Buprenorphine-naloxone (BNX) reduces the risk of mortality from untreated opioid use disorder by 50% or more. However, adverse effects of BNX can be a cause of inconsistent use or discontinuation. The buprenorphine monoproduct (BUP) is effective and is sometimes tolerated better, but practice guidelines and insurance restrictions discourage its prescription due to concerns about diversion and injection. An idiopathic reaction of bilateral flank pain reported by three patients is used as an example to show how to assess the success of a BUP trial. Sublingual absorption of naloxone is discussed as a potential cause of adverse effects of BNX in sensitive individuals. Issues in clinical decision-making are presented to help prescribers assess the risk-benefit ratio of a BUP trial for the individual patient, the prescriber, and society. This commentary may serve as a stimulus for changes in practice guidelines and insurance coverage policies to allow greater flexibility in the prescribing of BUP.