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The New Kid on the Block –incorporating buprenorphine into a Medical Toxicology

practice

Timothy J. Wiegand, MD, DABAM, FACMT, FAACT Director of Toxicology at Strong Memorial Hospital and the

University of Rochester Medical Center

Disclosures

• Paid consultant for the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS®) System was initiated in 2002 and is owned and operated independently by Denver Health and Hospital Authority, a not-for-profit safety net hospital.

• The RADARS System is supported by pharmaceutical company subscribers.

Opportunity for patient and physician

• Buprenorphine: – It’s a tool for the treatment of poisonings (e.g. precipitated

withdrawal) – It’s one of the more effective therapies when used appropriately for

both treating and preventing drug overdose deaths (2/3 of which are due to opioids), many are due to abuse

– It compliments other aspects of our practice (prevention and treatment)

– It’s even reimbursed better than other portions of acute care toxicology

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Patient A

• Normal –no craving

• EMBEDDED VIDEO CLIP***

30 year-old M IVDU with cellulitis on IV abx in hospital –goes into w/d

Codes: • 99233 • 99406 • H0033

• 68% Collected $393.61

Acute care and ‘carrot on stick’ link to treatment!

• 68% reimbursed Total of consult charges over 5 days: $ 800-900.00 reimbursed on charges.

• Additional: Day 1:99255 (105 min $573.00 charge/257.00 reimbursed) •  99233 (35 min $295.00 charge/150.52 reimbursed)

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Favorable properties? What if we had this for EtOH?

•  Buprenorphine can substitute for other opioid receptor agonists, yet is less apt to produce overdose reactions or dysphoria.

•  It can block the effects of opioids such as heroin and morphine. •  Buprenorphine has good SL bioavailability and a long half-life, making

administration on a once daily basis possible. •  Discontinuation is associated with only a mild withdrawal syndrome. •  Clinical trials have demonstrated that sublingual buprenorphine is effective in

both maintenance therapy and detoxification of individuals addicted to opioid. •  Formulation combining naloxone with buprenorphine further reduces the risk of

diversion to illicit intravenous use.

Objectives

1.) Review the pharmacology of buprenorphine and the basis by which it makes it an useful agent for treating opioid dependence. 2.) Review the mechanism by which a physician is certified to prescribe buprenorphine and what obligations and subsequent duties that entails. 3.) Describe the ‘non-certified’ use of buprenorphine including the 3-day “emergency rule” 4.) Review the induction, stabilization and maintenance process for use of buprenorphine and describe its appropriate use in outpatient Chemical Dependency treatment and in hospitalized patients

Specific opioid pharmacology

Full mu opioid agonists activate mu receptors. Increasing doses of full agonists produce increasing effects until a maximum effect is reached (the receptor is fully activated). morphine, heroin, methadone, oxycodone…

EFFECT

DOSE

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Partial agonist with high affinity and long duration

• Buprenorphine is a partial mu receptor agonist

• Kappa receptor antagonist • Buprenorphine half-life 4-6

hours but metabolites (nor buprenorphine) have a very long duration of action

• Peak analgesic effect = 4-6 hours

• Mu receptor affinity

The Heroin Blocker

• 42 year-old African-American Male presents to Suboxone® clinic for an intake assessment.

• Long history of chemical dependency with primarily opioids (heroin and ‘street’ methadone) and cocaine.

• Prior exposure to ‘street’ buprenorphine through primarily Suboxone® tabs being purchased when he cannot afford or cannot find heroin (5-8$/tab -8/2 mg Suboxone® tabs).

• Describes purchasing an 8/2 mg Suboxone® tab, several hours later coming into some money he purchases a “bundle” (10 bags) of heroin. Use of heroin completely blocked.

Heroin Heroin

Heroin

S U B O X O N E

Partial Agonists vs Full Agonists

• Embedded clip 2 –ppt w/d.

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Dose-effect with buprenorphine

Buprenorphine (C3) is less ‘abusable’ than other opioids (C2)

• Population vs Unique Rates of Drug Diversion using Researched Abuse Diversion and Addiction-Related Surveillance (RADARS®) system Poison Center data.

Dasgupta et al RADARS system presentation SAMHSA

Buprenorphine not non-toxic but less toxic than other opioids

-Dasgupta et al RADARS® data 3rd buprenorphine summit SAMHSA, 2010

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Buprenorphine can be used recklessly (or by vulnerable populations)

• Buprenorphine vs bup + benzodiazepines

“I have my sex life back on Subs!”

• Buprenorphine has less effect on testosterone levels and causes less impairment in certain clinical outcomes such as overall libido, less erectile sexual dysfunction or anorgasmia

Vulnerable patients –the agony and the partial agonist

• Embedded clip number 3 –pediatric exposure.

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So you are thinking about getting the waiver?

• Available in the US since 2002 as an office-based treatment for opioid dependence.

• Physicians who wish to prescribe the drug may under go a training program and become certified through the Substance Abuse and Mental Health Services Administration (SAMHSA)

• http://buprenorphine.samhsa.gov/

Why??? The Harrison Narcotics Tax Act

• The Harrison Narcotics Tax Act (Ch. 1, 38 Stat. 785) was a United States federal law that regulated and taxed the production, importation, and distribution of opiates. The act was approved on December 14, 1914.

•  "An Act To provide for the registration of, with collectors of internal revenue, and to impose a special tax on all persons who produce, import, manufacture, compound, deal in, dispense, sell, distribute, or give away opium or coca leaves, their salts, derivatives, or preparations, and for other purposes."

• The courts interpreted this to mean that physicians could prescribe narcotics to patients in the course of normal treatment, but not for the treatment of addiction.

DATA 2000 -Title XXXV Section 3502 …of the Children’s Health Act of 2000 Permits physicians who meet certain qualifications to treat opioid addiction with Schedule III, IV, and V narcotic medications that have been specifically approved by the Food and Drug Administration.

Such medications may be prescribed and dispensed by waived physicians in treatment settings other than the traditional Opioid Treatment Program (methadone clinic) setting.

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After taking the course and passing it

• The waiver notification section from SAMHSA describes how to obtain and submit a Notification of Intent form.

•  It goes to CSAT (Center for Substance Abuse Treatment) • The Notification of Intent can be submitted on-line from this

Web site, or via ground mail or fax

Who is eligible for the waiver?

•  Drug Enforcement Administration (DEA) assigns an ID # if the MD or DO meet one of the following:

– Addiction Psychiatry board certification – Addiction certification from American Society of Addiction Medicine

(ASAM) or American Osteopathic Association – Complete (not less than) 8 hours of training through classroom,

seminars, electronic resources or otherwise provided by AAP, AMA, AOA, ASAM

– Physician has participated as investigator in clinical trials leading to approval of “narcotic drug” in schedule III, IV or V for maintenance or detoxification

– State Medical Board says OK (training experience vetted) – Secretary of Health and Human Services says OK

Buprenorphine Providers

In 2010 there were about 19,000 US physicians are certified to prescribe buprenorphine.

For about 640,000 patients Compared with about 4,500 certified prescribers And 100,000 patients in 2005

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Buprenorphine prescribers

After one year can ! 100 patients/provider

•  In December of 2006 OBOT providers (SAMSHA certified) authorized to treat up to 100 patients at any one time.

• A.) Qualified under DATA 2000

• B.) At least one year since initial qualifications

• C.) Must certify their capacity for counseling and referral services

Buprenorphine SL Suboxone® video 5.22 min

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Video for Zubsolv® administration 4:23 seconds

Bunivail® BEMA® (BioErodible MucoAdhesive) video 1:50 min

YouTube® almost as popular as filming bong hits of salvia

-888,977 hits for buprenorphine SL administration-

“…I’m 11 hours and 35 minutes into it and starting to get the cold chills now…” pauses for dramatic effect, turns and while looking off camera shudders, “brrrr!”

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Candidates for buprenorphine: Rx opioid dependence

• KS is a 28 year-old married woman who has a prescription drug habit. She was prescribed Percocet® for a back injury, liked the way it made her feel, and she was soon getting them from friends and several providers (physicians/EDs). She describes always hustling around trying to get money so she would not be sick. Was given a Suboxone® by a friend one day at work because she hadn’t been able to find any Percocet® “it worked really well.”

Induction

• Patient needs to be in mild to moderate withdrawal. • COWS is performed after they arrive to the clinic (or have gone into withdrawal in the ED/hospital).

• A low dose of buprenorphine is used at first (2/0.5 mg Suboxone® SL admin and after 2 hours with no adverse effect the rest of an 8/2 mg dose is completed.

• Monitor for “all day” in reality most patients have tried it themselves on the street.

Home induction vs Office

• Not only feasible but may be associated with certain favorable outcomes compared to the standard office induction

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Not only does the other opioid use drop but…

• Between 2004 and 2007, of the 152,917 US individuals in 34 states newly diagnosed with new HIV infections

• 13% of them (n = 19,687) were IVDU according to the US Centers for Disease Control and Prevention

-MMWR Morbidity & Mortal Weekly Rep. 2009;58[46]:1291-1295

Improvement in risk factors that would have led to ‘bad things’

• Comparison of drug-related and sex-related risk behaviors in 166 buprenorphine treated individuals at baseline, 12 weeks, and 4 weeks.

• IVDU among buprenorphine treated individuals declined

-37% at baseline -12% at 12 weeks -7% at 24 weeks

-Sullivan LE et al. J Subst Abuse Treat. 2008;35[1]:87-92

CASE TL

• 41 year-old F with history of polydrug dependence is jailed for insurance fraud which she was performing to get money to fund her opioid dependence.

• The patient manages to get hydrocodone prescribed for orthopedic injuries during her incarceration.

• Immediately upon release the patient starts using Emergency Departments within Monroe County to support her opioid dependence.

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CASE T.L. continued

•  ED Encounters at single hospital over a 3-month period •  1.) 7/28/2011 •  2.) 7/29/2011 •  3.) 8/9/2011 •  4.) 8/19/2011-8/20/2011 (observation –chest pain) •  5.) 8/23/2011 (admitted for 2 day observation) •  6.) 9/1/2011 •  7.) 9/7/2011 •  8.) 10/1/2011 •  9.) 10/10/2011 •  10.) 10/14/2011 •  11.) 10/18/2011 •  12.) 10/24/2011 •  13.) 10/31/2011

T.L. Initial Presentation in July, 2011

• Patient states " I was in a fight with another female 2 days ago. It was a pretty bad fight. I was thrown against a brick wall". Patient has multiple bruising noted over upper body, arms bi-lateral, left scapula area. Patient c/o back pain with dark colored urine.

Second visit in July, 2011

• Pt to ED with R shoulder pain. States she injured the shoulder 1 week ago and was seen in ed. Denies new injury today but states she woke with a frozen shoulder. Unable to move it. C/o numbness in R arm.

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Outcome of second visit

• Diagnosis management comments: Patient seen by me today, 7/29/2011 at 4:06 AM

• Assessment: 39 year-old female comes to the ED with assault

• Differential Diagnosis includes kidney laceration, neck soft tissue injury, thoracic wall injury

• Plan: cbc, chem 7, UA, CT abdomen, pelvis, thorax, neck, IVF, morphine

Next visit

• HPI: Patient is a 40 year-old female who presents to the ED with left hand/arm pain x 3 days. Patient states she was on a roof 3 days ago (she is a roofer), had a "bundle" over her shoulder and began sliding on the roof. States she feel on the roof onto both her outstretched hands. She complains of left hand, wrist, arm, and elbow pain. Difficulty moving her left upper extremity. Has some numbness in hand.

Outcome of this visit

•  Number of Diagnoses or Management Options

•  Right shoulder strain: •  Trapezius muscle spasm: •  Diagnosis management comments: Patient seen by me today, 8/19/2011 at the

time of arrival 3:28 PM •  Assessment: 39 year-old., female comes to the ED with right shoulder pain •  Diagnosis includes right shoulder strain, trapezius muscle spasm •  Plan: rice, Dilaudid® and Valium® - feels better •  Dc- Percocet®, Valium® •  PCP referral •  Right shoulder- hardware intact, no fracture or dislocation

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Case TL continued

• 17 XR’s • 4 CT scans including 2 CT angio • Over 30 laboratory assays • XYZ other?

• Cost?

Stabilization –TL example detox--IOP

• TL had gone to a detoxification facility after she had been ‘caught’ using the ED and multiple providers (she was limited to a single pharmacy and provider).

• Induction went well in detox, was placed into an Intensive Outpatient Program (IOP) 3 x week groups, counseling, once/week check-in observed dosing, urine monitoring (levels) and dose adjustment until she’s clearly engaged in a recovery program (stable bup levels, attendance good, doing better -4-6 weeks. 8/2 mg SL BID.

Urine monitoring (and/or oral) induction

Elements   09/12/13 09:00 AM  

08/08/13 06:00 PM  

08/05/13 09:00 AM  

07/26/13 09:00 AM  

06/28/13 09:00 AM  

05/08/13 12:45 PM  

01/25/13 12:30 PM  

BUPRENORPHINE,UR*   < 3   < 3   < 3  

BUPREN GLUC,UR*   213   76   < 5  

TOTAL BUPREN,UR*   155   55   cancelled  TOTAL BUP/CREAT,UR*   129   26   cancelled  NORBUPRENORPHINE,UR*   71   52   < 3  NORBUPREN GLUC,UR*   367   294   < 2  TOTAL NORBUPREN,UR*   328   258   cancelled  

TOTAL NORBUP/CREAT,UR*   273   124   cancelled  

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Adulteration

Other things are indicative of not doing well Elements   09/12/13

04:30 PM  

08/15/13 04:00 PM  

06/13/13 04:35 PM  

05/16/13 05:00 PM  

03/21/13 03:00 PM  

02/25/13 12:30 PM  

02/14/13 04:00 PM  

01/22/13 05:30 PM  

Next  

AMPHETAMINES,UR*  NEG   NEG   NEG   NEG   NEG   NEG   NEG   NEG  

BARBITURATES,UR*  NEG   NEG   NEG   NEG   NEG   NEG   NEG   NEG  COCAINE/METAB,UR*   POS   NEG   NEG   NEG   NEG   NEG   NEG   NEG  

BENZODIAZPNS,UR*  POS   NEG   NEG   NEG   NEG   NEG   NEG   NEG  METHADN METAB,UR*   NEG   NEG   NEG   NEG   NEG   NEG   NEG   NEG  

OPIATES,UR*   POS   NEG   NEG   NEG   NEG   NEG   NEG   NEG  PHENCYCLIDINE,UR*   NEG   NEG   NEG   NEG   NEG   NEG   NEG   NEG  PROPOXYPHENE,UR*   NEG   NEG   NEG   NEG   NEG   NEG   NEG   NEG  THC METABOLITE,UR*   NEG   NEG   NEG   NEG   NEG   NEG   NEG   NEG  

A compliant patient on 16 mg/day of bup

Elements 08/08/13 05:45 PM

07/11/13 05:15 PM

06/18/13 03:30 PM

06/13/13 03:00 PM

06/06/13 01:30 PM

05/07/13 01:30 PM

04/23/13 01:30 PM

04/19/13 03:30 PM Next

BUPRENORPHINE,UR* 22 < 3 40 4 < 3 9 < 3 < 3

BUPREN GLUC,UR* 2050 505 2780 482 1460 447 279 733

TOTAL BUPREN,UR* 1510 367 2058 354 1060 334 203 532

TOTAL BUP/CREAT,UR* 599 282 702 192 362 198 97 283

NORBUPRENORPHINE,UR* 321 91 587 266 307 188 135 118

NORBUPREN GLUC,UR* 2840 921 2810 1460 2980 1110 932 648

TOTAL NORBUPREN,UR*

2312 737 2557 1289 2396 966 788 572

TOTAL NORBUP/CREAT,UR* 917 567 873 701 818 572 375 304

CREATININE, UR* 252 130 293 184 293 169 210 188

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Leaving a MAT program and relapse

• Risk of relapse for a person who was opioid addicted was highest during the first 3 to 6 months after cessation of opioid use. The risk declined for the first 12 months after cessation and continued to decrease, albeit at a much slower rate.

• Results from several studies indicate that roughly 80% of patients who are opioid addicted but leave MAT resume daily opioid use within 1 year of leaving treatment

– Magura and Rosenblum 2001

Maintenance --chemical Dependency as Chronic Medical Condition

Abuse Early Abstinence Sobriety Stable Maintenance

Relapse is common, success is measured by retention in recovery, decreased morbidity, life improvement

Buprenorphine and perception The emerging buprenorphine epidemic in the United States. (abstract

below)

The authors sampled for expanded drug testing of 1,061 urine specimens collected by Maryland Division of Parole and Probation staff. They found an increase in the percentage of individuals testing positive for buprenorphine and found that these specimens often contained other drugs, suggesting misuse. Subsequent interviews with 15 probationers and parolees in Baltimore, Maryland, showed wide-scale availability of buprenorphine on the street and in prisons.

Wish ED, Artigiani E, Billing A, et al. The Emerging Buprenorphine epidemic in the United States. Journal of Addictive Disorders. 2012 Jan; 31(1): 3-7.

“…CESAR Publishes Report Warning of Emerging Epidemic of Buprenorphine Misuse…”

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Voucher or treatment?

Buprenorphine and perception II

Although diversion control is an important part of Medication Assisted Treatment public policy usually places greater emphasis on protecting society from methadone (or buprenorphine) than on the addiction, violence, and infectious diseases that these medications help alleviate.

– Institute of Medicine 1995, Joseph et al. 2000, Nadelmann and McNeeley 1996

Buprenorphine and Perception –the reality

•  1000 patients enrolled from 100 drug abuse treatment programs (US) •  Question: was buprenorphine used in past 30 days “to get high”?

– 30-35% reported ‘inappropriate or ‘abuse’ of buprenorphine – One year later the % dropped to below 20% (lower than methadone)

Conclusions: I.) Some patients treated with buprenorphine experimented with this medication (special populations –prison, adolescents/teens) but less than other opioids II.) < 3% of sample provide endorsement of buprenorphine as a primary drug.

Cicero TJ, Surratt HL and Inciardi J. Use and Misuse of Buprenorphine in the Management of Opioid Addiction. J Opioid Manag. 2007 Nov-Dec;3(6):302-8.

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•  DESIGN, SETTING, AND PARTICIPANTS: •  8/1/09-10/31/12 663 hospitalized, opioid-dependent pts general medical hospital ID’d •  145 eligible patients consented to participation in RCT •  139 completed the baseline interview ! detoxification (n = 67) or linkage (n = 72) group.

•  INTERVENTIONS: •  Five-day buprenorphine detoxification protocol or buprenorphine induction, intrahospital dose

stabilization and link to treatment clinic with hospital.

•  RESULTS: •  During follow-up, linkage participants were more likely to enter buprenorphine OAT than

detoxification group (52 [72.2%] vs 8 [11.9%], P < .001). •  At 6 months, 12 linkage participants (16.7%) and 2 detoxification participants (3.0%) were

receiving buprenorphine OAT (P = .007). •  Compared with those in the detoxification group the linkage group reported less illicit opioid use

in the 30 days before the 6-month interview (incidence rate ratio, 0.60; 95% CI, 0.46-0.73; P < .01) in an intent-to-treat analysis.

Use of buprenorphine in the hospital

•  METHODS: •  Retrospective case series (n = 47).

•  RESULTS: •  Twenty-two (46.8%) patients successfully initiated buprenorphine treatment within 2

months of discharge. Those patients obtaining a referral to a specific program were more successful in continuing treatment, but this difference did not reach statistical significance (59.1% vs 39.1%, p = 0.18).

•  DISCUSSION AND CONCLUSIONS: •  Hospitalization may be an important opportunity to engage opioid dependent patients

to initiate buprenorphine treatment.

Buprenorphine for pain in dependent patients

•  Study outcomes of chronic pain pts tx’d with buprenorphine in an outpt psych consult clinic. •  METHODS: •  43 chronic pain patients with a DSM-IV dx of opioid dependence treated with bup (3 years) •  All dependent on drugs Rx’d for pain 2 groups: alcohol/drug depend vs no substance use disorder

•  RESULTS: •  Most patients male, not working, and between 45-60 years. •  Treatment with buprenorphine was effective. Most patients had improved pain with treatment of the

opioid dependence. •  There were no differences between those with or without a history of substance abuse.

•  DISCUSSION •  Patients with much less preoccupation with pain, and great satisfaction with buprenorphine treatment.

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Buprenorphine use on the consult service

• Patient Disposition N 19/23 " Linked to CDT (n=19; 83%) •  Lost to follow-up (n=5)

•  Successfully linked (n=14) −  Detoxification (n=2; 14%) −  Intensive outpatient programs (n=10; 71%) −  Inpatient program (n=2; 14%)

" Not linked to CDT (n=4; 17%) •  All received counseling/referral •  Known disposition in 3 patients − Tapered prior to d/c − Methadone maintenance − Oral naltrexone prior to d/c

Patient Characteristics (n = 23) Mean age, years (range) 38 (17-60) Male, n (%) 13 (57) Induction Setting

ED, n (%) 8 (35) Inpatient, n (%) 15 (65)

Common Encounter Diagnosis Withdrawal, n (%) 8 (35) Overdose/withdrawal, n (%) 4 (17) Cellulitis, n (%) 4 (17) Abscess, n (%) 3 (13)

Other Substance Abuse Cocaine, n (%) 13 (57) Benzodiazepines, n (%) 7 (30)

Length of hospital stay ED only, n (%) 8 (35) 2-5 days, n (%) 7 (30) 6-10 days, n (%) 4 (17) 11-20 days, n (%) 2 (9) >20 days, n (%) 2 (9)