Transcript Emerging technologies in MAT care

EMERGING
TECHNOLOGIES IN MAT
MEDICATION DELIVERY
William Roberts, RN, CRNA, MD, PhD
Diplomat, American Board of Addiction Medicine
Diplomat, American Board of Anesthesiology

None
CONFLICTS OF INTEREST
THIS TALK IS ABOUT EXPENSIVE OPTIONS, SO LETS
START WITH:
WHY SOCIETY SHOULD CARE?
LOST PRODUCTIVITY IS THE REAL COST
DOES MAT WORK?
AGONIST AND PARTIAL AGONIST OUTCOMES
FOR OPIATE MISUSE DISORDER ARE REAL
METHADONE AND BUPRENORPHINE DELIVERY
SYSTEMS SHARE A COMMON FLAW:
NON-COMPLIANCE UNDERMINES OUTCOMES
WHEN TREATMENT IS A “PROBLEM”
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The “majority of buprenorphine-certified physicians (81%) stated that
buprenorphine was easier to buy on the street than methadone”.
MOST OFTEN DIVERSION IS A “GIFT”
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Potential Patients know that “treatment as usual” is time consuming
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Travel limits access to methadone, especially in rural settings
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Methadone is frankly less safe when used without guidance
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Buprenorphine access is rapidly expanding since DATA 2000
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Compliance is less time consuming, but still limits employment
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The drugs are not the problem when delivered in a protocol
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Access while making an honest living while working is the problem
METHADONE VS BUPRENORPHINE
AND COMPLIANCE
WHY NOT JUST BE PORTUGAL?
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Twenty-eight instances of IVDA of buprenorphine were detected
in a population of 239 of my patients in a two year interval
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Urinary ratios of buprenorphine to nor-buprenorphine are an
indicator of IVDA of buprenorphine*
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*when obtained consistently and reviewed serially
The patients all agreed that they had an issue with injection
IVDA OF BUPRENORPHINE IS NOT MAT
IVDA OF BUPRENORPHINE IS DANGEROUS
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Variable uptake and distribution
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First pass metabolism
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Diversion
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Abuse
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IVDA
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Inventory
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Dependency
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The behavior of taking of a medication frequently
PROBLEMS WITH SUBLINGUAL
BUPRENORPHINE DELIVERY SYSTEMS
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So there has been a lot of activity directed at alternative delivery systems
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The emphasis has been identifying options that patients do not control
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Most of the issues have been shifted into the cost column
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Disposal becomes a larger issue
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Surgical techniques required
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Patients won’t like this
LONG TERM DELIVERY SYSTEMS
SOMETIMES IT IS JUST THE SAME OLD HORSE
BUTRANS FEATURES 7-DAY TRANSDERMAL
MATRIX TECHNOLOGY
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buprenorphine is delivered (5, 7.5, 10, 15, or 20 mcg/hour
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Issues:
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Residual drug content is high after use
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Inventory exchange necessary
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Delivery dose is low
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Expensive
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Lack of data regarding efficacy for opioid misuse disorder
BUTRANS AS A 7 DAY MAT OPTION?
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Burtans may have a place in:
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the weaning and discontinuance of MAT
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transition to implants
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patients returning to households with theft risks
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Transition to naltrexone or antagonists care MAT
“END OF CARE” CARE AND
TRANSITIONS
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Endo Pharmaceuticals Inc., a subsidiary of Endo International plc
(NASDAQ: ENDP) (TSX: ENL),
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Announced on June 3, 2016
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“new data support the safety and tolerability of BELBUCA™
(buprenorphine) buccal film for the long-term management of
chronic pain in patients requiring around-the-clock opioids”
HEADLINE: “NEW DATA DEMONSTRATE
SAFETY OF LONG-TERM, AROUND-THECLOCK TREATMENT WITH BELBUCA™
(BUPRENORPHINE) BUCCAL FILM FOR
CHRONIC PAIN”
EFFICACY IS REAL
“ALTERNATE” DELIVERY SYSTEMS
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Eighty-nine (51 women and 38 men); 81 with malignant pain and
8 with benign "refractory" pain.
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Pumps delivering buprenorphine into the CSF through the skin
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High rates of infection
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Placement issues
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Refill issues
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Costs
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Clin J Pain. 1992 Dec;8(4):324-37.
INTRATHECAL PUMPS
LONGER TERM DELIVERY
SYSTEMS
Drug eluting implants
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Each implant consists of ethylene vinyl acetate copolymer and
90 mg buprenorphine HCl, and measures 26 mm in length and
2.4 mm in diameter.
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Steady-state release in-vitro was 0.5 mg/implant/day.
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In-vivo pharmacokinetics and safety were examined for up to 52
weeks.
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Plasma buprenorphine concentrations correlated with the
number of implants administered.
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J Pharm Pharmacol. 2006 Mar;58(3):295-302.
IN VITRO TESTING
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Peak buprenorphine concentrations were generally reached
within 24 h after implantation.
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Steady-state plasma levels were attained between 3 and 8
weeks
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Steady-state plasma levels were maintained for study duration,
with a calculated mean release rate of 0.14+/-0.04
mg/implant/day.
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J Pharm Pharmacol. 2006 Mar;58(3):295-302.
BEAGLE DOGS RECEIVING 8, 16 OR 24
SUBCUTANEOUS IMPLANTS
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90 mg buprenorphine HCl x 24 implants = 2.16 Grams of buprenorphine
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How will the delivery system be installed and by whom?
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What is the serum dose equivalency in humans to sublingual?
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Wound complication rates?
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Who takes the implant out?
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Disposal of residual drug?
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Patient selection?
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Costs?
CON ARGUMENTS
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WARNING: IMPLANT MIGRATION, PROTRUSION, EXPULSION and NERVE DAMAGE ASSOCIATED
WITH INSERTION and REMOVAL
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Risk associated with Insertion and Removal
Insertion and removal of PROBUPHINE are associated with the risk of implant migration,
protrusion, expulsion, and nerve damage resulting from the procedure. Serious but rare
complications including nerve damage and migration resulting in embolism and death may
result from improper insertion of drug implants inserted in the upper arm. Additional
complications may include local migration, protrusion and expulsion. Incomplete insertions or
infections may lead to protrusion or expulsion. All Healthcare Providers must successfully
complete a live training program and become certified prior to performing insertion and/or
removal of PROBUPHINE implants.
Because of the risks associated with insertion and removal, PROBUPHINE is available only
through a restricted program called the PROBUPHINE REMS Program. All Healthcare Providers
must successfully complete a live training program on the insertion and removal procedures
and become certified, prior to performing insertions or prescribing PROBUPHINE implants.
Patients must be monitored to ensure that PROBUPHINE is removed by a healthcare provider
certified to perform insertions.
DEVICES ARE NOT SIMPLE NOR WITHOUT RISKS
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deterioration of the quality of the cervical mucus and sperm penetration is
evident by 24 hours after insertion
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not to a level that would suggest adequate protection until 72 hours after
insertion.
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Fertil Steril. 1998 Feb;69(2):258-66.
THINK “NORPLANT”
PROBUPHINE IS ONLY ONE OF FOUR
PRODUCTS FROM ONE COMPANY
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Braeburn Pharmaceuticals: Probuphine
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The FDA previously rejected Probuphine in 2012, judging the
delivered dose was too low to reliably help patients.
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Federal approval on Thursday, May 26, 2016
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Six month implant
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“implantable format could help patients avoid dangerous
relapses that can occur if they miss a medication”
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http://www.usnews.com/news/business/articles/2016-05-26/fdaapproves-first-drug-oozing-implant-to-control-addiction
“FDA APPROVES FIRST DRUG-OOZING
IMPLANT TO CONTROL ADDICTION”
USNEWS AND WORLD REPORT
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“Probuphine is intended for patients who have already been
stabilized on low-to-medium doses of buprenorphine for at least
a half year.”
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“Braeburn estimates that one fourth, or 325,000, of the 1.3 million
patients currently taking buprenorphine meet that criterion.”
APPROVED INDICATIONS
BRAEBURN IS NOT ALONE
INDIVIOR HAS A PIPELINE
WHAT IS THE REAL INNOVATION
OPTION?
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Persons aged 65 years and older comprise only 13 percent of the
population.
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Persons aged 65 years and older account for more than onethird of total outpatient spending on prescription medications in
the United States.
HTTPS://WWW.DRUGABUSE.GOV/PUBLICATIONS/RESEARCHREPORTS/PRESCRIPTION-DRUGS/TRENDS-IN-PRESCRIPTION-DRUGABUSE/OLDER-ADULTS
PATTERNS OF PRESCRIPTION OPIOID ABUSE AND CO-MORBIDITY IN AN AGING
TREATMENT POPULATION
HTTP://WWW.NCBI.NLM.NIH.GOV/PMC/ARTICLES/PMC3217134/
A NEW LINE HAS BEEN DEFINED
WHO HAS HAD THEIR PRESCRIPTIONS
DISCONTINUED OR REDUCED?
BOOMERS GET A POSITION ON THE
PLAYING FIELD
THIS HAS ALWAYS BEEN AN OLDER
PERSON PROBLEM
THIS HAS ALWAYS BEEN A PRESCRIPTION
PROBLEM
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Moderate to severe non-withdrawal related bodily pain – that
greatly limited social contacts and work – was common in most
of those entering treatment: 45% of those 18–24 years reported
moderate to severe pain.
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However, the incidence of this intense pain grew to well over 70%
in individuals 45 or older.
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The huge surge of youthful opioid abusers who began using drugs
in the 1993–2010 time-frame have not yet reached the age of 40.
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Therefore, the number of elderly people seeking treatment
should continue to rise over the next 5–10 years
HEROIN IS FOR YOUNG PEOPLE….
SO THE NEW TECHNOLOGY OF
GREATEST VALUE IS….
Prevention
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Limit dependence of older patients
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Limit diversion from aged patients
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Monitor everyone that has access to opiates/opioids
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Judge no one, except perhaps ourselves as clinicians
LONG TERM SUCCESS WILL BE BASED
ON PRACTICE PATTERNS