Orlistat Vs. Contrave: Drug Comparison

Orlistat is the active ingredient in the brand-name medication Xenical^®. The information below is about brand name Xenical. 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.”

Xenical (orlistat) is a prescription medication used for weight management by inhibiting the enzyme lipase, which reduces the absorption of dietary fats in the intestines, thereby helping with weight loss. Its FDA-approved indication is for obesity management, including weight loss and weight maintenance, in conjunction with a reduced-calorie diet. Xenical is available in capsule form and is typically taken three times daily with meals containing fat. Common side effects include gastrointestinal issues such as oily stools, flatulence, and frequent bowel movements, especially after consuming high-fat meals. Xenical can affect the absorption of fat-soluble vitamins, and patients are advised to take a multivitamin supplement to avoid deficiencies.

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.

Reversible inhibitor of gastrointestinal lipases

Naltrexone: opioid antagonist

Bupropion: aminoketone antidepressant

Xenical (orlistat) is indicated:

• For obesity management including weight loss and weight maintenance when used in conjunction with a reduced-calorie diet

• To reduce the risk for weight regain after prior weight loss

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 three times daily

• Comes in 120 mg capsules

• Typically taken orally twice daily

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

Most common treatment emergent adverse reactions (≥5% and at least twice that of placebo) include:

• Oily spotting

• Flatus with discharge

• Fecal urgency

• Fatty/Oily stool

• Oily evacuation

• Increased defecation

• Fecal incontinence

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

• Nausea

• Constipation

• Headache

• Vomiting

• Dizziness

• Insomnia

• Dry mouth

• Diarrhea

• Pregnancy

• Chronic malabsorption syndrome

• Cholestasis

• Known hypersensitivity to Xenical or to any component of this product

• Drug interactions: cyclosporine, fat-soluble vitamin supplements and analogues, levothyroxine, warfarin, amiodarone, antiepileptic drugs, antiretroviral drugs

• 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)

• Xenical has drug interactions and can decrease vitamin absorption

• Take a multivitamin supplement that contains fat-soluble vitamins to ensure adequate nutrition

• Rare cases of severe liver injury with hepatocellular necrosis or acute hepatic failure have been reported

• Patients may develop oxalate nephrolithiasis and oxalate nephropathy following treatment with Xenical

• Substantial weight loss can increase the risk of cholelithiasis

• Exclude organic causes of obesity (e.g., hypothyroidism) before prescribing Xenical

• Gastrointestinal events may increase when Xenical is taken with a diet high in fat (>30% total daily calories from fat)

• Breastfeeding: Caution should be exercised when administered to a nursing woman

• 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: 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 Xenical^®. See the Full Prescribing Information for more complete information. Orlistat, the active ingredient in Xenical, may also be the active ingredient in other medications, and this information may not be accurate for all medications that include the active ingredient orlistat.

*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.