Regulatory Decision Summary for Acetaminophen Injection

Acetaminophen Injection has been developed as a generic version of the United States Ofirmev and the European Unions Perfalgan with consideration given to the characteristics of the Canadian Ofirmev. Health Canada granted Ofirmev a Notice of Compliance (NOC) in 2013; however, this product was never marketed in Canada. In the absence of a Canadian Reference Product, the New Drug Submission for Acetaminophen Injection was filed in accordance with Health Canada Submissions Relying on Third Party Data guidance.

Based on physicochemical similarities between Acetaminophen Injection and the innovator products, the efficacy and safety for Acetaminophen Injection has been supported by clinical trial results for the innovator product available in the public domain. Efficacy in adults is supported by three phase III placebo controlled trials; two for the management of pain and one for the treatment of fever. Efficacy in the pediatric population (≥2 years of age) is supported by two active-controlled and three open-label safety and pharmacokinetic trials. Overall, efficacy of Acetaminophen Injection has been demonstrated in adult and pediatric populations over 2 years of age for the treatment of mild to moderate pain; moderate to severe pain with adjunctive opioids; and in the treatment of fever.

Safety data from clinical trials has demonstrated that Acetaminophen Injection is safe and well tolerated when used as prescribed for pain and fever. Observations from over ten years of extensive post-market experience in Europe further support the well-characterized safety of the product. Hepatotoxicity remains the most serious adverse event associated with Acetaminophen Injection. Additionally, in patients requiring weight-based dosing (i.e. adult and patients weighing less than 50 kg), there is a risk of medication error related to potential confusion between mg and ml during drug prescribing and administration. An error of this type could potentially lead to a 10 fold overdose situation.

Acetaminophen Injection contains the excipient povidone K12 which is not present in the innovator products. As this excipient is readily excreted by the kidney it is not expected to influence the efficacy or safety of Intravenous Acetaminophen in adults or pediatric patients two years of age and older. However, the effect of povidone K12 on Acetaminophen Injection safety in pediatric patients less than two years of age has not been adequately established.

A Risk Management Plan (RMP) for Acetaminophen Injection was included in this submission. Upon review, the RMP was considered to be acceptable. The RMP is designed to describe known and potential safety issues, to present the monitoring scheme, and when needed to describe measures that will be put in place to minimise risks associated with the product.

Based on the totality of the evidence, which includes the well-established safety profile of acetaminophen, the anticipated short-term use, and the close safety monitoring of a hospital setting, the benefit risk balance for Intravenous Acetaminophen is considered to be positive. The major risks of hepatotoxicity and medication dosing errors have been mitigated through clear labelling in the Product Monograph.