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

Medication Assisted Treatment

Michael Palladini, RPh MBA CACinfo@drugsofabuse.net

“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• 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 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

Current Medications:

History of MAT

Late 19th Early 20th CenturyPublic perceptions/useAddiction ≠ DiseaseIncreased use in 1950’s and 1960’sAddiction = DiseaseMethadone use

Methadone

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

Buprenorphine

• 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 ReceptorsReceptor 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

• 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

• 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/OverdoseUse 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

• 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

• 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

• 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 2-3 days•Plasma concentrations begin to decline at 14 days •Half life 5-10 days

Naltrexone Issues

• 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

• Harm Reduction vs. Drug Free Models• Diversion• Tapering/Detox• Profit Motives• Long Term Effects• Lack of Data