What are the second-generation dopamine antagonists for daily use?

Second-Generation Dopamine Antagonists for Daily Use

The second-generation dopamine antagonists available for daily use include metoclopramide (5-20 mg oral or IV, 3-4 times daily) and prochlorperazine (5-10 mg oral or IV, 3-4 times daily), which are primarily used as antiemetics in oncology and palliative care settings. 1

Primary Dopamine Antagonists

Metoclopramide

• Dosing: 5-20 mg oral or IV, administered 3-4 times daily 1
• Mechanism: Dual dopamine/5-HT3 receptor antagonist 1
• Clinical applications:
  • Chemotherapy-induced nausea and vomiting (CINV) 1
  • Radiation therapy-induced nausea and vomiting 1
  • Gastroparesis (10 mg PO four times daily, 30 minutes before meals and at bedtime) 1
  • Non-specific nausea and vomiting in palliative care 1

Prochlorperazine

• Dosing: 5-10 mg oral or IV, administered 3-4 times daily 1
• Clinical applications:
  • Used as rescue/breakthrough therapy for CINV 1
  • First-line option for non-specific nausea and vomiting in palliative care 1
  • Can be titrated up to maximum of 3-4 administrations daily 1

Additional Dopamine Antagonists

Domperidone

• Dosing: 20 mg, 3-4 times daily 1
• Note: Not available for intravenous use 1

Metopimazine

• Dosing: 15-30 mg, 1-4 times daily 1
• Note: Intravenous administration only as continuous infusion 1

Haloperidol

• Clinical use: Recommended for non-specific nausea and vomiting in palliative care settings 1
• Application: Can be used as continuous IV or subcutaneous infusion for intractable nausea and vomiting 1

Clinical Context and Usage Patterns

These dopamine antagonists are typically used as rescue or breakthrough therapy rather than first-line prophylaxis in most antiemetic protocols. 1 The ASCO guidelines position them as:

• Rescue therapy for minimal and low-emetic-risk radiation therapy 1
• Add-on therapy when 5-HT3 receptor antagonists and corticosteroids fail to control symptoms 1
• Refractory nausea: Add dopamine antagonists to serotonin antagonists and corticosteroids 1

Important Clinical Considerations

Dosing Frequency

Unlike 5-HT3 receptor antagonists and corticosteroids (which are typically dosed once daily), dopamine antagonists require 3-4 times daily administration for optimal efficacy. 1 This more frequent dosing schedule reflects their shorter duration of action.

Titration Strategy

• Start at lower end of dose range (metoclopramide 5 mg, prochlorperazine 5 mg) 1
• Titrate upward as needed based on symptom control 1
• Maximum metoclopramide: 16 mg oral or IV daily 1
• Maximum prochlorperazine: 3-4 administrations daily 1

Route of Administration

Both metoclopramide and prochlorperazine are available in oral and IV formulations, allowing flexibility based on patient status and ability to take oral medications. 1 For routine use, oral doses are recommended when feasible. 1

Common Pitfalls

Do not confuse these first-generation dopamine antagonists with second-generation antipsychotics (such as olanzapine, quetiapine, aripiprazole, asenapine), which also have dopamine antagonist properties but are used primarily for psychiatric indications and have different dosing schedules. 2, 3, 4, 5 While second-generation antipsychotics like olanzapine are increasingly used for refractory CINV, they are not classified as "dopamine antagonists" in the antiemetic context. 1