Medication-Assisted Treatment:

                      Buprenorphine/Naloxone
Peter LeMere PharmD. PGY1 Resident
 Medication-Assisted Treatment (MAT)
Use of medications, in combination with counseling and behavioral therapies, to provide a “whole-patient” approach
to the treatment of substance use disorders

Ultimate goal of MAT: full recovery

This treatment approach has been shown to:

• Improve patient survival

• Increase retention in treatment
• Decrease illicit opiate use and other criminal activity among people with substance use disorders
• Increase patients’ ability to gain and maintain employment
• Improve birth outcomes among women who have substance use disorders and are pregnant
Medication options for opioid use disorder:

• Methadone
• Buprenorphine products
• Naltrexone
2

Medication-Assisted Treatment (MAT). SAMHSA. Accessed September 2022.

 MAT Ordering vs. Prescribing

Inpatient Orders Outpatient Prescriptions

Methadone: prescribed at
ANY provider caring for specialty licensed clinics
the patient can initiate
and/or continue methadone, Buprenorphine: requires
buprenorphine products, or X-waiver
naltrexone*
Naltrexone: no restrictions

*Exception: Admission for OUD

(prescriber must have X-waiver to initiate)
3
Waller RC and Virva M, et al. Medication Assisted Treatment Guidelines for Opioid Use Disorders. MDCH 2014.
Cunningham C and Fishman M. The ASAM National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use. Accessed September 2022.
 MAT Ordering vs. Prescribing

Inpatient Orders Outpatient Prescriptions

Methadone: prescribed at
ANY provider caring for specialty licensed clinics
the patient can initiate
and/or continue methadone, Buprenorphine: requires
buprenorphine products, or X-waiver
naltrexone*
Naltrexone: no restrictions

*Exception: Admission for OUD

(prescriber must have X-waiver to initiate)
4
Waller RC and Virva M, et al. Medication Assisted Treatment Guidelines for Opioid Use Disorders. MDCH 2014.
Cunningham C and Fishman M. The ASAM National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use. Accessed September 2022.
 Buprenorphine Prescribing: What is new?
• Must have X-waiver to prescribe on discharge
• 8 hrs of approved training required for waiver
Before • Initial limit of 30 patients, could qualify for 100 patients after 1
April 2021 year of waiver

• Must have X-waiver to prescribe on discharge

• Training NOT required for X-waiver
After April • Limit of 30 patients, can complete 8 hr training to qualify for
2021 100 patients

Department of Health and Human Services. Practice Guidelines for the Administration of Buprenorphine for Treating Opioid Use Disorder. Accessed September 2022.
Signing up
 SAMHSA website (samhsa.gov)
 From menu bar select Programs --> Medication Assisted Treatment
(MAT)
⎻Left column select "Become a Buprenorphine Waivered
Practitioner"
⎻Now underneath, select "NOI Buprenorphine Waiver Application"
 Application
⎻State Medical License Number and DEA Registration Number
⎻For the "Certification of Qualifying Criteria" section:

Mid-level check SAMHSA’s Providers

enter "practice guidelines" in the text box
Practitioners Clinical Support System
for the date
(APRNs and PAs) (PCSS) 

enter "practice guidelines" in the text box for the

Physicians  select "Other" city of the training. The training date should be the
application date.

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 Waiver FAQs
Q A

How long does the application take to process? Can it be • Up to 45 days

expedited?
Do practitioners also still need to obtain and utilize the X-
number from the DEA to prescribe buprenorphine?
Does this limit increase each year? What if I want to treat
more than 30 patients?
What is the difference between a 30-level waiver and a 30E-
level waiver? 
How do I get a new DEA Card or check my DEA Registration
Status?  • Print a copy of your DEA certificate with the x-waiver listed.
• Contact if there is urgent need
• Yes - "X number" issued by DEA upon approval
• Must be written on prescription itself
• Used to verify validity of prescription at the pharmacy
• Limit does not increase, 30 patients maximum
• Complete/submit required training and sign new Notice of
Intent. Review further requirements for increasing to 100 patient
limit.
• 30 requires training; 8 hours for physicians, 24 hours for mid-
level practitioners
• 30E (E = "exempt") requires no training
• Call the DEA at 1-800-882-9539 or send an email to 
DEA.Registration.Help@usdoj.gov
 
Enter last name, business zip code listed on the DEA registration,
and social security number

FAQs about the new buprenorphine practice guidelines. SAMHSA. Accessed September 2022.
Verifying Waivers
 For pharmacy or medical office:
 Use the Buprenorphine Pharmacy Lookup tool:

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Buprenorphine/Naloxone
Sublingual Film/Tablets

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 Pharmacokinetics
Buprenorphine

Partial agonist at µ-opioid receptor (ceiling effect),

Mechanism high affinity binding
+ Naloxone
Distribution 96% protein bound [α/β globulin]
(Suboxone®/Zubsolv®)
Mechanism: full opioid antagonist
Half-life 24 - 42 hours PO bioavailability: <2%
Buccal film (Belbuca®): 55% Rationale for co-formulation:
Bioavailability Transdermal patch (Butrans®): 15%
prevent diversion
Sublingual film/tablet: 25%
Primarily hepatic via CYP3A4 to norbuprenorphine (active metabolite),
Metabolism which also undergoes glucuronidation via UGT1A3; extensive first-pass
effect
• Moderate hepatic impairment: Induction not recommended
Adjustments • Severe hepatic impairment: Avoid use
10

Buprenorphine [package insert]. Columbus, OH: Roxane Laboratories, Inc; 2015.

Indication and Products
Indication
• Combination product for treatment of OUD (compared to
buprenorphine for pain)
• To avoid precipitating withdrawal, initiation only when objective and
clear signs of withdrawal are present
Formulations [buprenorphine x mg / naloxone y mg]
• Suboxone® = sublingual film
• Utilized in outpatient/discharge setting
• Zubsolv® = sublingual tablets
• Utilized in the IU Health interchange
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 Formulations
Suboxone® Zubsolv® Bunavail® 
Sublingual Film Sublingual Tab Buccal Film
2 mg/0.5 mg 1.4 mg/0.36 mg N/A
4 mg/1 mg 2.9 mg/0.71 mg 2.1 mg/0.3 mg
8 mg/2 mg 5.7 mg/1.4 mg 4.2 mg/0.7 mg
12 mg/3 mg* 8.6 mg/2.1 mg 6.3 mg/1 mg
16 mg/4 mg** 11.4 mg/2.9 mg N/A
*One 8mg/2mg tablet AND two 2 mg/0.5 mg tablets
**Two 8mg/2mg tablets 12
Dose Conversion Calculator. Zubsolv. Available at: https://www.zubsolv.com/healthcareprofessionals/about-zubsolv/dose-conversion-calculator/
Bunavail [package insert]. Raleigh, NC: BioDelivery Services International, Inc; 2014
13
 Inpatient Dosing Guidance

Day 1 Day 2 Maintenance

• Last opioid use > 6-12 hrs ago
• Patient in moderate withdrawal
Give total daily
dose from Continue dose that
Give 2-4 mg abated withdrawal with
dose x 1 Day 1
review
 (MAX 32 mg/day, likely
Reassess in 2 hrs: Reassess in 2 hrs:
Withdrawal symptoms resolved? Withdrawal symptoms resolved?
target 8-16 mg/day)

Yes No Yes No

Give additional
Continue same Continue same Give additional 2-
2-4 mg dose
dose once daily dose once daily 4 mg doses PRN
(Day 1 MAX: 8
with review with review (Day 2 MAX: 16 mg)
mg)

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Substance Abuse and Mental Health Services Administration. Buprenorphine Quick Start Guide. Accessed August 4, 2021.
Initial Dosing Considerations

2 mg
Patient is heavy fentanyl user and/or you are worried
about precipitated withdrawal

4 mg Most common initial dose

May be considered for patients initiating treatment

8 mg
in outpatient setting

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 Considerations for Acute Pain

Continue maintenance • Initiate short-acting opioid PRN

therapy • Caution if buprenorphine therapy abruptly discontinued

Divide daily dose of • Can consider TID dosing with likely increase in daily dose
buprenorphine BID • Take advantage of the short-acting analgesic properties

Less preferred:
Discontinue buprenorphine • Not recommended
and initiate opioid therapy
16

Alford DP et al. Acute pain management for patients receiving maintenance methadone or buprenorphine therapy. Ann Intern Med 2006;144(2):127.
Restarting Therapy after Full Agonist Treatment
If therapy was stopped to treat acute pain with full agonists:
Wean full agonist to lowest tolerable dose
Completely stop full agonist for 12-24 hrs or until patient is in moderate
withdrawal
Give ½ of patient’s prior Suboxone® dose
After 2 hrs, give other ½ of patient’s prior Suboxone® dose

Patient will be back to previous dose of Suboxone® after 1 day

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Suboxone® Patient Accessibility
IU Arnett Retail Pharmacy
Estimated cash prices for #30 (generic)

 Suboxone 2 mg films:  $75

 Suboxone 4 mg films:  $150
 Suboxone 8 mg films :  $130
 Suboxone 2 mg tabs: $40
 Suboxone 8 mg tabs: $40
 Subutex 2 mg tabs:  $15
 With insurance: 
 Covers up to $75/mo on copay, limit 1 fill/mo  Subutex 8 mg tabs:  $22
 Without insurance:
 Covers from $0.96 - $3.84 per individual film 
 7 film minimum per redemption, max 4 fills/mo
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 Transitions of Care Recommendations

Outpatient referral Discharge prescription

• Unless patient’s PCP has X-waiver, will • Need provider with X-waiver
need to be referred to MAT Bridge Clinic • Current X-waivered providers: Chelsea
(Indy) for virtual follow-up Worstall (FM)
• Referral found in ED Medication for • If unable to find provider, Addiction
Addiction Treatment (MAT) Powerplan – Psychiatry NP Steven Guichelaar (MAT
go-live 08/2022 Bridge Clinic) has been willing to write
discharge prescriptions
• XDEA number needs to be free-texted
• Place referral AS SOON AS you know into discharge prescription
patient will be leaving on Suboxone® to
ensure virtual appt can be set up prior to
discharge
**If you have not gotten response from MAT Bridge Clinic prior to discharge, message Steve Guichelaar on Diagnotes 19
and send message to Jenny Slavens or Jenna Gerhardt to assist with the transition.
Indiana Law: 7 Day Prescribing Limit

7 Day Prescribing Limit [IN SEA 226; 2017]

 No more than 7 day supply for initial opioid prescription
 Limit applies to physician’s first opioid prescription for that
patient
 No specific exception for practitioners in same practice
 For patients < 18 years old, all opioid prescriptions limited to 7
day supply
 Exceptions: cancer, MAT for SUD, palliative care, professional
judgement (must document that non-opiate not appropriate and
physician is using professional judgement to prescribe > 7 day
supply)
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 3-Day Rule
Allows provider to administer Suboxone® for purpose of relieving acute
withdrawal while arranging for referral for treatment
Cannot give more than 1 day’s medication to patient at one time
Treatment cannot be carried out for more than 72 hrs or 3 days
72 hr/3 day window cannot be renewed or extended

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Code of Federal Regulations

Future Goals
Increase number of X-waivered providers able to write discharge
prescriptions
Family Medicine planning to create MAT clinic – likely Q1-Q2 2023
Increase pharmacist and provider comfort with initiation and dosing

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Medication-Assisted Treatment:
                      Buprenorphine/Naloxone
Peter LeMere PharmD. PGY1 Resident