Use of the Low-Dose Buprenorphine Patch: A Response

Abstract

Dear Editor: As the NDA holder and distributor of Butrans® (buprenorphine) Transdermal System, Purdue Pharma L.P. works to ensure the dissemination of accurate and complete information regarding our products. Purdue commends the Journal of Palliative Medicine on its commitment to end-of-life care and patients with intractable pain; however, we are writing to notify you of misinformation published in Fast Fact #268, “Low-Dose Buprenorphine Patch for Pain.” While the review was well written and informative, there are several statements about Butrans (i.e., low-dose buprenorphine patch) that warrant correction or clarification. Listed below by section of the article and article statement in quotes is a summary of significant misinformation that can lead to safety concerns and/or the improper use of Butrans. • Background: ∘ In addition to being approved for use in treatment of opioid addiction, buprenorphine is approved, as an injectable, for relief of moderate to severe pain, as referenced in the Equianalgesic Ratios section. The U.S. approval for this pain indication predates approval for use in addiction treatment by over 20 years (12/29/1981).1 • Pharmacology: ∘ Buprenorphine is described as providing “analgesia with decreased incidence of sedation, euphoria, and respiratory depression compared to other opioids.” There are no head-to-head studies evaluating these outcomes with Butrans in comparison to other opioids. Although buprenorphine is considered a partial agonist at mu opioid receptors, it can be expected to produce pharmacological effects similar to those of full mu-agonists, especially at the buprenorphine doses delivered by Butrans.2 Therefore, sedation, euphoria, and respiratory depression can occur. In fact, respiratory depression is the primary risk of Butrans.3 • Using the low-dose buprenorphine patch: ∘ This section states, “The U.S. formulation of the buprenorphine transdermal system is recommended for opioid tolerant patients requiring up to 80 mg/day of oral morphine equivalents.” The use of Butrans is not limited to opioid-tolerant patients. Butrans has been studied and is approved for use in opioid-naive patients or in opioid-experienced patients requiring up to 80 mg/day of oral morphine equivalents.3–5 ∘ Butrans is described as being “available in strengths of 5, 10, and 20 mcg/hour.” Butrans 15 mcg/hour was approved in July 2013 and Butrans is now available in four dosage strengths.3 We understand that the reason for this omission is because the new strength became available after the writing of this article. ∘ Withdrawal symptoms are described as “symptoms tend to be milder than with other long-acting opioids.” Although this has been demonstrated with other buprenorphine formulations, clinical studies comparing withdrawal symptoms with Butrans to other long-acting opioids have not been conducted. When a patient no longer requires therapy with Butrans, a gradual downward titration of the dose every seven days to prevent signs and symptoms of withdrawal in the physically dependent patient is recommended. Butrans should not be abruptly discontinued.3 ∘ The article states, “Use of more than one patch at a time is not recommended due to risk of QT prolongation.” Although applying more than one patch at a time is not recommended, it is important to clarify that QTc interval prolongation is not dependent on the number of patches worn, but rather on the buprenorphine dose delivered. The maximum dose of Butrans is 20 mcg/hour due to the risk of QTc interval prolongation (which was detected at a dose of 40 mcg/hour).3 • Clinical applications: ∘ This section states, “Other advantages of buprenorphine include a decreased risk of respiratory depression.” While this effect may have been demonstrated with other buprenorphine products, it has not been demonstrated with Butrans. Respiratory depression is the primary risk of Butrans.3 • Summary: ∘ The article concludes by stating, “The low-dose transdermal buprenorphine patch is effective for mild to moderate chronic pain, both malignant and nonmalignant.” Butrans is not recommended for use in treating mild chronic pain. Butrans is indicated for the management of moderate to severe chronic pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time.3 ∘ The low-dose buprenorphine patch is described as being “a reasonable second- or third-line option in patients with low opioid requirements who experience intolerable side effects with other opioids.” Categorizing Butrans as an option for patients only with low opioid requirements misrepresents the patient population for which Butrans is approved. Butrans is approved for use in opioid-naive patients as the first opioid analgesic, as well as in opioid-experienced patients requiring up to 80 mg/day of oral morphine equivalents.3–5 This article provides clinicians with a concise overview of the low-dose buprenorphine patch. We would appreciate a correction that accurately presents the product information in order for clinicians to have the necessary information to use Butrans safely and effectively.