What is the safest approach to adding chlorpromazine 50mg IM to a patient's hyperemesis gravidarum regimen, which includes ondansetron (Zofran) 4mg IV Q4hr, prochlorperazine (Compazine) 5mg IV once, metoclopramide (Reglan) 10mg IV Q6hr, and diphenhydramine (Benadryl) 25mg IV Q6hr, given the patient received prochlorperazine (Compazine) at 9am?

Management of Chlorpromazine Addition in Hyperemesis Gravidarum with Potential Drug Interaction

Wait at least 6 hours after the last dose of prochlorperazine before administering chlorpromazine to minimize the risk of extrapyramidal side effects.

Understanding the Current Medication Regimen

The patient is currently receiving multiple antiemetics for hyperemesis gravidarum:

• Ondansetron (Zofran) 4mg IV Q4hr
• Prochlorperazine (Compazine) 5mg IV once at 9am
• Metoclopramide (Reglan) 10mg IV Q6hr
• Diphenhydramine (Benadryl) 25mg IV Q6hr

Drug Interaction Concern

The primary concern is the interaction between chlorpromazine and prochlorperazine, both of which are phenothiazine antipsychotics. When administered too closely together, these medications can cause:

1. Additive extrapyramidal symptoms (EPS) including akathisia and dystonic reactions
2. Enhanced sedation
3. Increased risk of QT prolongation
4. Potential for oculogyric crisis 1

Safe Administration Algorithm

1. Timing consideration:

   • Since prochlorperazine was administered at 9am, allow at least 6 hours before giving chlorpromazine
   • Earliest safe administration time would be 3pm or later

2. Pre-administration assessment:

   • Check for signs of existing EPS from current medications
   • Assess baseline vital signs, particularly blood pressure (chlorpromazine can cause hypotension)
   • Ensure diphenhydramine is on board as it helps prevent EPS

3. Administration protocol:

   • Administer chlorpromazine 50mg IM deep into the upper outer quadrant of buttock
   • Keep patient lying down for at least 30 minutes after injection to prevent hypotension 2
   • Monitor vital signs every 15 minutes for the first hour

Monitoring After Administration

• Observe for signs of extrapyramidal symptoms:
  • Akathisia (restlessness, inability to sit still)
  • Dystonia (muscle spasms, particularly of the neck, tongue, or eyes)
  • Oculogyric crisis (fixed upward gaze)
• Monitor for excessive sedation
• Check blood pressure regularly for hypotension

Alternative Approaches

If the patient requires immediate antiemetic therapy and cannot wait the full 6 hours:

1. Consider increasing ondansetron dosing instead of adding chlorpromazine
2. Add dexamethasone 12mg IV which has shown efficacy in hyperemesis gravidarum and doesn't interact with phenothiazines 3
3. Consider haloperidol 1-2mg IV as an alternative to chlorpromazine with potentially less interaction concern 3

Special Considerations for Pregnancy

• Diphenhydramine (already in the regimen) is helpful not only for its antiemetic properties but also for preventing and treating EPS 3
• The combination of multiple antiemetics with different mechanisms of action is appropriate for severe hyperemesis gravidarum resistant to standard therapy 4
• Ondansetron has demonstrated safety and efficacy in hyperemesis gravidarum 5

Remember that proper spacing of phenothiazine administration is crucial to minimize the risk of serious adverse effects while still providing effective control of severe nausea and vomiting in hyperemesis gravidarum.