1. Allegheny County Overdose Prevention Coalition
Pharmacotherapy
Allegheny County Overdose Prevention Coalition

2. Suggested Intervention Guidelines
4/05/2011
Suggested Intervention Guidelines
LETHALITY
ALCOHOL 11-17
ALCOHOL 18-26
ALCOHOL 26+
DRUGS/TOBACCO 4-11
DRUGS/TOBACCO 12-26
DRUGS/TOBACCO 26+
RECEPTIVITY
LOW
MODERATE
HIGH
Brief Intervention
Naloxone
Recovery Support
Possible Suboxone Induction
Likely Suboxone Induction

3. Opioid Agonist Therapy is Lifesaving
“…the all cause mortality rate for patients receiving methadone maintenance treatment was similar to the mortality rate for the general population whereas the mortality rate of untreated individuals using heroin was more than 15 times higher.”
Bell 2000

4. Benefits of Treatment
Opioid maintenance therapy with buprenorphine or methadone is the most effective intervention to prevent overdose. Detoxification is associated with higher subsequent risk of death due to lack of rehabilitation and follow-up medical/ psychiatric care.
Bell 2000 and Saitz 2007
Bell 2000 and Saitz 2007

5. Opioid Agonist Therapy Prevents Overdose
4/05/2011
Opioid Agonist Therapy Prevents Overdose
Since the institution of buprenorphine and methadone maintenance in 1996, heroin overdose dropped by 79% in France.
1969
1971
1973
1975
1977
1979
1981
1983
1985
1987
1989
1991
1993
1995
Year
No. of deaths
600
500
400
300
200
100
1996
Patients receiving buprenorphine (1998): N= 55,000
Patients receiving methadone (1998): N= 5,360
French population in = 60,000,000
Auriacombe et al., 2001

6. Buprenorphine in medical withdrawal and maintenance20 15
Maintenance
Number remaining in treatment 10
Pharmacologic treatment combined with psychosocial interventions enhances treatment effectiveness:
Retention after 1 year treatment: 75% and 0% in buprenorphine and placebo groups respectively (Kakko et al, 2003)
Pharmacotherapy helps patients stay in treatment:
Reduces illicit drug use by decreasing cravings and withdrawal
Reduces mortality by up to 4 fold (Kreek and Vocci, 2002) 5
P=0.0001
Control
100
150
200
250
300
350 50
Time from randomization (days)
Kaplan-Meier curve of cumulative retention in treatment
(Kakko et al, 2003)

7. Naloxone Prescriptions by PPP July 2005 – July 2009
477 persons receiving prescriptions reported, at the time of training:
570 overdoses (self)
1,995 overdoses witnessed
149 deaths witnessed
310 refills yielded:
307 successful reversals (173 required rescue breathing)
2 deaths
1 unknown outcome

8. Naloxone with Safe Landing
4/05/2011
Naloxone with Safe Landing

9. Allegheny County Overdose Deaths with at least one Substance Responsive to Naloxone 2000-2007
Allegheny County Coroner’s Office
Alex Walley Fellows Report 9 9

10. Naloxone Pharmacology
Potent mu antagonist
Safety demonstrated to 10mg.
Elimination half-life is 30min.
Well absorbed orally poor bioavailability due 95% first- pass metabolism.
Readily crosses blood-brain barrier.
Reversal of morphine occurs within 1 to 2 minutes. If no response in 4 to 10 minutes = not an opioid overdose.
van Dorp, 2007
van Dorp, 2007

11. Naloxone Safety
Only contra-indication is allergy, however, allergy to naloxone is rare.
Not yet studied in pregnancy but should be used when there is a clear maternal indication to prevent morbidity and mortality from hypoxia.
Available over the counter in Great Britain.
FDA; Bailey 2003
FDA; Bailey 2003

12. Naloxone Qualities No abuse potential Not controlled IV vs. IM vs. IN
Various concentrations
Effectiveness is comparable
Strong interest in possible use of Intra-nasal administration.

13. Intranasal Naloxone
Intranasal is proving equally effective as IM or IV.
Intranasal works slightly slower than IV but faster than IM and produces less agitation.
Intranasal may require more frequent “rescue dose.” Caveat: Rescue dose administration has thus far been subjective judgment of person who knew investigative application in use.
Not yet commercially available.

14. Peer Reversal of Overdose with Naloxone
Does not increase drug use frequency or quantity or risk taking.
IM most widely taught and used in peer administration.
Rescue breathing may still be required.
Patient should still have medical evaluation but not necessarily via ambulance or in the ED.

15. Naloxone with Safe Landing
4/05/2011
Naloxone with Safe Landing
Patients determined to likely benefit from naloxone prescription will be prescribed one 10cc vial of 0.4mg/ml naloxone and three 3cc IM syringes with needles.
Naloxone within Safe Landing protocol is only for patients being discharged from the facility to the community.

16. Buprenorphine with Safe Landing
4/05/2011
Buprenorphine with Safe Landing

17. Buprenorphine Benefits
Buprenorphine aids management of naloxone induced acute opioid withdrawal in the ED.
Patients experiencing naloxone induced acute withdrawal may elope from the ED before they are medically stable.
Repeat substance use is virtually guaranteed creating the risk of recurrent overdose when naloxone wears off.
Opportunity opens for diversion to treatment or other risk reduction services.

18. Buprenorphine Pharmacology
Partial agonist antagonist of the mu opioid receptor.
Limits development of tolerance.
Reduces risk of respiratory depression.
High receptor affinity accounts for rapid onset and long duration of action and antagonism of other opioids.
Together will produce acute precipitated opioid withdrawal in an opioid dependent person.

19. Suboxone® A formulation of buprenorphine with naloxone.
Buprenorphine is absorbed sublingually.
Naloxone is minimally absorbed and not biologically available.
If the tablet is dissolved and injected the user will experience acute withdrawal.
Available in 2mg and 8mg tablets, costing $4 to $5 a piece.
Also available in a sublingual film.

20. Regulation of Buprenorphine
Prescribed as a maintenance therapy by any physician who completes a required 8 hour training and obtains a waiver from the DEA.
Physicians can treat up to 30 patients at a time the first year, then up to 100.
Dispensed at the pharmacy.
Insurance typically pays the physician and for medication.

21. Buprenorphine Dosing
For safe administration of buprenorphine, the patient must exhibit objective signs of moderate withdrawal.
95% receptor occupancy is expected at 16mg once daily.
2mg to 8mg may be needed to at least partially relieve acute withdrawal for 2 to 8 hours.
Greenwald et al, 2003
Greenwald et al, 2003

22. Buprenorphine Management
4/05/2011
Buprenorphine Management
Provided the nursing assessed COWS score is consistent with the clinical judgment of the treating physician:
Scores ≥12 may be administered 2mg of buprenorphine
Scores ≥24 may be administered 4mg of buprenorphine
Scores ≥36 may be administered 8mg of buprenorphine
Patient can be reassessed in 30 to 60 minutes and receive a repeat dose according to the subsequent score until score is 10 or lower.
This will typically be accomplished within two doses of buprenorphine.
Discuss how this will work in your ED

23. Buprenorphine with Safe Landing
Abolish the most severe and/or destabilizing signs and symptoms of acute withdrawal.
Increase likelihood of complete medical and psychiatric management.
Increase tolerability of behavioral and social work interventions.
Allow patient to attend to educational and referral opportunities.