is a weak CYP2D6 inhibitor and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Coadministration of vemurafenib and dextromethorphan increased the AUC of dextromethorphan by 47% and the dextromethorphan Cmax by 36%.
Venlafaxine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with venlafaxine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
Vilazodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with vilazodone. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Viloxazine: (Moderate) Monitor for an increase in dextromethorphan-related adverse effects if concomitant use of viloxazine is necessary. Concomitant use may increase dextromethorphan exposure; viloxazine is a weak CYP2D6 inhibitor and dextromethorphan is a CYP2D6 substrate.
Vortioxetine: (Major) The primary isoenzyme involved in the metabolim of vortioxetine is CYP2D6; therefore, the manufacturer recommends a reduction in the vortioxetine dose by one-half during co-administration with strong inhibitors of CYP2D6 such as bupropion. The vortioxetine dose should be increased to the original level when the CYP2D6 inhibitor is discontinued. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with vortioxetine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Warfarin: (Moderate) When bupropion is used for smoking cessation, be aware that changes in the INR may occur in patients previously stabilized on warfarin as tobacco smoking is reduced or halted, as smoking affects CYP1A2, one of the enzymes involved in warfarin metabolism. Physiological changes resulting from smoking cessation, with or without treatment with bupropion, may alter the pharmacokinetics or pharmacodynamics of certain drugs (e.g.,warfarin) for which dosage adjustment may be necessary. A case report of potential interaction with warfarin and bupropion used for depression has been reported; when bupropion was abruptly halted in the patient prior to surgery, the patient's INR increased to 8.0. The authors could not discern a probable mechanism for the potential interaction, but the patient was also reducing his daily tobacco smoking status, Patients who are receiving warfarin with bupropion should be carefully monitored if the patient is also altering their smoking status.
Ziprasidone: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored.
Zolmitriptan: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Dextromethorphan; bupropion is a combination of dextromethorphan, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist and a sigma-1 receptor agonist, and bupropion, a relatively weak norepinephrine and dopamine neuronal reuptake inhibitor. When used together, bupropion increases plasma levels of dextromethorphan via competitive inhibition of cytochrome P450 2D6, which is the major metabolic pathway for dextromethorphan. The mechanism of dextromethorphan in the treatment of major depressive disorder is unclear.
Dextromethorphan; bupropion extended-release tablets are administered orally. Dextromethorphan is primarily metabolized in the liver by CYP2D6 to dextrorphan. Bupropion is a CYP2D6 inhibitor, thereby increasing plasma concentrations of dextromethorphan.
-Dextromethorphan: Plasma protein binding of dextromethorphan is 60 to 70%. In CYP2D6 extensive metabolizers, approximately 37 to 52% of the orally administered dose of dextromethorphan is recovered in the urine. Less than 2% of the administered dose is excreted as unchanged parent drug in the urine. In contrast, for CYP2D6 poor metabolizers approximately 45 to 83% of the administered dose is recovered in the urine. Approximately 26% of the administered dose is excreted as unchanged parent drug in the urine. Excretion of dextromethorphan is primarily by renal elimination of metabolites, and the mean elimination half-life was 22 hours when administered in combination with bupropion (a 3-fold increase from the elimination half-life of dextromethorphan when used as monotherapy).
-Bupropion: Plasma protein binding of bupropion is 84%. Bupropion is metabolized by CYP2B6 and is a potent inhibitor of CYP2D6. Bupropion is extensively metabolized to 3 active metabolites; hydroxybupropion, which is formed via hydroxylation of the tert-butyl group of bupropion, and the amino-alcohol isomers, threohydroxybupropion, and erythrohydroxybupropion, which are formed via reduction of the carbonyl group. In vitro findings indicate that CYP2B6 is the principal isoenzyme involved in the formation of hydroxybupropion, while CYP450 enzymes are not involved in the formation of the other metabolites. Based on results of an antidepressant screening test in mice, hydroxybupropion appears to be one-half as potent as bupropion, while threohydroxybupropion and erythrohydroxybupropion are 5-fold less potent. The major urinary metabolite is formed from oxidation of the bupropion side chain, which results in the formation of a glycine conjugate of meta-chlorobenzoic acid. Following oral administration of 200 mg bupropion, 87% and 10% of the radioactive dose was recovered in the urine and feces, respectively; only 0.5% of the oral dose was excreted as unchanged bupropion.The mean elimination half-life of bupropion is 15 hours. Half-lives of hydroxybupropion, erythrohydroxybupropion, and threohydroxybupropion are 35 hours, 44 hours, and 33 hours, respectively.
Affected Cytochrome P450 isoenzymes and drug transporters: CYP2D6, CYP2B6, OCT2, P-glycoprotein (P-gp)
-Dextromethorphan: Dextromethorphan is primarily metabolized by CYP2D6 isoenzyme and is a sensitive substrate; thus, clinically significant drug interactions are possible when coadministered with potent CYP2D6 inhibitors or inducers. Dextromethorphan is also a P-gp substrate. Dextromethorphan does not inhibit or induce CYP450 isoenzymes.
-Bupropion: Bupropion undergoes extensive metabolism by CYP2B6; clinically significant drug interactions are possible with drugs that are metabolized by or are inhibitors or inducers of this isoenzyme. In vitro data indicate that bupropion and hydroxybupropion are inhibitors of CYP2D6. In vitro data has also shown that bupropion and its 3 metabolites are also inhibitors of the renal organic transporter OCT2 to a clinically significant extent; however, in vivo drug interaction studies have not found clinically significant drug-drug interactions with OCT-2 substrates.
-Route-Specific Pharmacokinetics
Oral Route
Following oral administration of dextromethorphan; bupropion, dextromethorphan exhibits non-linear pharmacokinetics at steady-state with greater than dose-proportional changes in AUC and Cmax for varying doses of dextromethorphan [60 mg to 120 mg (0.67 to 1.33 times the maximum recommended dose of dextromethorphan; bupropion)] and less than dose-proportional changes for varying doses of bupropion [150 mg to 300 mg (0.71 to 1.43 times the maximum recommended dose of dextromethorphan; bupropion)]. Steady-state plasma concentration of dextromethorphan and bupropion are achieved within 8 days with dextromethorphan; bupropion. Following administration of dextromethorphan; bupropion, the accumulation ratios for dextromethorphan at steady-state are 20 and 32, respectively, based on Cmax and AUC0-12, compared to 1.3 and 1.4, respectively, for dextromethorphan given without bupropion. The accumulation ratios for bupropion at steady-state are 1.1 and 1.5, respectively based on Cmax and AUC0-12. Median Tmax was 3 hours for dextromethorphan and 2 hours for bupropion following administration of dextromethorphan; bupropion extended-release tablets. Cmax of the hydroxybupropion metabolite occurred approximately 3 hours post-dose and was approximately 14 times the peak level of bupropion and AUC was almost 19 times that of bupropion. The Cmax of the erythrohydroxybupropion and threohydroxybupropion metabolites occurred approximately 4 hours post-dose and were approximately equal to and 5 times greater than the parent compound, respectively and AUC values were 1.2 and 7 times that of bupropion, respectively. When dextromethorphan; bupropion was taken with food, Cmax was unchanged for dextromethorphan and increased by 3% for bupropion, while the AUC0-12 was reduced by 14 % and increased by 6%, respectively. Dextromethorphan; bupropion may be taken with or without food.
-Special Populations
Hepatic Impairment
No dose adjustment of dextromethorphan; bupropion is necessary for patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment. The pharmacokinetics of dextromethorphan; bupropion have not been evaluated in patients with severe (Child-Pugh class C); use is not recommended in these patients.
Renal Impairment
A reduced dose of dextromethorphan; bupropion is recommended for patients with moderate renal impairment (eGFR 30 to 59 mL/minute/1.73 m2). The pharmacokinetics of dextromethorphan; bupropion have not been evaluated in patients with severe renal impairment (eGFR less than 30 mL/minute/1.73 m2); use is not recommended.
Pediatrics
No studies were conducted to evaluate the pharmacokinetics of dextromethorphan; bupropion in the pediatric population.
Geriatric
No studies were conducted to evaluate the pharmacokinetics of dextromethorphan; bupropion in patients 65 years of age or older.
Gender Differences
No clinically significant pharmacokinetic differences based on sex have been observed for dextromethorphan; bupropion.
Ethnic Differences
No clinically significant pharmacokinetic differences based on race or ethnicity have been observed for dextromethorphan; bupropion.