Dosing & Uses
Dosing Forms & Strengths
bupropion/naltrexone
extended release tablet
- 90mg/8mg
Obesity
For use as adjunct to reduced-calorie diet and increased physical activity for long-term weight management in adults with initial body mass index of ≥30 kg/m² (obese) or ≥27 kg/m² (overweight) in presence of at least 1 weight-related comorbidity (eg, hypertension, type 2 diabetes, or dyslipidemia)
1 tablet (90mg/8mg) initially week 1; increase by 1 tablet/day each subsequent week until daily maintenance dose of 2 tablets twice daily (360 mg bupropion/32 mg naltrexone) is achieved at the start of week 4
Dosage Modifications
Coadministration with CYP2B6 inhibitors (eg, ticlopidine or clopidogrel): Not to exceed 1 tablet BID
Hepatic impairment
- Mild to moderate: 2 tablets (one tablet each morning and evening)
- Severe hepatic impairment: Not recommended
Renal impairment
- Mild: Not studied
- Moderate-to-severe: Not to exceed 1 tablet BID
- End-stage renal disease: Not recommended
Dosing Considerations
Clinical response should be observed by 4 months of treatment
Discontinue therapy if clinically meaningful weight loss (≥5%) not exhibited after 4 months; other weight management strategies should be considered
Effect on cardiovascular morbidity not established
Safety and efficacy when used in combination with other weight-loss products, including over-the-counter drugs and herbal preparations, not established
Do not administer within 14 days of taking a monoamine oxidase inhibitor for depression
Recommendations to reduce risk of seizure
- Bupropion component may increase the risk of seizures
- Do not exceed 360 mg bupropion component (4 tablets daily)
- Administer daily dose in divided doses (twice daily)
- Escalate dose gradually
- Do not take more than 2 tablets at one time
- Avoid coadministration with high-fat meals
- If dose is missed, wait until next scheduled dose to resume regular dosing schedule
Safety and efficacy not established
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Adverse Effects
>10%
Nausea (32.5%)
Constipation (19.2%)
Headache (17.6%)
Vomiting (10.7%)
1-10%
Dizziness (9.9%)
Insomnia (9.2%)
Dry mouth (8.1%)
Diarrhea (7.1%)
Anxiety (4.2%)
Hot flash (4.2%)
Fatigue (4%)
Tremor (4%)
Upper abdominal pain (3.5%)
Viral gastroenteritis (3.5%)
Influenza (3.4%)
Tinnitus (3.3%)
Urinary tract infection (3.3%)
Hypertension (3.2%)
Abdominal pain (2.8%)
Hyperhidrosis (2.6%)
Irritability (2.6%)
Increased blood pressure (2.4%)
Dysgeusia (2.4%)
Rash (2.4%)
Muscle strain (2.2%)
Palpitations (2.1%)
Frequency Not Defined
Tachycardia
Myocardial infarction
Vertigo
Motion sickness
Lower abdominal pain
Eructation
Lip swelling
Hematochezia
Hernia
Feeling jittery
Thirst
Feeling hot
Asthenia
Cholecystitis
Pneumonia
Staphylococcal infection
Kidney infection
Increased creatinine clearance
Increased hepatic enzymes
Decreased hematocrit
Dehydration
Intervertebral disc protrusion
Jaw pain
Disturbance in attention
Lethargy
Intention tremor
Balance disorder
Memory impairment
Amnesia
Mental impairment
Presyncope
Abnormal dreams
Nervousness
Dissociation (feeling spacy)
Tension
Agitation
Mood swings
Vaginal hemorrhage
Irregular menstruation
Erectile dysfunction
Vulvovaginal dryness
Alopecia
Postmarketing Reports
Loss of consciousness, malaise
Warnings
Black Box Warnings
Not approved for treatment of major depressive disorder or psychiatric disorders
Antidepressants like bupropion increase the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials but were not seen in patients ≥24 years and a lower risk was seen in patients ≥65 years; patients of all ages should be monitored closely for suicidal thoughts and behaviors
Serious neuropsychiatric reactions reported in patients taking bupropion for smoking cessation that occurred during therapy or while discontinuing therapy; patients should be monitored for neuropsychiatric reactions
Contraindications
Uncontrolled hypertension
Seizure disorder or a history of seizures
Use of other bupropion-containing products
Bulimia or anorexia nervosa, which may increase risk of seizures
Long-term opioid or opiate agonists use or acute opiate withdrawal
Patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
Within 14 days of monoamine oxidase inhibitor therapy
Hypersensitivity
Pregnancy
Cautions
Monitor patients for suicidal ideation or behavior and for unusual changes in behavior (see black box warning)
Discontinue therapy and do not restart if seizure occurs while on therapy; use caution when prescribing to patients with predisposing risk factors for seizures
Not for administration to patients receiving long-term opioids, owing to naltrexone component (opioid antagonist); discontinue therapy if long-term opiate therapy required
Following therapy, patients may be more sensitive to opioids, even at lower doses
A patient should not attempt to overcome naltrexone opioid blockade by administering large amounts of exogenous opioids; may lead to fatal overdose
Opioid-dependent patients, including those being treated for alcohol dependence, should be opioid-free (including tramadol) before therapy is initiated; opioid-free interval of a minimum of 7-10 days is recommended for patients previously dependent on short-acting opioids; patients transitioning from buprenorphine or methadone may need as long as 2 weeks
Blood pressure and pulse should be measured prior to starting therapy and should be monitored at regular intervals, particularly among patients with controlled hypertension prior to treatment
Discontinue therapy if symptoms or signs of acute hepatitis occur
Screen patients for a history of bipolar disorder and the presence of risk factors for bipolar disorder; therapy was not studied in patients receiving antidepressant medications patients with a history of bipolar disorder or recent hospitalization foor psychiatric illness were excluded from clinical trials
Angle-closure attack may occur in patients with anatomically narrow angles that do not have a patent iridectomy
Measure blood glucose levels prior to and during therapy; patients who develop hypoglycemia after initiating Contrave therapy should adjust antidiabetic drug regimen
Use caution in patients with history of tumor or infection of the brain or spine
Initiation of therapy in patients receiving linezolid or intravenous (IV) methylene blue
Use caution in hepatic impairment
May precipitate a manic, mixed, or hypomanic episode; risk higher in patients with bipolar disorders or have risk factors for bipolar disorder, including family history of bipolar disorder, suicide, or depression; not FDA approved for bipolar depression
Some patients who stopped smoking reported to have experienced symptoms of nicotine withdrawal, including depressed mood; depression, rarely including suicidal ideation, reported in smokers undergoing a smoking cessation attempt without medication; however, some of these adverse events occurred in patients taking bupropion who continued to smoke
Neuropsychiatric adverse events reported in patients without and with pre-existing psychiatric disease; some patients experienced worsening of their psychiatric illnesses; observe patients for occurrence of neuropsychiatric adverse events; patient should stop therapy and contact healthcare provider immediately if agitation, depressed mood, or changes in behavior or thinking that are not typical for patient are observed, or if patient develops suicidal ideation or suicidal behavior; symptoms may persist after discontinuation of therapy; in some cases; monitoring and supportive care should be provided until symptoms resolve
Pregnancy & Lactation
Pregnancy
Weight loss offers no benefit to a pregnant patient and may cause fetal harm; when a pregnancy is recognized, advise pregnant patient of risk to fetus, and discontinue therapy; available pharmacovigilance data and data from clinical trials with individual components of combination drug use in pregnant patients have not demonstrated a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes
Bupropion
- Data from epidemiological studies of pregnant patients exposed to bupropion in first trimester have not identified an increased risk of congenital malformations overall
- When bupropion was administered to pregnant rats during organogenesis, there was no evidence of fetal malformations at doses up to approximately 20 times maximum recommended human dose (MRHD) of 360 mg/day
- When given to pregnant rabbits during organogenesis, non-dose–related increases in incidence of fetal malformations, and skeletal variations were observed at doses approximately twice the MRHD and greater; decreased fetal weights were seen at doses 5 times MRHD and greater
Naltrexone
- Limited case report data of pregnant patients exposed to naltrexone in first trimester have not identified an increased risk of congenital malformations overall; daily oral administration of naltrexone during period of organogenesis has been shown to increase incidence of early fetal loss in rats and rabbits at doses ≥15 times and ≥60 times MRHD of 32 mg/day respectively
- There was no evidence of fetal malformations in rats and rabbits at doses up to approximately 100 and 200 times the MHRD, respectively
- Appropriate weight gain based on pre-pregnancy weight is currently recommended for all pregnant patients, including those who are already overweight or obese, due to obligatory weight gain that occurs in maternal tissues during pregnancy
Lactation
Data from published literature report the presence of bupropion and its metabolites in human milk
Limited data from postmarketing reports with bupropion use during lactation have not identified a clear association of adverse effects on a breastfed infant
Naltrexone and its major metabolite, 6 β-naltrexol, are present in human milk; there are no data on bupropion, naltrexone, or their metabolites on milk production; the developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from drug combination or from mother’s underlying condition
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Bupropion: Increases dopamine activity in the brain, which appears to lead to a reduction in appetite and increase in energy expenditure by increasing activity of pro-opiomelanocortin (POMC) neurons
Naltrexone: Blocks opioid receptors on the POMC neurons, preventing feedback inhibition of these neurons and further increasing POMC activity
Combination may regulate activity in the dopamine reward system of the brain that helps control food cravings and overeating behaviors
Absorption
Naltrexone
- Peak time: 2 hr
Bupropion
- Peak time: 3 hr
Metabolism
Naltrexone
- Hepatic
Bupropion
- Hepatic, via CYP2B6
Distribution
Naltrexone
- Protein bound: 21%
Bupropion
- Protein bound: 84%
Elimination
Naltrexone
- Excretion: Urine (53-79%)
- Half-life: 5 hr
Bupropion
- Excretion: Urine (87%); feces (10%)
- Half-life: 21 hr
Administration
Oral Administration
Take by mouth in the morning and evening
Do not crush, chew, or cut tablets
Doses >32 mg/360 mg per day not recommended
Do not administer with high-fat meal as it may result in significant increase in bupropion and naltrexone exposure
Therapy may cause elevation in blood pressure or heart rate, especially during initial 3 months of therapy; patients with hypertension should be monitored closely
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Patient Handout
Formulary
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