NAPLEX Question of the Week: The Weight is Over

Obesity management is at the forefront of healthcare currently. Are you ready to take on the challenge of this week's question?
NAPLEX Question of the Week: The Weight is Over
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FT, a 61-year-old male, presents to the Pharmacotherapy clinic for a follow-up appointment regarding weight loss management. At the last visit with his PCP, he expressed interest in becoming healthier and initiating medications to help with losing weight. He had attempted lifestyle modifications in the past but could not keep his cravings under control. He was given a prescription for Contrave.

PMH: Diabetes, Hyperlipidemia

BMI 28.3 kg/m2

Vitals: BP 119/70 mmHg, HR 68 bpm

Labs from most recent PCP visit

A1c 6.4%

TC 187 mg/dL, HDL 45 mg/dL, LDL 63 mg/dL, TG 112 mg/dL

Current medications:

Fortamet 2000 mg PO QD

Jardiance 10 mg PO QD

Zocor 20 mg PO QD

Contrave 1 tablet PO QD

Which of the following statement(s) is/are correct regarding Contrave? Select all that apply.

A. Contrave contains an aminoketone antidepressant with significant effects serotonin reuptake inhibition

B. Contrave contains a competitive opioid antagonist at opioid receptor sites

C. Contrave has a boxed warning for suicidal thoughts and behaviors

D. Contrave should be taken with high-fat meals to improve absorption

E. Avoid Contrave in patients with uncontrolled hypertension

Answer with Rationale

Earlier this year, ASHP reported a 13.5% increase in spending on prescription medications in the US in 2023, which was attributed mainly to the enormous growth in weight-loss medications. The weight-loss drugs market size is forecasted to continue to grow exponentially over the next few years, reaching $12.17 billion in 2028. Demands for these drugs surge in recent years due to multiple factors – increasing rates of obesity, changes in lifestyle, heightened awareness and education about weight-related issues, early diagnosis of medical conditions, etc. There are currently eight FDA-approved drugs for chronic weight management – Xenical, Alli, Contrave, Saxenda, Qsymia, Imcivree, Wegovy, and Zepbound. Some of these drugs share similar mechanisms of action, with others having unique mechanisms of action. Xenical or Alli, also known as orlistat, reduces the amount of fat absorbed in the gut after eating. Qsymia, or the phentermine-topiramate combination, works in the brain to reduce your appetite. Zepbound, also known as tirzepatide, is a dual-acting glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, activating these hormones to make you feel full. Contrave contains both bupropion and naltrexone that synergistically work to aid in weight management. 

Answer A is incorrect. Bupropion is an aminoketone antidepressant structurally different from all other marketed antidepressants. It is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine. Its dopamine activity is why bupropion under the trade name Zyban is used for smoking cessation.  It does not inhibit monoamine oxidase or the reuptake of serotonin.

Answer B is correct. Naltrexone is a cyclopropyl derivative of oxymorphone similar in structure to naloxone and nalorphine. It acts as a competitive antagonist at opioid receptor sites, showing the highest affinity for mu receptors. It also modifies the hypothalamic-pituitary-adrenal axis to suppress alcohol consumption

Answer C is correct.  Antidepressants are known to increase the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials. In patients of all ages who are started on any medication containing bupropion, they should be monitored closely for worsening, and for the emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber if these occur. Contrave is not approved for use in pediatric patients. 

Answer D is incorrect. When given with high-fat meals, Contrave may result in a significant increase in bupropion and naltrexone systemic exposure, which can consequently increase the risk of seizures. Therefore high fat meals should be avoided with administration. 

Answer E is correct. Contrave’s contraindications include uncontrolled hypertension, seizure disorder, eating disorder, use of other bupropion-containing products, chronic opioid use, or use within 14 days of monoamine oxidase inhibitors. It can cause an increase in systolic and/or diastolic blood pressure, as well as an increase in resting heart rate. FT's blood pressure and heart rate are appropriate for Contrave use. 

Generic/Brand: Bupropion/Naltrexone (Contrave), Metformin XR (Fortamet), Empagliflozin (Jardiance), Simvastatin (Zocor)

NAPLEX Core Competencies Covered:

  • 1.1 – From instruments, screening tools, laboratory, genomic or genetic information, or diagnostic findings
  • 1.2 – From patients: treatment adherence, or medication-taking behavior; chief complaint, medication history, medical history, family history, social history, lifestyle habits, socioeconomic background
  • 2.1 – Pharmacology, mechanism of action, or therapeutic class
  • 2.2 – Commercial availability; prescription or non-prescription status; brand, generic, or biosimilar names; physical descriptions; or how supplied
  • 2.3 – Boxed warnings or REMS
  • 3.6 – Drug contraindications, allergies, or precautions
  • 5.5 – Instructions or techniques for drug administration

 

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