## Chemotherapy-Induced Nausea and Vomiting (CINV) Management **Key Point:** Aprepitant, a neurokinin-1 (NK1) receptor antagonist, is the gold standard for prevention of acute and delayed CINV in highly emetogenic chemotherapy regimens like cisplatin. ### Mechanism of Action Aprepitant blocks NK1 receptors in the chemoreceptor trigger zone and vomiting centre, addressing both acute (0–24 hours) and delayed (24–120 hours) emesis, particularly the delayed phase driven by substance P. ### Comparison of Antiemetics in CINV | Drug Class | Agent | Onset | Best For | Limitation | | --- | --- | --- | --- | --- | | **5-HT3 antagonist** | Ondansetron | Rapid | Acute CINV | Poor for delayed emesis | | **NK1 antagonist** | Aprepitant | 1–3 hours | Acute + delayed CINV | High cost, drug interactions | | **D2 antagonist** | Metoclopramide | 30–60 min | Mild–moderate CINV | Weak efficacy in high-dose chemo | | **H1 antagonist** | Promethazine | 20–30 min | Mild nausea | Sedation, anticholinergic effects | **High-Yield:** In highly emetogenic chemotherapy (e.g., cisplatin >50 mg/m², doxorubicin, ifosfamide), the **standard regimen is a 3-drug combination: aprepitant + 5-HT3 antagonist + corticosteroid** (dexamethasone). Aprepitant is essential for controlling delayed emesis. ### Clinical Pearl Ondansetron alone is insufficient for cisplatin-induced CINV because it does not adequately prevent delayed emesis (which peaks 48–72 hours post-chemotherapy). Aprepitant fills this gap by blocking substance P-mediated delayed emesis. ### Why Aprepitant is Superior 1. Covers both acute and delayed phases 2. Crosses blood–brain barrier effectively 3. Long half-life (~40 hours) provides sustained coverage 4. Evidence-based guideline recommendation (ASCO, NCCN) **Warning:** Aprepitant is a strong CYP3A4 inhibitor — check for drug interactions with concurrent medications (e.g., warfarin, docetaxel).
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