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Medication Assisted
Treatment
Michael Palladini, RPh MBA CAC
[email protected]
“BUNAVAIL is the first and only FDA-approved
buccal film formulation of buprenorphine and
naloxone and will compete in the $1.7 billion and
growing U.S. opioid dependence market.”
-NASDAQ, 9/3/14
Objectives
 List the medications by generic and brand name, as
well as appropriate starting and maintenance dosages
for each, utilized for medication assisted treatment.
 Identify the pharmacological properties of the
medications used for opioid dependence treatment,
how these properties benefit patients, and the proper
use in a clinical setting.
 Describe the withdrawal symptoms of opioid
dependence and the significance of these symptoms in
initiating and maintaining treatment with specific
medications.
Vermont Governor Shumlin's
2014 State of the State Address
Opiates/Opioids
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Morphine
Codeine
Heroin
Oxycodone
Hydrocodone
Oxymorphone
Hydromorphone
Fentanyl
Buprenorphine
Methadone
“Traditional Pain Relievers”
Opioids
Therapeutic Effects
• Analgesia
• Sedation/Relaxation
• Euphoria
• Cough Suppression
Side Effects
• Nausea/Vomiting
• Dizziness
• Headache
• Constipation
• Sweating
• Pruritus
• Dry mouth
• Miosis
• Respiratory Depression
Tolerance
1. Pharmacokinetic
2. Pharmacodynamic
3. Learned
Early Withdrawal
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Muscle aches
restlessness
anxiety
lacrimation (eyes
tearing up)
runny nose
excessive sweating
inability to sleep
yawning very often
Fully Developed Withdrawal
• diarrhea
• abdominal cramping
• goose bumps on the
skin
• nausea and vomiting
• dilated pupils and
possibly blurry vision
• rapid heartbeat
• high blood pressure
Current Medications:
History of MAT
Late 19th Early 20th Century
Public perceptions/use
Addiction ≠ Disease
Increased use in 1950’s
and 1960’s
Addiction = Disease
Methadone use
Methadone
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Synthetic opioid
“Full agonist action”
Use in opioid dependence circa 1965
Narcotic Addict Treatment Act of 1974
Considerable federal and state regulations
Buprenorphine
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DATA 2000
Semi synthetic opioid
“Partial agonist action”
The “DEA physician waiver”
Naltrexone
• Synthetic molecule
• “Antagonist action”
• FDA original approval for opioid dependence
1984
• FDA approved for alcohol dependence 1994
• Vivitrol® FDA approved in 2006 (alcohol),
2010 (opioid)
Opiate Receptors
Receptor
Location
Function
Mu1
Brain, Spinal Cord, Intestinal
Tract
Analgesia, Physical
Dependence
Mu2
Brain, Spinal Cord, Intestinal
Tract
Respiratory Depression,
Euphoria, Miosis, GI
Motility, Physical
Dependence
Delta
Brain, Peripheral Sensory
Neurons
Analgesia, Physical
Dependence,
Antidepressant Effects
Kappa
Brain, Spinal Cord, Peripheral
Sensory Neurons
Dissociative, Dysphoria,
Miosis, Sedation
Mu Receptor
Treatment
• Methadone (Highly Regulated)
• Buprenorphine (Moderately Regulated)
• Naltrexone (Slightly Regulated)
Methadone
• DEA Schedule 2
• Clinic Setting Only
• 28 PA. CODE CH 715
-Clinic policy/procedures
-Physician/Staffing criteria
Methadone
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Generic drug (Roxane, Mallinckrodt Pharma)
Available in 5mg, 10mg Tablets
“Methadose” 40mg wafer
10mg/ml liquid syrup
Oral dosage formulations
Methadone
• Starting Dose = 30mg
• Institute upward titration
• Maintenance Dosage ranges from:
1 or 2 mg to >200mg/daily
• Once daily dosing
• “Privilege” dosing schedules
Step 0 through Step 6
Methadone
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Inactive metabolites
Half-life avg. of 30hrs; range of 4 to 91 hrs
2 to 4 hrs peak
Metabolized extensively by CYP450 system
Cost = $100/week
Methadone Issues
• Abuse/Diversion/Overdose
Use of other drugs
-Opiates/Cocaine/Benzodiazepines
• Drug Interactions
-Significant
• Dosing Issues
-Complex/Extensive Metabolism
-Prolonged Withdrawal
Buprenorphine
• DEA Schedule 3
• Only FDA approved medication for OP
(Physician-Office Based) treatment of opiate
dependence
• DATA 2000
• Sublingual Formulation
Buprenorphine
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Suboxone® (Reckitt-Benckiser)
Buprenorphine (Formerly Subutex®, Generic)
Zubsolv® (Orexo Pharma)
Bunavail® (BioDelivery Sciences)
Suboxone
Zubsolv
Bunavail
Administration of Buprenorphine
Sublingual
Buccal
Buprenorphine
• Starting dose = 16mg bid or 32mg tid
• Variable maintenance dosing
-2mg to 24mg daily
-single or divided dosing
Buprenorphine
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1 to 4 hours peak
Half life of 20 to 73 hours
8 -12 hrs duration (<4mg)
24 -72 hrs duration (>16mg)
Partial mu agonist/Kappa antagonist
Active metabolites
Cost = Office visit ($100 to $400/month)
Cost = Medication ( $5 to $8/dose)
Buprenorphine Issues
• Abuse/Diversion/Overdose
• Treatment/Counseling issues
-DATA 2000 requirements
-Payer requirements
• Drug Interactions
Naltrexone
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Non-scheduled medication
Vivitrol® (Alkermes)
380mg IM q28 days
7-10 days opiate free period
Cost= $800+ per monthly injection
Naltrexone
Naltrexone
•Initial peak at 2
hours
•Second peak at 23 days
•Plasma
concentrations
begin to decline at
14 days
•Half life 5-10 days
Naltrexone Issues
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Vulnerability to opioid overdose
Precipitation of opioid withdrawal
Switching from agonist therapy
Cost
“You can check
out any time you
like, but you can
never leave”
MAT Issues/Questions/Concerns
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Harm Reduction vs. Drug Free Models
Diversion
Tapering/Detox
Profit Motives
Long Term Effects
Lack of Data