Version July 2025
Contrave is not approved for use in the treatment of major depressive disorder or other psychiatric disorders. Contrave contains bupropion, the same active ingredient as some other antidepressant medications (including, but not limited to, Wellbutrin, Wellbutrin SR, Wellbutrin XL, and Aplenzin). Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials. These trials did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in subjects over age 24; there was a reduction in risk with antidepressant use in subjects aged 65 and older. In patients of all ages who are started on Contrave, monitor closely for worsening, and for the emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber. Contrave is not approved for use in pediatric patients.
Weight management, chronic (alternative agent):
Note: For use as an adjunct to diet and exercise in patients who cannot take preferred agents and who have a BMI ≥30 kg/m2 or patients with a BMI ≥27 kg/m2 and ≥1 weight-associated comorbidity (eg, dyslipidemia) (Ref). Avoid use in patients with uncontrolled hypertension, seizure disorder, eating disorder, use of other bupropion-containing products, chronic opioid use, or use within 14 days of monoamine oxidase inhibitors. Although may have benefit in patients with excess caloric intake from alcohol, avoid use in patients with risk of alcohol withdrawal due to bupropion component lowering seizure threshold (Ref).
Oral: Initial: One tablet (naltrexone 8 mg/bupropion 90 mg) once daily in the morning for 1 week; increase as tolerated in weekly intervals: 1 tablet twice daily for 1 week; then 2 tablets in the morning and 1 tablet in the evening for 1 week; and then 2 tablets twice daily (maximum dose: 4 tablets/day [naltrexone 32 mg/bupropion 360 mg per day]). Consider discontinuation if weight loss is <4% to 5% of baseline after 3 months (Ref).
Discontinuation of therapy: When discontinuing antidepressant therapy that has lasted for ≥4 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to allow for the detection of reemerging symptoms. For brief treatment (eg, 2 to 3 weeks) may taper over 1 to 2 weeks; <2 weeks treatment generally does not warrant tapering (Ref). Withdrawal symptoms resulting from abrupt discontinuation are unlikely because bupropion has minimal serotonergic activity (Ref).
Switching antidepressants: Evidence for ideal antidepressant switching strategies is limited; strategies include cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant) and direct switch (abruptly discontinuing the first antidepressant and then starting the new antidepressant at an equivalent dose or lower dose and increasing it gradually). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches but is contraindicated when switching to or from a monoamine oxidase inhibitor (MAOI). A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between 2 selective serotonin reuptake inhibitors), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, pharmacodynamics), and the degree of symptom control desired (Ref).
Switching to or from a monoamine oxidase inhibitor:
Allow 14 days to elapse between discontinuing a monoamine oxidase inhibitor (MAOI) and initiation of bupropion.
Allow 14 days to elapse between discontinuing bupropion and initiation of a MAOI.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild impairment: No dosage adjustment necessary.
Moderate or severe impairment: Maximum dose: One tablet (naltrexone 8 mg/bupropion 90 mg) twice daily
End-stage renal disease: Use is not recommended.
Mild impairment: No dosage adjustment necessary.
Moderate impairment: Maximum dose: 1 tablet (naltrexone 8 mg/bupropion 90 mg) twice daily.
Severe impairment: Use is not recommended.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults. Also see individual agents.
>10%:
Gastrointestinal: Constipation (19%), nausea (33%), vomiting (11%)
Nervous system: Headache (18%), insomnia (9% to 11%), sleep disturbance (14%)
1% to 10%:
Cardiovascular: Acute myocardial infarction (<2%), hypertension (≤6%), palpitations (2%), presyncope (<2%), tachycardia (<2%)
Dermatologic: Alopecia (<2%), hyperhidrosis (3%)
Endocrine & metabolic: Dehydration (<2%), hot flash (4%), increased thirst (<2%), irregular menses (<2%)
Gastrointestinal: Abdominal pain (3%), cholecystitis (<2%), diarrhea (7%), dysgeusia (2%), eructation (<2%), hematochezia (<2%), hernia of abdominal cavity (<2%), lower abdominal pain (<2%), motion sickness (<2%), upper abdominal pain (4%), viral gastroenteritis (4%), xerostomia (8%)
Genitourinary: Erectile dysfunction (<2%), urinary urgency (<2%), vaginal dryness (<2%), vaginal hemorrhage (<2%)
Hematologic & oncologic: Decreased hematocrit (<2%)
Hepatic: Increased liver enzymes (<2%)
Hypersensitivity: Swelling of lips (<2%)
Infection: Kidney infection (<2%), staphylococcal infection (<2%)
Nervous system: Abnormal dreams (<2%), agitation (<2%), altered mental status (<2%), amnesia (<2%), anxiety (4% to 6%), asthenia (<2%), balance impairment (<2%), depression (7%), derealization (<2%), disturbance in attention (3%), dizziness (10%), emotional lability (<2%), fatigue (4%), feeling hot (<2%), intention tremor (<2%), irritability (3%), jitteriness (<2%), lethargy (<2%), memory impairment (<2%), nervousness (<2%), tension (<2%), tremor (4%), vertigo (<2%)
Neuromuscular & skeletal: Herniated disc (<2%), jaw pain (<2%)
Otic: Tinnitus (3%)
Renal: Increased serum creatinine (<2%)
Respiratory: Pneumonia (<2%)
<1%: Cardiovascular: Syncope
Postmarketing:
Cardiovascular: ECG abnormality (Brugada pattern/syndrome)
Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms
Nervous system: Loss of consciousness, malaise
Hypersensitivity to bupropion, naltrexone, or any other component of the formulation; concomitant use of other bupropion-containing products (eg, including [but not limited to] Wellbutrin, Wellbutrin SR, Wellbutrin XL, Aplenzin, Zyban); chronic opioid, opiate agonist (eg, methadone) or partial agonist (eg, buprenorphine) use; acute opioid withdrawal; uncontrolled hypertension; seizure disorder or a history of seizures; bulimia or anorexia nervosa; patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiseizure drugs; concomitant use of MAOIs (concurrently or within 14 days of discontinuing the MAOI or naltrexone/bupropion); initiation of naltrexone/bupropion in a patient receiving linezolid or IV methylene blue.
Canadian labeling: Additional contraindications (not in US labeling): Concomitant use of thioridazine; severe hepatic impairment; end-stage renal failure
Major psychiatric warnings (use in treating psychiatric disorders):
• Suicidal thinking/behavior (use in treating psychiatric disorders): [US Boxed Warning]: Naltrexone/bupropion is not approved for use in the treatment of major depressive or psychiatric disorders; it contains bupropion the same active ingredient in some other antidepressant medications. Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies of antidepressants did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with health care provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription.
• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.
• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their health care provider if any of these symptoms or worsening depression or psychosis occur.
Concerns related to adverse effects:
• Accidental opioid overdose: Patients treated with naltrexone may respond to lower opioid doses than previously used. This could result in potentially life-threatening opioid intoxication. Warn patients that any attempt to overcome opioid blockade during naltrexone therapy is dangerous and could potentially lead to fatal opioid overdose; the opioid competitive receptor blockade produced by naltrexone is potentially surmountable in the presence of large amounts of opioids. If chronic opiate therapy is required, naltrexone/bupropion should be stopped; if intermittent opiate therapy is required, temporarily discontinue naltrexone/bupropion and lower doses of opioids may be needed.
• Acute opioid withdrawal: May precipitate symptoms of acute withdrawal in opioid-dependent patients. An opioid-free interval of a at least 7 to 10 days is recommended for patients previously dependent on short-acting opioids (including tramadol); consider an opioid-free interval of up to 2 weeks in patients transitioning from buprenorphine or methadone.
• Cardiovascular effects: May elevate heart rate, blood pressure and cause hypertension; use is contraindicated in patients with uncontrolled hypertension. Events have been observed in patients with or without evidence of preexisting hypertension. Risks may be greater during the initial 3 months of therapy. Assess heart rate and blood pressure before initiating treatment and monitor periodically.
• Hepatotoxicity: Cases of hepatitis, significant liver dysfunction, and transient, asymptomatic hepatic transaminase elevations have been observed with naltrexone use. Discontinue therapy if signs/symptoms of acute hepatitis develop. Clinicians should note that elevated transaminases may be a result of preexisting alcoholic liver disease, hepatitis B and/or C infection, or concomitant use of other hepatotoxic drugs; abrupt opioid withdrawal may also lead to acute liver injury.
• Hypersensitivity reactions: Anaphylactoid/anaphylactic reactions have occurred, including pruritus, urticaria, angioedema, and dyspnea. Serious reactions have been (rarely) reported with bupropion, including erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock. Arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity resembling serum sickness have been reported with bupropion.
• Neuropsychiatric effect: Although naltrexone/bupropion is not approved for smoking cessation, serious neuropsychiatric events have occurred in patients taking bupropion for smoking cessation, including changes in mood (eg, depression, mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, aggression, anxiety, panic, suicidal ideation, suicide attempt, and completed suicide. The majority of these reactions occurred during bupropion treatment; however some occurred during treatment discontinuation. A causal relationship is uncertain as depressed mood may be a symptom of nicotine withdrawal. Some cases also occurred in patients taking bupropion who continued to smoke. Neuropsychiatric effects occurred in patients with and without preexisting psychiatric disease; some patients experienced a worsening of their psychiatric illnesses. Observe all patients taking bupropion for neuropsychiatric reactions. Instruct patients to stop taking naltrexone/bupropion and contact a health care provider if neuropsychiatric reactions occur. Depression, suicide, attempted suicide, and suicidal ideation have also been reported with naltrexone use for the treatment of opioid dependence; however, no causal relationship has been demonstrated.
• Ocular effects: Bupropion may cause mild pupillary dilation, which in susceptible individuals can lead to an episode of narrow-angle glaucoma. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors.
• Seizures: Bupropion may cause a dose-related risk of seizures. Use is contraindicated in patients with a seizure disorder or a history of seizures, current or past diagnosis of bulimia or anorexia nervosa, or those undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiseizure drugs. Use caution with concurrent use of antipsychotics, antidepressants, theophylline, systemic corticosteroids, or hypoglycemic agents, or with excessive use of ethanol, benzodiazepines, sedative/hypnotics, or opioids. Use with caution in seizure-potentiating metabolic disorders (hypoglycemia, hyponatremia, severe hepatic impairment, and hypoxia), in patients with a cocaine use disorder or stimulant use disorder, in patients withdrawing from sedatives, and in patients with a history of head trauma, severe stroke, arteriovenous malformation, or central nervous system tumor or infection. To minimize the risk of seizures, increase the dose gradually, administer the dose twice daily with no more than 2 tablets taken at a time, avoid administration with high-fat meals, skip missed doses, and limit the daily dose of bupropion to ≤360 mg. Use of multiple bupropion formulations is contraindicated. Permanently discontinue if seizure occurs during therapy.
Disease-related concerns:
• Bariatric surgery: Document presurgical assessment of goals of therapy to enable postsurgical assessment. A small PK study shows alteration in exposure up to 1 year after Roux-en-Y gastric bypass for bupropion (Puris 2019). Evaluate the need for continued anti-obesity medications after bariatric surgery and discontinue if appropriate. Patients who fail to meet weight loss goals or regain weight after bariatric surgery may safely use naltrexone and bupropion to augment weight loss; however, other weight loss medications appear more effective (Stanford 2017).
• Cardiovascular disease: Use with caution in patients with cardiovascular disease; naltrexone/bupropion may cause an increase in blood pressure and heart rate.
• Diabetes mellitus: Weight loss may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with insulin and/or insulin secretagogues. Monitor blood glucose levels at baseline and periodically during treatment. Consider decreases in doses for concurrent antidiabetic medications which are non-glucose-dependent; adjust antidiabetic drug regimens if hypoglycemia develops during treatment.
• Hepatic impairment: Use with caution in patients with hepatic impairment and use extreme caution in patients with severe hepatic cirrhosis; plasma concentrations of bupropion are increased. Reduced doses are recommended. Use caution in patients with hepatic encephalopathy due to the risk of neurocognitive effects (Mauri 2014; Mullish 2014).
• Mania/hypomania: May precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Combination therapy with an antidepressant and a mood stabilizer should also be avoided in acute mania or mixed episodes, as well as maintenance treatment in bipolar disorder due to the mood-destabilizing effects of antidepressants (CANMAT [Yatham 2018]; WFSBP [Grunze 2018]). Patients presenting with depressive symptoms should be screened for bipolar disorder. Naltrexone/bupropion is not FDA approved for the treatment of bipolar depression.
• Renal impairment: Dosage reductions are necessary with moderate to severe impairment; avoid use in patients with end-stage renal disease.
Special populations:
• Older adult: Use with caution in older adults; may be at greater risk of drug accumulation during chronic dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release 12 Hour, Oral:
Contrave: Naltrexone hydrochloride 8 mg and bupropion hydrochloride 90 mg [contains edetate (edta) disodium, fd&c blue #2 (indigo carm) aluminum lake]
No
Tablet, 12-hour (Contrave Oral)
8-90 mg (per each): $6.25
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release 12 Hour, Oral:
Contrave: Naltrexone hydrochloride 8 mg and bupropion hydrochloride 90 mg [contains edetate (edta) disodium, fd&c blue #2 (indigo carm) aluminum lake]
Oral: Administer twice daily doses in the morning and in the evening; do not administer with high-fat meals. Do not cut, chew, or crush tablets.
Bariatric surgery: Naltrexone and bupropion is available in an ER formulation and the release characteristics may be significantly altered in an unknown manner in patients who have undergone bariatric surgery. Providers should determine if the condition being treated can be safely monitored or if a switch to an alternative is necessary (Ref).
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Contrave: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/200063s021lbl.pdf#page=40
Weight management, chronic: Adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of ≥30 kg/m2 or ≥27 kg/m2 in the presence of at least one weight-related comorbid condition (eg, type 2 diabetes mellitus, dyslipidemia)
Limitations of use: The effect of naltrexone/bupropion on cardiovascular morbidity and mortality has not been established. The safety and effectiveness of naltrexone/bupropion in combination with other products intended for weight loss, including prescription drugs, over-the-counter drugs, and herbal preparations, have not been established.
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents With Seizure Threshold Lowering Potential: BuPROPion may increase neuroexcitatory and/or seizure-potentiating effects of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor
Ajmaline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Ajmaline. Risk C: Monitor
Alcohol (Ethyl): May increase adverse/toxic effects of BuPROPion. Specifically, seizure threshold may be lowered. BuPROPion may increase adverse/toxic effects of Alcohol (Ethyl). Specifically, alcohol tolerance may decrease during treatment. Management: Patients receiving bupropion should be advised to minimize or avoid alcohol consumption due to possible lower alcohol tolerance, and lower seizure threshold associated with heavy alcohol consumption/abrupt discontinuation of heavy consumption. Risk D: Consider Therapy Modification
Aldesleukin: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Amifampridine: Agents With Seizure Threshold Lowering Potential may increase neuroexcitatory and/or seizure-potentiating effects of Amifampridine. Risk C: Monitor
Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor
Anti-Parkinson Agents (Dopamine Agonist): May increase adverse/toxic effects of BuPROPion. Risk C: Monitor
Antihepaciviral Combination Products: May decrease serum concentration of BuPROPion. Risk C: Monitor
ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of ARIPiprazole Lauroxil. Management: Decrease aripiprazole lauroxil dose to next lower strength if used with strong CYP2D6 inhibitors for over 14 days. No dose adjustment needed if using the lowest dose (441 mg) or if a CYP2D6 PM. Max dose is 441 mg if also taking strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
ARIPiprazole: CYP2D6 Inhibitors (Strong) may increase serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions or avoidance are required for indications other than major depressive disorder. Dose adjustments vary based on formulation, initial starting dose, and the additional use of CYP3A4 inhibitors. See interact monograph for details Risk D: Consider Therapy Modification
Asenapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Atomoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Atomoxetine. Management: Initiate atomoxetine at a reduced dose (patients who weigh up to 70 kg: 0.5 mg/kg/day; adults or patients who weigh 70 kg or more: 40 mg/day) in patients receiving a strong CYP2D6 inhibitor. Increase to usual target dose after 4 weeks if needed. Risk D: Consider Therapy Modification
Benperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Blonanserin: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Blonanserin. Specifically, the risk of seizures may be increased. Risk C: Monitor
Bremelanotide: May decrease serum concentration of Naltrexone. Risk X: Avoid
Brexanolone: BuPROPion may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brexpiprazole: May increase adverse/toxic effects of BuPROPion. Specifically, the risk for seizures may be increased. BuPROPion may increase serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual dose with bupropion; reduce to 25% of usual if used with both bupropion and a strong or moderate CYP3A4 inhibitor. These recommendations do not apply if treating major depressive disorder. Monitor for seizures. Risk D: Consider Therapy Modification
Bromperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Bromperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Broom: CYP2D6 Inhibitors (Strong) may increase serum concentration of Broom. Specifically, the concentrations of sparteine, a constituent of broom, may be increased. Risk C: Monitor
Cariprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Carvedilol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Carvedilol. Risk C: Monitor
Chlorpheniramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Chlorpheniramine. Risk C: Monitor
ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor
Citalopram: BuPROPion may increase adverse/toxic effects of Citalopram. BuPROPion may increase serum concentration of Citalopram. Management: Initiate citalopram at the lower end of the normal dose range in patients receiving bupropion and consider limiting the maximum citalopram adult dose to 20 mg/day during concomitant bupropion treatment. Monitor for citalopram toxicities. Risk D: Consider Therapy Modification
Clothiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
CloZAPine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor
CloZAPine: CYP2D6 Inhibitors (Strong) may increase serum concentration of CloZAPine. Risk C: Monitor
CYP2B6 Inducers (Moderate): May decrease serum concentration of BuPROPion. Risk C: Monitor
CYP2B6 Inducers (Weak): May decrease serum concentration of BuPROPion. Risk C: Monitor
CYP2B6 Inhibitors (Weak): May increase serum concentration of BuPROPion. Risk C: Monitor
Dapoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Dapoxetine. Risk C: Monitor
Deutetrabenazine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Deutetrabenazine. Management: The total daily dose of deutetrabenazine should not exceed 36 mg with concurrent use of a strong CYP2D6 inhibitor. Risk D: Consider Therapy Modification
Dextromethorphan: CYP2D6 Inhibitors (Strong) may increase serum concentration of Dextromethorphan. Risk C: Monitor
Digoxin: BuPROPion may decrease serum concentration of Digoxin. Risk C: Monitor
Dinutuximab Beta: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Direct Oral Anticoagulants (DOACs): BuPROPion may increase anticoagulant effects of Direct Oral Anticoagulants (DOACs). Risk C: Monitor
DOXOrubicin (Conventional): CYP2D6 Inhibitors (Strong) may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DroPERidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of DroPERidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
DULoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of DULoxetine. Risk C: Monitor
Eliglustat: CYP2D6 Inhibitors (Strong) may increase serum concentration of Eliglustat. Management: Eliglustat dose is 84 mg daily with CYP2D6 inhibitors. Use is contraindicated (COI) when also combined with strong CYP3A4 inhibitors. When also combined with a moderate CYP3A4 inhibitor, use is COI in CYP2D6 EMs or IMs and should be avoided in CYP2D6 PMs. Risk D: Consider Therapy Modification
Elranatamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Epcoritamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Escitalopram: BuPROPion may increase adverse/toxic effects of Escitalopram. Risk C: Monitor
Fenfluramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Fenfluramine. Management: Limit fenfluramine dose to 20 mg/day without concurrent stiripentol or to 17 mg/day with concomitant stiripentol and clobazam when used with a strong CYP2D6 inhibitor. Risk D: Consider Therapy Modification
Fesoterodine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Fesoterodine. Risk C: Monitor
Fexinidazole: May decrease serum concentration of CYP2B6 Substrates (High risk with Inducers). Management: Avoid concomitant use of fexinidazole and CYP2B6 substrates when possible. If combined, monitor for reduced efficacy of the CYP2B6 substrate. Risk D: Consider Therapy Modification
Flecainide: CYP2D6 Inhibitors (Strong) may increase serum concentration of Flecainide. Risk C: Monitor
FLUoxetine: May increase neuroexcitatory and/or seizure-potentiating effects of BuPROPion. BuPROPion may increase serum concentration of FLUoxetine. Risk C: Monitor
Flupentixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor
FluPHENAZine: CYP2D6 Inhibitors (Strong) may increase serum concentration of FluPHENAZine. Risk C: Monitor
FluvoxaMINE: BuPROPion may increase adverse/toxic effects of FluvoxaMINE. Risk C: Monitor
Gefitinib: CYP2D6 Inhibitors (Strong) may increase serum concentration of Gefitinib. Risk C: Monitor
Glofitamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
GlyBURIDE: May increase serum concentration of Naltrexone. Risk C: Monitor
Haloperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Haloperidol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Haloperidol. Risk C: Monitor
Iboga: CYP2D6 Inhibitors (Strong) may increase serum concentration of Iboga. Risk C: Monitor
Iloperidone: May increase adverse/toxic effects of BuPROPion. Specifically, the risk for seizures may be increased. BuPROPion may decrease active metabolite exposure of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. BuPROPion may increase active metabolite exposure of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. BuPROPion may increase serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with bupropion. Monitor for increased iloperidone toxicities, including QTc prolongation and arrhythmias. Additionally, monitor for increased risk of seizures when these agents are combined. Risk D: Consider Therapy Modification
Indoramin: CYP2D6 Inhibitors (Strong) may increase serum concentration of Indoramin. Risk C: Monitor
Iobenguane Radiopharmaceutical Products: BuPROPion may decrease therapeutic effects of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer bupropion until at least 7 days after each iobenguane dose. Risk X: Avoid
Ioflupane I 123: Coadministration of BuPROPion and Ioflupane I 123 may alter diagnostic results. Risk C: Monitor
Iohexol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Lofexidine: May decrease serum concentration of Naltrexone. Risk C: Monitor
Loxapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Loxapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lumacaftor and Ivacaftor: May decrease serum concentration of CYP2B6 Substrates (High risk with Inducers). Risk C: Monitor
Lumateperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lurasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Maprotiline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Maprotiline. Risk C: Monitor
Mequitazine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Mequitazine. Risk X: Avoid
Methotrimeprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Methotrimeprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Methylnaltrexone: May increase adverse/toxic effects of Opioid Antagonists. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid
Metoclopramide: CYP2D6 Inhibitors (Strong) may increase serum concentration of Metoclopramide. Management: For gastroparesis: reduce metoclopramide dose to 5mg 4 times/day and limit to 20mg/day; nasal spray not recommended. For GERD: reduce metoclopramide dose to 5mg 4 times/day or to 10mg 3 times/day and limit to 30mg/day. Monitor for toxicity when combined. Risk D: Consider Therapy Modification
Metoprolol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Metoprolol. Risk C: Monitor
Mexiletine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Mexiletine. Risk C: Monitor
MiFEPRIStone: May increase serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Risk C: Monitor
Molindone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Monoamine Oxidase Inhibitors: May increase hypertensive effects of BuPROPion. Risk X: Avoid
Mosunetuzumab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Naldemedine: Opioid Antagonists may increase adverse/toxic effects of Naldemedine. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid
Naloxegol: Opioid Antagonists may increase adverse/toxic effects of Naloxegol. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid
Nebivolol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Nebivolol. Risk C: Monitor
Nicergoline: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Nicergoline. Specifically, concentrations of the MMDL metabolite may be increased. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Nicergoline. Specifically, concentrations of the MDL metabolite may be decreased. Risk C: Monitor
Nirmatrelvir and Ritonavir: May decrease serum concentration of BuPROPion. Risk C: Monitor
OLANZapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Olmutinib: CYP2D6 Inhibitors (Strong) may increase serum concentration of Olmutinib. Risk C: Monitor
Opioid Agonists: Naltrexone may decrease therapeutic effects of Opioid Agonists. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Risk X: Avoid
Opipramol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Opipramol. Risk C: Monitor
Paliperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
PARoxetine: BuPROPion may increase adverse/toxic effects of PARoxetine. Risk C: Monitor
Perhexiline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Perhexiline. Risk C: Monitor
Periciazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Perphenazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Perphenazine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Perphenazine. Risk C: Monitor
Pimozide: CYP2D6 Inhibitors (Strong) may increase serum concentration of Pimozide. Risk X: Avoid
Pipamperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pipamperone. Specifically, the risk of seizures may be increased. Risk X: Avoid
Pitolisant: CYP2D6 Inhibitors (Strong) may increase serum concentration of Pitolisant. Management: Reduce the pitolisant dose by 50% if a strong CYP2D6 inhibitor is initiated. For patients already receiving strong CYP2D6 inhibitors, initial doses of pitolisant should be reduced and depends on age and patient weight. See full monograph for details. Risk D: Consider Therapy Modification
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor
Primaquine: CYP2D6 Inhibitors (Strong) may decrease therapeutic effects of Primaquine. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Primaquine. Management: Consider alternatives to the combination of primaquine and strong CYP2D6 inhibitors. If concomitant use is necessary, monitor for signs and symptoms of possible primaquine treatment failure. Risk D: Consider Therapy Modification
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Promazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Propafenone: CYP2D6 Inhibitors (Strong) may increase serum concentration of Propafenone. Risk C: Monitor
Propranolol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Propranolol. Risk C: Monitor
Psilocybin: Antidepressants may decrease therapeutic effects of Psilocybin. Risk C: Monitor
QUEtiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
RisperiDONE: CYP2D6 Inhibitors (Strong) may increase serum concentration of RisperiDONE. Management: Careful monitoring for risperidone toxicities and possible dose adjustment are recommended when combined with strong CYP2D6 inhibitors. See full interaction monograph for details. Risk D: Consider Therapy Modification
Sertindole: CYP2D6 Inhibitors (Strong) may increase serum concentration of Sertindole. Management: Consider alternatives to this combination when possible. If combined, consider using lower doses of sertindole and monitor the ECG closely for evidence of QTc interval prolongation. Risk D: Consider Therapy Modification
Sertraline: BuPROPion may increase adverse/toxic effects of Sertraline. Risk C: Monitor
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor
Sofpironium: CYP2D6 Inhibitors (Strong) may increase serum concentration of Sofpironium. Risk X: Avoid
Sulpiride: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sulpiride. Specifically, the risk of seizures may be increased. Risk C: Monitor
Talquetamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Avoid concurrent use of strong CYP2D6 inhibitors with tamoxifen when possible, as the combination may be associated with a reduced clinical effectiveness of tamoxifen. Risk D: Consider Therapy Modification
Tamsulosin: CYP2D6 Inhibitors (Strong) may increase serum concentration of Tamsulosin. Risk C: Monitor
Tarlatamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Taurursodiol: May increase serum concentration of CYP2B6 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Teclistamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Limit the tetrabenazine dose to 50 mg per day (25 mg per single dose) in patients taking strong CYP2D6 inhibitors. Risk D: Consider Therapy Modification
Thioridazine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Thioridazine. Risk X: Avoid
Thiotepa: May increase serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Risk C: Monitor
Thiothixene: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor
Timolol (Ophthalmic): CYP2D6 Inhibitors (Strong) may increase serum concentration of Timolol (Ophthalmic). Risk C: Monitor
Timolol (Systemic): CYP2D6 Inhibitors (Strong) may increase serum concentration of Timolol (Systemic). Risk C: Monitor
Tolterodine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Tolterodine. Risk C: Monitor
Tricyclic Antidepressants: May increase neuroexcitatory and/or seizure-potentiating effects of BuPROPion. BuPROPion may increase serum concentration of Tricyclic Antidepressants. Risk C: Monitor
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Valbenazine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Valbenazine. Management: Reduce valbenazine dose to 40 mg once daily when combined with a strong CYP2D6 inhibitor. Monitor for increased valbenazine effects/toxicities. Risk D: Consider Therapy Modification
Vilazodone: BuPROPion may increase adverse/toxic effects of Vilazodone. Risk C: Monitor
Vortioxetine: BuPROPion may increase adverse/toxic effects of Vortioxetine. BuPROPion may increase serum concentration of Vortioxetine. Management: The vortioxetine dose should be reduced by 50% when used together with bupropion. Following cessation of bupropion, the vortioxetine dose should be returned to the normal level. Risk D: Consider Therapy Modification
Xanomeline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Xanomeline. Risk C: Monitor
Ziprasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Ziprasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Zuclopenthixol: May increase adverse/toxic effects of BuPROPion. Specifically, the risk for seizures may be increased. BuPROPion may increase serum concentration of Zuclopenthixol. Risk C: Monitor
Obesity increases the risk of infertility. Optimal weight control prior to conception improves pregnancy outcomes. However, medications for weight loss are not recommended prior to pregnancy due to safety issues and adverse events. Weight loss medications should be discontinued prior to conception (ACOG 2021; Wharton 2020).
Information related to the use of this combination in pregnancy is limited.
An increased risk of adverse maternal and fetal events is associated with obesity. However, moderate gestational weight gain based on pre-pregnancy BMI is required for positive fetal outcomes in all pregnancies, including patients with overweight or obesity. Therefore, medications for weight loss therapy are not recommended during pregnancy (ACOG 2021; Wharton 2020). Due to the lack of clinical benefit and potential for fetal harm associated with weight loss in pregnancy, naltrexone/bupropion should be discontinued once pregnancy is detected.
Also refer to individual monographs for additional information.
Naltrexone, bupropion, and their metabolites are present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Due to safety concerns, medications for weight loss therapy are not recommended for patients who are breastfeeding (Wharton 2020).
Also refer to individual monographs for additional information.
Do not administer with high-fat meals; may result in a significant increase in bupropion and naltrexone systemic exposure.
Blood pressure and heart rate (baseline and periodic); blood glucose (baseline and periodic); weight; BMI; renal and liver function (base and periodic); mental status for depression, suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, and panic attacks.
Adult classification of weight by BMI (kg/m2):
Underweight: <18.5
Normal: 18.5 to 24.9
Overweight: 25 to 29.9
Obesity, class I: 30 to 34.9
Obesity, class II: 35 to 39.9
Obesity, class III: ≥40
Waist circumference: In adults with a BMI of 25 to 34.9 kg/m2, high-risk waist circumference for adiposity-related disease is defined as (AACE/ACE [Garvey 2016]):
Males >102 cm (>40 in).
Females >88 cm (>35 in).
Naltrexone is a pure opioid antagonist, and bupropion is a relatively weak inhibitor of the neuronal reuptake of dopamine and norepinephrine. The exact neurochemical effects of naltrexone/bupropion leading to weight loss are not fully understood. Effects may result from action on areas of the brain involved in the regulation of food intake: the hypothalamus (appetite regulatory center) and the mesolimbic dopamine circuit (reward system).
See individual agents.
