Journal of Pain & Palliative Care Pharmacotherapy. 2014;28:415–416. Copyright © 2014 Informa Healthcare USA, Inc. ISSN: 1536-0288 print / 1536-0539 online DOI: 10.3109/15360288.2014.972489
LETTER TO THE EDITOR
Clarification on Transdermal Buprenorphine Editor’s Note: This letter was sent to the original authors of the Patient Education and Self Advocacy: Questions and Responses on Pain Management article and they indicated that what they wrote speaks to a much broader view of buprenorphine, not just the Butrans patch. They therefore elected not to reply to the Purdue Pharma letter.
of function, side effects, and evidence of abuse or abnormal behaviors.” The answer presents limited information regarding the abuse potential of Butrans. As stated in the Boxed Warning of the Butrans Full Prescribing Information (FPI), Butrans exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing Butrans, and monitor all patients regularly for the development of these behaviors or conditions.1 The third paragraph in this section states “. . .it has a ceiling effect on slowing down breathing with increased doses and it is easier to withdraw from buprenorphine compared to methadone.” Although a ceiling effect to respiratory depression has been shown in studies with other buprenorphine formulations, serious, life-threatening, or fatal respiratory depression may still occur with use of Butrans.1 In addition, clinical studies comparing withdrawal symptoms of Butrans to methadone have not been conducted. Butrans has not been studied and is not approved for use in the management of opioiduse disorders. When a patient being treated with Butrans for chronic pain no longer requires therapy with Butrans, a gradual downward titration of the dose every 7 days is recommended to prevent signs and symptoms of withdrawal in the physicallydependent patient. Consideration should be given to the introduction of an appropriate immediate-release opioid medication. Butrans should not be abruptly discontinued.1 The fourth paragraph in this section identifies 2001 as the year the transdermal formulation of buprenorphine was launched. Butrans was approved in 2010 and launched in 2011.2,3 Butrans is also described as being “available as 5, 10, and 20 mcg/hour strengths.” Butrans 15 mcg/hour was approved in July 2013 and Butrans 7.5 mcg/hour was approved in June 2014, so Butrans is now available in five dosage strengths.1
To the Editor: R As the NDA holder and distributor of Butrans (buprenorphine) Transdermal System CIII, one objective of Purdue Pharma L.P. is to ensure the dissemination of accurate and complete information regarding our products. While Purdue commends the Journal of Pain and Palliative Care Pharmacotherapy on its commitment to acute, chronic, and end-of-life symptom management, we are writing to notify you of misinformation published in the article “Buprenorphine for Chronic Pain” described in the “Patient Education and Self Advocacy: Questions and Responses on Pain Management” section (pages 402–405) of the December 2013 issue (Volume 27, No. 4). While the review was well written and informative, there are statements pertaining to Butrans (i.e., “buprenorphine patch”) that warrant correction or clarification. Some of the statements in the article seem to apply to other formulations of buprenorphine used for opioid dependence and not necessarily to transdermal buprenorphine used for chronic pain. Listed below by section of the article is significant misinformation that can lead to safety concerns and/or the improper use of Butrans.
Answer: The first paragraph in this section states “Prior to beginning any chronic opioid therapy, it is important to determine whether you are a good candidate. This is evaluated by assessing pain relief, improvement Address correspondence to: Dr. J David Haddox, Vice President for Health Policy, Purdue Pharma, One Stanford Forum, Stanford CT 06901.
415
416
Arthur G. Lipman
Buprenorphine for Pain: This section makes reference to a 35 mcg/hour patch and cites two trials [Bohme et al. and Sittl et al.] evaluating both cancer and noncancer pain patients. These studies did not involve Butrans but, rather, pertain to a different transdermal formulation of buprenorphine that has been available for a number of years in countries outside of the United States. This formulation provides transdermal delivery of higher doses of buprenorphine (35, 52.5, and 70 mcg/hour) in a 3-to-4-day transdermal maR , Grunenthal GmbH).4 Each trix system (Transtec Butrans transdermal system is intended to be worn for 7 days. The maximum recommended dose of Butrans in the United States is 20 mcg/hour due to the risk of QTc interval prolongation.1 The efficacy of 7-day Butrans in the United States was demonstrated in two pivotal studies in patients with moderate to severe chronic low back pain. Butrans has been studied and is approved for use in appropriate opioid-naive or opioid-experienced patients requiring up to 80 mg/day of oral morphine equivalents (i.e., 40 mg/day of hydrocodone or oxycodone).1,5,6 Effects on Respiratory Depression (Slowing Down Breathing): The second paragraph of this section again describes the effects on respiratory depression and specifically states “In contrast to other potent opioids, buprenorphine has a ceiling effect when it comes (to) the side effect of respiratory depression. Increasing doses of buprenorphine will continue to give analgesia without significantly slowing down breathing. Thus, it may be considered safer than other opioids in this regard.” As previously stated, while a ceiling effect to respiratory depression has been shown in studies with other buprenorphine formulations, serious, lifethreatening, or fatal respiratory depression may still occur with the use of Butrans.1 Calculation for Starting Dose: This section begins with the statement “Once the determination is made that a patient is a good candidate for buprenorphine therapy, one must calculate how much opioid pain medication the patient is currently consuming [emphasis added].” The use of Butrans is not limited to patients currently taking opioids. 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 (i.e., 40 mg/day of hydrocodone or oxycodone).6 This section also states, “In patients with an oral morphine equivalent of 30–60 mg, a Butrans patch of 10 mcg/hour would be recommended.” As stated in the Dosage and Administration section of the enclosed Butrans FPI, Butrans 10 mcgfhour is the recommended starting dose for patients whose prior total daily opioid dose was between 30 and 80 mg of oral morphine equivalents [emphasis added].1 Lastly this section states, “For those with greater than 80 mg oral morphine equivalent, a 20 mcg/hour Butrans patch may be used but it may not provide adequate analgesia so an alternative analgesic may be considered. “The enclosed Butrans FPI states, Butrans 20 mcg/hour may not provide adequate analgesia for patients requiring greater than 80 mg/day oral morphine equivalents. Consider the use of an alternate analgesic.1 This should be construed as meaning that starting Butrans in patients whose prior opioid daily dose exceeds 80 mg/day oral morphine equivalents is not recommended. Preventing Withdrawal: This section discusses principles surrounding the initiation of buprenorphine in patients who are on other opioids. The information provided in this section is applicable to other formulations of buprenorphine available in higher doses used for the treatment of opioid dependence. This information is not consistent with the recommendations provided in the Dosage and Administration section 2.1, Initial Dosing of the enclosed Butrans FPL When converting from other opioids to Butrans, it can be initiated at the next dosing interval. Please consult section 2.1 of the Butrans FPI for additional details on how to appropriately initiate Butrans in opioid-experienced patients. Declaration of interest: Both authors are employees of Purdue Pharma. Erica H. Dankiewicz, PharmD, Senior Medical Services Specialist J. David Haddox, DDS, MD, Vice President, Health Policy Purdue Pharma L.P. One Stamford Forum, Stamford, CT 06901
Journal of Pain & Palliative Care Pharmacotherapy
Copyright of Journal of Pain & Palliative Care Pharmacotherapy is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
LETTER TO THE EDITOR
Clarification on Transdermal Buprenorphine Editor’s Note: This letter was sent to the original authors of the Patient Education and Self Advocacy: Questions and Responses on Pain Management article and they indicated that what they wrote speaks to a much broader view of buprenorphine, not just the Butrans patch. They therefore elected not to reply to the Purdue Pharma letter.
of function, side effects, and evidence of abuse or abnormal behaviors.” The answer presents limited information regarding the abuse potential of Butrans. As stated in the Boxed Warning of the Butrans Full Prescribing Information (FPI), Butrans exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing Butrans, and monitor all patients regularly for the development of these behaviors or conditions.1 The third paragraph in this section states “. . .it has a ceiling effect on slowing down breathing with increased doses and it is easier to withdraw from buprenorphine compared to methadone.” Although a ceiling effect to respiratory depression has been shown in studies with other buprenorphine formulations, serious, life-threatening, or fatal respiratory depression may still occur with use of Butrans.1 In addition, clinical studies comparing withdrawal symptoms of Butrans to methadone have not been conducted. Butrans has not been studied and is not approved for use in the management of opioiduse disorders. When a patient being treated with Butrans for chronic pain no longer requires therapy with Butrans, a gradual downward titration of the dose every 7 days is recommended to prevent signs and symptoms of withdrawal in the physicallydependent patient. Consideration should be given to the introduction of an appropriate immediate-release opioid medication. Butrans should not be abruptly discontinued.1 The fourth paragraph in this section identifies 2001 as the year the transdermal formulation of buprenorphine was launched. Butrans was approved in 2010 and launched in 2011.2,3 Butrans is also described as being “available as 5, 10, and 20 mcg/hour strengths.” Butrans 15 mcg/hour was approved in July 2013 and Butrans 7.5 mcg/hour was approved in June 2014, so Butrans is now available in five dosage strengths.1
To the Editor: R As the NDA holder and distributor of Butrans (buprenorphine) Transdermal System CIII, one objective of Purdue Pharma L.P. is to ensure the dissemination of accurate and complete information regarding our products. While Purdue commends the Journal of Pain and Palliative Care Pharmacotherapy on its commitment to acute, chronic, and end-of-life symptom management, we are writing to notify you of misinformation published in the article “Buprenorphine for Chronic Pain” described in the “Patient Education and Self Advocacy: Questions and Responses on Pain Management” section (pages 402–405) of the December 2013 issue (Volume 27, No. 4). While the review was well written and informative, there are statements pertaining to Butrans (i.e., “buprenorphine patch”) that warrant correction or clarification. Some of the statements in the article seem to apply to other formulations of buprenorphine used for opioid dependence and not necessarily to transdermal buprenorphine used for chronic pain. Listed below by section of the article is significant misinformation that can lead to safety concerns and/or the improper use of Butrans.
Answer: The first paragraph in this section states “Prior to beginning any chronic opioid therapy, it is important to determine whether you are a good candidate. This is evaluated by assessing pain relief, improvement Address correspondence to: Dr. J David Haddox, Vice President for Health Policy, Purdue Pharma, One Stanford Forum, Stanford CT 06901.
415
416
Arthur G. Lipman
Buprenorphine for Pain: This section makes reference to a 35 mcg/hour patch and cites two trials [Bohme et al. and Sittl et al.] evaluating both cancer and noncancer pain patients. These studies did not involve Butrans but, rather, pertain to a different transdermal formulation of buprenorphine that has been available for a number of years in countries outside of the United States. This formulation provides transdermal delivery of higher doses of buprenorphine (35, 52.5, and 70 mcg/hour) in a 3-to-4-day transdermal maR , Grunenthal GmbH).4 Each trix system (Transtec Butrans transdermal system is intended to be worn for 7 days. The maximum recommended dose of Butrans in the United States is 20 mcg/hour due to the risk of QTc interval prolongation.1 The efficacy of 7-day Butrans in the United States was demonstrated in two pivotal studies in patients with moderate to severe chronic low back pain. Butrans has been studied and is approved for use in appropriate opioid-naive or opioid-experienced patients requiring up to 80 mg/day of oral morphine equivalents (i.e., 40 mg/day of hydrocodone or oxycodone).1,5,6 Effects on Respiratory Depression (Slowing Down Breathing): The second paragraph of this section again describes the effects on respiratory depression and specifically states “In contrast to other potent opioids, buprenorphine has a ceiling effect when it comes (to) the side effect of respiratory depression. Increasing doses of buprenorphine will continue to give analgesia without significantly slowing down breathing. Thus, it may be considered safer than other opioids in this regard.” As previously stated, while a ceiling effect to respiratory depression has been shown in studies with other buprenorphine formulations, serious, lifethreatening, or fatal respiratory depression may still occur with the use of Butrans.1 Calculation for Starting Dose: This section begins with the statement “Once the determination is made that a patient is a good candidate for buprenorphine therapy, one must calculate how much opioid pain medication the patient is currently consuming [emphasis added].” The use of Butrans is not limited to patients currently taking opioids. 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 (i.e., 40 mg/day of hydrocodone or oxycodone).6 This section also states, “In patients with an oral morphine equivalent of 30–60 mg, a Butrans patch of 10 mcg/hour would be recommended.” As stated in the Dosage and Administration section of the enclosed Butrans FPI, Butrans 10 mcgfhour is the recommended starting dose for patients whose prior total daily opioid dose was between 30 and 80 mg of oral morphine equivalents [emphasis added].1 Lastly this section states, “For those with greater than 80 mg oral morphine equivalent, a 20 mcg/hour Butrans patch may be used but it may not provide adequate analgesia so an alternative analgesic may be considered. “The enclosed Butrans FPI states, Butrans 20 mcg/hour may not provide adequate analgesia for patients requiring greater than 80 mg/day oral morphine equivalents. Consider the use of an alternate analgesic.1 This should be construed as meaning that starting Butrans in patients whose prior opioid daily dose exceeds 80 mg/day oral morphine equivalents is not recommended. Preventing Withdrawal: This section discusses principles surrounding the initiation of buprenorphine in patients who are on other opioids. The information provided in this section is applicable to other formulations of buprenorphine available in higher doses used for the treatment of opioid dependence. This information is not consistent with the recommendations provided in the Dosage and Administration section 2.1, Initial Dosing of the enclosed Butrans FPL When converting from other opioids to Butrans, it can be initiated at the next dosing interval. Please consult section 2.1 of the Butrans FPI for additional details on how to appropriately initiate Butrans in opioid-experienced patients. Declaration of interest: Both authors are employees of Purdue Pharma. Erica H. Dankiewicz, PharmD, Senior Medical Services Specialist J. David Haddox, DDS, MD, Vice President, Health Policy Purdue Pharma L.P. One Stamford Forum, Stamford, CT 06901
Journal of Pain & Palliative Care Pharmacotherapy
Copyright of Journal of Pain & Palliative Care Pharmacotherapy is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
