The FDA has approved Apadaz (KemPharm), a short-acting, fixed-dose combination of benzhydrocodone and acetaminophen, for short-term management (≤14 days) of acute pain severe enough to require an opioid and for which alternative treatment options are inadequate. Benzhydrocodone is a prodrug of hydrocodone. Fixed-dose combinations of short-acting hydrocodone and acetaminophen or ibuprofen have been available for years and are the most abused opioid products in the US. Apadaz was developed under the presumption that inclusion of the inactive prodrug would reduce the potential for abuse of the combination by non-oral routes such as smoking, snorting, or injection, but the FDA did not approve Apadaz as an abuse-deterrent formulation.

Use of nonopioid drugs for pain was reviewed in a previous issue. For many types of moderate to severe acute pain, acetaminophen and/or an NSAID may be as effective as an opioid. Immediate-release formulations of full opioid agonists should generally be used for acute pain that is severe enough to require treatment with an opioid. Use of extended-release or long-acting opioid formulations initially and treatment durations >1 week have been associated with an increased risk of unintended long-term use.

The FDA has issued new warnings about the use of the opioid analgesics codeine and tramadol in children, particularly those <12 years old, and in breastfeeding women due to concerns about the risk of respiratory depression and death. The FDA previously issued warnings about these drugs in 2013 and 2015.

The FDA has approved tramadol hydrochloride extended-release (Ryzolt – Purdue) for treatment of moderate to moderately severe chronic pain in adults. Tramadol is already available in another extended-release formulation (Ultram ER) and in immediate-release tablets alone (Ultram, and others) and combined with acetaminophen (Ultracet, and others).