| Active ingredient | Naltrexone hydrochloride and bupropion hydrochlorideCombination opioid antagonist and aminoketone antidepressant | Phentermine and topiramate extended-releaseCombination anorectic and antiepileptic |
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| Supply | Prescription | Prescription |
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| Boxed warning | WARNING: SUICIDAL THOUGHTS AND BEHAVIORS | None |
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| What the FDA approved it for | - CONTRAVE is indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults with obesity or overweight in the presence of at least one weight-related comorbid condition.
- CONTRAVE is a combination of naltrexone, an opioid antagonist, and bupropion, an aminoketone antidepressant, indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults with obesity or overweight in the presence of at least one weight-related comorbid condition.
- Limitations of Use: The effect of CONTRAVE on cardiovascular morbidity and mortality has not been established.
- Coadministration with other naltrexone-containing products is not recommended.
| - QSYMIA is indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in: Adults and pediatric patients aged 12 years and older with obesity Adults with overweight in the presence of at least one weight-related comorbid condition QSYMIA is a combination of phentermine, a sympathomimetic amine anorectic,...
- Adults with overweight in the presence of at least one weight-related comorbid condition.
- Limitations of Use: The effect of QSYMIA on cardiovascular morbidity and mortality has not been established.
- The safety and effectiveness of QSYMIA in combination with other products intended for weight loss, including prescription and over-the-counter drugs, and herbal preparations, have not been established.
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| Forms and strengths | - CONTRAVE extended-release tablets: 8 mg/90 mg are blue, round, bi-convex, film-coated, and debossed with "NB-890" on one side.
- Extended-Release Tablets: 8 mg naltrexone hydrochloride (HCl) /90 mg bupropion HCl
| - QSYMIA extended-release capsules are available in four strengths (phentermine mg/topiramate mg): 3.75 mg/23 mg - purple cap imprinted with VIVUS and purple body imprinted with 3.75/23 7.5 mg/46 mg -...
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| How the label says it is taken | - CONTRAVE dose escalation schedule: Morning Dose Evening Dose Week 1 1 tablet None Week 2 1 tablet 1 tablet Week 3 2 tablets 1 tablet Week 4 - Onward 2 tablets 2 tablets
| - Take orally once daily in morning.
- Avoid administration in evening to prevent insomnia.
- Recommended starting dosage is 3.75 mg/23 mg (phentermine mg/topiramate mg) daily for 14 days; then increase to 7.5 mg/46 mg daily.
- Escalate dosage based on weight loss in adults or BMI reduction in pediatric patients.
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| Most common adverse reactions | - Most common adverse reactions (greater than or equal to 5%): nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth and diarrhea.
| - Most common adverse reactions in: Adults (incidence ≥ 5% and at least 1.5 times placebo) are: paraesthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth.
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| Warnings and precautions | - Suicidal Behavior and Ideation: Monitor for depression or suicidal thoughts. Discontinue CONTRAVE if symptoms develop.
- Neuropsychiatric Adverse Events During Smoking Cessation: Postmarketing reports of serious or clinically significant neuropsychiatric adverse events have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed...
- Risk of seizure may be minimized by adhering to the recommended dosing schedule and avoiding coadministration with high-fat meal.
- Increase in Blood Pressure and Heart Rate: Monitor blood pressure and heart rate in all patients, especially those with cardiac or cerebrovascular disease.
- Hepatotoxicity: Cases of hepatitis and clinically significant liver dysfunction observed with naltrexone exposure.
- Angle-closure glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants.
- Use of Antidiabetic Medications: Weight loss may cause hypoglycemia. Monitor blood glucose.
| - Embryo-Fetal Toxicity: Can cause fetal harm.
- In patients who can become pregnant, a negative pregnancy test is recommended before initiating QSYMIA and monthly during therapy; advise use of effective contraception.
- QSYMIA is available through a limited program under a Risk Evaluation and Mitigation Strategy (REMS).
- Suicidal Behavior and Ideation: Monitor for depression or suicidal thoughts.
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| Contraindications | - CONTRAVE is contraindicated in Uncontrolled hypertension Seizure disorder or a history of seizures Use of other bupropion-containing products (including, but not limited to, WELLBUTRIN, WELLBUTRIN SR, WELLBUTRIN XL, APLENZIN and ZYBAN) Bulimia or anorexia nervosa, which increase the risk for seizure Chronic opioid or opiate agonist (e.g., methadone) or partial agonists (e.g., buprenorphine) use,...
- At least 14 days should elapse between discontinuation of MAOI and initiation of treatment with CONTRAVE.
- There is an increased risk of hypertensive reactions when CONTRAVE is used concomitantly with MAOIs.
- Starting CONTRAVE in a patient treated with reversible MAOIs such as linezolid or intravenous methylene blue is also contraindicated Known allergy to bupropion, naltrexone or any other component of CONTRAVE.
| - QSYMIA is contraindicated in patients: Who are pregnant With glaucoma With hyperthyroidism Taking or within 14 days of stopping a monoamine oxidase inhibitors With known hypersensitivity to phentermine, topiramate or any of the excipients in QSYMIA, or idiosyncrasy to the sympathomimetic amines.
- Anaphylaxis and angioedema have occurred with topiramate Pregnancy Glaucoma Hyperthyroidism Taking or within 14 days of stopping monoamine oxidase inhibitors Known hypersensitivity to any component of QSYMIA or idiosyncrasy to sympathomimetic amines
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| Drug interactions | - MAOIs: Increased risk of hypertensive reactions can occur when used concomitantly.
- Drugs Metabolized by CYP2D6: Bupropion inhibits CYP2D6 and can increase concentrations of antidepressants, (e.g., selective serotonin reuptake inhibitors and many tricyclics), antipsychotics (e.g., haloperidol, risperidone and thioridazine), beta-blockers (e.g., metoprolol) and Type 1C antiarrhythmics (e.g., propafenone and flecainide). Consider dose reduction when using with CONTRAVE.
- Digoxin: May decrease plasma digoxin levels. Monitor digoxin levels.
- Concomitant Treatment with CYP2B6 Inhibitors (e.g., ticlopidine or clopidogrel) can increase bupropion exposure. Do not exceed one tablet twice daily when taken with CYP2B6 inhibitors.
- CYP2B6 Inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin) may reduce efficacy by reducing bupropion exposure, avoid concomitant use.
- Drugs that Lower Seizure Threshold: Dose CONTRAVE with caution.
| - Table 5 displays clinically significant drug interactions with QSYMIA.
- Clinically Significant Drug Interactions with QSYMIA Monoamine Oxidase Inhibitors Clinical Impact Concomitant use of phentermine with monoamine oxidase inhibitors (MAOIs) increases the risk of hypertensive crisis.
- Intervention Concomitant use of QSYMIA is contraindicated during MAOI treatment and within 14 days of stopping an MAOI.
- Oral Contraceptives Clinical Impact Co-administration of multiple-dose QSYMIA 15 mg/92 mg once daily with a single dose of oral contraceptive containing 35 µg ethinyl estradiol (estrogen component) and 1 mg norethindrone (progestin component), in obese otherwise healthy volunteers, decreased the exposure of ethinyl estradiol by 16% and increased the exposure of norethindrone by 22%.
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| Label version | 10 November 2025 | 22 April 2026 |
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