Download KCQ4_Adverse_Events_June1_11

KCQ 4: Adverse Events
http://www.gacguidelines.ca/index.cfm?pagepath=Contact_Us&id=21076
Sep 24/10
27 April 2009. Oct 19/09 Rev. June 30 10 July 19/10 (Arjun). Aug 23/10 (CH). Sep 13AK Sep 20CH, June 2011 PS
CH notes Aug 26 & 28/10
Revisit uncontrolled studies: In or Out?
A. Summary Table
Adverse Events Studies
Study name
Lofwall 2005
245
Umbricht
2004
238. Stoller
2001
Strain
1997
Study Type
No difference in adverse events
Favours buprenorphine over
between buprenorphine and
comparison
comparison
Respiratory Depression



RCT
BMT vs MMT
Opioid dependent




Crossover. N= 6
IV Bupe vs placebo
Opioid users




Crossover. N=10
IM, SL bupe vs
hydromorphone vs
placebo.
Opioid dependent
Crossover. N=8
IM, bupe vs
hydromorphone vs
placebo in pts on bupe
Opioid dependent


Retrospective cohort
Heroin users



No difference in vital signs

Favours comparison over
buprenorphine



Other

Some respiratory rate and and
02 saturation changes in bupe
group vs placebo


Some desaturation with both
buprenorphine and
hydromorphone




No difference in respiratory
rate



Overdoses
DiGuisto 2004
493711535


Last printed 6/27/2017 9:29:00 PM

Favors methadone over bupe,
but not statistically significant

Agonist treatment
superior to naltrexone
1


Nielson 2008
Nielson 2007





Bupe vs Meth
Retrospective cohort.
/case control
Opioid overdose cases
Bupe vs meth
Cross-sectional
Opioid dependent
patients
Bupe vs meth


Favors bupe over methadone




Favors bupe over methadone





Prolonged QT
 Favors bupe






1 case series
and 3 case
report of
pediatric
ingestions of
bupe.

Wedam 2007

RCT of BMT/MMT/LAAM
Athanasos
2008

Cross sectional
Fanoe 2007

Cross sectional

237
Soyka
2005


RCT
BMT vs MMT


Prospective cohort/?cross
sectional
Bupe vs meth
Cross-sectional
BMT vs MMT
Cross Sectional
Bupe vs meth
Cross sectional
Bupe vs meth
Baewert 2007
Loeber 2008
Piratsu 2006
Rapeli 2007









No significant difference
between meth, bupe or
control
More U waves in methadone
group.
 Favors bupe
Cognitive and psychomotor functioning



No difference between bupe
and meth


Favors bupe



Favors bupe over MMT but not
placebo






Slightly favors bupe



Favors bupe



No fatalities, but often
lethargic and some with
respiratory depression
Both groups impaired
compared to placebo
Placebo superior to
both groups

Precipitated withdrawal
Rosado 2007
493711535

Descriptive


Last printed 6/27/2017 9:29:00 PM


Wide variety of dose of
bupe required to
2
precipitate withdrawal
from 4mg to 32mg
1 case report

Barrau 2001






Diversion
Cross sectional
BMT vs MMT



Less IV/IN with methadone


Roux 2008

Uncontrolled descriptive



Lo 2006

Uncontrolled study



Smith 2007
Guichard
2003
9 Case
reports.
Also Bell RCT
from KCQ 2-3











Descriptive study



32% of patients on
bupe maintenance had
injected bupe in 6 mos
of treatment
IV bupe skin
complications
Similar rates of abuse
of both Subutex and
Suboxone

9 case reports of IV/IN abuse
of bupe

Sexual dysfunction
4 crosssectional
studies



Favors bupe in all 4 studies


Transaminases

1 RCT, 3
case reports
and 1
uncontrolled
study (Petry
2000)
493711535



Last printed 6/27/2017 9:29:00 PM


Elevation with bupe in
uncontrolled study.
Could be associated
with IV use of bupe or
use in pre-existing liver
disease
RCT Lofwall 2005 did
not demonstrate a
difference between
Meth and Bupe, but
may not have been
3
powered for such an
outcome.
Unspecified adverse events
Magura 2009
Soyka 2008
Lange 1990
Maremmani
2007
Fiellin
2008


RCT
MMT vs BMT



RCT
MMT vs BMT
Cohort BMT vs MMT

Cohort



Uncontrolled study



“None serious”




No difference




“No difference”





Favors meth over bupe, but all
minor side effects


“no serious adverse
events”
Some other single episode case reports (seizure, pulmonary edema, hallucinations, Candida optic neuritis, gastroparesis, serotonin syndrome, cerebral hemorrhage)
493711535
Last printed 6/27/2017 9:29:00 PM
4
Thorn 1988
Samee 2004
Lintzeris 2006
Teoh 2003
Zybelberg
2000
CH to update
further
493711535






Post-op pts
Post-op pts
Effect of BZ when using
bupe
Effect of cocaine when
using bupe
Ultrasound of
gallbladder.? Can’t
distinguish meth vs bupe
pts


? Exclude (?)






















Last printed 6/27/2017 9:29:00 PM
5
B. Detailed Study Tables
Randomized Trials
Study
Ref
(S=In
# pts
summary
table)
Study Design
Intervention
Primary Outcome
Measures
Primary Outcome Results

245
Umbricht
2004
S
493711535
6 pts IV opioid
and cocaine
experienced,
but not
physically
dependent



Crossover
Blind, placebo
controlled
Lived on
inpatient
research ward
for 5-6 weeks


Placebo,
Buprenorphine
12mg SL, 2mg IV,
4mg IV, 8mg IV,
12mg IV, 16mg IV


Physiologic
measures

Last printed 6/27/2017 9:29:00 PM
High-dose bupe groups had
decreased breaths per
minute of 10 or more in 4
sessions
2 participants had
significant O2 desaturation
(at 8 and 12mg) that
resolved with “mild auditory
stimulation”
Ceiling effect was observed
in cardiorespiratory
parameters
Secondary Outcome
Measures
Secondary Outcome
Results


Participant-rated
measures


Participants
noticed a “drug
effect” (p=0.007)
with
buprenorphine
Higher scores for
“Good effects”,
“Liking” and”
“High”, but NS
“Ceiling effect”
noted for
subjective “liking”
scales
Comments


“Safe” at dose
range of up to
16mg IV
Main side effects
sedation,
nausea and
itching
Include
?
Yes
6
Study
Ref
(S=In
summary
table)
# pts
Study Design
Intervention
Primary Outcome
Measures
Primary Outcome Results
Secondary Outcome
Measures
Secondary Outcome
Results
Comments


Lofwall 2005
S
164 opioid
dependence
(IV)

RCT



BMT vs MMT
Flexible dosing
Over 16 weeks

LFTs

No difference between
medications


Vital signs
No significant
differences
between
medications

493711535
Last printed 6/27/2017 9:29:00 PM
Very
complicated
results
Looked at both
86 pts who
completed the
study and
compared to the
drop outs (78)
Only difference
in drop outs
were younger by
2.7 yrs
Study efficacy
data previously
reported (Strain
et al-in Mattick
Include
?
Yes
7
Study
Ref
(S=In
summary
table)
# pts
Study Design
Intervention
Primary Outcome
Measures
Primary Outcome Results
Secondary Outcome
Measures
Secondary Outcome
Results
Comments






238. Stoller
2001
10 heroin
dependent
S
493711535

Crossover
design






Admitted to
inpatient unit and
initially given IM
hydromorphone
(HM) 10mg QID
Placebo
10mg IM HM
Naloxone 0.25 IM
Bupe 8mg IM
Bupe 8mg SL
Bupe/naloxone
varying doses both
Self Report



Physiologic
measures
Last printed 6/27/2017 9:29:00 PM

Constipation more in bupe
(0.020)
Nausea more in bupe
(0.021)
Buprenorphine-treated
subjects also had higher
symptom ratings than
methadone treated subjects
for heart racing, often
thirsty, dry mouth, ringing in
the ears, blurred vision, skin
rash, trouble swallowing,
and dizziness/faintness
(although still low in overall
severity)

No change in resp rate
The 8mg IM bupe and
hydromorphone groups
experienced desaturation
2 highest bupe/naloxone
doses increased DBP and
HR, but not in a manner felt
to be clinically significant
(max BP 139/84) HR
increased by 10 bpm


Medical reports

No difference
between
medication


Include
?
2008 review)
Comment that
may not be
powered to
detect
differences in
LFTs
Looked at
intermediary
outcomes (LFTs
etc) but not at
clinically
significant
outcomes.
Follow up short
(16 wks)
Dosing was low
– avg 8.9mg bup
and 54 mg
methadone
Yes
8
Study
Ref
(S=In
summary
table)
# pts
Study Design
Intervention
Primary Outcome
Measures
Primary Outcome Results
Secondary Outcome
Measures
Secondary Outcome
Results
Comments
Include
?
SL and IM


Subjective
effects


IM bupe had similar agonist
effects as IM HM
IM bupe/naloxone showed
no real effect
SL bupe naloxone had
more “withdrawal”
symptoms than placebo


Strain
1997
S
493711535
8 IV opioid
dependent
volunteers

Crossover
design
Stabilized on 8mg
SL bupe over 2
weeks as
outpatient then
went inpatient.
 When inpatient,
given:
o I.M. Bupr (4, 8
or 16mg)
o I.M.
Hydromorphon
e (HM) (9 or
18mg):
o IM placebo

Physiologic
al
response(Vi
tals and
pupils)
Last printed 6/27/2017 9:29:00 PM



No difference in resp rate
9mg hydromorphone
increased HR and 16 mg
bupe increase SBP
compared to placebo
Pupils in all active groups
smaller than placebo

Subject/Observer
measures (VAS
and adjective
rating scale)


Both
hydromorphone
doses produced
similar opioid
effects (“Good
Effects”, “Liking”,
“High”)
Only 16mg dose
produced opioid
effects as strong
as the HM
injections.
No significant
effects on the
observer scale

8mg/d s.l. bupr
does not block
the opioid
agonist effects
of illicit opioids,
including more
buprenorphine.
Yes
9
Study
Ref
(S=In
summary
table)
# pts
Study Design



Wedam
2007
154
S




RCT of:
BMT (1632mg), 3x/wk
Low dose
MMT
(20mg)daily
(NR due to
dropout of
80%)
High dose
MMT (60100mg)daily
LAAM (75mg115mg)
3x/wk
All doses
individualized
except low
dose meth
Intervention
S
493711535
62
(22 BMT, 24
MMT, 16 lost
to f/u)

RCT
Primary Outcome Results
Secondary Outcome
Measures
Secondary Outcome
Results
Comments



ECGs q 4 weeks
until week 17 or
client D/C


QT interval


237
Soyka
2005
Primary Outcome
Measures


Opioid dependent
pts randomized to
enroll in BMT or
MMT
Baseline cognitive
functioning the
same.
Psychological
testing done at
weeks 8-10.
QT>470 (M) or 490 (F):
o LAAM 28%
o Meth 23%
o Bupe 0%
o P<0.001
Increase >60msec from
baseline
o LAAM: 21%
o Meth: 12%
o Bupe: 2%
o (p<0.001)
Other variations of data
presented…no difference in
outcomes from above.






Cognitive
and
psychomoto
r functioning
Last printed 6/27/2017 9:29:00 PM

BMT patients scored
significantly better in 2 out 5
tests


Subanalysis of
previous RCT of
efficacy
(Johnson 2000)
which showed
equal efficacy.
Look at
important covariates for
prolonged QT
(even though
RCT should take
care of this)
Meth and LAAM
also increased
progressively
with fixed dose
85% were using
other
substances
concomitantly at
weeks 8-10
(cannabis,
opioid, benzos).
Specific agents
not detailed
Include
?
Yes
Yes
10
Study
Ref
(S=In
summary
table)
# pts
Study Design
Intervention
Primary Outcome
Measures
Primary Outcome Results
Secondary Outcome
Measures


Magura
2009


116
S
RCT
Heroin
dependent not
on OAT
incarcerated
at Rikers
(USA) for 1090 days



S
493711535
140



Randomized,
Prospective
Clinical study







Methadone
44-50mg
Buprenorphine
9-12mg

Comments


Rearrest

NS




Reporting
for
treatment
after
release
Retention
rate
Last printed 6/27/2017 9:29:00 PM



48% bupe
14% meth
p<0.001

Completion rates at 26
weeks:
Meth 55.3%
Bup 48.4%
No sig. diff in retention rates



A/Es reported

Some others as
well

Correlation
between side
effects and drop
out rates

“None serious”

Much more
diversion
attempts with
Suboxone over
methadone (6 to
1)
“the data from
this study did not
show any
significant
difference

Include
?
NS
82% bupe
75% meth
NS
Methadone (max
70mg)
Bupe (Suboxone)
(Max 32mg)
Flex dosing up to
max

Soyka
2008
Treatment
completion
while in jail
Illicit opioid use
after release
Secondary Outcome
Results

22% of those
assigned to
bupe did not
start treatment
due to the delay
in starting bupe
All meth patients
started their
program
Took nurses 15
mins to give
bupe and 1-3
mins to give
meth
Yes
Primarily IV
heroin users
Yes
11
Study
Ref
(S=In
summary
table)
# pts
Study Design
Intervention

flexible dosing
Primary Outcome
Measures



Substance
use
WD
symptoms
Side effects
Primary Outcome Results

Secondary Outcome
Measures
Secondary Outcome
Results
16 women
ages 20-50

Randomized
double blind



Post op receipt of:
SL BUPE vs
IM ketobemidone
(synthetic opioid)

Post op receipt of
either:
-pentazocine
30mg IM
-bupe 0.3mgIM
-tramadol 100mg
IM
all q 8 hrs
S
226. Samee
2004
S
CH/PS
60 C-section
patients

RCT but
blinding not
reported




493711535


Post-op
Pain control
Vital signs
in ICU
Last printed 6/27/2017 9:29:00 PM



Bupe and pentazocine
caused respiratory
depression. Tramadol no.
Include
?
between
methadone and
buprenorphine”
No sig. diff in concomitant
drug use, WD Sx, or side
effects

244
Thorn
1988
Comments
Respiratory
parameters


Study abandoned
due to serious
late-onset
respiratory
depression in 3
women in the
bupe group who
received a
second dose of
bupe, nonresponsive to
naloxone 0.2mg
Also more
nausea and
sedation than
with tramadol

Patients had
anaesthetics,
including
fentanyl and
pancuronium
during surgery
IM dose of buprenorphine
single dose post op.
Unable to consider the
cumulative effect and
relevance to opioid
dependent population
treated with bup as an
outpatient.
No
No
12
Study
Ref
(S=In
summary
table)
# pts
Study Design
Intervention
Primary Outcome
Measures
Primary Outcome Results
Secondary Outcome
Measures
Secondary Outcome
Results

236. Sorge
2004

137

RCT
No

Lintzeris
2006 #25

16
CH/PS
Double-blind,
randomized
withinsubjects
design




493711535
Transdermal bupe
vs placebo for
chronic cancer and
noncancer pain
8 methadone
pts(30-100mg) & 8
buprenor (4-16mg)
stable x at least
2wks
Administered
diazepam
0,10mg,20mg
Single dose
counterbalanced
3 sessions, 1 wk
apart
Diazepam given at
the same time as
M/B







Physiologic
al (BP,PR,
RR,pO2);pe
rformance&
subj.measur
es(sedation)
At baseline
& q1h x 6
Last printed 6/27/2017 9:29:00 PM





Minimal physiological
effects – all conditions
10 &20mg similar effect in
M & B on subj.eff.(sedation)
M+diaz >effect on
performance than B+diaz
M+diaz significant
deterioration in reaction
time,DSST & cancellation
time;
B+diaz –significant only in
cancellation time
Buprenorphine-delay in
episodic memory measure significant
Adverse events

Overall:
o 52% bupe
gp
o 43% placebo
gp
o (NS)
Systemic side
effects (not
dermal in nature)
o 28.9% bupe
o 27.6%
placebo
o (NS)
Comments







Include
?
No difference
between groups
Transderm in
pain…not
specifically
powered for
adverse events
No
Author’s
conclusion:
concern
re:extent of
deterioration of
performance
M+diaz at therap
dose can be
associated with
considerable
impairment of
function
Single
administration ;
small sample
size; repeated
admin-tolerance
No
13
Study
Ref
(S=In
summary
table)
# pts
Study Design
Intervention

242
Teoh
1993
20
?No
Needs 2nd


Crossover
Single blind


SaarialhoKere
1987
No
493711535

12


Double Blind
Crossover
study
Administer IV
cocaine (30mg)
and IV morphine
(10mg) or saline
before and during
bupe maintenance
of either
4 or 8 mg/d
buprenorphine
Inpatient for 30
days
Administration of
bupe (0.4mg/d) or
amitriptyline (up to
75mg/d) alone and
in combination to
opioid naive
volunteers
Primary Outcome
Measures



change in
BP, pulse
RR or
temperature
Performanc
e
Respiration
(ETCO2
and minute
ventilation)
Last printed 6/27/2017 9:29:00 PM
Primary Outcome Results



Cardiovascular response to
cocaine and morphine
equivalent under drug-free
and bupe maintenance
conditions
No sig. diff in No sig. diff in
Bupr and Amitriptyline had
moderate effect on
psychomotor performance
Bupe alone does decrease
respiratory function. Some
at 2 hrs…more at 4 hrs
Secondary Outcome
Measures


EKG and
bloodwork
changes
Interactions
Secondary Outcome
Results
Comments


None

The interaction
between both
agents was mild.
Worse resp
depression with
both drugs



?BUP safe to
administer in pt
using cocaine
and opiates
Subjects were
opioid naïve
volunteers.
? Clinical
significance of
the physiologic
findings wrt
respiration
Include
?
Yes
CH says
no
No ( CH
agrees
…getting
a bit far
from our
patient
populati
on)
14
Prospective Cohort Studies
Study
# pts
Ref
Study Design
Intervention
Primary Outcome
Measures
Primary Outcome Results
Secondary Outcome
Measures
Secondary Outcome
Results
Comments



Baewert
2007
S
40
(drug of abuse
not indicated)


Prospective
open-label
controlled trial
?Crosssectional


Methadone range
21-80mg,
Buprenorphine
range 6-20
All patients were
stable on OST with
no other drug use
for past two
months


ART 2020
Standard
(Act and
React Test)
at peak
(1.5h) and
trough (20h)


Peak vs trough (both): at
trough more incorrect rx,
simple errors
Meth: at trough more
incorrect rxs, lower
perception scores
Bupe: at trough more
incorrect rxs, multiple
errors, fewer delayed rxs,
better visual structuring
scores
Meth vs Bupe: in dynamic
environment, bupe pts
scored better (based on
reaction times, and decision
making)





Lange 1990
S
493711535
18 heroin
dependent


Clinical Trial
(Not random)
Bupe 8mg OD or
8mg EOD days
19-36 after 3 day
induction to and
18days at 8mg.
Bupe then d/ced
abruptly and pts
followed for 20
days and then 4
weeks post D/C


Self-report
of adverse
effects
Last printed 6/27/2017 9:29:00 PM


No difference between the
2 groups
Probably sedation (3
reports)
Probably constipation (42
reports)


Lab measures
71% overall
showed increased
transaminases
from baseline, but
no difference
between groups


Include?
Overall scores
and
performance
indices of
reaction in a
dynamic
environment –
bupe pts scored
better than meth
pts, but controls
performed better
than both
groups (effect
more
pronounced at
trough levels)
Less than half of
pts in treatment
group had
driving license,
all controls did.
Concomitant
drug or alcohol
users excluded
Poor study. N of
18 for 3 mos
No statistical
data
15
Study
Ref
# pts
Study Design
Intervention
Primary Outcome
Measures
Primary Outcome Results
Secondary Outcome
Measures

Maremmani
2007
S
493711535


213 patients in
Italy

Prospective
cohort
DSM-IV opioid
dependence

On BMT (avg dose
7.6mg) or MMT
(avg dose 69.4mg)
for 3 mos.
Measures at 3
months (baseline)
and 12 months
Combo of:
 Quality of
Life
questionnair
e (QLQ)
 Symptom
checklist
(SCL) 90
 DSM-IV
GAF scale
Last printed 6/27/2017 9:29:00 PM


QoL 3 mos
o BMT: 299.62
o MMT: 258.96
o (p=0.03)
o [350 is “fairly
successful”]
QoL 12 mos
o NR (“NS”)

Secondary Outcome
Results
Retention in
treatment at 12
mos




2
BMT: 78.3%
MMT: 74.76%
P=0.818
Side Effects





# pts: BMT 16%
MMT 6.5%
P=0.02
# effects: p=0.54
(all “minor”)
Comments




Clean UDS at 3
mos and 12 mos

p NS
Include?
At 3 mos BMT
had less illness
severity (better
QoL and work)
than MMT
Authors
accounted for
significant
baseline
covariates
Only measured
those still in
treatment at 12
mos.
16
Retrospective Cohort Studies
Study
# pts
Study Design
Ref
Intervention
Primary Outcome
Measures
Primary Outcome Results
Secondary Outcome
Measures
Secondary Outcome
Results

Diguisto
2004

1244 heroin
users, 394
person years
S

Observational
study of
patients
entering &
leaving opioid
treatment



Death rates
(In mortality
table)



Nielsen
2008
S
493711535
243 opioid
overdose
cases; 228
unique pts

Retrospective
cohort/Case
control
From 20012005; data
mining of
ambulance
records for
calls involving
bupe or meth


Presentatio
n severity


19 times higher in patients
leaving treatment than
patients in treatment
Much higher OD rate (7.6x)
on leaving treatment for
naltrexone than for
methadone or
buprenorphine (p=0.018)


Poly-drug
use
Last printed 6/27/2017 9:29:00 PM


Include?
3 x higher in pts
leaving treatment
than in patients on
treatment (for
overdoses).
5 heroin OD (nonfatal) for 402 bup
patients, vs 0
heroin OD for 403
meth patients.
(p=0.08)
Meth 5x more likely to be
unconscious (GCS=3)
Resp rate lower for meth
(p=0.011)
33% of bupe calls involved
IV use of bupe
Bupe vs meth

Serious adverse
events
Comments

Methadone 3x more likely
to have BZ or other drugs
used
17
Cross-sectional Studies
Study
# pts
Ref
Al-Gommer
2007
91 opioid
dependent
Study Design

Crosssectional
S
Bliesener
2005
S
493711535



Heroin (30)
BMT x 6 mos (28)
MMT x 6 mos (33)
Primary Outcome
Measures
 Loyola
University
Clinicspecial
history
sheet for
men
 Reports of
sex drive,
sexual
fantasy,
morning
erection,
premature
ejaculation
etc
Primary Outcome Results


Fewer patients on
burprenorphine vs heroin or
methadone experienced
sexual dysfunction.
Statistically significant
Secondary Outcome
Measures

Secondary Outcome
Results
54 on OAT
51 controls

128

Crosssectional
Cross
sectional




17 Bupe x 6 mos
37 meth x 6 mos
On MMT or BMT.
Both compared to
community
references



Sexual
function


Sexual
dysfunction
[IIEF scores
(<25 = ED)]
and the “EF
domain”
Last printed 6/27/2017 9:29:00 PM

Lower frequency of sexual
dysfunction in bup men vs
meth (p<0.0001)
Partnered men on MMT
had lower IIEF scores
(50.4) compared to
community reference
(61.4). p<0.0001
No difference between
partnered men on bupe and
community references

Comments


S
Hallinan
2008
Intervention
Testosterone
level

Yes
Higher level in bup
than meth
(statistically
significant)
Bup level same as
controls
Yes



Include?
Authors
acknowledge
they were not
able to account
for all
confounders in
the multivariate
analysis
Yes
18
Study
Ref
# pts
Study Design
Intervention

Quaglio
2008

201 heroin
dependence


Cross
sectional
Multi-centre
Italy


S
MMT or BMT for
30 days
Median bupe
dose: 6mg/d (124mg)
Median meth
dose: 40mg/d
(10mg-180mg)



Hallinan
2007
CH Aug
201/0
Needs
second
Primary Outcome
Measures
103 on opioid
maintenance

Cross
sectional

On MMT (84) or
BMT (19)
Erectile
Dysfunction
(ED) in BUP
(n=58%) vs
METH
(n=42%)
users
Total
testosterone
(TT) either
prior to or
within 60
mins of
bupe dosing
Primary Outcome Results



Univariate analysis
demonstrated lower rates of
ED in BUP pts (36.3%) vs
METH pts
(51.6%)(P=0.018) [not
confirmed with multivariate
analysis]
No difference in severe ED
(around 18% per group)
64.5% of methadone and
27.8% of bupe patients had
TT levels below the
reference range (Adjusted
p<0.001)
Secondary Outcome
Measures


Effect of other
factors
Secondary Outcome
Results
 Dose had no effect
 Higher rates of ED
if:
o Living alone
o Living with
heroin user
o No steady
partner
o Bi/homosexua
l
o Depressed
Comments



Athanasos
2008
S
493711535
71


Observational
?CrossSectional

35 methadone
patients (MMT) &
19 buprenorphine
(BMT) patients &
17 control patients
 ECG
characteristics
Last printed 6/27/2017 9:29:00 PM

No difference in QTc
between controls,
methadone, and bup
patients, but QTc longer
(but still normal) in
methadone patients
> 60mg/d,
Methadone patient 8x more
likely to have U waves


Yes
Yes


First trial of this
size using
validated test
that shows some
predictors for ED
ED could effect
retention in
treatment
Include?
“given the
association
between U
waves and
cardiac
arrhythmia, the
prevalence of U
waves in the
higher dose
methadone
group is a matter
of concern”
19
Study
Ref
# pts
Study Design

Fanoe 2007
450

S
Heroin users
on methadone
or bup
Crosssectional
study/intervie
ws
Intervention

Cross-sectional,
patients had ECG
& asked about
syncope
Barrau 2001
CH Needs
second
493711535
Methadone
N= 424
high dose bup
N= 616


1462 subjects
S
Primary Outcome
Measures

Crosssectional
survey

BMT vs MMT in
France
Primary Outcome Results

Sociodemographi
c variables
and druguse over
previous
week
Last printed 6/27/2017 9:29:00 PM

Not relevant
Secondary Outcome
Measures
 28% of
methadone pts
had prolonged
QT.
 Meth dose
increased QT by
0.140 ms/mg.
 No bup patients
had long QT
(440 ms).
 50 mg or more
of methadone
had OR 1.2 (1.11.4) of syncope.

Secondary Outcome
Results
Include?


Non-SL routes
of taking bupe or
meth
Comments


BMT: 100/616 IV
and 23/616 nasal
MMT: no IV or
nasal use
P<0.001
20
Study
Ref
# pts
Study Design
Intervention
Primary Outcome
Measures
Primary Outcome Results
Secondary Outcome
Measures
Secondary Outcome
Results
 More illicit use in
"no protocol"
group:



Within protocol
bupe group
(N=559) vs no
protocol (N=57)
high dose bupe
group






224. Roux
2008

111


493711535
Crosssectional
Office-based
buprenorphine
Pts receving
bupe for 3
months
Does not


Pt interviewed at
baseline and 6
months in 2005
Bupe
injection
Last printed 6/27/2017 9:29:00 PM


36/111 (32%) injected bupe
since treatment initiation
At first interview 6/111
injected every bupe dose


Bupe dose

Comments
Include?
IV use of bupe:
28% vs 15%
p<0.01)
Nasal use of bupe:
19% vs 2%
(p<0.001)
Heroin: 33% vs
10% (p unclear)
Cocaine: 19% vs
7% (p<0.001)
Psychotropics (incl
BZ): 44% vs 20%
(p unclear)
More IV 40% vs
21% (p<0.001)
Similar statistical
findings of above
when bupe
administered by
GP vs “centre”
follow up.
Median bupe dose
6mg
26/111 (14%)
found this
inadequate
Yes
21
Study
Ref
# pts
Study Design
Intervention
Primary Outcome
Measures
Primary Outcome Results

specify, but
appears all
were IVDUs
(97% had
used heroin
and cocaine in
their lives)

Factors
associated
with bupe
injection


Guichard
2003
CH Aug
3010

339

Cross
sectional
survey
France

Needs 2nd

58% methadone
treatment (avg
dose 67mg)
42%
buprenorphine
treatment (avg
dose 10.7mg)

Injection
practices


Obadia 2001
CH Aug
3010
Needs 2nd
493711535


343

Cross
sectional
survey
France


IDUs
32.7% were on
buprenorphine
treatment

Injection
practices
Last printed 6/27/2017 9:29:00 PM

Multivariate analysis:
o Perceiving dose as
inadequate OR 2.7
(1.1-7.0)
o Also those with suicidal
ideation OR 2.6 (1.25.7)
o The higher the dose of
bupe the greater the
risk of injection OR
1.07 (1.02-1.14) for
each 1mg increase
15% methadone patients
had used IV drugs in the
past one month. 40% of
bupe patients (p<0.01)
<1% of methadone patients
had injected methadone.
36% of bupe pts had
injected bupe
After logistic regression,
injection was associated
with being prescribed
buprenorphine (OR 4.9,
2.8-8.8)
Higher doses of
buprenorphine equaled
more injection (OR 6.2, 2.019.7)
Overall 57.7% had injected
buprenorphine in the
previous 6 mos
70.5% of those in a bupe
program had IV misuse of
bupe in the previous 6 mos
on the program
Secondary Outcome
Measures
Secondary Outcome
Results
Comments








Include?
Buprenorphine
monoproduct
51.8% of
methadone
patients
monitored by GP
77.5% of bupe
patients followed
by GP
Buprenorphine
monoproduct
22
Study
Ref
Vidal-Trecan
2003
CH Aug
3010
# pts
Study Design

404

Cross
sectional
survey
France
Intervention

Needs 2nd
Jenkinson
2005
CH Aug
3010
156


Cross
sectional
Australia
Consecutive
admission for
opioid dependent
pts for
buprenorophine
maintenance

Sample of IDUs
from database


Sample of IDUs
Homeless vs
housed
Primary Outcome
Measures


Frequency
of injection
of
buprenorphi
ne
Frequency
of
buprenorphi
ne injection
Primary Outcome Results


46.5% at least once
49.4% first injected within a
month of the first
prescription
Secondary Outcome
Measures

Secondary Outcome
Results

Comments

Buprenorphine
monoproduct

Buprenorphine
monoproduct
Being on
methadone was
protective of
injecting bupe
(?due to
precipitated
withdrawal)



37% had injected bupe
47% injected another
person‘s bupe



Homeless men had more
injection of bupe than
housed men (67% vs 47%,
p<0.001)


Needs 2nd
Blanchon
2003
CH Aug
3010
779


Cross
sectional
France

Frequency
of bupe
injection

Buprenorphine
monoproduct


In India in 1980s
Purely
descriptive…no
statistical work
done
whatsoever
Include?
Needs 2nd
116.
Chowdhury
1990
493711535

997
Cross
sectional at 3
time points
over 3 years

None

Buprenorphi
ne abuse
Last printed 6/27/2017 9:29:00 PM



1987: 0%
1988: 4.8%
1989: 10.6%

Those who
become
addicted to bupe
after inpt detox

1989: 23.7%
No
23
Study
Ref
# pts
Study Design
Intervention
Primary Outcome
Measures
Primary Outcome Results

54 IV opioid
Loeber 2008
dependent
patients
S


Crosssectional

2 groups on either
BUP (N=24) or
METH (N=30)
Patients on stable
dose for 14 days
before testing




Piratsu 2006
69
S
493711535

Cross sectional
Various
psychological tests
on BMT (18) vs
MMT (30) vs non
opioid dependent
controls (21)



Scores on
neuropsych
ological
assessment
tools

Gambling
Test (test of
decision
making)

WSCT
IQ
Visual
retention
Last printed 6/27/2017 9:29:00 PM

No difference in results b/w
2 groups.
Cognitive impairment
increases with increasing
METH dose but not with
increasing bupe dose
Both groups impaired
compared to normative
control samples
BMT better (<0.05)
compared to MMT. NS wrt
control
Secondary Outcome
Measures

BMT=MMT and both
generally significantly worse
than non-opioid control
Comments

Higher baseline
head injuries in
Meth group.
Otherwise
groups same

Baseline groups
fairly similar.
Gambling test
not just a
function of IQ as
this was found
to be equal b/w
MMT and BMT




Secondary Outcome
Results

Include?
24
Study
Ref
# pts
Study Design
Intervention
Primary Outcome
Measures
Primary Outcome Results
Secondary Outcome
Measures
Secondary Outcome
Results
Comments



Rapeli 2007
50
S

Crosssectional
Methadone (dose
range 30-105mg)
vs.
buprenorphine/nal
oxone (dose range
8-24mg)

Attention,
working
memory,
verbal
memory



493711535
Last printed 6/27/2017 9:29:00 PM
Reaction time: meth pt
slower vs bupe, control
(P<0.01)
Seems dose dep (high dose
mean 67, low dose mean
40) (P=0.025)
Verbal memory: both gps
slower vs controls
(B:P=0.05, M:P=0.01)
Story recall: meth slower vs
control



Include?
Methadone
patients in early
OST (first 6
weeks)
displayed
cognitive
performance
deficits
compared to
buprenorphine/n
aloxone,
controls. This
may be dosedependent, and
influenced by
concurrent use
of benzos
Bup was drug of
abuse in MMT
and BMT pts
and continued to
be abused
during study,as
well as
concurrent
benzo abuse
high in both
groups MMT pts
still in
stabilization
phase (first 6
week)
25
Study
Ref
Nielsen
2007
# pts
Study Design

250
opioid
dependent
patients
S
Self –report
cross
sectional
survey of
opioid
dependent
patients
Intervention

Study
Questionnaire for
current and former
Bupr and MMT
users.
Primary Outcome
Measures

Reports of
Benzo use
among Bupr
MT clients.
Primary Outcome Results


247. Petry
2000

120

Cross
sectional

Patients in Bupe
clinic

Transamina
ses


493711535
Last printed 6/27/2017 9:29:00 PM
2/3 of Bupr MT clients used
benzos too. Most were from
illicit/multiple sources.
Non-hepatitis:
o ALT change of zero
o AST change of 0.5
Hx of hepatitis:
o ALT + 8.5 (p=0.04)
o AST + 9.5 (p=0.06)
Those who had significant
transaminases (ALT 200+
and AST 150+) (N=9). 3/9
actually improved
14 subjects had ALT/AST
go up 100.
Secondary Outcome
Measures

Comparison of
opioid overdose
freq. among
MMT vs BMT
clients.
Secondary Outcome
Results
 10x more MMT
clients reported
opioid toxicity then
Bupr users.
 Overdose:
o Meth 6.7%
o Bupe 1.2%
o (OR 10, 1.68219)
 Extreme
drowsiness:
o Meth 42%
o Bupe 24%
o (OR 2.71,
1.55-4.72)
 Unconsciousness
o Meth 7.3%
o Bupe 3%
o (OR 2.44,
0.86-7.58)


Bupe dose

AST increased OR
1.23 (1.02-1.50)
per mg increase in
bupe dose
Same not seen for
ALT
Comments





Include?
Doses of
Bupr/MMT were
unknown.
Only 20% said
they only got
benzos from
illicit sources.
Rest were at
least partially
prescribed.
Recruited from
needle
exchange pgms.
? Clinical
significance
May not be
related to
bupe…no
control
Yes
26
Study
Ref
# pts
Study Design
Intervention

Zylberberg
2000
36/
334

Prospective



36 HCV infected
pts on
methadone(21)/bu
prenorphine(15)
?Doses
Durarion of
substitution: 15+/8mon
(males)
21+-35month
(females)
July ‘95-Dec ‘97
Primary Outcome
Measures
Primary Outcome Results


Ultrasound
of bile duct;
pts with
abnormalitie
s:
endoscopic
ultrasound


8% (3) of pts had >9mm
dilatation (9mm=N)
Unsure if the 3 were
methadone or
buprenorphine patients
Not age related (all
50)endoscopic ultrasound
rulled out obstruction of
billiary tract thus authors
assume that dilatation was
a result of opioid
substitution;
Secondary Outcome
Measures

Secondary Outcome
Results
Comments

No


150. Ho
2009
130



IV bupe misuse
Cutanoeous
complicatio
ns




Cellulitis 29%
Thrombophlebitis 20%
Abscess 18%
Others…



493711535
Last printed 6/27/2017 9:29:00 PM
Include?
Many also
injected benzos
Not sure if these
persons were
actually being
prescribed the
bupe they were
injecting
No reason to
think that this is
unique to bupe
No
27
Case reports
Study
Ref
# pts
Study Design
Intervention


Herve 2004
7

Case reports

6 pts on SL
bupren; 1 injection
Prescribed 212mg/d
Pts on
buprenorphine for
30-153 days prior
to symptom onset
Primary Outcome
Measures
 Average
ALT level
39x
normal(968); no
signs of
hepatic
failure
 Anti-HCV
antibodies
+ve in all
pts & HCVRNA +ve in
2pts
 Other
virology &
immunologc
al tests
negative
Primary Outcome Results





98. Berson
2001
105 Bruce
2007
493711535
4

Case series



4

Case reports
Buprenorphine
Bup/Naloxone
All four patients
had acute HCV
infection at BUP
initiation


Cases of
severe
hepatitis
AST/ALT
Last printed 6/27/2017 9:29:00 PM
Global RUCAM/CIOMS
score =6 in 5pts & 7in2pts
= probable buprenorphineinduced hepatitis
Resolved without treatment
by 3rd week. 3 pts with 50%
dose reduction and 4 pts
without dose reduction;
All thought to be due to IV
(and one ?SL case with
concurrent acetaminophen)

Improved when IV bupe
was D/Ced (even if SL bupe
continued)

All four patients showed
normalization in AST/ALT
levels over 60 days
Secondary Outcome
Measures
Secondary Outcome
Results






Comments
Only 2 of 7 had
detectable HCV
RNA…?due to
insensitivity of the assay
Include?
Yes
Yes
Yes
28
Study
Ref
Sekar
1987
148
Hayes
2008
# pts
1
86
Study Design


Intervention

Case Report
Case Series

s.l. bupr (0.2mg SL
q 6 hrs for pain)
+ po benzo use
Primary Outcome
Measures



Primary Outcome Results

Outcome
measures
BUP
Overdose in
paeds

54/86 developed toxicity


No deaths,
Lethary (55%), vomiting
(21%), miosis (21%), resp
dep (7%) ,
agitation/irritability, pallor
and coma (2%)
Mean time to onset 64 min,
< 50% req’d naloxone


137. Gaulier
2004
1

115
Cho
2006
Crakowski
1999
493711535
1
1

Case report of
4 year old girl
who
swallowed
4mg of her
father’s
prescribed
Subutex.
Case report of
accidental non
lethal
ingestion of
BUP in 9
month old
infan
Case report of
22 y.o. male

None



N/A

Nasal inhalation
abuse of 8mg
bupe

Last printed 6/27/2017 9:29:00 PM
Bupr MT user suffered
significant respiratory
depression after g.a. and po
benzos

“Mild consequences…child
D/Ced in 24hrs”


Secondary Outcome
Measures


None
Comments
Include?
G.A. complication
significant? But N=1
No
Only 7% of kids
experienced serious
CNS/resp SE. 2% coma
Yes
Largest
study of
All kids < 2 years old its kind to
ingesting > 2mg should
date
be referred to ER




Was given charcoal in ER

Reversal required a
considerable amount of
naloxone (5mg)

Authors feel opoids
should generally be
cardioprotective. This is a
paradoxical case (pt had
hyperhomocysteinemia)

MI
None
Secondary Outcome
Results

Yes
No
CH says
yes
29
Study
Ref
# pts
Study Design
Intervention
Primary Outcome
Measures
Primary Outcome Results


Strang
letter




Yeo 2006
8

Descriptive
case series of
8 patients
admitted in
Singapore
Mar-Aug 2005
with
complications
of subutex
abuse


Subutex

190. Loo
2005
4
233 Sharma
2005
1
228
Schwarz
2007
493711535



Case report
Case report
Case report



Myofasciits and
polyneuritis related
to IM bup abuse
ER observation in
paediatric OD
Adverse
effects of
subutex
abuse

Bupe
injection
into groin
causing
vascular
complicatio
ns (ie.
pseudoaneu
rysns)
patient report and provider
observation of increased IN
abuse of bup in local
population
AE included arterial
pseudoaneurysm, infective
venous thrombus, venous
thrombus, end arterial
spasms, and sympathetic
dystrophy
Secondary Outcome
Measures


Secondary Outcome
Results
Comments


Include?
No
Authors wonder if bupe
as a drug makes this
more likely than other
opioids.
They call for ban on
Subutex and discuss
possible improvements
with Suboxone
Authors call for tight
regulation over Subutex
Limb
complicatio
ns from
parental
abuse of
Subutex





2 vascular complications, 1
severe hand abscess, and
1 median nerve injury


Limitation inherent to
case reports
No
Cannot draw conclusions
about outcomes due to
IVDU alone or IVDU of
Subutex



Same as above
No

Case report of accidental
non lethal ingestion of
BUP (8mg) in 2 year child
No
No naloxone used
Last printed 6/27/2017 9:29:00 PM
30
Study
Ref
235
Singh
2004
# pts
Study Design

18
Intervention
Primary Outcome
Measures
Primary Outcome Results

Case series of
IV bupe
dependence
from 19871990




All IV BUP use (1-7 mg)
often mixed with BZD
BUP was used as cheaper
substitute for heroin and
injected with BZD to
increase euphoria
6/18 got bupe from MD
Secondary Outcome
Measures


Seet
2006
2
132. Feeney
2003
231. Seet
2005
1
1



Case Reports
Case Report
Case report


493711535
1

Case Report

Single dose of
Diverted BUP
causing
precipitated
withdrawal
Complicatio
ns reported

Groin tissue
necrosis

Diffuse
cystic
leukoencep
halopathy


119 Clark
2002
Iv injection of bupr.

Last printed 6/27/2017 9:29:00 PM
Secondary Outcome
Results


Rhabdomyolysis and sciatic
neuropathy

Followed IV use of
buprenorphine (obtained by
distracting pharmacist and
diverting one of the
dispensed bupe tabs). She
was receiving 16mg bupe
EOD


From IV bupe. 18M
injecting bupe into neck






Outcome

Comments
After detox 8/18
were abstaining at
This was bupe being
last follow up visit
prescribed
for analgesia
(but no UDSs) and
only ¼ came for
the full year
Both treated with
conservative
measures.
Include?
No
Severe complications, but
is only 2 case reports.
Both patients were
prescribed the bupe for
heroin dependence
In France: 57.7% of IDUs
surveyed had injected
bupe in the past 6
months. Of the 32% on
BMT 70% had injected
bupe in that time period
Obadia. Addiction
2001;96: 267
No
No
No
Stable BUP tx 1 yr–
reinitiated heroin use and
hoarded BUP tbs.
Single
Several weeks of no
case BUP, took 88mg over 24 speaks to
period – no respiratory
Safety
depression – highlights
safety profile of BUP
31
Study
Ref
243.
Thammaku
mpee 1994
# pts
1
Study Design


Case report
0.2mg SL
bupe by nurse
without
prescription
151
Isenberg
2008
1

Case report
153.
Jakuboviz
2007
1

Case report

Case reportwoman on
bupe for 8 yrs
and cannabis
and cigarette
smoker with
cerebral
hemorrage
and
vasospasm
222. Renard
2008
1
Paraskevaid
1 case report
es
493711535

letter
Intervention

Primary Outcome
Measures


Dose and route of
Bup/N not given


Inpt bupe detox



Primary Outcome Results

ADR


Last printed 6/27/2017 9:29:00 PM
Pulmonary edema
Secondary Outcome
Measures

Secondary Outcome
Results


Serotonin syndrome



Gastroparesis



Cerbral hemorrhage



1 case report of auditory
hallucination following
analgesic use of 200mg
(??????) s/L bup , lead to
near fatal self harm


Comments
Authors state that this
has never been
described previously with
bupe but is possible with
other opoids
No blood levels done to
confirm amount taken
on morphine
(?prescribed); urinalysis
+ve for methadone
(source? on MMT?);
Include?
No
No
No
Authors are concluding
that one of the drugs
likely caused this as it all
improved when the doses
were reduced.
No
No
32
Post-mortem file reviews
Study
# pts
Ref
Study Design

216.
Schifano
2005
493711535
43


Retrospective
analysis of
coroner
reports.
UK
1980 - 2002
Intervention
Primary Outcome
Measures
Primary Outcome Results


None

Deaths
Last printed 6/27/2017 9:29:00 PM

For 7/43 deaths (16%),
Bupr was the only drug
involved in death.
Most deaths were in
combination with Benzos
23/45 (51%) and other
opioids 17/43 (40%).
Secondary Outcome
Measures
Secondary Outcome
Results
Comments
Include?
“Largest collection of
bupe mortality data from
UK”

?Seizures with
high dose bupe

High mortality for Bupr
only deaths.
Yes
No clear correlation
between amt of bupr
rx’ed and frequency of
deaths
33
Clinical Reviews
Study
# pts
Ref
Study Design
Intervention
Primary Outcome
Measures
Primary Outcome Results
Secondary Outcome
Measures



Auriacombe
2004

Clinical review
of bupe in
France
Not
“systematic”


Overdose
rates in
France(pg
9-10).
[Authors
reference
government
data and
Auriacombe
2001.]

1995-1999 decrease by
79%, from 564 to 120
annual overdose deaths




493711535
Last printed 6/27/2017 9:29:00 PM
Bupe deaths
compared to
methadone [Ref
Auriacombe
2001]
Bupe-related
deaths
(?Modified from
Kintz)
Number of
opioid-abusing
individuals in
OAT treatment
A/Es
Secondary Outcome
Results
 Methadone deaths
10x higher
(Auriacombe
2001)
 1996-2000 137
deaths. Only one
was bupe alone.
Avg 3
psychotropics/pt.
BZ 78%, cannabis
50%, neuroleptics
32%, alcohol 29%
 From 1995-1999
increased from
2,000/yr to
60,000/yr
 No fatalities
among infants who
have ingested
 Candida optic
neuritis
 IV bupe=abcesses
 IV bupe =Arterial
ischemia
 IV bupe=non-fatal
resp depression
 Hepatitis: usually if
Hep C or if IV
Comments
Include?
MORTALITY
Consistent decrease in
overdose deaths. Author
agrees that one may not
be able to conclude bupe
is the reason.
State that bupe
prescribing actually
began in 1994, where
there was a very high
number of OD deaths
Comment that Suboxone
may help with the
diversion problem.
34
Uncontrolled studies
Study
# pts
Ref
Singal 2008
19
Study Design

No
Interventional
study
Intervention

Maintenance Bupr.
dose followed by
three extra doses
of Bupr.
Primary Outcome
Measures


171
Mintzer
2004

8

No

Baker 2006
No
223 Rosado
2007
50

Double blind
crossover
design.
Opioid
dependent
volunteers
Prospective,
open-label,
with-in subject
study
? cohort



16

Descriptive

Descriptive
study of bupe
patients who
S
Fiellin
2008
493711535
53


Suboxone given
for 7d in doses of
8/2, 16/4, or 32/8
and impairment
assessed. No
comparison
groups.
Buprenorphine for
2 weeks, then
bupe and ARV for
5-15 days
Escalating doses
of SL Bup/nalox in
pts initially
stabilized on
methadone
100mg/d
Suboxone
maintenance
2-5 yrs in



Psychomoto
r effects of
giving extra
Bupr.
Performanc
e on a
battery of
mental
function
tests of
psychomoto
r speed.
(DSST) and
TMT, others
QT intervals
on ECGs
Establish
bupe dose
required to
precipitate
withdrawal
Retention in
treatment
Last printed 6/27/2017 9:29:00 PM
Primary Outcome Results
Secondary Outcome
Measures


No significant difference in
performance.


There was no significant
impairment found in any
group


No QT interval increase on
bupe alone.
Statistical, but not clinically
significant QT interval
increase on bup + ARV
Greatest increase in QT
with bup + dalvirdine or
ritonivir







6 – did not complete
4 – 4mg/1mg
2 – 8mg/2mg
1 – 32mg/8mg
3 – no wd up to max dose
of 32



1 year: 28/53
2 year: 20/53
3 year: 13/53
Secondary Outcome
Results



Determine if this
dose, split in half
and separated
by two hours,
will be better
tolerated than
single dose
Other measures
Improvement of
performance on
some psychomotor
tests.
Comments
No placebo control
Include?
CH Says
no as no
control
group

In–pt setting with no other
drugs used.

CH says
“Buprenorphine/naloxone
no as
did not alter QTc
uncontroll
intervals, therefore the
ed
combination might offer
an advantage over
?Special
MMT…”
Pops


Subjective
measures found to
be less severe,
objective
measures same
Client satisfaction
with tx: 90%.
No
Yes
Note poor retention.
Study is done in primary
Yes.
35
had already
achieved at
least 9
consecutive
weeks of
abstinence
with bupe over
6 months
S
53

S
Descriptive
Study
Smith 2007

77

Descriptive
Study in USA

Post
Marketing
Surveillance
study
Observational
S
5551


230 Seet
2007
493711535


Lo 2006
221
Ray
2004

51 IV BUP
“Abusers”

Chart Reviews
2002-2005


treatment
Flex dose. Max
24mg
Dispensed thrice
weekly, weekly or
q 2 weeks
depending on
stability


Outcomes of
parental Subutex
users admitted to
a Singapore
hospital in a 5 mo
period in 2005.
Data from 18
poison control
centres covering
103 million people
from 2003 to 2005


BUP for opiate
dependence in
India
IV Abusers of BUP

Percentage
of opioid
negative
urines
Analyze
surgical
complicatio
ns of this
group
related to tx
of iv Bupr
use.
Rate of
intentional
improper
use of
Subutex/Su
boxone
Study
adverse
effects of
‘new’ 2 mg
dose
Length of
hospital
stay
Last printed 6/27/2017 9:29:00 PM


4 year: 6/53
5 year: 3/53




9% - used illicit opioids
4% used cocaine.
2% used benzos.
- 38% 2 yr retention.

Transaminases

17% required surgery for
grafts, debridements.
Ischaemia and gangrene of
the limbs and digits were
common.

Type of
complication


Adverse events


No elevation of
serum
transaminases.

Most
complications are
localized skin
infections.







Suboxone: 0.16 abuse
cases/1000 Rx’s.
Subutex: 0.08 abuse
cases/1000 Rx’s.
SE were mild and did not
require cessation of therapy
44.5% reported feeling
“high”
No deaths reported
Prolonged hospital stay
correlated with: infective
endocarditis, venous
thrombosis, respiratory
failure

“No serious
adverse events”
Magnitude of
difference
between
Subutex and
Suboxone.




care. No comparison
group therefore not for
effectiveness, but yes for
adverse events
This is specifically
Suboxone
No comment on whether
subjects were prescribed
the bupe
Suboxone has higher
7.8% of abuse
rates of abuse but the
cases involved
number of cases of
Subutex, 92.2%
abuse is low relative to
involved Suboxone
the number of Rx’s
which reflects the
dispensed.
percentages of the
prescriptions
Unclear if “abuse
written
cases”=IV abuse?
Poorly controlled study
<1% of patients had
bloodwork
very low doses used
median 3 mg
Study of hospital stay
Yes
Yes
No
No
36
Pinto 2008
(Attitudes)
No
493711535

Survey &
interview

NA. Sample of
patients who
chose bupe or
MMT


Patient
beliefs
Last printed 6/27/2017 9:29:00 PM
Meth pts chose because
they were more familiar with
it bupe because they
thought it would be easier
to stop, less intoxication.


Pts rely on their own &
peer’s experience than
on agencies
CH says
no as not
an
adverse
effect
study
37