1. Sublingual Buprenorphine and Pain
Michelle Geier, PharmD
Psychiatric Clinical Pharmacist
Substance Use Disorders Clinical Pharmacist
San Francisco Department of Public Health

2. Overview Pharmacology and Formulations
Sublingual Buprenorphine in Pain

3. Buprenorphine Pharmacology and Formulations

4. Buprenorphine Pharmacology
Mechanism of action:
µ opioid partial agonist
Analgesia
Mitigates opioid withdrawal symptoms
Binds with high affinity and dissociates slowly
Blocks other opioids from receptor binding
ĸ antagonist
Reduces opioid tolerance

5. Buprenorphine Formulations
Brand Name
Approval Date
Route of Administration
Co-formulated with Naloxone?
FDA Approved Indication(s)
Buprenex
1981
IV, IM No
Moderate to severe pain
Subutex
2002 SL
Opioid dependence
Suboxone
SL tablet
Yes
2010
SL film
Butrans
Transdermal
Severe pain requiring daily, around-the-clock, long-term opioid treatment for which alternative treatment options are inadequate
Zubsolv
2013
Bunavail
2014
Buccal

6. Buprenorphine Dosing Sublingual Buprenorphine Dosing Frequency:
Opioid replacement therapy
Daily
Chronic pain
BID – QID

7. Sublingual Buprenorphine in Pain

8. Buprenorphine and Pain
Buprenorphine was first indicated for pain
Potent analgesic effects
Buprenorphine IV is 25-40x as potent as morphine IV1
Transdermal buprenorphine has demonstrated efficacy for chronic noncancer and cancer patients2
Case studies of buprenorphine transdermal product being effective for neuropathic pain
Pickworth, et al. Clin Pharmacol Ther. 1993;53:570–576.
Mellar, et al. J Support Oncol. 2012;10:

9. Evidence Review: Co-Occuring Disorders Clinic
VA Medical Center in Albuquerque, New Mexico
Began a Co-Occuring Disorders Clinic (COD)
Manages challenging patients with chronic pain and substance abuse
Included high-risk opioid use, substance use disorders and high-dose or complex therapeutic pain management regimens
Referrals came from primary care, pain management specialists, surgery specialties and substance use disorder clinic
Pade, et al. Journal of Substance Abuse Treatment. 2012;43:

10. Evidence Review: Co-Occuring Disorders Clinic
Intake included:
Detailed pain, substance abuse and psychiatric history
Physical exam
Urine toxicology
Review of prescription drug monitoring program
30% of referrals met criteria for opioid dependence and were offered buprenorphine/naloxone
The remaining patients that did not meet criteria were monitoring 1-2x/month at the COD clinic for 12 months
Clients were also offered adjunctive non-opioid pain medications throughout treatment

11. Evidence Review: Co-Occuring Disorders Clinic
Buprenorphine Induction
Patients using short acting opioids
Start buprenorphine 12 – 24 hours after stopping other opioid
Patient using long acting opioid without chronic pain
Start buprenorphine 24 – 36 hours after stopping other opioid
Patient prescribed long acting opioid from VA for chronic pain
Tapered to dose of ≤90mg morphine equivalents, then switched to short-acting opioid for 2-4 weeks
Then treated as above “Patients using short acting opioids”

12. Evidence Review: Co-Occuring Disorders Clinic
Buprenorphine/naloxone was discontinued if:
Patients resumed opioid use without provider consent
3 urine toxicology tests positive for illicit drugs
3 missed visits
3 early refill requests
Discontinued clients were referred to higher level of care including methadone maintenance
Also discontinued in those with:
Intolerable side effects
Uncontrolled pain at a buprenorphine dose of 28mg/day

13. Evidence Review: Co-Occuring Disorders Clinic
Retrospective chart review of 143 patients started on buprenorphine/naloxone at the COD clinic between
Patients
Gender: 93% male
Mean age: 52 years old
Co-morbid psychiatric diagnosis: 71%
Mean daily dose in morphine equivalents on intake: 184mg
Range: 30 – 375mg
Most common opioids
Oxycodone: 44%; Methadone: 16%; Heroin: 11%
Pain complaint
Musculoskeletal: 56%; Mixed nociceptive and neuropathic: 39%

14. Evidence Review: Co-Occuring Disorders Clinic
Results
Mean total daily buprenorphine dose: 16mg
Most commonly prescribed regimens:
8mg/2mg BID: 26%
8mg/2mg TID: 19%
4mg/1mg TID: 18%
93 of 143 patients (65%) remained on buprenorphine/naloxone and did not relapse to opioids
Determined by: pharmacy records, state prescription monitoring programs and urine toxicology
92% of these patients stayed on buprenorphine 6 months or longer

15. Evidence Review: Co-Occuring Disorders Clinic
50 of 143 patients were lost to follow-up or discontinued buprenorphine
Reason for Discontinuation
Number of Patients (%)
Patient request
13 (26%)
Moved
9 (18%)
Side effects
Ongoing pain
8 (16%)
Noncompliance/illicit drugs
6 (12%)
Deceased
2 (4%)
Hospice
1 (2%)
Unknown

16. Evidence Review: Co-Occuring Disorders Clinic
The mean pain score decreased from 6.39 to 5.6 with buprenorphine/naloxone treatment, P<0.001
Preferred Opioid
Number of Patients
Mean difference in pain score
Number of current patients (%)
Heroin 16
-0.7
10 (63%)
Methadone 23
-0.3
17 (74%)
Oxycodone 63
-1.0
40 (63%)
Hydrocodone 18
-0.1
13 (72%)
Fentanyl 9
-1.1
3 (33%)
Morphine 12
-1.2
9 (75%)
Codeine 1
-7.8
1 (100%)
Hydromorphone
+0.6
0 (0%)

17. Take Home Points Buprenorphine is a potent analgesic medication
Buprenorphine has efficacy for chronic pain
Buprenorphine sublingually has efficacy for opioid dependence and chronic non-cancer pain
Buprenorphine for chronic pain requires BID to QID dosing

18. Questions?