Regulatory Decision Summary for Zynrelef

Zynrelef (bupivacaine/meloxicam) has demonstrable efficacy for post-operative analgesia for bunionectomy, open inguinal herniorrhaphy, and total knee arthroplasty. The analgesic effect for bunionectomy was moderate as observed within the multimodal analgesia (MMA) framework for post-operative pain management. The duration of the effect lasted approximately 60 hours. Its effect for herniorrhaphy was mild to moderate within the MMA framework. The duration of the effect was shorter, lasting approximately 24 hours. Its effect for arthroplasty was moderate and lasting longer than the study specified 48 hours, even though the study had significant conduct issues.

Zynrelef was associated with observable wound healing adverse reactions, but the reactions tended to dissipate without clinical intervention. The risk of Local Anesthetic Systemic Toxicity (LAST) was more likely in the context of a drug-drug interaction with another local anesthetic or pro-epileptic drug. There is a potential risk of exacerbating the adverse reactions to cyclooxygenase (COX)-inhibitors (NSAIDs – non-steroidal anti-inflammatory drugs), especially those with a higher selectivity of COX2 inhibition. In patients with a known history of hepatic injury linked with bupivacaine, Zynrelef should be avoided. It further carries significant safety and efficacy uncertainties in pregnant women and for women undergoing Caesarean Section.

When weighing the evidence supporting safety and efficacy, Zynrelef has a favorable profile of benefit-harm-uncertainty only when it is used according to the indication wording, and associated use instructions, based on the key clinical studies, with risk language to manage the identified safety signals.

For further details about Zynrelef, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.