What are the recommended premedication and hydration regimens for patients undergoing chemotherapy to prevent nausea, vomiting, and kidney damage?

Premedication and Hydration in Chemotherapy

Antiemetic Premedication Based on Chemotherapy Emetogenicity

For highly emetogenic chemotherapy (HEC), administer a three-drug regimen 30 minutes before chemotherapy: a 5-HT3 antagonist (ondansetron 8 mg IV or palonosetron 0.25 mg IV), dexamethasone 12 mg IV (reduced from 20 mg when combined with aprepitant), and aprepitant 125 mg PO on day 1, followed by aprepitant 80 mg PO on days 2-3. 1, 2

Highly Emetogenic Chemotherapy (HEC)

• Day 1 premedication (30-60 minutes before chemotherapy): 1

  • 5-HT3 antagonist options: Ondansetron 8 mg IV, granisetron 1 mg IV, dolasetron 100 mg IV, or palonosetron 0.25 mg IV 1
  • Dexamethasone 12 mg IV (when combined with aprepitant; use 20 mg IV if aprepitant not given) 1, 2
  • Aprepitant 125 mg PO or fosaprepitant 150 mg IV 3, 2

• Days 2-3 continuation: 1, 3

  • Aprepitant 80 mg PO daily 3
  • Dexamethasone 8 mg PO twice daily on days 2-4 1

• Alternative single-dose regimen: Fosaprepitant 150 mg IV on day 1 only (noninferior to 3-day oral aprepitant regimen), combined with dexamethasone 12 mg IV and a 5-HT3 antagonist 3, 2

Moderately Emetogenic Chemotherapy (MEC)

For moderately emetogenic chemotherapy, use a two-drug regimen: palonosetron 0.25 mg IV plus dexamethasone 12 mg IV on day 1, with optional continuation of dexamethasone 8 mg PO daily on days 2-3. 1

• Day 1 premedication (30 minutes before chemotherapy): 1

  • Palonosetron 0.25 mg IV (preferred) or other 5-HT3 antagonist (ondansetron 8 mg IV, granisetron 1 mg IV) 1
  • Dexamethasone 12 mg PO or IV 1

• For anthracycline-cyclophosphamide (AC) combinations (now classified as highly emetogenic): 1

  • Add aprepitant 125 mg PO day 1, then 80 mg PO days 2-3 1, 3
  • Reduce dexamethasone to 12 mg on day 1 when combined with aprepitant 1

• Days 2-3 for non-AC MEC: 1

  • Dexamethasone 8 mg PO daily (optional, based on delayed emesis risk) 1

Low Emetogenic Chemotherapy

• Single agent on day 1: Dexamethasone 8-12 mg PO or IV before chemotherapy 1
• Alternative: Metoclopramide 10-40 mg PO/IV every 4-6 hours or prochlorperazine 10 mg PO/IV every 4-6 hours 1

Minimal Emetogenic Chemotherapy

• No routine prophylaxis recommended 1
• Antiemetics given only as needed for breakthrough symptoms 1

Critical Dosing Adjustments and Drug Interactions

When aprepitant is combined with dexamethasone, reduce the dexamethasone dose by 50% due to CYP3A4 inhibition by aprepitant. 1, 3, 2

• Aprepitant affects metabolism of chemotherapy agents metabolized via CYP3A4 (docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, vinorelbine, vincristine) and other medications like warfarin 3
• Absolute contraindications for aprepitant: concurrent use with pimozide, terfenadine, astemizole, or cisapride 3

Breakthrough Nausea Management

For breakthrough nausea despite adequate prophylaxis, add medications from different drug classes rather than simply increasing the same antiemetic—combine ondansetron with metoclopramide 10-40 mg IV and/or dexamethasone if not already prescribed. 1, 4

• First-line breakthrough agents: 1, 4

  • Metoclopramide 10-40 mg PO/IV every 4-6 hours 1, 4
  • Prochlorperazine 10 mg PO/IV every 4-6 hours or 25 mg suppository every 12 hours 1, 4
  • Ondansetron 16 mg PO or 8 mg IV daily (if not already on scheduled dosing) 1, 4

• Switch from PRN to scheduled around-the-clock dosing for at least 24-48 hours if nausea persists 4

• Before adding medications, exclude treatable causes: constipation (especially with 5-HT3 antagonists), electrolyte abnormalities, bowel obstruction, increased intracranial pressure, inadequate hydration 4

Delayed Nausea and Vomiting Prevention

For delayed emesis following HEC, continue aprepitant 80 mg PO and dexamethasone 8 mg PO twice daily on days 2-4 after chemotherapy. 1

• For MEC with significant delayed emesis risk: Dexamethasone 8 mg PO daily on days 2-3 1
• Corticosteroids given twice daily for delayed emesis (unlike once-daily dosing for acute emesis) 1

Hydration Protocols

While the provided evidence focuses primarily on antiemetic prophylaxis rather than hydration protocols, standard practice for nephrotoxic agents (particularly cisplatin) includes:

• Pre-hydration with normal saline to maintain adequate urine output
• Monitoring of renal function and electrolytes
• Post-chemotherapy hydration as clinically indicated

Common Pitfalls to Avoid

• Do not use ondansetron monotherapy for moderate-to-high emetogenic chemotherapy—combination therapy with dexamethasone is superior 5
• Do not exceed ondansetron 16 mg single IV dose due to cardiac safety concerns (QT prolongation) 4, 6
• Anticipate constipation with 5-HT3 antagonists (ondansetron, granisetron)—this can worsen nausea if not addressed 4, 5
• Avoid first-generation antihistamines (diphenhydramine) as primary antiemetics—they can exacerbate hypotension, tachycardia, and sedation 4
• Do not forget to reduce dexamethasone dose by 50% when combining with aprepitant 1, 3, 2

Route of Administration Considerations

• Oral and IV formulations of 5-HT3 antagonists are equally effective for prophylaxis 1
• If patient has active nausea/vomiting, administer antiemetics intravenously 1
• Palonosetron is only available as IV formulation 1

Adjunctive Medications

• Lorazepam 0.5-2 mg PO/IV every 4-6 hours is useful for anticipatory nausea and as adjunct to antiemetics, but not recommended as single-agent therapy 1, 4
• H2 blockers or proton pump inhibitors may be added for patients with epigastric discomfort 1