Tirzepatide Vs. Contrave: Drug Comparison

Tirzepatide is the active ingredient in the brand-name medication Zepbound^®. The information below is about brand name Zepbound. According to the FDA, “Generic medicines use the same active ingredients as brand-name medicines and work the same way, so they have the same risks and benefits as the brand-name medicines.”

Zepbound (tirzepatide) is an injectable medication approved by the FDA for chronic weight management in adults with obesity or overweight who have at least one weight-related condition. It works by activating both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) hormone receptors, which help reduce appetite and food intake. It is taken once a week as an injection and is gradually increased over time to achieve effective weight loss results. Common side effects include nausea, diarrhea, constipation, and abdominal pain, with more serious risks like thyroid tumors and pancreatitis necessitating careful patient screening. This medication should be used alongside a reduced-calorie diet and increased physical activity for best results.

Contrave^® (naltrexone hydrochloride and bupropion hydrochloride) is a prescription medication used for weight management in adults, combining two active ingredients: naltrexone, which affects the brain's reward system, and bupropion, which influences appetite and cravings. It works by targeting the hypothalamus to reduce hunger and the mesolimbic reward system (a pathway in the brain that plays a key role in regulating feelings of pleasure, motivation, and reinforcement) to curb food cravings. Contrave is FDA-approved for chronic weight management. Common side effects include nausea, constipation, headache, and insomnia, while drug interactions can occur with MAO inhibitors, opioid pain medications, and drugs that lower the seizure threshold. Contrave carries a boxed warning for an increased risk of suicidal thoughts and behaviors, particularly in young adults, due to its bupropion component.

Glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist

Naltrexone: opioid antagonist

Bupropion: aminoketone antidepressant

Zepbound (tirzepatide) is indicated:

• As an 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 greater (obesity) or

  • 27 kg/m² or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes mellitus, obstructive sleep apnea or cardiovascular disease)

Contrave (naltrexone hydrochloride and bupropion hydrochloride) is indicated:

• As an 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 greater (obese)

  • 27 kg/m² or greater (overweight) in the presence of at least one weight-related comorbidity (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia)

• Typically taken as an injection once weekly

• Comes in 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg per 0.5 mL single-dose pens or single-dose vials

• Typically taken orally twice daily

• Comes as 8 mg/90 mg extended-release tablets

The most common adverse reactions, reported in ≥5% of patients treated with Zepbound are:

• Nausea

• Diarrhea

• Vomiting

• Constipation

• Abdominal pain

• Indigestion

• Injection site reactions

• Fatigue

• Hypersensitivity reactions

• Belching

• Hair loss

• Gastroesophageal reflux disease (heartburn)

Most common adverse reactions (greater than or equal to 5%):

• Nausea

• Constipation

• Headache

• Vomiting

• Dizziness

• Insomnia

• Dry mouth

• Diarrhea

• Personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2

• Known serious hypersensitivity to tirzepatide or any of the excipients in Zepbound

• Drug interactions: Zepbound delays gastric emptying and has the potential to impact the absorption of concomitantly administered oral medications

• Uncontrolled hypertension

• Seizure disorders, anorexia nervosa or bulimia, or undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs

• Use of other bupropion-containing products

• Chronic opioid use

• During or within 14 days of taking monoamine oxidase inhibitors (MAOI)

• Known allergy to any of the ingredients in Contrave

• Drug interactions: MAOIs, antidepressants (e.g., selective serotonin reuptake inhibitors and many tricyclics), antipsychotics (e.g., haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), type 1C antiarrhythmics (e.g., propafenone and flecainide), digoxin, CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel), CYP2B6 inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin), drugs that lower seizure threshold, dopaminergic drugs (levodopa and amantadine)

• Severe gastrointestinal disease

• Acute kidney injury

• Acute gallbladder disease

• Acute pancreatitis

• Hypersensitivity reactions

• Low blood sugar: Concomitant use with an insulin secretagogue or insulin may increase the risk of low blood sugar, including severe low blood sugar

• Diabetic retinopathy complications in patients with type 2 diabetes mellitus

• Suicidal behavior and ideation

• Pregnancy: May cause fetal harm. When pregnancy is recognized, discontinue Zepbound

• Females of reproductive potential: Females using oral contraceptives should consider switching to a non-oral contraceptive method or add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation

• Suicidal behavior and ideation

• Neuropsychiatric adverse events during smoking cessation

• 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

• Liver toxicity

• Angle-closure glaucoma

• Use of antidiabetic medications: Weight loss may cause hypoglycemia

• Pregnancy: Weight loss during pregnancy may cause fetal harm. Discontinue when a pregnancy is recognized

WARNING: RISK OF THYROID C-CELL TUMORS

In rats, tirzepatide causes thyroid C-cell tumors. It is unknown whether Zepbound causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined.

Zepbound is contraindicated in patients with a personal or family history of MTC or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC and symptoms of thyroid tumors.

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorder and other psychiatric disorders. Monitor for worsening and emergence of suicidal thoughts and behaviors.

Contrave has not been studied in pediatric patients.

*This information is from the label for brand name Zepbound^®. See the Full Prescribing Information for more complete information. Tirzepatide, the active ingredient in Zepbound, may also be the active ingredient in other medications, and this information may not be accurate for all medications that include the active ingredient tirzepatide.

*This information is from the label for brand name Contrave^®. See the Full Prescribing Information for more complete information. Naltrexone and bupropion, the active ingredients in Contrave, may also be the active ingredients in other medications, and this information may not be accurate for all medications that include the active ingredients naltrexone and bupropion.