Overview. Opioids and HIV Infection: From Pain Management to Addiction Treatment

Transcription

1 FORMATTED: 01/23/2017 New York, New York: February 24, 2017 Opioids and HIV Infection: From Pain Management to Addiction Treatment Chinazo Cunningham, MD, MS Professor of Medicine Albert Einstein College of Medicine Bronx, New York Slide 3 of 33 Learning Objectives After attending this presentation, learners will be able to: Name pain management strategies consistent with national guidelines Describe common mistakes in interpreting urine toxicology test results Describe benefits of integrating buprenorphine and HIV treatment Overview The opioid epidemic Challenges in pain management with opioids Opioid use and HIV outcomes Integration of buprenorphine & HIV treatment Slide 4 of 33 New York, New York: February 24,

2 Drug overdose deaths in the U.S Hedegaard H, NCHS Data Brief, March 2015 Slide 5 of 33 Drug overdose deaths in the U.S Hedegaard H, NCHS Data Brief, March 2015 Slide 6 of 33 Heroin overdose deaths in the U.S MMWR 2017;65:1497. Slide 7 of 33 New York, New York: February 24,

3 Thousands Gap in treatment for opioid use disorder, ,500 2,000 opioid analgesics heroin Slide 8 of 33 1,500 1, Abuse or Dependence NDUHS 2013; TEDS Opioid Agonist Tx Case JR is a 45 y.o. Hispanic male with HIV, depression, opioid use disorder in remission (last used heroin 8 years ago), who is receiving HIV primary care from you for the past two years without problems. HIV: Taking efavirenz/emtricitabine/tenofovir disoproxil fumarate (>95% adherence) Labs: VL<45 copies/ml, CD4=480 cells/mm 3 He s had low-level constant right hip pain for a few months, but now reports pain is getting worse. He s tried acetaminophen, NSAIDs, and physical therapy with little improvement. However, when he tried his friend s oxycodone, it helped relieve his pain. What issues should you be concerned about? Slide 9 of 33 Pain & opioid analgesics in HIV+ individuals Chronic pain More common in HIV+ than HIV % of HIV+ individuals have chronic pain Diverse etiologies: HIV, aging, medications Opioid analgesics More commonly prescribed in HIV+ than HIV % of HIV+ individuals are prescribed opioids Higher doses in HIV+ than HIV- Comorbid illnesses Substance use more common in HIV+ than HIV- Mental illness more common in HIV+ than HIV- Slide 10 of 33 Risk of misuse or disorders higher in HIV+ than HIV- Breitbart 2002; Tsao 2004, 2007, 2012; Edelman 2013; Frich 2000; Dobalian 2004; Silverberg 2012; Jeevanjee 2013; Koeppe 2013 New York, New York: February 24,

4 Case After gathering more history and conducting a physical exam, you are confident that JR s pain is due to osteoarthritis. You talk to JR about your hesitancy to prescribe opioid analgesics because of his risks of having a poor outcome (e.g., depression and prior heroin use). You both agree that referral to an orthopedic surgeon is a good next step. One month later, JR reports the pain continued to worsen after his last visit with you. He went to the ER, and was prescribed oxycodone/acetaminophen. This worked for his pain, and he is asking you to prescribe more. Now what? Slide 11 of 33 Slide 13 of 33 CDC guideline for prescribing opioids for chronic pain When to initiate or continue opioids for chronic pain Non-pharmacologic and non-opioid therapies are preferred Establish treatment goals (pain & function) Discuss risks/benefits of opioids, and patient/provider responsibilities Opioid selection, dose, duration, follow-up, discontinuation Prescribe immediate release (not long-acting) formulations Prescribe lowest effective opioid dose (<50-90 MME) Prescribe no greater quantity than needed (<3-7 days) Re-evaluate effectiveness; if risk>harms then taper or discontinue Assessing risk and addressing harms of opioid use Evaluate and mitigate harms, consider naloxone Use the Prescription Drug Monitoring Program (PDMP) Order urine drug tests Avoid concurrent opioids and benzodiazepines Offer/arrange for buprenorphine or methadone to treat opioid use disorder Dowell How are opioids associated with HIV outcomes? Few studies have examined the relationship between opioids and HIV - conflicting findings Any (vs. no) opioid analgesics HAART utilization: 1 study, 3 studies HAART adherence: 1 study VL: 2 studies, 2 studies Misuse (vs. no misuse) of opioid analgesics HAART adherence: 2 studies Onen 2012; Silverberg 2012; Edelman 2013; Koeppe 2010; Jeevanjee 2013; Robinson-Papp 2012 Slide 15 of 33 New York, New York: February 24,

5 Case Slide 16 of 33 Using your state PDMP, you confirm that JR was prescribed oxycodone/acetaminophen by the ER. You make an agreement to continue prescribing this, but only for 1 week. You order a urine drug test during this visit. He agrees to address his osteoarthritis by seeing an orthopedic surgeon. Urine drug test results Slide 17 of 33 Substance Amphetamines Benzodiazepines Cannabinoids Cocaine Opiates Methadone Oxycodone Buprenorphine Result Negative Negative Negative Negative Positive Negative Positive Negative Slide 19 of 33 Interpretation of urine drug test results is complicated!! Starrels 2010 New York, New York: February 24,

6 Slide 20 of 33 Common mistakes interpreting urine drug test results Oxycodone Must have an assay that specifically examines oxycodone (not just opiate) If taken in high enough doses, can spill over to cause opiates to be positive Fentanyl Metabolites are NOT detected in screening assays. Very difficult to detect. Benzodiazepines Patients taking clonazepam typically have urine toxicology tests negative for benzodiazepines Must understand metabolic pathway and what metabolites are tested in the screening assays When in doubt, order GC/MS confirmatory tests! Case After reviewing the results of JR s urine drug test, you order a confirmatory GC/MS for opiates. This test demonstrates both oxycodone and 6-monoacetylmorphine (6-MAM), which is specific to heroin use. JR misses his next appointment with you, but reschedules it a few weeks later. At that visit, you discuss the urine toxicology test results with him. JR reveals that he relapsed with heroin because he couldn t take the pain. He also ran out of his efavirenz/emtricitabine/tenofovir disoproxil fumarate because of missing his appointment with you. Now what? Slide 21 of 33 Medication-assisted treatment of opioid use disorder Pharmacology Opioid antagonist: naltrexone Opioid agonist: buprenorphine & methadone Effectiveness of buprenorphine HIV treatment outcomes Drug treatment outcomes Other outcomes Slide 22 of 33 New York, New York: February 24,

7 Pharmacology Methadone Buprenorphine Mechanism of action FULL opioid agonist PARTIAL opioid agonist Receptors opioid receptor opioid receptor Receptor affinity Moderate VERY HIGH Absorption Oral Sublingual Formulation Liquid Tab or film Half life hrs hrs Metabolism Liver, P450 system Liver, P450 system Slide 23 of 33 Differences in opioid effect by type of agonism Full agonist (methadone) Slide 24 of 33 Opioid effect Partial agonist (buprenorphine) Log dose Antagonist Treatment delivery Methadone Buprenorphine Regulations Highly regulated Minimally regulated Location Licensed MMTP Anywhere Provider MD at MMTP MD, DO, NP, PA 8-24 hour training DEA X number Counseling Regulated Ability to refer Visits Regulated -- Urine toxicology tests Regulated -- Dosing Regulated -- Dispensing At MMTP Community pharmacy Prescriptions Regulated 30-day supply w/ refills Treatment slots Regulated pts/md Slide 25 of 33 New York, New York: February 24,

8 Slide 26 of 33 Key differences between buprenorphine and other opioids Pharmacology: PARTIAL opioid agonist Formulation: Buprenorphine/naloxone Sublingual as directed Buprenorphine moderate absorption Naloxone miniscule absorption IV to get high Buprenorphine full absorption Naloxone - full absorption Case After realizing that you can offer JR buprenorphine to treat his opioid use disorder, you take the 8-hour training, become certified to prescribe buprenorphine, and get your DEA X number. At your next visit with JR, you offer him buprenorphine treatment. He s heard about buprenorphine, but has never taken it. He knows other people who are taking it, but none of them are HIV+. He s worried about an interaction between buprenorphine and his HIV. JR asks how well does buprenorphine work for people with HIV? Slide 27 of 33 Buprenorphine & HIV Study BHIVES = multisite study examining integration of buprenorphine and HIV treatment 10 sites Variable study design: prospective cohort study or RCT Participants followed for 12 months 386 participants HIV+ adults Opioid-dependent Eligible for buprenorphine tx Data sources Interviews every 3 months Medical record review JAIDS Supplement 56(S1) 2011 Slide 28 of 33 New York, New York: February 24,

9 Improved HIV outcomes with buprenorphine retention Slide 29 of 33 Altice 2011 Improved drug treatment outcomes with buprenorphine retention Illicit drug use by buprenorphine retention 90% 80% Opioids Stimulants Sedatives 70% 60% 50% 40% 30% 20% 10% 0% Baseline Quarter 1 Quarter 2 Quarter 3 Quarter 4 Fiellin 2011 Slide 30 of 33 Other outcomes associated with buprenorphine treatment Slide 31 of 33 Treatment outcomes Cocaine Quality of life Physical health Mental health Safety/Drug interactions Hepatic enzymes Buprenorphine dose with atazanavir Buprenorphine treatment retention No change No change Korthuis 2011; Sullivan 2011; Cunningham 2013; Vergara-Rodriguez 2011; Lucas 2010 New York, New York: February 24,

10 Summary Slide 32 of 33 The opioid epidemic continues to grow Plateau of opioid analgesics, but increase in heroin Large gap in treatment continues There are many challenges to managing pain with opioids Interpretation of urine toxicology tests It remains unclear how opioid analgesic use is associated with HIV outcomes Integration of buprenorphine with HIV treatment is associated with many positive outcomes Colleagues A. Giovanniello, PharmD J. Starrels, MD, MS A. Fox, MD, MS J. Arnsten, MD, MPH Buprenorphine & HIV+ patients Acknowledgments Slide 33 of 33 Funders NIH/NIDA - K24DA036955, R34DA031066, R25DA023021, K23DA027719, K23DA HRSA - H97HA03793, U90HA29236 RWJ Foundation NYC DOHMH - 09SA027400R0X00 New York, New York: February 24,

11 Interpreting UDT Results What if result is positive for a non-prescribed drug? Possibilities are: 1. False positive (on screen) -- order confirmatory test 2. Substance detected is a metabolite of a prescribed drug (see metabolic pathways) 3. Patient ingested the drug, or drug that metabolizes to it (see Opioid Metabolic Pathways) 4. Lab error or contamination *Consider all the possibilities before acting on UDT results What if result is negative for the prescribed drug? Possibilities are: 1. Urine drug screen won t reliably detect the prescribed drug (see Table) -- order confirmatory test 2. Drug present but concentration is below the cutoff for a positive result (on screen) -- order confirmatory test 3. Urine is diluted (physiologic or tampering) 4. Patient is a fast-metabolizer 5. Patient has not taken drug recently 6. Patient is diverting medication 7. Urine is adulterated or substituted *Consider all the possibilities before acting on UDT results Discussing UDT Before requesting urine, always ask: When did you take your last dose? How much? In the past week, have you taken any other pain medicine? In the past week, have you used any drugs? *Documentation of this is crucial for interpreting UDT results Language for introducing drug testing As part of treating [pain] with medications like [X], I order urine tests to get more information about how safe they are for patients. The test measures a number of medications and drugs that could interfere with your treatment. This is something I do with ALL patients on these medications. If I find something unexpected, we ll talk about it and work together to address it. Opioid Metabolic Pathways URINE DRUG TESTING A Reference Guide for Clinicians In this guide: When to order UDT Two types of tests Interpreting UDT results Discussing UDT with patients Is the specimen valid? A valid urine sample has the following: Temperature F (within 4 minutes of voiding) ph 4.5 to 8.5 Creatinine >20mg/dl <20mg/dl is dilute <5 is not consistent with human urine Created by Joanna L. Starrels, MD, MS and Bryan Wu, MS. Albert Einstein College of Medicine & Montefiore Medical Center. Bronx, NY. Supported by the National Institute on Drug Abuse (5K23DA027719). Updated May jostarre@montefiore.org

12 Ordering Urine Drug Tests Table: Quick Guide to Urine Drug Testing When should I order urine drug tests? 1. Before prescribing controlled substances 2. Regularly throughout treatment For all patients, at least every 6 months More frequently for higher risk patients Risk factors include: personal or family history of substance abuse, tobacco dependence, mental health disorders, young age (<45), caucasian race, and previous red flag behaviors like requesting early refills, losing prescriptions, obtaining opioids from other sources, or unexpected UDT results Which type of test should I order? SCREENING TEST Method: Enzyme-based immunoassay (EIA) Logistics: Inexpensive Fast Widely available Results: Susceptible to false positive & false negative results (see table) Opiate screen not sensitive for semisynthetic (e.g., oxycodone) or synthetic opioids (e.g., fentanyl) -or- CONFIRMATORY TEST Method: Gas chromotography/ mass spectrometry (GC/MS) or Liquid chromotography & tandem MS Logistics: More expensive Takes longer Often sent-out Results: Highly sensitive Highly specific Specifies drugs within class Reports concentration even if low (no cut-off) DRUGS TAKEN a Should be + c Might be + F Potential false + Prescription Opioids Illicit Drugs Other Amphetamines Barbiturates Benzodiazepines Buprenorphine Cocaine Methadone Opiates Oxycodone PCP Cannabis Buprenorphine a a 1-6 days Codeine a a c 1-3 days Fentanyl a 24 hours Hydrocodone c 1 a c 1-3 days Hydromorphone c 1 a 1-3 days Meperidine a 2-3 days Methadone a a 1-3 days 2 Morphine a c a 1-3 days 2 Oxycodone c 1 a a c 24 hours Oxymorphone a a 24 hours 2 Amphetamines a Screening Test Results (EIA) RESULTS Buprenorphine, norbup. Confirmatory Test Results (GCMS) Fentanyl Codeine, norcodeine Hydrocodone Hydromorphone Methadone Meperidine, normep. Morphine Oxycodone Oxymorphone Heroin (6-MAM) Common Detection Time 1-3 days Barbiturates a 24 hours 2 Benzodiazepines c 3 3 days 2 Cocaine a 1-4 days 2 Heroin a c c 1-3 days 2 PCP a 1-3 days 2 Cannabis a 1-3 days 2 Poppy seeds 4 F F F Other medications 5 F F F F F F F F F F 1. Sensitivity of opiate screen to semi-synthetic opioids varies by lab. Generally, hydrocodone > hydromorphone > oxycodone. Higher dose is more likely to yield a + opiate screen. Consider confirmatory test, especially to confirm negative for rx d drug. 2. Chronic use may result in longer detection times. 6-MAM is pathognomonic for heroin use, detection time is hours. 3. Benzodiazepine screen likely positive if alprazolam or diazepam taken, likely negative if clonazepam, lorazepam. Varies by lab. 4. Heavy poppy seed ingestion (3+ bagels) may test positive for opiates-- repeat off poppy seeds. 5. Some commonly used medications reported to cause false + results on screening assays are below-- order confirmatory test. Amphetamine: buproprion, SSRIs, chlorpromazine, mexilitene, pseudoephedrine, decongestants, ranitidine, trazodone, labetalol Barbiturate: ibuprofen, naproxyn, phenytoin. Benzodiazepine: sertraline, oxaprozin. Buprenorphine: tramadol, other opioids. Cocaine: none confirmed. Coca leaves or dental use cause rare true +. Methadone: diphenhydramine, doxylamine, clomipramine, chlorpromazine, quetiapine, thioridazine, tramadol, verapamil. Opiate: dextromethorphan, diphenhydramine, fluoroquinolones, quinine, rifampin. Oxycodone: naloxone, see list for opiates. PCP: dextromethorphan, diphenhydramine, ibuprofen, tramadol, venlafaxine. Cannabis: dronabinol, PPIs. Note that ibuprofen does NOT cause false + using modern tests (previously did).