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Naloxegol for Treating Opioid-Induced Constipation n Patients with Non-Cancer Pain (S710)
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Poster Abstracts
Naloxegol for Treating Opioid-Induced Constipation n Patients with Non-Cancer Pain (S710) Corie Shoop, PharmD, Astrazeneca Pharmaceuticals LP, Wilmington, DE. Yiqun Hu, MD PhD, Astrazeneca, Wilmington, DE. Objectives Become familiar with the safety and efficacy profile of naloxegol as a treatment for opioidinduced constipation in patients with chronic non-cancer pain. Understand the mechanism of action of peripherally acting mu-opioid receptor antagonists and how this method of action differs from that of standard laxatives. Original Research Background. Opioid-induced constipation (OIC) affects 40%e80% of patients receiving opioids to manage chronic non-cancer pain, which can negatively impact quality of life and effective pain management. OIC results when opioid agonist effects at mu-opioid receptors in the enteric nervous system reduce gastrointestinal (GI) transit and secretions. Over-the-counter laxatives are often ineffective. Naloxegol is an approved, orally administered, peripherally acting mu-opioid receptor antagonist (PAMORA) that specifically targets the mechanism of OIC. Research Objectives. To summarize phase 3 clinical trial data for naloxegol. Methods. Data were reviewed from two phase 3 randomized, double-blind, 12-week studies conducted in outpatients with non-cancer pain and OIC (KODIAC-04, [NCT01309841]; KODIAC-05, [NCT01323790]) and a 52-week, phase 3 safety study (KODIAC-08 [NCT01336205]). Results. KODIAC-04 (n¼652) and KODIAC-05 (n¼700) compared the efficacy (primary endpoint: response over 12 weeks) and safety of daily administration of naloxegol 12.5 or 25 mg vs. placebo. A key secondary endpoint included the 12-week response rate in laxative users with OIC symptoms. Both studies reported significantly higher response rates for naloxegol 25 mg vs. placebo in the overall population and among laxative users with OIC symptoms. KODIAC-08 (n¼844) compared the safety and tolerability of naloxegol with usual care, and demonstrated a long-term safety profile similar to that seen in the 12-week studies. In all three studies, most common adverse events (AEs) on naloxegol were GI AEs, which occurred early in treatment, were mild or moderate in severity, and resolved during treatment or after discontinuation. Pain scores and opioid doses remained stable. The mechanism of action of naloxegol will be discussed.
Vol. 51 No. 2 February 2016
Conclusion. Naloxegol is a safe and efficacious treatment for OIC in adults with chronic non-cancer pain.
Implications for Research, Policy or Practice. Clinicians may consider naloxegol therapy for patients with chronic non-cancer pain reporting OIC.
A Systematic Review of Subcutaneous Medication Dosing Guidelines in Palliative Care (S711) Michael Hurst, MD, University of Alabama Birmingham, Birmingham, AL. Neal Steil, MD, University of Alabama Birmingham, Birmingham VA, Birmingham, AL. Objectives Understand the appropriate use and dosing ranges of palliative medications delivered subcutaneously, based on available literature. Develop an understanding of how common medications can be delivered by a novel, subcutaneous route. Systemic Review Background. Subcutaneous medication administration has been a mainstay of palliative care for several decades, offering multiple advantages over both IV and PO administration in many cases. The evidence for conventional administration routes is more developed than for that of the same medications given subcutaneously. Subcutaneous comfort medication use has not been standardized, administration being determined primarily by clinical experience. While this method of practice can be used with reasonable efficacy, particularly in experienced clinicians, there is a need for evidence-based practices to be developed as reference for more standardized care. Aims. The aim of our systematic literature review was to assimilate the published information for subcutaneous administration of 10 commonly used medications in palliative practice, creating a resource of accepted dosing guidelines. Methods/Session Descriptions. A comprehensive literature review of major databases was performed following PRISMA guidelines. Attempts were made to include any published literature that included a description of subcutaneous dosing practices for morphine, levetiracetam, ranitidine, metoclopramide, dexamethasone, furosemide, haloperidol, glycopyrrolate, fentanyl, and midazolam. Relevant articles were reviewed, and data on subcutaneous dosing were recorded. Ranges of the studied medications that had been administered safely and efficaciously were compiled. Conclusion. While there is a dearth of objective data and a lack of FDA approval for subcutaneous administration of most of the medications commonly used in palliative care, an attempt has been made to create a
Poster Abstracts
Naloxegol for Treating Opioid-Induced Constipation n Patients with Non-Cancer Pain (S710) Corie Shoop, PharmD, Astrazeneca Pharmaceuticals LP, Wilmington, DE. Yiqun Hu, MD PhD, Astrazeneca, Wilmington, DE. Objectives Become familiar with the safety and efficacy profile of naloxegol as a treatment for opioidinduced constipation in patients with chronic non-cancer pain. Understand the mechanism of action of peripherally acting mu-opioid receptor antagonists and how this method of action differs from that of standard laxatives. Original Research Background. Opioid-induced constipation (OIC) affects 40%e80% of patients receiving opioids to manage chronic non-cancer pain, which can negatively impact quality of life and effective pain management. OIC results when opioid agonist effects at mu-opioid receptors in the enteric nervous system reduce gastrointestinal (GI) transit and secretions. Over-the-counter laxatives are often ineffective. Naloxegol is an approved, orally administered, peripherally acting mu-opioid receptor antagonist (PAMORA) that specifically targets the mechanism of OIC. Research Objectives. To summarize phase 3 clinical trial data for naloxegol. Methods. Data were reviewed from two phase 3 randomized, double-blind, 12-week studies conducted in outpatients with non-cancer pain and OIC (KODIAC-04, [NCT01309841]; KODIAC-05, [NCT01323790]) and a 52-week, phase 3 safety study (KODIAC-08 [NCT01336205]). Results. KODIAC-04 (n¼652) and KODIAC-05 (n¼700) compared the efficacy (primary endpoint: response over 12 weeks) and safety of daily administration of naloxegol 12.5 or 25 mg vs. placebo. A key secondary endpoint included the 12-week response rate in laxative users with OIC symptoms. Both studies reported significantly higher response rates for naloxegol 25 mg vs. placebo in the overall population and among laxative users with OIC symptoms. KODIAC-08 (n¼844) compared the safety and tolerability of naloxegol with usual care, and demonstrated a long-term safety profile similar to that seen in the 12-week studies. In all three studies, most common adverse events (AEs) on naloxegol were GI AEs, which occurred early in treatment, were mild or moderate in severity, and resolved during treatment or after discontinuation. Pain scores and opioid doses remained stable. The mechanism of action of naloxegol will be discussed.
Vol. 51 No. 2 February 2016
Conclusion. Naloxegol is a safe and efficacious treatment for OIC in adults with chronic non-cancer pain.
Implications for Research, Policy or Practice. Clinicians may consider naloxegol therapy for patients with chronic non-cancer pain reporting OIC.
A Systematic Review of Subcutaneous Medication Dosing Guidelines in Palliative Care (S711) Michael Hurst, MD, University of Alabama Birmingham, Birmingham, AL. Neal Steil, MD, University of Alabama Birmingham, Birmingham VA, Birmingham, AL. Objectives Understand the appropriate use and dosing ranges of palliative medications delivered subcutaneously, based on available literature. Develop an understanding of how common medications can be delivered by a novel, subcutaneous route. Systemic Review Background. Subcutaneous medication administration has been a mainstay of palliative care for several decades, offering multiple advantages over both IV and PO administration in many cases. The evidence for conventional administration routes is more developed than for that of the same medications given subcutaneously. Subcutaneous comfort medication use has not been standardized, administration being determined primarily by clinical experience. While this method of practice can be used with reasonable efficacy, particularly in experienced clinicians, there is a need for evidence-based practices to be developed as reference for more standardized care. Aims. The aim of our systematic literature review was to assimilate the published information for subcutaneous administration of 10 commonly used medications in palliative practice, creating a resource of accepted dosing guidelines. Methods/Session Descriptions. A comprehensive literature review of major databases was performed following PRISMA guidelines. Attempts were made to include any published literature that included a description of subcutaneous dosing practices for morphine, levetiracetam, ranitidine, metoclopramide, dexamethasone, furosemide, haloperidol, glycopyrrolate, fentanyl, and midazolam. Relevant articles were reviewed, and data on subcutaneous dosing were recorded. Ranges of the studied medications that had been administered safely and efficaciously were compiled. Conclusion. While there is a dearth of objective data and a lack of FDA approval for subcutaneous administration of most of the medications commonly used in palliative care, an attempt has been made to create a