FDA Approves KemPharm's Benzhydrocodone, Acetaminophen for Short-Term Acute Pain

The US Food and Drug Association (FDA) approved KemPharm, Inc.’s new drug application for benzhydrocodone, acetaminophen (Apadaz) for short-term — no more than 14 days — management of acute pain severe enough to require an opioid analgesic, and in which alternative treatments are inadequate.

The FDA approval via the 505(b) (2) pathway, was based on pharmacokinetic studies with hydrocodone and ibuprofen (Vicoprofen), tramadol hydrochloride and acetaminophen tablets (Ultracet), and acetaminophen/hydrocodone (Norco) in which Apadaz demonstrated exposure to hydrocodone and acetaminophen that’s expected to result in therapeutic effects parallel to currently approved immediate-release hydrocodone acetaminophen combination products when administered orally.

“The approval of Apadaz is a significant milestone for KemPharm as it creates the opportunity to introduce what we believe is a differentiated product for the short-term management of acute pain,” Travis Mickle, PhD, president and chief executive officer, KemPharm, said in a statement.

Apadaz, unique among prescription opioids in that it contains a prodrug that’s inactive on its own, is an immediate release combination of benzhydrocodone and acetaminophen.

When ingested, enzymes in the gastrointestinal tract slice the ligand from the prodrug (benzhydrocodone) and release the parent drug (hydrocodone) which can exert its therapeutic effect.

The overall clinical results indicate that Apadaz did not demonstrate abuse-deterrence by current measurement standards.

“In addition to today’s approval, the US Food and Drug Enforcement Administration (DEA) has indicated that it is their intent to schedule Apadaz as a C-II product and will provide an allocation of the Active Pharmaceutical Ingredient consistent with those scheduling provisions,” Mickle said. “This prompt decision by the DEA essentially completes the regulatory process with both agencies and allows us to shift our focus towards the product launch.”

The most common adverse reactions >5% include nausea, somnolence, vomiting, constipation, pruritus, dizziness and headache.

Apadaz, even at recommended doses, is suggested for patients that have tried alternative treatment options that are not tolerated.

KemPharm resubmitted the marketing application for review in September 2017, after appealing against the complete response letter rejecting the new drug application in June 2016.

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