Materia Medica

opiate antagonist and bupropion HCl is a weak inhibitor of the neuronal reuptake of dopamine and norepinephrine. The exact neurochemical effects of Contrave leading to weight loss is not fully understood; however, nonclinical studies have found that naltrexone and bupropion have effects on the hypothalamus and the mesolimbic dopamine circuit which are involved in the regulation of food intake.5 Common adverse reactions include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth and diarrhea. This medication is contraindicated in uncontrolled hypertension, seizure disorders, anorexia nervosa or bulimia or undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates and antiepileptic drugs. It is also contraindicated in patients with chronic opioid use or during or within 14 days of taking a monoamine oxidase inhibitor (MAOI).1, 6 This medication also carries warnings and precautions for patients with a history of suicidal behavior and ideation, hepatoxicity and angle-closure glaucoma. Contrave is also not recommended for use during pregnancy.5, 6

Qsymia (phentermine/topiramate ER) is also an FDA approved medication for weight management. This medication is taken orally. Phentermine is a sympathomimetic amine. Its role in weight management is likely mediated by release of catecholamines in the hypothalamus which result in reduced appetite and decrease food consumption, although the exact mechanism is unknown.7 Topiramate’s mechanism is also unknown, but is thought to be due to its effects on both appetite suppression and satiety enhancement through its enhancement of gamma-aminobutyric acid (GABA) activity.7 Common adverse reactions include paresthesia, dizziness, dysgeusia, insomnia, constipation and dry mouth. This medication is contraindicated in pregnancy, glaucoma, hyperthyroidism and when taking or within 14 days of stopping MAOIs. Qsymia also carries warnings and precautions in embryo-fetal toxicity, increase in heart rate, suicidal behavior and ideations, risks of acute myopia and secondary angle closure glaucoma and mood and sleep disorders.1, 7

Xenical (orlistat) is a reversible gastrointestinal lipase inhibitor. It exerts its therapeutic activity in the lumen of the stomach and small intestine by forming a covalent bond with the active serine residue site of gastric and pancreatic lipases and inhibits the absorption of dietary fats. As undigested triglycerides are not absorbed, the resulting caloric deficit may have a positive effect on weight control.8 This oral medication is also available over the counter as Alli. Common adverse reactions include oily spotting, flatus with discharge, fecal urgency, fatty/oily stool, increased defecation and fecal incontinence.1,8 Xenical is contraindicated in pregnancy, chronic malabsorption syndrome and cholestasis. There are warnings and precautions to use in patients with renal insufficiency and severe liver injury. Gastrointestinal events may also increase with a high fat diet (>30% total daily calories from fat).8

Patient-centered Approach

Management of weight loss should be patient-centered and individualized based on the patient’s comorbid conditions, goals, lifestyle and affordability. It is pertinent to consider all aspects of each of the medications when making treatment decisions, as there are many limitations for use for each of the pharmacologic treatment options. Multidisciplinary approaches to weight management have been proven to be highly efficacious in the long-term management of weight loss and thus should be utilized in practice to support the best outcomes for our patients.

References:

1. Garvey WT, Mechanick JL, Brett EM, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients With Obesity. Endocr Pract. 2016;22(suppl 3);1-205.

2. Prescription Medications to Treat Overweight & Obesity. Available at: https://www.niddk. nih.gov/health-information/weight-management/prescription-medications-treat-overweight-obesity. Accessed March 20, 2023.

3. American Diabetes Association; 8. Obesity Management for the Treatment of Type 2 Diabetes: Standards of Medical Care in Diabetes—2021. Diabetes Care 1 January 2021; 44 (Supplement_1): S100–S110.

4. WEGOVY. Package insert. Novo Nordisk, 2017.

5. CONTRAVE. Package insert. Currax, 2014.

6. Gohil K. Pharmaceutical approval update. P T. 2014;39(11):746-772.

7. QSYMIA. Package insert. Vivus, 2012.

8. XENICAL. Package insert. Cheplapharm, 1999.

Dr. Sadkin is a PGY-1 Acute Care – Ambulatory Focused Pharmacy Practice resident at Allegheny General Hospital. For any questions concerning this article, please contact Dr. Sadkin at the Allegheny Health Network, Allegheny General Hospital, Center for Pharmaceutical Care, Pittsburgh Pa., (412) 359-3706 or email Sydney.sadkin@ahn.org.