VOLUME
33
䡠
NUMBER
3
䡠
JANUARY
20
2015
JOURNAL OF CLINICAL ONCOLOGY
D I A G N O S I S
O N C O L O G Y
gastrostomy tube was clamped for 30 minutes after the administration of each oral medication.
What Is Your Gut Feeling About Opioid Rotation?
Discussion HMER is available in a nondeformable tablet form. It is long acting because of its preparation rather than because of its innate nature.2,3 Given that the casings did not pass beyond the stomach region, the nature of drug delivery in this patient was difficult to understand. The equivalent dose of methadone for an MEDD of 440 mg is approximately 30 to 40 mg. However, because HMER absorption was likely unreliable in this patient, we initiated a starting dose of oral methadone of 5 mg twice per day. At a follow-up visit to the clinic a month later, the patient had excellent and sustained pain control and was receiving a total MEDD of about 100 mg in the form of methadone 5 mg twice per day and one to two doses of immediate-release hydromorphone 4 mg taken for breakthrough pain. This strongly suggests that the absorption of HMER was profoundly impaired in this patient with a partial bowel obstruction. An opioid rotation that was conducted assuming good bioavailability of HMER would have resulted in severe toxicity to methadone. The package inserts for extended-release preparations of morphine, oxycodone, and hydromorphone state that use in patients with a bowel blockage or GI narrowing should be avoided.2,4,5 However, it is important to attempt pain control with an oral regimen of longacting pain medications, given that the ease of administration ensures a better quality of life for our patients. HMER is delivered via an oral osmotic system, which consists of a semipermeable membrane with the drug and an active push compartment. As water passes through the membrane and the active push is expanded, the drug is released slowly through the GI tract. This system allows for the continuous slow release of the drug without noticeable peaks and troughs.2,3 However, methadone is long acting because of the pharmacokinetic properties of the drug rather than the delivery formulation.
Introduction During opioid rotation, one opioid is substituted for another using equianalgesic tables, mainly to alleviate uncontrolled pain or opioid-related adverse effects.1 Herein, we describe a case in which opioid rotation was administered for an unusual reason. Case Report Our patient, a 62-year-old man, was diagnosed with metastatic appendiceal cancer at our institute 3 years ago. Despite multiple abdominal surgeries and chemotherapy regimens, his disease progressed and he developed chronic partial small bowel obstruction. However, he was able to take oral medications, occasional nausea and vomiting notwithstanding. Total parenteral nutrition was initiated. Oral extended-release morphine sulfate was initially prescribed for his abdominal pain and was later changed to a fentanyl transdermal patch because of opioid-induced neurotoxicity.1 Given that his pain persisted, fentanyl was subsequently switched to three 12-mg extendedrelease hydromorphone (HMER) tablets (36 mg) twice per day plus immediate-release hydromorphone at a dose of 4 mg taken orally every 4 hours as needed for breakthrough pain. The morphine equivalent daily dose (MEDD) was 440 mg. The patient’s nausea and vomiting worsened and necessitated the placement of a venting gastrostomy tube. The patient also experienced uncontrolled pain. During the endoscopic procedure, numerous empty casings of HMER were extracted from the gastric region. Figure 1 shows the endoscopic extraction of HMER casings via a Roth Net (US Endoscopy, Mentor, OH) from the stomach. After extensive discussions with the patient and the primary team, opioid rotation to oral methadone was initiated, and the venting
A
I N
B
C
Fig 1. Journal of Clinical Oncology, Vol 33, No 3 (January 20), 2015: pp e11-e12
© 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at YALE MEDICAL LIBRARY on May 18, 2015 from Copyright © 2015 American Society of Clinical Oncology. All rights reserved. 130.132.123.28
e11
Didwaniya et al
On the basis of the findings described herein, methadone, which has a long half-life and is rapidly absorbed higher in the GI tract, and transdermal formulations such as fentanyl, may be preferred over oral extended-release formulations of opioids in patients with a partial bowel obstruction. Our patient case emphasizes the importance of understanding the pharmacologic intricacies of opioids, not only to benefit our patients but also to avoid causing iatrogenic harm. Our patient was able to enjoy a weeklong vacation with his wife shortly after the follow-up clinic visit.
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. REFERENCES
ACKNOWLEDGMENT
1. Reddy A, Yennurajalingam S, Pulivarthi K, et al: Frequency, outcome, and predictors of success within 6 weeks of an opioid rotation among outpatients with cancer receiving strong opioids. Oncologist 18:212-220, 2013 2. Mallinckrodt Brand Pharmaceuticals: Exalgo: Hydromorphone HCl extendedrelease tablets [package insert]. Hazelwood, MO, Mallinckrodt Brand Pharmaceuticals, 2010 3. Cruciani RA, Katz N, Portenoy RK: Dose equivalence of immediate-release hydromorphone and once-daily osmotic-controlled extended-release hydromorphone: A randomized, double-blind trial incorporating a measure of assay sensitivity. J Pain 13:379-389, 2012 4. Purdue Pharma: MS-Contin: Morphine sulfate controlled-release tablets [package insert]. Stamford, CT, Purdue Pharma, 2009 5. Purdue Plarma: OxyContin: Oxycodone hydrochloride controlled-release tablets [package insert]. Stamford, CT, Purdue Plarma, 2010
We thank our patient for allowing us to submit his case description and endoscopy images for publication. N.D. and A.R. contributed equally to this article.
DOI: 10.1200/JCO.2013.49.8204; published online ahead of print at www.jco.org on March 3, 2014
Neha Didwaniya, Akhila Reddy, Raju S. Gottumukkala, and Eduardo Bruera The University of Texas MD Anderson Cancer Center, Houston, TX
■ ■ ■
e12
© 2014 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at YALE MEDICAL LIBRARY on May 18, 2015 from Copyright © 2015 American Society of Clinical Oncology. All rights reserved. 130.132.123.28
33
䡠
NUMBER
3
䡠
JANUARY
20
2015
JOURNAL OF CLINICAL ONCOLOGY
D I A G N O S I S
O N C O L O G Y
gastrostomy tube was clamped for 30 minutes after the administration of each oral medication.
What Is Your Gut Feeling About Opioid Rotation?
Discussion HMER is available in a nondeformable tablet form. It is long acting because of its preparation rather than because of its innate nature.2,3 Given that the casings did not pass beyond the stomach region, the nature of drug delivery in this patient was difficult to understand. The equivalent dose of methadone for an MEDD of 440 mg is approximately 30 to 40 mg. However, because HMER absorption was likely unreliable in this patient, we initiated a starting dose of oral methadone of 5 mg twice per day. At a follow-up visit to the clinic a month later, the patient had excellent and sustained pain control and was receiving a total MEDD of about 100 mg in the form of methadone 5 mg twice per day and one to two doses of immediate-release hydromorphone 4 mg taken for breakthrough pain. This strongly suggests that the absorption of HMER was profoundly impaired in this patient with a partial bowel obstruction. An opioid rotation that was conducted assuming good bioavailability of HMER would have resulted in severe toxicity to methadone. The package inserts for extended-release preparations of morphine, oxycodone, and hydromorphone state that use in patients with a bowel blockage or GI narrowing should be avoided.2,4,5 However, it is important to attempt pain control with an oral regimen of longacting pain medications, given that the ease of administration ensures a better quality of life for our patients. HMER is delivered via an oral osmotic system, which consists of a semipermeable membrane with the drug and an active push compartment. As water passes through the membrane and the active push is expanded, the drug is released slowly through the GI tract. This system allows for the continuous slow release of the drug without noticeable peaks and troughs.2,3 However, methadone is long acting because of the pharmacokinetic properties of the drug rather than the delivery formulation.
Introduction During opioid rotation, one opioid is substituted for another using equianalgesic tables, mainly to alleviate uncontrolled pain or opioid-related adverse effects.1 Herein, we describe a case in which opioid rotation was administered for an unusual reason. Case Report Our patient, a 62-year-old man, was diagnosed with metastatic appendiceal cancer at our institute 3 years ago. Despite multiple abdominal surgeries and chemotherapy regimens, his disease progressed and he developed chronic partial small bowel obstruction. However, he was able to take oral medications, occasional nausea and vomiting notwithstanding. Total parenteral nutrition was initiated. Oral extended-release morphine sulfate was initially prescribed for his abdominal pain and was later changed to a fentanyl transdermal patch because of opioid-induced neurotoxicity.1 Given that his pain persisted, fentanyl was subsequently switched to three 12-mg extendedrelease hydromorphone (HMER) tablets (36 mg) twice per day plus immediate-release hydromorphone at a dose of 4 mg taken orally every 4 hours as needed for breakthrough pain. The morphine equivalent daily dose (MEDD) was 440 mg. The patient’s nausea and vomiting worsened and necessitated the placement of a venting gastrostomy tube. The patient also experienced uncontrolled pain. During the endoscopic procedure, numerous empty casings of HMER were extracted from the gastric region. Figure 1 shows the endoscopic extraction of HMER casings via a Roth Net (US Endoscopy, Mentor, OH) from the stomach. After extensive discussions with the patient and the primary team, opioid rotation to oral methadone was initiated, and the venting
A
I N
B
C
Fig 1. Journal of Clinical Oncology, Vol 33, No 3 (January 20), 2015: pp e11-e12
© 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at YALE MEDICAL LIBRARY on May 18, 2015 from Copyright © 2015 American Society of Clinical Oncology. All rights reserved. 130.132.123.28
e11
Didwaniya et al
On the basis of the findings described herein, methadone, which has a long half-life and is rapidly absorbed higher in the GI tract, and transdermal formulations such as fentanyl, may be preferred over oral extended-release formulations of opioids in patients with a partial bowel obstruction. Our patient case emphasizes the importance of understanding the pharmacologic intricacies of opioids, not only to benefit our patients but also to avoid causing iatrogenic harm. Our patient was able to enjoy a weeklong vacation with his wife shortly after the follow-up clinic visit.
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. REFERENCES
ACKNOWLEDGMENT
1. Reddy A, Yennurajalingam S, Pulivarthi K, et al: Frequency, outcome, and predictors of success within 6 weeks of an opioid rotation among outpatients with cancer receiving strong opioids. Oncologist 18:212-220, 2013 2. Mallinckrodt Brand Pharmaceuticals: Exalgo: Hydromorphone HCl extendedrelease tablets [package insert]. Hazelwood, MO, Mallinckrodt Brand Pharmaceuticals, 2010 3. Cruciani RA, Katz N, Portenoy RK: Dose equivalence of immediate-release hydromorphone and once-daily osmotic-controlled extended-release hydromorphone: A randomized, double-blind trial incorporating a measure of assay sensitivity. J Pain 13:379-389, 2012 4. Purdue Pharma: MS-Contin: Morphine sulfate controlled-release tablets [package insert]. Stamford, CT, Purdue Pharma, 2009 5. Purdue Plarma: OxyContin: Oxycodone hydrochloride controlled-release tablets [package insert]. Stamford, CT, Purdue Plarma, 2010
We thank our patient for allowing us to submit his case description and endoscopy images for publication. N.D. and A.R. contributed equally to this article.
DOI: 10.1200/JCO.2013.49.8204; published online ahead of print at www.jco.org on March 3, 2014
Neha Didwaniya, Akhila Reddy, Raju S. Gottumukkala, and Eduardo Bruera The University of Texas MD Anderson Cancer Center, Houston, TX
■ ■ ■
e12
© 2014 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at YALE MEDICAL LIBRARY on May 18, 2015 from Copyright © 2015 American Society of Clinical Oncology. All rights reserved. 130.132.123.28
