BY, a 64-year-old female, presents to the oncology infusion center for her second cycle of chemotherapy. She was recently diagnosed with Stage II left breast cancer (ER-/PR+/HER2-) & her oncologist decided to treat her with the following regimen.

Doxorubicin 60 mg/m² IV + Cyclophosphamide 600 mg/m² IV Q2 weeks for 4 doses

Followed by:

Paclitaxel 80 mg/m² IV weekly for 12 doses 

Due to the regimen’s high emetic risk, BY was also prescribed a 4-drug regimen, which includes ondansetron, Decadron, rolapitant, & Zyprexa, for chemotherapy-induced nausea & vomiting (CINV) prophylaxis. In addition, Transderm-Scop patch was added as treatment for breakthrough CINV. 

PMH: Hypertension, Diabetes, Stage II left breast cancer (ER-/PR+/HER2-)

Vitals: BP 123/76 mmHg, HR 81 bpm

Labs:

A1c 6.1%

SCr 0.8 mg/dL

ALT 23 U/L, AST 19 U/L, Bilirubin 0.7 mg/dL

Current medications:

Lisinopril 40 mg QD

Glumetza 1000 mg QD

Ondansetron 24 mg on Day 1 of cycles

Decadron 20 mg on Day 1, 8 mg BID on Days 2-4 of cycles

Rolapitant 180 mg on Day 1 of cycles

Zyprexa 5 mg QD on Days 1-4 of cycles

Transderm-Scop 1.5 mg/3 days PRN 

At the clinic today, BY reports symptoms of dry mouth, blurred vision, & urinary retention that has started recently. She reports using all 5 medications.  Which of the following medications is most likely the culprit?

A. Decadron

B. Rolapitant

C. Zofran

D. Transderm-Scop

Answer with Rationale

Chemotherapy-induced nausea & vomiting (CINV), a debilitating side effect of cancer treatment, occurs as a result of neurotransmitter imbalances. It is both a physiological & psychological process that can lead to decreased quality of life & chemotherapy compliance. Antineoplastic therapy damages enterochromaffin cells lining the gastrointestinal tract which releases serotonin. Chemotherapy also alters modulation of dopamine & substance P in the CNS. Risk factors for CINV can be either patient-specific (female, age < 50 years, history of motion or morning sickness, etc.) or treatment-specific (emetogenicity of the agents in the regimen, dose/schedule/target area if radiation is used, etc). Studies have shown consistently that antiemetics, including 5-HT₃ receptor antagonists, steroids, NK₁ receptor antagonists, & atypical antipsychotics (e.g. olanzapine), are most effective as prophylaxis! 

Answer A is incorrect. Decadron suppresses normal immune response by decreasing inflammation through suppression of neutrophil migration, decreased production of inflammatory mediators, & reversal of increased capillary permeability. It also induces apoptosis in multiple myeloma cells. Its mechanism of antiemetic activity is unknown. Common side effects include adrenal suppression, euphoria/anxiety, insomnia, increase appetite, hyperglycemia, & osteoporosis. But the current side effects BY is experiencing are not associated primarily with corticosteroids. 

Answer B is incorrect. Rolapitant selectively & competitively inhibits substance P/neurokinin 1 (NK₁) receptor to prevent delayed nausea & vomiting associated with emetogenic chemotherapy. Common side effects include hiccups, increased liver function tests, constipation, weakness, & fatigue.

Answer C is incorrect. Ondansetron, a selective 5-HT₃ receptor antagonist, works by blocking serotonin both peripherally on vagal nerve terminals & centrally in the chemoreceptor trigger zone. Common side effects include QT prolongation, headache, somnolence, dizziness, constipation, & diarrhea.

Answer D is correct. Transderm-Scop blocks the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, & the CNS. Common side effects include dry mouth, visual disturbances (blurred vision, mydriasis, etc.), urinary retention, & sedation. Onset of anticholinergic effects is very rapid with visual disturbances occurring within 1-2 days of patch application.

Generic/Brand: Doxorubicin (Adriamycin), Cyclophosphamide (Procytox), Paclitaxel (Taxol), Lisinopril (Zestril), Metformin (Glumetza or Glucophage), Ondansetron (Zofran), Dexamethasone (Decadron), Rolapitant (Varubi), Olanzapine (Zyprexa), Scopolamine (Transderm-Scop)

NAPLEX Core Competencies Covered:

• 1.2 – From patients: treatment adherence, or medication-taking behavior; chief complaint, medication history, medical history, family history, social history, lifestyle habits, socioeconomic background
• 1.5 – Signs or symptoms of medical conditions, healthy physiology, etiology of diseases, or pathophysiology
• 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
• 3.7 – Adverse drug effects, toxicology, or overdose