Can Tigan (trimethobenzamide) be given if Zofran (ondansetron) is ineffective?

Using Tigan (Trimethobenzamide) When Zofran (Ondansetron) is Ineffective

Yes, Tigan (trimethobenzamide) can be given when Zofran (ondansetron) is ineffective for nausea and vomiting, as it works through a different mechanism and is specifically listed as an alternative agent for breakthrough emesis in clinical guidelines.

Rationale for Using Tigan After Zofran Failure

When ondansetron (Zofran) fails to control nausea and vomiting, clinical guidelines support using medications from different antiemetic classes:

• Ondansetron works as a 5-HT3 receptor antagonist
• Trimethobenzamide (Tigan) works as a dopamine antagonist with a different mechanism of action
• Guidelines specifically recommend using agents from different drug classes for breakthrough emesis 1

Dosing and Administration

• Trimethobenzamide (Tigan): 300 mg three times daily 1
• Can be administered orally, but rectal or intravenous routes may be necessary if ongoing vomiting makes oral administration unfeasible 1

Evidence-Based Approach to Antiemetic Failure

The NCCN guidelines specifically state that for breakthrough emesis: "The general principle of breakthrough treatment is to give an additional agent as needed from a different drug class" 1. This supports using trimethobenzamide when ondansetron has failed.

Algorithm for Managing Ondansetron Failure

1. Confirm ondansetron failure: Ensure adequate dosing of ondansetron was used (typically 4-8 mg 2-3 times daily) 1

2. Rule out underlying causes: Before adding another antiemetic, consider potential causes for refractory nausea/vomiting:

   • Electrolyte abnormalities
   • Brain metastases (if in cancer patients)
   • GI abnormalities
   • Other comorbidities 1

3. Add trimethobenzamide: 300 mg three times daily 1

4. Consider additional agents if needed:

   • Dopamine antagonists (metoclopramide)
   • Haloperidol
   • Corticosteroids
   • Lorazepam 1

5. Ensure adequate hydration and correct any electrolyte abnormalities 1

Important Considerations

• Trimethobenzamide is considered off-label for most indications (except for FDA approval for postoperative nausea/vomiting)
• Monitor for side effects including drowsiness and potential extrapyramidal symptoms
• For severe, persistent nausea/vomiting despite multiple agents, consider alternative routes of administration or multiple concurrent agents 1

Pitfalls to Avoid

• Don't continue using the same drug class: If a 5-HT3 antagonist (ondansetron) fails, adding another 5-HT3 antagonist (like granisetron) may not be as effective as switching to a different class
• Don't ignore underlying causes: Always assess for correctable causes of refractory nausea/vomiting
• Don't undertreat: For severe nausea/vomiting, scheduled dosing is more effective than as-needed (PRN) administration 1

Using trimethobenzamide when ondansetron fails is a reasonable approach supported by clinical guidelines that recommend using agents from different antiemetic classes for breakthrough nausea and vomiting.