(293) Opioid-Induced Nausea - A Population-Based Active-Comparator Symmetry Analysis

Publication Number: 624

Background: Nausea is one of the most common adverse effects of opioid-treatment. In our everyday practice, we are often confronted with the statement that oxycodone is less likely to induce nausea than morphine. However, the evidence of this statement is sparse.

Objectives: To assess the association between initiation of opioids and antiemetic therapy, and assess the difference in risk among initiators of morphine and oxycodone.

Methods: A symmetry analysis was employed on all adults living in Denmark (2020: 4,666,625), who filled in their first prescription of a strong opioid, morphine or oxycodone, in the period of 1996-2019 and initiated antiemetic therapy (propulsives and serotonin-agonists) 30 days prior to or after this date. Individuals with a diagnosis of cancer up to opioid-initiation were excluded. A symmetrical distribution of prescriptions before and after opioid-initiation is expected if no association between opioids and antiemetics exists (i.e. a sequence ratio (SR) of 1.0). Using morphine as the active comparator, we estimated the active comparator adjusted SR of being prescribed antiemetic therapy up to 30 days after initiating oxycodone compared to initiating morphine. The active comparator adjusted SR for oxycodone was estimated using the simple ratio approach.

Results: A total of 17,274 individuals filled in their first-ever prescription of antiemetic therapy within 30 days before or after their first ever opioid prescription; 12,229 individuals filled their prescription of an opioid before filling a prescription of antiemetic therapy, and 5,045 individuals filled their prescriptions in the opposite order (SR 2.42, 95%CI 2.35-2.51). The majority were females (n=11,772, 68,1%) with a median age of 73 years (IQR 58-84 years).
The SR was 1.96 (95%CI 1.88-2.05) if the initial opioid prescription was morphine, and 3.28 (95%CI 3.11-3.46) if the initial opioid was oxycodone. The OR for oxycodone with morphine as reference was 1.68 (95%CI 1.57-1.80). The absolute risk of filling a prescription of antiemetic therapy within 30 days following initiation of oxycodone was 1127 per 100,000 adult oxycodone users without cancer. For patients initiating antiemetic therapy within 30 days following initiation of morphine, the absolute risk was 770 per 100,000 adult morphine users without cancer.

Conclusions: Individuals initiating oxycodone as their first opioid for non-cancer pain were more likely to be prescribed antiemetic therapy compared to individuals initiating morphine as their initial opioid. This suggests that oxycodone may be more emetogenic than morphine.