What adjunctive medication is given with dexamethasone?

Adjunctive Medications Used with Dexamethasone for Antiemetic Therapy

The most common adjunctive medications given with dexamethasone for antiemetic therapy are 5-HT3 receptor antagonists (such as ondansetron, granisetron, or palonosetron) and NK1 receptor antagonists (such as aprepitant), with the specific combination depending on the emetogenic potential of the chemotherapy regimen.

Antiemetic Combinations Based on Emetogenic Risk

Highly Emetogenic Chemotherapy

• First-line regimen (Category 1):

  • 5-HT3 receptor antagonist (preferably palonosetron)
  • Dexamethasone (12 mg on day 1, then 8 mg on days 2-4)
  • NK1 receptor antagonist (e.g., aprepitant 125 mg on day 1, then 80 mg on days 2-3)
  • ± Lorazepam (0.5-2 mg every 4-6 hours as needed)
  • ± H2 blocker or proton pump inhibitor 1

• For cisplatin-based regimens, dexamethasone dose is reduced to 12 mg on day 1 when given with aprepitant due to drug interactions 2

Moderately Emetogenic Chemotherapy

• Recommended regimen:
  • 5-HT3 receptor antagonist
  • Dexamethasone (8-12 mg on day 1)
  • ± NK1 receptor antagonist (for select patients including those receiving anthracycline-cyclophosphamide combinations)
  • ± Lorazepam (0.5-2 mg every 4-6 hours as needed)
  • ± H2 blocker or proton pump inhibitor 1

Low Emetogenic Chemotherapy

• Recommended regimen:
  • Dexamethasone 8 mg alone 1

Specific 5-HT3 Receptor Antagonists

1. Palonosetron: Preferred 5-HT3 antagonist for highly emetogenic chemotherapy due to superior efficacy in preventing both acute and delayed nausea and vomiting 1

   • Dosage: 0.25 mg IV on day 1 only

2. Ondansetron:

   • Dosage: 8-16 mg IV or 16-24 mg PO on day 1 1

3. Granisetron:

   • Dosage: 1-2 mg PO or 0.01 mg/kg (maximum 1 mg) IV on day 1 1

NK1 Receptor Antagonists

1. Aprepitant:

   • Dosage: 125 mg PO on day 1, then 80 mg PO on days 2-3
   • Important note: When given with aprepitant, dexamethasone dose should be reduced to 12 mg on day 1 due to drug interactions 2

2. Fosaprepitant:

   • Dosage: 150 mg IV on day 1 only (can substitute for oral aprepitant on day 1) 1

Adjunctive Medications for Breakthrough Nausea/Vomiting

If the primary antiemetic regimen fails, additional agents can be added:

• Lorazepam: 0.5-2 mg PO/SL/IV every 6 hours
• Olanzapine: 5-10 mg PO daily (category 1 evidence)
• Haloperidol: 0.5-2 mg PO/IV every 4-6 hours
• Metoclopramide: 10-20 mg PO/IV every 4-6 hours
• Scopolamine: 1.5 mg transdermal patch every 72 hours 1

Mechanism of Action and Synergy

Dexamethasone enhances antiemetic efficacy when combined with other agents through multiple mechanisms:

1. Anti-inflammatory effects
2. Direct central action at the solitary tract nucleus
3. Interaction with neurotransmitters and receptor proteins
4. Maintaining normal physiological functions
5. Regulation of the hypothalamic-pituitary-adrenal axis 3

Evidence for Combination Therapy

A meta-analysis demonstrated that the combination of dexamethasone with a 5-HT3 antagonist is superior to a 5-HT3 antagonist alone in preventing chemotherapy-induced nausea and vomiting. In chemotherapy-naive patients, the combination provided 81% complete protection from emesis versus 64% with ondansetron alone (p=0.04) 4.

Common Pitfalls and Considerations

1. Dose adjustment: When using aprepitant with dexamethasone, reduce dexamethasone dose due to drug interactions (aprepitant increases dexamethasone levels 2.2-fold) 2

2. Duration of therapy: 5-HT3 antagonists are typically given only on day 1, while dexamethasone and NK1 antagonists may continue for 2-4 days 1

3. Patient-specific factors: For elderly patients, consider starting with lower doses of all agents and titrate slowly due to increased risk of side effects 5

4. Anticipatory nausea and vomiting: Consider adding lorazepam 1 mg PO at bedtime the night before chemotherapy and 1 mg the morning of chemotherapy 1

5. Breakthrough symptoms: Add an agent from a different drug class rather than increasing doses of existing medications 1

By following these evidence-based recommendations for combining dexamethasone with appropriate adjunctive medications based on the emetogenic potential of chemotherapy, clinicians can significantly improve control of nausea and vomiting, leading to better quality of life and treatment adherence for patients.