A Review of the Opioid Analgesic Benzhydrocodone-Acetaminophen

Abstract

There is an undeniable opioid crisis in the United States that has caused significant negative consequences including many lives lost due to opioid overdoses. Currently, researchers are searching for alternatives for pain management as well as developing abuse-deterrent agents. In February 2018, the Food and Drug Administration (FDA) approved benzhydrocodone and acetaminophen (Apadaz™) for the short-term (no more than 14 days) management of acute pain severe enough to require an opioid analgesic and where alternative treatments are inadequate. This article looks further into this oral opioid prodrug and assesses its clinical pharmacology, pharmacokinetics, clinical trials and safety considerations that led to approval. Even though this prodrug provides a novel approach to analgesia, it was not classified as an abuse-deterrent agent and therefore still has the potential for abuse and misuse. This new agent potentially runs a higher risk of augmenting the opioid crisis rather than curtailing it. Innovative approaches to discover opioid alternatives are warranted.

Structural Modification in Anesthetic Drug Development for Prodrugs and Soft Drugs

“…Benzhydrocodone, a synthetic opioid, is a prodrug of hydrocodone (Mustafa et al, 2018). The physicochemical effect after adding benzoic acid functional groups to hydrocodone results in improved oral absorption and a reduction in parenteral bioavailability of the active metabolite (Cassidy et al, 2017;Guenther et al, 2018).…”

“…In other words, a prodrug could potentially allow for better management of opioids toxicity. Benzhydrocodone in combination with acetaminophen (APAP) under the trade name Apadaz ™ received FDA approval in February 2018 for the short-term management of severe acute pain (Mustafa et al, 2018). However, given that benzhydrocodone/APAP is still susceptible to oral abuse, it has not been confirmed as an abuse-deterrent opioid formulation.…”

Preclinical and Clinical Pharmacology of Hydrocodone for Chronic Pain: A Mini Review

“…In February 2018, the FDA approved the association between the prodrug benzhydrocodone and acetaminophen ( Mustafa et al, 2018 ). However, therapeutic indication for both these drugs is for the short-term management of acute pain.…”

Switching on prodrugs using radiotherapy

“…For instance, Apadaz™ releases its parent drug (hydrocodone) by enzymatic cleavage in the gastrointestinal tract. 7 Polyethylene glycol (PEG) “protected or blocked” interleukin-2 (IL-2) is a biologic prodrug with IL-2 liberated by in vivo release of the PEG chains. 8 Other, more academic prodrug stimuli have been explored in a variety of models, including electrochemical activation of metal-based prodrugs, 9 ultrasound-induced release, 10 or light mediated activation.…”