Does prochlorperazine potentiate the effects of oxycodone?

Prochlorperazine's Effect on Oxycodone

Prochlorperazine can potentiate the effects of oxycodone, primarily by increasing the risk of sedation and central nervous system depression, while potentially offering some protective effect against respiratory depression. 1, 2

Mechanism of Interaction

The interaction between prochlorperazine and oxycodone occurs through several mechanisms:

1. Pharmacodynamic interaction: Both medications have central nervous system depressant effects that can be additive when combined 3

2. Antiemetic effects: Prochlorperazine is often used to prevent opioid-induced nausea and vomiting when initiating opioid therapy, including oxycodone 1, 2

3. Respiratory effects: Interestingly, prochlorperazine may actually reverse some of the respiratory depression caused by opioids by stimulating the ventilatory response to hypoxia 4

Clinical Evidence

A retrospective study examining cancer patients receiving oxycodone (10 mg/day) with prochlorperazine (10-15 mg/day) found:

• Effective prevention of oxycodone-induced nausea and vomiting (only 8% of patients experienced these side effects)
• However, 14% of patients developed extrapyramidal symptoms, primarily akathisia, within one week 2

Another study demonstrated that prochlorperazine actually reversed morphine-induced depression of ventilatory response to asphyxia, suggesting a potentially protective effect against opioid-induced respiratory depression 4.

Clinical Implications

When using prochlorperazine with oxycodone:

Benefits:

• Effective prevention of opioid-induced nausea and vomiting 1, 2
• Possible protective effect against respiratory depression 4

Risks:

• Increased sedation and CNS depression 3
• Higher risk of extrapyramidal symptoms (14% incidence), particularly akathisia 2
• Potential for falls due to combined effects on motor function and sensory stability 3
• Possible QT interval prolongation when combined with other QT-prolonging medications 1

Recommendations for Clinical Practice

1. Start with appropriate dosing:

   • Prochlorperazine: 5-10 mg orally every 6-8 hours (maximum 40 mg daily) 5
   • Use the lowest effective dose of oxycodone for the shortest period of time 1

2. Monitor for adverse effects:

   • Extrapyramidal symptoms, particularly akathisia (restlessness, inability to sit still)
   • Excessive sedation
   • Signs of respiratory depression
   • Fall risk, especially in elderly patients 3

3. Consider alternatives if side effects occur:

   • Atypical antipsychotics (e.g., quetiapine) may be considered as alternative antiemetics, though they may have their own interaction profile with oxycodone 2, 6
   • Ondansetron or metoclopramide are other antiemetic options 5

4. Use caution in specific populations:

   • Elderly patients (increased sensitivity to both medications)
   • Patients with hepatic or renal impairment
   • Patients taking other CNS depressants 3

Genetic Considerations

Genetic factors may influence the interaction between prochlorperazine and oxycodone:

• DRD2 TaqIA polymorphism affects antiemetic efficacy (A1A2+A1A1 genotypes associated with higher incidence of nausea despite prochlorperazine)
• OPRM1 A118G polymorphism affects prolactin secretion in response to prochlorperazine 7

The combination of prochlorperazine and oxycodone requires careful monitoring, but when used appropriately, can effectively manage pain while minimizing opioid-induced nausea and vomiting.