1. Medication Assisted Treatment Michael Palladini, RPh MBA CAC info@drugsofabuse.net

2. “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
2013: US estimates nearly 2 million opioid dependent individuals; 9.2 million globally
DATA 2000 (2002) Physician Waiver
2013 Suboxone sales=$1.2 billion

3. 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.

4. Methadone, buprenorphine and naltrexone
Differences? Similarities

5. Dancing with the Devil: History of opiate use/risks

6. Vermont Governor Shumlin's 2014 State of the State Address
State of heroin/opiate use in Vermont, other US states.

7. Opiates/Opioids Morphine Codeine Heroin Oxycodone Hydrocodone
Oxymorphone
Hydromorphone
Fentanyl
Buprenorphine
Methadone
“Traditional Pain Relievers”

8. Opioids Therapeutic Effects Side Effects Analgesia Sedation/Relaxation
Euphoria
Cough Suppression
Nausea/Vomiting
Dizziness
Headache
Constipation
Sweating
Pruritus
Dry mouth
Miosis
Respiratory Depression

9. Tolerance
1. Pharmacokinetic
2. Pharmacodynamic
3. Learned

10. Early Withdrawal Fully Developed Withdrawal
Muscle aches
restlessness
anxiety
lacrimation (eyes tearing up)
runny nose
excessive sweating
inability to sleep
yawning very often
diarrhea
abdominal cramping
goose bumps on the skin
nausea and vomiting
dilated pupils and possibly blurry vision
rapid heartbeat
high blood pressure

11. Current Medications:
Current medications: methadone/buprenorphine/naltrexone
Formulation considerations: oral/sublingual/injectable

12. 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

13. Methadone Synthetic opioid “Full agonist action”
Use in opioid dependence circa 1965
Narcotic Addict Treatment Act of 1974
Considerable federal and state regulations

14. Buprenorphine DATA 2000 Semi synthetic opioid “Partial agonist action”
The “DEA physician waiver”

15. 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)

17. Opiate Receptors Receptor Location Function Mu1
Brain, Spinal Cord, Intestinal Tract
Analgesia, Physical Dependence
Mu2
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

18. Mu Receptor

20. Treatment Methadone (Highly Regulated)
Buprenorphine (Moderately Regulated)
Naltrexone (Slightly Regulated)

21. Methadone DEA Schedule 2 Clinic Setting Only 28 PA. CODE CH 715
-Clinic policy/procedures
-Physician/Staffing criteria

22. Methadone Generic drug (Roxane, Mallinckrodt Pharma)
Available in 5mg, 10mg Tablets
“Methadose” 40mg wafer
10mg/ml liquid syrup
Oral dosage formulations

23. 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

24. Methadone 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

25. Methadone Issues Abuse/Diversion/Overdose Use of other drugs
-Opiates/Cocaine/Benzodiazepines
Drug Interactions
-Significant
Dosing Issues
-Complex/Extensive Metabolism
-Prolonged Withdrawal

26. Buprenorphine DEA Schedule 3
Only FDA approved medication for OP (Physician-Office Based) treatment of opiate dependence
DATA 2000
Sublingual Formulation

27. Buprenorphine Suboxone® (Reckitt-Benckiser)
Buprenorphine (Formerly Subutex®, Generic)
Zubsolv® (Orexo Pharma)
Bunavail® (BioDelivery Sciences)

28. Suboxone

29. Zubsolv

30. Bunavail

31. Administration of Buprenorphine
Sublingual
Buccal

32. Buprenorphine Starting dose = 16mg bid or 32mg tid
Variable maintenance dosing
-2mg to 24mg daily
-single or divided dosing

33. Buprenorphine 1 to 4 hours peak Half life of 20 to 73 hours
8 -12 hrs duration (<4mg)
hrs duration (>16mg)
Partial mu agonist/Kappa antagonist
Active metabolites
Cost = Office visit ($100 to $400/month)
Cost = Medication ( $5 to $8/dose)

34. Buprenorphine Issues Abuse/Diversion/Overdose
Treatment/Counseling issues
-DATA 2000 requirements
-Payer requirements
Drug Interactions

35. Naltrexone Non-scheduled medication Vivitrol® (Alkermes)
380mg IM q28 days
7-10 days opiate free period
Cost= $800+ per monthly injection

36. Naltrexone

37. Naltrexone Initial peak at 2 hours Second peak at 2-3 days
Plasma concentrations begin to decline at 14 days
Half life 5-10 days

38. Naltrexone Issues Vulnerability to opioid overdose
Precipitation of opioid withdrawal
Switching from agonist therapy
Cost

39. “You can check out any time you like, but you can never leave”

40. MAT Issues/Questions/Concerns
Harm Reduction vs. Drug Free Models
Diversion
Tapering/Detox
Profit Motives
Long Term Effects
Lack of Data