Acute Pain Management for Patients Receiving Buprenorphine Therapy Relatively Painless: Acute Pain Management for Patients Receiving Buprenorphine Therapy Kimmy Nguyen, PharmD PGY-1 Pharmacy Practice Resident Corporal Michael J. Crescenz VA Medical Center May 2017

Financial Disclosures I have not received any commercial or financial support for this program. I will not discuss off-label or investigational use of medications.

Objectives Identify treatment options for acute pain management in the post-operative setting for patients receiving buprenorphine therapy for opioid use disorder (OUD) Describe re-induction protocol when restarting buprenorphine therapy

Case Vignette LC is a 46-year-old male with a PMH of depression, anxiety, alcohol/benzodiazepine/opioid use disorder and squamous cell carcinoma of the left temporal bone scheduled for a left ear mastoidectomy. He recently underwent opioid detox and was started on Suboxone® (buprenorphine 4 mg/naloxone 1 mg) once daily. What should be done with the buprenorphine/naloxone to ensure adequate pain management during and after the procedure?

Opioid Use Disorder (OUD) DSM-5 Diagnostic Criteria Cravings Tolerance Withdrawal Continued use despite adverse consequences Persistent or unsuccessful efforts to cut down on use Large amount of time spent obtaining, using, or recovering Opioids taken in larger amounts or for longer than intended . Category Criteria Timeframe Mild 2 – 3 Within a 12-month period Moderate 4 – 5 Severe ≥6 American Psychiatric Association. DSM-5. 2013. Kasper D, et. al. Harrison’s Principles of Internal Medicine, 19e. 2015. Diagnostic and Statistical Manual of Mental Disorders

Opioid Statistics (2015) 33,091 opioid-related deaths/year  91 deaths/day 3,264 deaths in Pennsylvania Prescription opioids: >15,000 deaths Heroin: Approximately 13,000 deaths Top 5 states with the highest rates of overdose deaths: 1 WV 41.5 per 100,000 2 NH 34.3 per 100,000 3 KY 29.9 per 100,000 4 OH 29.9 per 100,000 5 RI 28.2 per 100,000 Centers for Disease Control and Prevention. MMWR MorbMortal WklyRep. 2016:65(50-51);1445-52.

Treatment of OUD Opioid Agonist Opioid Antagonist Buprenorphine Methadone Opioid Antagonist Naltrexone Psychosocial Treatment American Psychiatric Association. DSM-5. 2013. Kasper D, et. al. Harrison’s Principles of Internal Medicine, 19e. 2015.

Common Misconception = FALSE Maintenance opioid agonists provide adequate analgesia Analgesic action: 4-8 hours Suppression of opioid withdrawal: 24-42 hours = FALSE Alford DP, et. al. Ann Intern Med. 2006;144:127-34. Suboxone®. Prescribing information. Indivior Inc. 2016.

Buprenorphine/Naloxone Buprenorphine – partial agonist at the mu-opioid receptor and antagonist at the kappa-opioid receptor Naloxone – antagonist at mu-opioid receptors Produces opioid withdrawal signs/symptoms in individuals with physical dependence Suboxone®. Prescribing information. Indivior Inc. 2016.

Opioid Receptor Full Opioid Agonist Analgesia Opioid Receptor Euphoria

Withdrawal Full Opioid Agonist Opioid Receptor Withdrawal

Buprenorphine Buprenorphine Opioid Receptor Full Opioid Agonist Full

Case Vignette LC is a 46-year-old male with a PMH of depression, anxiety, alcohol/benzodiazepine/opioid use disorder and squamous cell carcinoma of the left temporal bone scheduled for a left ear mastoidectomy. He recently underwent opioid detox and was started on Suboxone® (buprenorphine 4 mg/naloxone 1 mg) once daily. Suboxone® was held prior to surgery. After the procedure, the patient was on hydromorphone 8 mg q3h with plans to re-initiate Suboxone® at the same time.

The Concern Buprenorphine Opioid Receptor Withdrawal Analgesia Full Agonist Opioid Receptor Analgesia Withdrawal

General Recommendations Multimodal analgesia Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (APAP) Analgesic dosing as continuous or scheduled rather than “as needed” Re-emergence of pain  Unnecessary suffering Naloxone and respiratory support available as rescue measures Alford DP, et. al. Ann Intern Med. 2006;144:127-34. Kasper D, et. al. Harrison’s Principles of Internal Medicine, 19e. 2015.

Management Strategies Buprenorphine + Short-acting opioids Overcome buprenorphine antagonism at receptor Buprenorphine alone Maximum 32 mg/day dosed every 6-8 hours Switch to methadone + Short-acting opioids Convert back to buprenorphine or stay on methadone Mitra S and Sinatra RS. Anesthesiology.2004;101(1):212-27. Alford DP, et. al. Ann Intern Med. 2006;144:127-34. Johnson RE, et. al. J Pain Symptom Manage. 2005;29(3):297-326. Suboxone®. Prescribing information. Indivior Inc. 2016.

Stopping Buprenorphine Stop buprenorphine Use opioid analgesics for pain Higher doses initially to overcome receptor blockade Restart buprenorphine with guidance from provider trained in buprenorphine therapy for OUD Alford DP, et. al. Ann Intern Med. 2006;144:127-34. Suboxone®. Prescribing information. Indivior Inc. 2016.

Stop and Restart Method Stop buprenorphine 24-36 hours prior to surgery Give short-acting opioids during and/or after surgery Re-initiate buprenorphine therapy when pain management allows Re-start once opioid-free for at least 6 hours Observable, objective signs of opioid withdrawal Clinical Opiate Withdrawal Scale (COWS) Kampman K and Jarvis M. ASAM. 2015;9(5):358-67.

Restarting Buprenorphine Day 1: Start with… buprenorphine 2 mg/naloxone 0.5 mg (2:0.5) OR buprenorphine 4 mg/naloxone 1 mg (4:1) Titrate dose based on control of acute withdrawal symptoms every 2-4 hours up to a total dose of 8:2 Day 2: Titrate up to buprenorphine 16 mg/naloxone 4 mg (16:4) once daily Alford DP, et. al. Ann Intern Med. 2006;144:127-34. Kampman K and Jarvis M. ASAM. 2015;9(5):358-67. Suboxone®. Prescribing information. Indivior Inc. 2016.

Case Vignette LC is a 46-year-old male with a PMH of depression, anxiety, alcohol/benzodiazepine/opioid use disorder and squamous cell carcinoma of the left temporal bone scheduled for a left ear mastoidectomy. He recently underwent opioid detox and was started on Suboxone® (buprenorphine 4 mg/naloxone 1 mg) once daily. What should be done with the buprenorphine/naloxone to ensure adequate pain management during and after the procedure?

When should buprenorphine/naloxone be stopped Question 1 When should buprenorphine/naloxone be stopped prior to surgery? 6-12 hours prior to procedure 24-36 hours prior to procedure 48-72 hours prior to procedure One week prior to procedure

Question 2 Which of the following should be done upon buprenorphine/naloxone re-initiation? Re-start once opioid-free for at least 72 hours Titrate dose rapidly up to buprenorphine 16 mg/naloxone 4 mg (16:4) once daily on day 1 Re-start in presence of observable signs of withdrawal Have naltrexone available as a rescue measure

Conclusion Buprenorphine binds with high affinity to displace and prevent other opioids from binding to the receptor Strategies for acute pain management in the post-operative setting are based on expert opinion rather than high-quality evidence Naloxone and respiratory support should be available as rescue measures Consult with provider trained in buprenorphine therapy for OUD

Questions

References American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington, VA 2013.  Kasper D, et. al. Chapter 468e: Opioid-Related Disorders. Harrison’s Principles of Internal Medicine 19th edition. 2015. Centers for Disease Control and Prevention. MMWR MorbMortal WklyRep. 2016:65(50-51);1445-52. Alford DP, Compton P, Samet JH. Acute pain management for patients receiving maintenance methadone or buprenorphine therapy. Ann Intern Med. 2006;144:127-34. Suboxone® (buprenorphine/naloxone) [prescribing information]. Richmond, VA: Indivior Inc.; Dec 2016. Mitra S and Sinatra RS. Perioperative management of acute pain in the opioid-dependent patient. Anesthesiology. 2004;101(1):212-27. Johnson RE, Fudala PJ, Payne R. Buprenorphine: considerations for pain management. J Pain Symptom Manage. 2005;29(3):297-326. Kampman K and Jarvis M. American Society of Addiction Medicine (ASAM) national practice guideline for the use of medications in the treatment of addiction involving opioid use. ASAM. 2015;9(5):358-67.