Download An Overview of Suboxone and Its Relevance to the Inner City Health

An Overview of Suboxone and Its Relevance to the Inner City Health Program
M.R. is a patient that has been with the Inner City Health Program for approximately six
months. She is a chronic user of heroin and morphine, and satisfies the criteria for
opioid dependence. In the last few years, she has been on and off of methadone. She
finds it difficult to attend her regular methadone appointments and often uses morphine
or heroin bought on the street on top of her methadone, putting her at risk for overdose.
Currently, she is presenting to the health care team because she is “tired of it all, tired of
being dope-sick, tired of going out every morning to look for drugs.” She has been off of
methadone for two weeks though she continues to want maintenance treatment. Her
methadone provider is on holiday for the next two weeks, and in the meantime she is
requesting opioid from the health care team. Suboxone is considered as a potential
treatment option.
Introduction
Opioid dependence is a major individual and public health issue. It is known that opioid
addiction put patients at risk for other diseases as well, such as HIV, hepatitis C, and
tuberculosis.i In addition, chronic opioid dependence by definition impairs functioning
on social, political, and economic levels. At the Inner City Health Program, staff are
witness to the devastating medical and psychosocial effects of opioid dependence on a
daily basis.
Regardless of how abstinence is achieved, opioid dependence is considered a chronic
illness. Few people remain abstinent after detoxifcation, and we have few effective
strategies for preventing relapse. It is well known in the literature that maintenance
therapy is more effective than detoxification therapy in treating opioid dependence. In
maintenance therapy compared to detoxification, patients are more likely to stay in the
program, less likely to take other opioids, display decreased criminal activity, and have a
decreased rate of HIV transmission.ii
Currently in Canada, the only maintenance therapy for opioid dependence covered by
Ontario Drug Benefits is methadone. Unfortunately, in Ottawa, we face long waiting lists
for patients to enter into treatment with methadone. In addition, as the example above of
patient M. R. illustrates, not all patients are as suitable as others for long-term methadone
treatment.
Suboxone is a new combination pill with buprenorphine and naloxone that was recently
approved in Canada for the treatment of opioid dependence. This drug is not yet covered
under Ontario Drug Benefits, and costs $90-460 per month plus dispensing fees. There is
hope that this medication will soon be covered by Ontario Drug Benefits, as it is currently
under review. Some patients in Canada have been using Suboxone because it is covered
under their private drug plan, or they are willing to pay because the cost is less than the
opioids they are currently buying in the street.
While funding is currently a barrier, the efficacy of suboxone, its safety profile, and its
prescription model that is easily amenable to primary care shows great promise. In the
United States, regulation that has allowed physicians to prescribe suboxone in their
outpatient offices has expanded the availability of opioid dependence treatment
significantly.iii This paper will provide an introduction to suboxone and its use in
primary care in the hope that this medication may one day expand the availability of
effective and safe opioid dependence treatment in Ottawa through primary care agencies
such as the Inner City Health Project.
Pharmacology
Suboxone is made by Schering-Plough Canada and comes in formulations of
buprenorphine 2mg with naloxone 0.5mg and buprenorphine 8mg with naloxone 2mg.
Buprenorphine is the opioid component of the combination pill. Pharmacologically,
buprenorphine is a partial mu-opioid receptor agonist and a kappa receptor antagonist.iv
As a partial agonist at the mu-opioid receptor, buprenorphine only partially stimulates
this receptor to produce opioid-like effects. This means it produces milder sensations of
euphoria, sedation, analgesia, and less respiratory depression, hypotension, nausea,
constipation, and papillary constriction than other opioids. By contrast, heroin,
methadone, morphine, and oxycodone are full agonists at the mu-opioid receptor. The
partial agonist effect on the mu-opioid receptor leads to a “ceiling effect” property of
buprenorphine, where increasing the dose of buprenorphine has little to no physical
effects.v This reduces suboxone’s potential for abuse and makes it safer in overdose.vi
In addition, buprenorphine has a very high affinity for the mu-opioid receptor, and thus
blocks the effect of other opioid agonists.vii Therefore, if another opioid agonist is taken
with buprenorphine it will have little effect, and taking buprenorphine while on another
opioid agonist can precipitate withdrawal. This makes patients on suboxone less likely to
abuse other opioids. Finally, the tight adherence of buprenorphine to the mu-opioid
receptor is associated with a slow dissociation from that receptor, leading to a longer
duration of action than other opioids (except methadone, which has the longest duration
of action).viii
According to the manufacturer, the half-life of buprenorphine is thirty-seven hours.ix
However, in practice there is inter-individual variation such that the half-life is twentyfour to sixty-nine hours.x As would be expected, the effective plasma concentration in
individual patients at any one time on any given dose is therefore difficult to predict.xi It
starts to work within half and hour to an hour and peaks at one to four hours. The
duration of action is dose dependent, being up to twelve hours at low doses and up to two
to three days at higher doses. Unlike methadone, which can take weeks to titrate,
suboxone reaches a steady state after three to seven days.xii
The slow dissociation of buprenorphine also creates a milder withdrawal syndrome
compared to other opioids, including methadone.xiii
Finally, buprenorphine acts as antagonist at the kappa-opioid receptor, which
theoretically may have antipsychotic and antidepressant effects. However, there have not
been studies that show that this is a clinically relevant effect of buprenorphine in the
literature.
Naloxone, the other component of suboxone, is a competitive opioid antagonist at the mu,
kappa, and sigma receptors.xiv Naloxone does not have clinical effects when
administered sublingually for two reasons: naloxone is poorly absorbed by the sublingual
route, and buprenorphine has a much longer half life than naloxone.xv However, when
injected, it can precipitate withdrawal. Thus, in one study, it was found that of those who
had injected suboxone, eighty percent had a “bad experience,” and the same study found
that the buprenorphine and naloxone combination of suboxone had less than half the
street value of buprenorphine alone.xvi Thus, the addition of naloxone to the
buprenorphine makes suboxone less attractive as a drug of abuse. The combination pill
of buprenorphine with naloxone has been shown to be equally effective to buprenorphine
alone in treating opioid dependence.xvii
Prescribing
1. USES
Buprenorphine is used to treat opioid dependence through maintenance or withdrawal
therapy. On at least one occasion, it has also been successfully used to reverse a heroine
overdose.xviii However, reversal of overdose is an off-label use of buprenorphine.
One study looking at opioid-addicted youth found that, over a twelve week period,
maintenance therapy with suboxone was more effective than detoxification treatment
with suboxone including better retention in treatment (p<0.001), less opioid use
(p<0.001), less injecting (p<0.001), and less nonstudy addiction treatment (p<0.001).xix
This reflects studies in the adult population, which have determined that the most
effective treatment for opioid dependence is maintenance therapy plus counseling.xx
Suboxone has been prescribed at Centre for Addiction and Mental Health (CAMH) in
Toronto since about 2003.xxi Thirty thousand prescriptions for suboxone were written in
Ontario in the first six months of 2009.xxii Thus, there is experience within this province
in suboxone, and organizations such as CAMH are available for support.
Buprenorphine’s analgesic potency is about twenty-five to forty times greater than
morphine.xxiii This is important in terms of estimating the dose of suboxone a patient will
need, however, currently it is recommended that for safety reasons, all patients be started
at the low dose of 4mg of suboxone and tapered up.
2. ADVERSE EFFECTS
Adverse effects of suboxone are dose-related and similar to other opioids, including
constipation, headache, sedation, euphoria, sweating, nausea, insomnia, and orthostatic
hypotension. Serious adverse events in studies include elevated LFTs in 4.4%, depression
including suicidal ideation or suicide attempt (2.6%), infection (1.0%), accident (1.0%),
abscess (0.9%), chest pain (0.6%), and GI issues (0.5%); these occurred in patients on
high doses, and most could be attributed to some other cause than suboxone, such as
those with raised LFTs mostly had hepatitis, and those with depression were all at one
centre so may have been a centre-specific phenomenon.xxiv
Suboxone can also induce withdrawal, as it displaces other opioids in the patient’s system
due to its strong association to the mu-opioid receptor. Symptoms of withdrawal include
muscle and joint pains, restlessness, irritability, nausea, vomiting, diarrhea, and insomnia.
Signs of withdrawal are diaphoresis, rhinorrhea, piloerection, tachycardia, hypertension.
Suboxone can also cause hepatic abnormalities, and it is wise to do baseline liver
function tests and subsequent tests every three to six months for monitoring.xxv While
theoretically patients with hepatic disease would clear buprenorphine less efficiently,
limited data suggest that clinically no dose adjustments are required in patients with
hepatic disease.xxvi Suboxone is well tolerated in patients with renal failure.
Buprenorphine has been used in France since about 1996, for maintenance therapy.
Overall, the safety profile has been excellent, however, there have been at least twenty
deaths attributable to overdose by parentaral use while taking other CNS depressants
(these deaths were in patients taking buprenorphine without the nalaxone
combination).xxvii When overdose does occur, either with suboxone alone or in
combination with other respiratory depressants, the respiratory depression may be
prolonged and more difficult to treat with naloxone due to buprenorphine’s high affinity
for the mu-opioid receptor.xxviii Even where there are milder symptoms, patients may
need to be admitted to hospital for monitoring, as symptoms of overdose can persist for
twelve to twenty-four hours.xxix
Certainly, suboxone does represent a hazard to pediatric patients, and can lead to
significant centreal nervous system and respiratory depressant effects.xxx Care should be
taken to ensure that any take-home doses are stored away from children in child-proof
containers, and patients should be counseled in this regard.
3. INTERACTIONS WITH OTHER MEDICATIONS
Buprenorphine is metabolized by P450(CYP)3A4 in the liver to the active metabolite
nubuprenorphine.xxxi This notable in terms of possible adverse effects when suboxone is
prescribed with other medications. Inducers of CYP3A4, which would decrease the
buprenorphine level, include phenytoin, carbamazepine, phenobarbital, and rifampin.
Inhibitors, which would increase the buprenorphine level, include ketoconazole,
fluvoxamine, erythromycin, indinavir, saquinavire.
For patients who are HIV positive, it is important to note that suboxone interacts less with
HART medications than methadone.
4. PRESCRIBING
In terms of detailed information on how to prescribed suboxone for maintenance
treatment, please see the prescribing algorithm (see Appendix A).
To use suboxone for detoxification, induction of suboxone should be achieved until
withdrawal symptoms are under control. The dose can then be tapered over three to ten
days or longer.xxxii If naltrexone management is to be used after suboxone tapering, it
should not be started for at least seven days after the last dose of suboxone.xxxiii A longer
tapering schedule does not appear to improve outcomes in withdrawal treatment.xxxiv
Besides a physician and nurses to prescribe and administer suboxone, a suboxone
program requires other interdisciplinary team members. As is emphasized in the
prescribing algorithm, when used for maintenance therapy prescriptions of suboxone
should be accompanied by a full program including counseling. Counseling should focus
on behaviour modification, social reintegration, coping skills, and motivation.xxxv On-site
urine drug screening is very valuable, whether carried out by a lab technician or a nurse.
A strong working relationship with a pharmacy that has experience with methadone or
suboxone is an asset. Frequent communication between the pharmacist and the rest of
the health care team is key in terms of safety.
A debate that is logistically relevant to Inner City Health is whether or not patients must
always be observed when taking suboxone. One RCT showed that retention in the
maintenance program and heroin use were not significantly different between groups that
were observed taking suboxone and those that were unobserved.xxxvi At the same time,
unobserved dosing was much more cost effective.xxxvii Even more convenient for patients
and prescribers is that suboxone can be dispensed less frequently than once daily, down
to thrice weekly, once the patient is on a stable dose and this does not appear to decrease
efficacy.xxxviii
Comparison to Methadone
Buprenorphine is as effective as methadone in treating opioid dependence.xxxix This has
been well established, and clearly gives suboxone an important role in alleviating the
methadone provider shortage.
When used for withdrawal from opioids, a Cochrane review concluded that more data is
required, but current studies indicate that withdrawal from buprenorphine may be more
successful than withdrawal from methadone.xl Certainly, compared to clonidine or
lofexidine, buprenorphine is more effective in reducing the symptoms of withdrawal, and
patients on buprenorphine treatment are more likely to stay in treatment and to complete
withdrawal treatment.xli
Suboxone is easier to prescribe than methadone. It takes a few days to one week to titrate
suboxone to an effective dose, whereas methadone titration can take weeks.xlii Similarly,
suboxone is can be more easily and quickly tapered than methadone.xliii
According to a Cochrane review, the severity of withdrawal from buprenorphine and
methadone are the same, but withdrawal may resolve more quickly with
buprenorphine.xliv
Suboxone has been shown to be safer in overdose than methadone.xlv This is very
significant, as the risk of overdose is so high amongst methadone users. For patients at
high risk of overdose, such as the patient case at the beginning of this paper of M. R.,
suboxone may be a better choice. However, it must be remembered that if suboxone is
combined with other respiratory depressants, such as alcohol or benzodiazepines, it can
still be fatal secondary to respiratory depression.
When suboxone is prescribed at maximal doses, it may not always be sufficient for
patients who use high doses of opioid daily. In this case, the recommendation is to
switch treatment to methadone, which can be titrated to a higher dose than suboxone.xlvi
For patients who use very high amounts of opioid, the best treatment may still be
methadone if you anticipate they will not be able to achieve full remission on suboxone.
For pregnant patients, methadone is still the gold standard of treatment.
Suboxone can be prescribed in any outpatient office. The CPSO does have guidelines for
physicians prescribing suboxone that recommend that physicians have experience with
addictions and education in suboxone before prescribing it (see Appendix B). For many
patients, such as those at Inner City Health, it is more convenient for them to receive
suboxone from their primary practitioner rather than having a special addictions doctor,
which is required for methadone. This allows for them to receive more holistic care.
Office-based treatment has many other advantages, including reduced stigma, increased
availability, more flexibility to cater to individual patients’ needs, and limiting of
patients’ contact with other drug addicted patients.xlvii
Conclusion
Suboxone holds a lot of promise as an alternative to methadone that can be prescribed
within the Inner City Health framework. It is safe, effective, and relatively easy to
manage and prescribe.
However, there are a few obstacles that can be expected in implementing a suboxone
maintenance and/or detoxification program. Firstly, maintenance treatment is by
definition long-term, even lifelong, and patients at Inner City Health are with the program
for variable periods of time. Practitioners that are willing to take on these patients when
they leave the Inner City Health Program and continue their suboxone treatment will
have to be set-up before therapy can start. In addition, the demands of supervised dosing
and frequent dosing and urine drug screening may prove to be heavy demands on already
hard worked staff at Inner City Health.
On the other hand, the advantages of the Inner City Health set-up for prescribing
suboxone are many. Maintenance and withdrawal treatment should always be
accompanied by supportive counseling and attention to all of the social determinants of
health – areas in which Inner City Health excels with its dedicated nursing and support
staff that know the patients well. Inner City Health also has ample experience in
addictions and concurrent disorders that they can bring to prescribing this new therapy.
As with any new medication, there will be a learning curve if suboxone is introduced to
the Inner City Health Program. Please access the below resources for more information
and continued support.
Further training:
• SAMHSA training module:
http://buprenorphine.samhsa.gov/tip43_curriculum.pdf
• SAMHSA guidelines: http://buprenorphine.samhsa.gov/Bup_Guidelines.pdf
i
Bridge TP, Fudala PJ, Herbert S, Leiderman DB. Safety and health policy considerations related to the use
of buprenorphine/naloxone as an office-based treatment for opiate dependence. Drug Alcohol Depend.
2003 May 21;70(2 Suppl):S79-85.
ii
Collins GB, McAllister MS. Buprenorphine maintenance: A new treatment for opioid dependence.
Cleveland Clinic Journal of Medicine 2007;74(7):514-520.
iii
Collins GB, McAllister MS. Buprenorphine maintenance: A new treatment for opioid dependence.
Cleveland Clinic Journal of Medicine 2007;74(7):514-520.
iv
Schering-Plough Canada I. SuboxoneTM Product Monograph. 2007.
v
Walsh SL, Preston KL, Stitzer ML, et al. Clinical pharmacology of buprenorphine: Ceiling effects at high
doses. Clin Pharmacol Ther 1994;55:569-580.
vi
Collins GB, McAllister MS. Buprenorphine maintenance: A new treatment for opioid dependence.
Cleveland Clinic Journal of Medicine 2007;74(7):514-520.
Cicero TJ, Inciardi JA. Potential for abuse of buprenorphine in office-based treatment of opioid
dependence. N Eng J Med 2005;353:1863-1865
vii
Schering-Plough Canada I. SuboxoneTM Product Monograph. 2007.
viii
Schering-Plough Canada I. SuboxoneTM Product Monograph. 2007.
ix
Schering-Plough Canada I. SuboxoneTM Product Monograph. 2007.
x
Elkader A, Sproule BA. Buprenorphine: Clinical pharmacokinetics in the treatment of opioid dependence.
Clinical Pharmacokinetics 2005;44:661-680.
xi
Chiang CN, Hawks RL.Pharmacokinetics of the combination tablet of buprenorphine and naloxone. Drug
Alcohol Depend. 2003 May 21;70(2 Suppl):S39-47.
xii
Schering-Plough Canada I. SuboxoneTM Product Monograph. 2007.
xiii
Isaac P, Janecek E, Kalvik A, Sproute B. Buprenorphine: a new treatment for opioid dependence.
Pharmacy Connection 2008; CAMH.
xiv
Helm II S, Trescot AM, Colson H, et al. Opioid antagonists, partial agonists, and agonists/antagonists:
the role of office-based detoxification. Pain Physician 2008;11:225-235.
xv
Chiang CN, Hawks RL.Pharmacokinetics of the combination tablet of buprenorphine and naloxone. Drug
Alcohol Depend. 2003 May 21;70(2 Suppl):S39-47.
xvi
Alho H, Sinclair D, Vuori E, Holopainen A. Abuse liability of buprenorphine-naloxone tablets in
untreated IV drug users. Drug Alcohol Depend. 2007 Apr 17;88(1):75-8.
xvii
Chiang CN, Hawks RL.Pharmacokinetics of the combination tablet of buprenorphine and naloxone.
Drug Alcohol Depend. 2003 May 21;70(2 Suppl):S39-47.
xviii
Welsh C, Sherman SG, Tobin KE. A case of heroin overdose reversed by sublingually administered
buprenorphine/naloxone (Suboxone). Addiction. 2008 Jul;103(7):1226-8.
xix
Woody GE, Poole SA, Subramaniam G, Dugosh K, Bogenschutz M, Abbott P, Patkar A, Publicker M,
McCain K, Potter JS, Forman R, Vetter V, McNicholas L, Blaine J, Lynch KG, Fudala P. Extended vs
short-term buprenorphine-naloxone for treatment of opioid-addicted youth: a randomized trial. JAMA.
2008 Nov 5;300(17):2003-11.
xx
Collins GB, McAllister MS. Buprenorphine maintenance: A new treatment for opioid dependence.
Cleveland Clinic Journal of Medicine 2007;74(7):514-520.
xxi
Isaac P, Janecek E, Kalvik A, Sproute B. Buprenorphine: a new treatment for opioid dependence.
Pharmacy Connection 2008; CAMH.
xxii
Silversides, A. Ontario takes aim at painkiller abuse. CMAJ 2009; 181(8):E141.
xxiii
Sporer KA. Buprenorphine: A primary for emergency physicians. Ann of Emerg Med 2004;43(5):580583
xxiv
Bridge TP, Fudala PJ, Herbert S, Leiderman DB. Safety and health policy considerations related to the
use of buprenorphine/naloxone as an office-based treatment for opiate dependence. Drug and Alcohol
Depend 2003;70(suppl):S79-S85
xxv
Collins GB, McAllister MS. Buprenorphine maintenance: A new treatment for opioid dependence.
Cleveland Clinic Journal of Medicine 2007;74(7):514-520.
xxvi
Bridge TP, Fudala PJ, Herbert S, Leiderman DB. Safety and health policy considerations related to the
use of buprenorphine/naloxone as an office-based treatment for opiate dependence. Drug and Alcohol
Depend 2003;70(suppl):S79-S85
xxvii
Bridge TP, Fudala PJ, Herbert S, Leiderman DB. Safety and health policy considerations related to the
use of buprenorphine/naloxone as an office-based treatment for opiate dependence. Drug and Alcohol
Depend 2003;70(suppl):S79-S85
xxviii
Isaac P, Janecek E, Kalvik A, Sproute B. Buprenorphine: a new treatment for opioid dependence.
Pharmacy Connection 2008; CAMH.
xxix
Sporer KA. Buprenorphine: A primary for emergency physicians. Ann of Emerg Med 2004;43(5):580583
xxx
Schwarz KA, Cantrell FL, Vohra RB, Clark RF. Suboxone (buprenorphine/naloxone) toxicity in
pediatric patients: a case report. Pediatr Emerg Care. 2007 Sep;23(9):651-2.
xxxi
Elkader A, Sproule BA. Buprenorphine: Clinical pharmacokinetics in the treatment of opioid
dependence. Clinical Pharmacokinetics 2005;44:661-680.
xxxii
Collins GB, McAllister MS. Buprenorphine maintenance: A new treatment for opioid dependence.
Cleveland Clinic Journal of Medicine 2007;74(7):514-520.
xxxiii
Collins GB, McAllister MS. Buprenorphine maintenance: A new treatment for opioid dependence.
Cleveland Clinic Journal of Medicine 2007;74(7):514-520.
xxxiv
Orman JS, Keating GM. Buprenorphine/Naloxone: a review of its use in the treatment of opioid
dependence. Drugs 2009;69(5):577-607.
xxxv
Collins GB, McAllister MS. Buprenorphine maintenance: A new treatment for opioid dependence.
Cleveland Clinic Journal of Medicine 2007;74(7):514-520.
xxxvi
Bell J, Shanahan M, Mutch C, Rea F, Ryan A, Batey R, Dunlop A, Winstock A. A randomized trial of
effectiveness and cost-effectiveness of observed versus unobserved administration of buprenorphinenaloxone for heroin dependence. Addiction. 2007 Dec;102(12):1899-907. Epub 2007 Sep 3.
xxxvii
Bell J, Shanahan M, Mutch C, Rea F, Ryan A, Batey R, Dunlop A, Winstock A. A randomized trial of
effectiveness and cost-effectiveness of observed versus unobserved administration of buprenorphinenaloxone for heroin dependence. Addiction. 2007 Dec;102(12):1899-907. Epub 2007 Sep 3.
xxxviii
Orman JS, Keating GM. Spotlight on buprenorphine/naloxone in the treatment of opioid dependence.
CNS Drugs. 2009 Oct 1;23(10):899-902.
xxxix
West SL, O’Neal KK, Graham CW. A meta-analysis comparing the effectiveness of buprenorphine
and methadone. J of Subst Abuse 2000;12:405-414
Ling W, Wesson DR. Clinical efficacy of buprenorphine: Comparisons to methadone and placebo. Drug
Alcohol Depend 2003;70(suppl):S49-S57
xl
Gowing L, Ali R, White JM. Buprenorphine for the management of opioid withdrawal. The Cochrane
Library: John Wiley & Sons Ltd; 2009, issue 4.
xli
Gowing L, Ali R, White JM. Buprenorphine for the management of opioid withdrawal. The Cochrane
Library: John Wiley & Sons Ltd; 2009, issue 4.
xlii
Isaac P, Janecek E, Kalvik A, Sproute B. Buprenorphine: a new treatment for opioid dependence.
Pharmacy Connection 2008; CAMH.
xliii
Isaac P, Janecek E, Kalvik A, Sproute B. Buprenorphine: a new treatment for opioid dependence.
Pharmacy Connection 2008; CAMH.
xliv
Gowing L, Ali R, White JM. Buprenorphine for the management of opioid withdrawal. The Cochrane
Library: John Wiley & Sons Ltd; 2009, issue 4.
xlv
Robinson SE. Buprenorphine-containing treatments. Place in the management of opioid addiction. CNS
Drugs 2006;29: 697-712.
xlvi
Isaac P, Janecek E, Kalvik A, Sproute B. Buprenorphine: a new treatment for opioid dependence.
Pharmacy Connection 2008; CAMH.
xlvii
Bridge TP, Fudala PJ, Herbert S, Leiderman DB. Safety and health policy considerations related to the
use of buprenorphine/naloxone as an office-based treatment for opiate dependence. Drug and Alcohol
Depend 2003;70(suppl):S79-S85
Appendix A: Suboxone Protocol for Ottawa Inner City Health
This protocol is adapted from the following:
1. the online educational module for Suboxone CMEi
2. CPSO policy on buprenorphine hydrochlorideii
3. CAMH toolkit for buprenorphine and methadone providersiii
Training for nurses and nurse practitioners:
1. nurses should have experience and training in opioid addictions
2. complete the online suboxone CME training program at www.suboxonecme.ca
3. attend a clinical observership for one day methadone clinics to become familiar
with the current treatment of chronic opioid dependence
Initial Assessment: Identifying patients who may benefit from suboxone and
gathering patient information
1. History
a.) inquire about substance use, directly inquiring about each substance:
- opioids
- stimulants, sedatives, cannabis
- alcohol
- tobacco
- buprenorphine, methadone
b.) for each substance that is used:
- age at first use
- quantity, frequency, routes of administration, time of last use
- whether withdrawal symptoms have been experienced
- consequences of use: job, family, legal
- the stage of change the patient is in regarding quitting the
substance (see Prochaska’s Stages of Change below)
- past attempts at treatment
c.) past medical history:
- all chronic conditions, past hospitalizations, surgeries
- HIV/Hepatitis status
- ask whether immunized against Hepatitis A and B
- if IVDU, ask about complications such as abscesses,
endocarditis, septic arthritis
- obstetrics and gyne history: LMP, regularity of periods, birth
control, pregnancies, births
- psychiatric history: anxiety, depression, mania, psychosis, eating
disorders, personality disorders, suicide attempts, suicidal
ideation
d.) medications:
- document all medications, asking in particular about prescription
antipsychotics, sleeping agents, anxiolytics
-
e.)
f.)
g.)
h.)
i.)
if on methadone, document length of treatment, number of
relapses, S/E of treatment, attempts at overdose on methadone,
use of other opioids while on methadone
- inquire about allergies to medications
social history:
- housing situation, including whether patient lives with other drug
users
- whether the patient lives with or cares for children
- employment
- drug coverage
- domestic violence
- high risk activities such as unprotected sex, sharing needles,
impaired driving
- legal issues
- current social supports and likelihood of patient accessing them
effectively
family history of substance abuse
obtain collateral hx, only if consent from the patient is given, by
contacting family/friends and obtaining past medical records
consider completing a standardized tool, such as the baseline Maudsley
Addiction Profile (available online for free at
http://www.iop.kcl.ac.uk/iopweb/blob/downloads/locator/l_346_MAP.pdf
)
for a good initial assessment, see the sample form used at CAMH in
Toronto (see Toolkit item A)
Actions depending on above:
• if not immunized for Hepatitis A and B, offer this to patient
• if of childbearing age and no desire for pregnancy, counsel regarding birth
control
• begin process of optimizing chronic medical conditions
• according to need for housing and social support, refer patient to appropriate
social services
• consider involving CAS if children are involved for protection and support
• consider filling out MOT form regarding concerns about impaired driving if
patient discloses impaired driving
• consider suboxone only if patient meets DSMIV criteria for opioid dependence,
not simply opioid use or abuse:
-
DSMIV Criteria for substance dependence: maladaptive pattern of substance use
leading to clinically significant impairment or distress as manifested by ≥3
occurring at any time in the same 12 month period:
tolerance (need for increased amount to achieve intoxication or diminished
effect with same amount of substance)
withdrawal/use to avoid withdrawal
taken in larger amount or over longer period than intended
persistent desire or unsuccessful efforts to cut down
-
•
if patient has opioid dependence, consider suggesting suboxone only if the patient
is in the contemplation or planning stage of quitting; if pre-contemplative, refer
for further counseling
-
•
•
•
•
•
•
excessive time to procure, use substance, or recover from its effects
important interests/activities given up or reduced
continued use despite physical/psychological problem caused/exacerbated by
substance
Prochaska’s stages of change:
precontemplation
contemplation
preparation
action
maintenance
termination (see the excellent American Family Physician review article on
the stages of change available for free at
http://www.aafp.org/afp/20000301/1409.html)
if using opioids along with sedatives such as benzodiazepines and alcohol, the
patient is not safe to use suboxone until they cease using sedatives due to the
increased risk of respiratory depression, coma, and even death
pregnant patients should be referred for methadone
HIV positive patients should be referred for suboxone because there are less
interaction with HAART compared to methadone
counsel patient regarding their choice of methadone vs suboxone if eligible for
both
if using methadone, the patient is not eligible to switch to suboxone if methadone
treatment is progressing well. In communication with the patient’s methadone
provider, consider a change to suboxone only if:
- the patient is experiencing significant side effects from
methadone
- the patient is at risk of overdose
- the patient is using other opioids on top of methadone regularly
- the patient is failing methadone treatment i.e. relapsing very
often
- the patient has been informed and understands that the
methadone needs to be tapered first and this will take time
currently suboxone is not covered by ODSB, and if the patient does not have drug
coverage, they would need to be willing and able to afford $90-460 a month for
suboxone
2. Physical Exam
a.) vital signs
b.) general appearance
- euphoria/dysphoria
- motor retardation
- slowed/slurred/pressured speech
c.)
d.)
e.)
f.)
g.)
h.)
i.)
j.)
k.)
- sedation
- affect
consider MMSE
head and neck
- cervical lymph nodes
- evidence of thrush
cardiac
- murmurs
- indications of endocarditis: splinter hemorrhages in nails,
janeway lesions
respiratory
- signs of pneumonia, COPD, TB
abdominal
- signs of chronic liver disease: jaundice, hepatosplenomegaly,
ascites, pedal edema, asterixis, palmar erythema, leukonycia,
spider nevi, gynecomastia, testicular atrophy
pelvic: consider pap test and/or STI screening if indicated
peripheral vascular
dermatological
- skin and soft tissue infections
- evidence of IVDU
- evidence of Kaposi’s sarcoma
neurological
- pupils
- gait
- observe for tremor: action, intention, rest
- cerebellar testing: tandem gait, finger-to-nose, heel-to-shin,
dysdiadokinesis
3. Investigations
a.) baseline bloodwork: CBC with differential, creatinine, urea, electrolytes,
LFTs
b.) urine pregnancy test
c.) urine toxicology screening
d.) offer and counsel regarding HIV, hepatitis B and C, and syphilis testing
e.) consider Mantoux test if risk factors
f.) consider CXR if querying TB, aspiration pneumonia
g.) consider ECG if on methadone to identify prolonged QT interval
Action on above: refer to physician with results of physical exam and investigations.
Managing Treatment Initiation: Follow-up in the first two months of treatment
1. obtain a copy of the written contract signed by the patient and physician (see
Toolkit item B for a sample contract); review terms of contract with patient as
needed
2. the first dose of suboxone should be administered by a physician who then
follows that patient for the next 24hrs (see Initiation of Suboxone Appendix C)
- observation of withdrawal symptoms within the first 45-90min after the
administration of suboxone indicates precipitated withdrawal and requires
physician management to manage withdrawal symptoms with non-opioid,
non-sedating agents
- observation of withdrawal symptoms 5-24hrs after the first dose of
suboxone indicates inadequate dosage of suboxone and requires physician
management to increase suboxone
3. the physician will monitor dosage of suboxone and may increase the dose
incrementally with the suboxone dose never exceeding 24mg SL OD
4. daily administration of suboxone
- confirm the patient’s identity
- the sublingual tablet takes 2-10min to dissolve; observe the patient in a
private area to ensure the entire dose is taken
- record the time and date of the dose in a patient log
- withhold dose if patient displays signs of intoxication and contact the
physician
- do not replace a dose of suboxone, even if the patient swallows or vomits
it
5. missed doses of suboxone
- if misses <3 days of suboxone therapy, document reason for missing and
continue at regular dose
- if misses >3 days of suboxone therapy, needs full reassessment by
physician and re-induction with suboxone
6. urine drug screening
- performed twice weekly to weekly
- do not observe the patient voiding; to test for adulteration of urine, check that
urine is at body temperature and pH is 4.5-8
7. supportive counseling
8. monitoring for adverse events, which are most commonly due to withdrawal or
agonist effects:
Location
Body as a
Whole
Cardiovascular
System
Digestive
System
Central
Nervous
System (CNS)
Musculoskelet
al System
Metabolism
Common Adverse events (≥5%)
Headache, pain, withdrawal syndrome, infection, back pain,
flu syndrome, abdominal pain, accidental injury,
asthenia, chills, fever
Vasodilation
Constipation, nausea, vomiting, diarrhea, dyspepsia, tooth
disorder
Insomnia, depression, anxiety, nervousness, somnolence,
dizziness, paresthesia
Myalgia
Peripheral Edema
and Nutritional
Disorders
Respiratory
System
Skin
Rhinitis, pharyngitis, increased cough
Sweating
9. Report adverse events to Health Canada
10. continue to optimize other medical conditions
11. continue to offer social supports
Action depending on above:
• inform physician if you suspect diversion of suboxone
• inform physician of every positive drug screen
• inform physician if you suspect adulteration of urine drug screens
• inform physician of missed doses of suboxone
• inform physician of adverse effects
Managing Long-Term Treatment: Follow-up during the maintenance period of
treatment
1. administration of suboxone
- the physician may start to dose suboxone every other day or three times a
week once a stable dose has been achieved
2. tapering suboxone should be done by a physician (see Tapering of Suboxone,
Appendix D). During tapering, it is important to monitor:
- whether the patient is using other opioids or other drugs
- medical condition
- psychiatric condition
- psychosocial functioning
3. urine drug screening
- urine drug screening should continue on a weekly basis until there has been six
months of negative screens
- after six months of negative screens, start screening biweekly and consider
monthly screening
4. continue to optimize other medical conditions
5. continue to offer social supports
Action depending on above:
• inform physician if you suspect diversion of suboxone
• inform physician of every positive drug screen
Managing Withdrawal: Follow narcotic withdrawal protocol
Action for above: contact patient’s physician prescriber of Suboxone
i
CPC Healthcare Communications for Scherling-Plough Canada. Suboxone Education
Program. Accessed at www.suboxonecme.ca on Feb 24th 2010.
ii
CPSO. Buprenorphine Hydrochloride for the Treatment of Opioid Dependence. 2007.
Accessed at http://www.cpso.on.ca/policies/policies/default.aspx?ID=1826 on Feb 26th
2010.
iii
CAMH. The CAMH Toolkit for Buprenorphine and Methadone Providers. Accessed at
http://www.camh.net/Publications/Resources_for_Professionals/clinic_toolkit_methadon
e/clinic_toolkit_methadone.html on Feb 25th 2010.
Appendix B: CPSO Physician Requirements to Prescribe Suboxone
Physician training recommendations by the CPSOi:
a.) physicians do not need to complete a section 56 methadone exemption1
from Health Canada to prescribe suboxone, but the CPSO recommends
that physicians obtain one
b.) the CPSO recommends the following training:
- successful completion of a prescribing course in buprenorphine that
provides appropriate training for treating opioid dependency
- completion of a one-day clinical observership of an opioid-dependency
practice e.g. where methadone and/or buprenorphine are currently
prescribed
- ongoing CME in opioid-dependency treatment and/or addiction medicine
c.) there are no guidelines currently for suboxone by the CPSO; physicians
are expected to refer to the 2005 Methadone guidelines
d.) buprenorphine is a narcotic, therefore its prescription must comply with
the Controlled Drugs and Substances Act
i
CPSO. Buprenorphine Hydrochloride for the Treatment of Opioid Dependence. 2007.
Accessed at http://www.cpso.on.ca/policies/policies/default.aspx?ID=1826 on Feb 26th,
2010.
Appendix C: Initiation of Suboxone Maintenance Therapy
This protocol is adapted from the following:
1. the online educational module for Suboxone CMEi
2. CPSO policy on buprenorphine hydrochlorideii
3. CAMH toolkit for buprenorphine and methadone providersiii
1. arrange for early morning dosing of suboxone so that withdrawal symptoms can
be monitored through the day
2. do a urine toxicology screen prior to initiation
3. ensure the patient has taken no sedatives recently and reinforce the danger of
taking sedatives with suboxone
4. consider relative and absolute contraindicaions:
a.) relative contraindications: benzodiazepine use
b.) absolute contraindications: breastfeeding, pregnancy
c.) other opioids should not be used for analgesic relief, as they will not be
effective and this may result in the patient overdosing
5. consider type of opioid addiction:
- if the patient is taking heroin or other short-acting opioids, suboxone should not
be started until at least 4hrs after the last dose of opioid and preferably once
withdrawal symptoms have begun to present themselves
- if the patient is taking methadone, the dose of methadone should be tapered to
30mg per day first and then suboxone should not be started until at least 24hrs
after the last dose of methadone and preferably once withdrawal symptoms have
begun to present themselves -> this should be done in consultation with the
patient’s methadone prescriber
6. prescriptions must specify the following:
- date
- doctor’s name, address, prescribing number
- name of drug
- dosage in numbers and words
- start and end dates
- days to be observed and days for carries
- patient’s name and address
- pharmacy name – as the patient should always be using the same pharmacy for
safety and so the physician can communicate with their pharmacist
- physician’s signature and full name
- no refills are allowed
- a new prescription must be written if the patient is switching pharmacies
7. start every patient on a 4mg SL dose of suboxone as a starting dose
8. observe the patient taking suboxone sublingually until the medication has fully
dissolved
9. see patient approximately 90min after administering the first dose -> if
experiencing withdrawal symptoms, this is precipitated withdrawal
- reassure the patient that these symptoms will resolve within a few hours
-
emphasize that using another opioid will not alleviate symptoms and will interfere
with the induction process
- offer non-sedating, non-opioid symptomatic treatments e.g. anti-emetics,
clonidine, NSAIDs, anti-diarrheals
10. be available to the patient in the next 24hrs if they should start to experience
withdrawal symptoms that start after the first 4hrs of treatment, as this is
indicative of acute withdrawal and a higher dose of suboxone is needed
- reassure the patient that the dose of suboxone will be titrated up
- may provide another 4mg SL dose of suboxone in the first 24hrs
11. titration of suboxone dose
- maximum dose of suboxone is 24mg SL OD
- less opioid use and better treatment retention at doses >16mg SL OD
- example of a monitored induction from suboxone training program:
Day
1
2
3
4
5
6+
-
•
•
•
i
Potential Regime
4 mg
6 mg
8 mg
10 mg
12 mg
Dose titration stops once
patient is stable and
not experiencing withdrawal.
Daily Dose
8 mg
4-10 mg
6-12 mg
8-14 mg
10-16 mg
16-18 mg
during initiation, monitor the patient on a daily basis
once the dose of suboxone has stabilized, the patient may choose to have every
other day or three times weekly dosing of suboxone
every other day dosing: every other day twice the individually titrated dose is
given, never exceeding more than 24mg SL OD
three times weekly dosing: Monday and Wednesday twice the individually titrated
dose is given, and Friday three times the individually titrated dose is given, never
exceeding more than 24mg SL OD
in the first two months of therapy, take-home doses are only allowed on weekends
and statutory holidays
after at least two months of therapy, can consider take-home doses of suboxone
ensure the patient has a safe place to store the medication
consider specifying childproof packaging on the prescription
missed doses:
<3 days of maintenance therapy missed -> continue on same dose, reassess
stability, document reasons for missing doses
>3 days of maintenance therapy missed -> fully reassess the patient, begin
induction again
CPC Healthcare Communications for Scherling-Plough Canada. Suboxone Education Program. Accessed
at www.suboxonecme.ca on Feb 24th 2010.
ii
CPSO. Buprenorphine Hydrochloride for the Treatment of Opioid Dependence. 2007. Accessed at
http://www.cpso.on.ca/policies/policies/default.aspx?ID=1826 on Feb 26th 2010.
iii
CAMH. The CAMH Toolkit for Buprenorphine and Methadone Providers. Accessed at
http://www.camh.net/Publications/Resources_for_Professionals/clinic_toolkit_methadone/clinic_toolkit_m
ethadone.html on Feb 25th 2010.
Appendix D: Tapering of Suboxone
1. determine the likelihood of success that the patient will remain drug-free after
tapering by first addressing poor prognostic factors:
- continues to use other opioids or other drugs
- unstable medical condition
- unstable psychiatric condition
- poor psychosocial functioning
- continues to be surrounded by same environment or elements of the same
environment they associate with using
2. patients who are pregnant and likely to use again should not have their suboxone
tapered
3. the patient must be fully informed about the process of tapering, and expectations
must be discussed
4. a plan should be made for increasing monitoring and assessments
5. if the tapering is gradual, which can take up to one year, the patient should not
need supplementary medications
6. have a plan for post-tapering treatment options e.g. long-term counseling,
psychiatric follow-up, medical follow-up
7. to taper, according to the Suboxone education module:
Daily Dose
>16 mg
4-16 mg
Progressively reduce dose by:
2-4 mg/week
2 mg/week
Addiction Medicine First Assessment Form
1 Client Data
Name: _______________________________________ MRN: ___________ Date: _______________
DOB:
________/________/_____ ___
Age: _____
Phone : (
) ______________________
Address: ___________________________________________________________________________
ODB#: __________________________ Family Physician: ___________________________________
Specialist(s): _______________________________________________________________________
Referral Source: _________________________ Physician’s Phone: (
) _______________________
Emergency Contact Name: __________________________ Phone: (
) _______________________
2 Confidentiality
Please review the following information with the client, answer any questions he or she may
have about confidentiality and ask for a signature.
Everything that you tell the clinic staff is confidential except under the
following circumstances, when we must report something you tell us to the
appropriate authority:
• If we suspect that a child is being abused or neglected, it is the law that
we report this information.
• If you reveal to the staff that you intend to harm another person, we are
obliged to protect that person by notifying the appropriate authority.
• If a court subpoenas your chart we must release it to the party that
requests it.
• If you become suicidal or homicidal, or are unable to take care of yourself
due to a psychiatric condition, you might be held against your will to be
assessed by a psychiatrist.
• If it is suspected that you are unable to drive a car due to a medical
condition (which includes intoxication from alcohol or drugs), we are
obliged to notify the Ministry of Transportation of this and may
confiscate your car keys.
• Certain infectious diseases, when detected, must be reported to the
Public Health Department. Examples include tuberculosis and HIV.
Confidentiality has been explained to me and my questions about it have been
answered to my satisfaction.
______________________________
Client Signature
___________
Date
1
3 Profile
(age, marital status, living arrangements, occupation, children)
______________________________________________________________________
______________________________________________________________________
4 Reason for Referral
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
5 History of Primary Substance Use
What is/are the client’s substance(s) of choice?
______________________________________________________________________
______________________________________________________________________
Describe the characteristics of use (amount, frequency of use [now, 1st use, 1st regular
use], route, whether substance is prescribed):
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
Does the client use alone or with others?
______________________________________________________________________
**For EtOH or benzo abuse only: Is there a history of withdrawal seizures? If so, how
often? What is date of last seizure? ________________________________________
____________________________________________________________________
What medical complications of drug use has the client experienced?
______________________________________________________________________
2
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
Which treatment is desired?
______________________________________________________________________
Why is the client coming for help now?
______________________________________________________________________
Indicate below what other drugs of abuse the client has used or currently uses.
Drug
Opioids
Amount
Route
Pattern / Duration
Last Use
Ethanol
Tobacco
THC
Sedatives
Cocaine
Stimulants
Hallucinogens/GHB
Solvents
6 Substance Use Treatment
3
Describe the current and/or planned treatment.
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
Describe any past treatment or detox the client has undergone for substance use.
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
7 High-Risk Behaviour
Does the client’s behaviour include
yes no
impaired driving?
________________________________________________________________
IV drug use / sharing of paraphernalia /
blood transfusions / tattoos?
yes no
________________________________________________________________
unprotected sex?
yes no
________________________________________________________________
possibility of pregnancy?
yes no
________________________________________________________________
Date of client’s last HIV test:_____________
Last Hep B/C test:_______________
Other comments on high-risk behaviour: ____________________________________
_____________________________________________________________________
4
8 Consequences of Substance Use
Describe the major consequences of the client’s substance use.
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
9 Medical History
Describe the client’s past medical history.
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
List any medications that are currently prescribed to the client.
Name:_______________________ Dose: ____________ Frequency: ___________
Name:_______________________ Dose: ____________ Frequency: ___________
Name:_______________________ Dose: ____________ Frequency: ___________
Name:_______________________ Dose: ____________ Frequency: ___________
Name:_______________________ Dose: ____________ Frequency: ___________
List any OTC medications the client currently uses.
Name:_________________________Dose: ______________Frequency: ___________
Name:_________________________Dose: ______________Frequency: ___________
5
Describe any allergies the client has.
_____________________________________________________________________
_____________________________________________________________________
10 Psychiatric History
Psychiatric diagnosis:_______________________________________________
_____________________________________________
Year: ____________
Psychiatrist: ________________________________________________________
Hospitalizations (date, duration and diagnosis):
_________________________________________________________________
_________________________________________________________________
_________________________________________________________________
Is the client currently suicidal?
yes no
__________________________________________________________________
Does the client have a history of suicide attempts?
yes no
__________________________________________________________________
11 Legal Problems
Describe any legal problems that have resulted from the client’s substance use.
______________________________________________________________________
______________________________________________________________________
Does the client have a history of being violent?
yes no
______________________________________________________________________
6
______________________________________________________________________
12 Relevant Family History
Describe any history of addictions and/or mental health problems in the client’s family.
____________________________________________________________________
____________________________________________________________________
13 DSM-IV Criteria
Please review these statements with reference to the client’s primary substance of choice and
check off those to which the response is “yes”:
In the last 12 months,
Do you need more and more of the drug you are using to get the same effect?
Describe what symptoms you experience if you suddenly stop taking the drug.
______________________________________________________________
______________________________________________________________
Do you frequently take more drugs then you planned, or use a drug for longer than
you had planned to?
Have you had many unsuccessful attempts to cut down on your drug use?
Do you spend a lot of your day getting, using and recovering from the effects of
drugs?
Have you given up work, social activities or other things you used to do because of
your drug use?
Do you keep taking drugs despite the harm and problems their use is causing you?
7
14 Examination
BP: _____/_____
HR: ______
RR:______/min.
Temp:______ °C
Ht: ____cm
Wt: ____kg
Orientated?
yes
Smell of ethanol?
yes no
no
Breathalyzer result: ___________
Mental status: _______________________________________________________
___________________________________________________________________
ENT:__________________________________________________________________
Neuro:________________________________________________________________
Chest:________________________________________________________________
CVS:_________________________________________________________________
Abd:__________________________________________________________________
Skin:__________________________________________________________________
Tattoos? yes
Tracks? yes
Piercing? yes
no ____________________________________________
no ____________________________________________
no ____________________________________________________________
Stigmata of liver disease? yes
no
_____________________________________
Other:_________________________________________________________________
15 Problem List
1. ______________________________________________
2. ______________________________________________
3. ______________________________________________
4. ______________________________________________
5. ______________________________________________
6. ______________________________________________
8
16 Plan
Describe the treatment plan. _____________________________________________
____________________________________________________________________
____________________________________________________________________
Describe the psychosocial support plan. ____________________________________
____________________________________________________________________
____________________________________________________________________
What laboratory tests are suggested?
CBC
INR
ALT
bilirubin
albumin
creatinine
UDS
HBsAg
HCAb
HIV
BHCG
anti-HBsAg
AST
GGT
TB
Other: _________________________________________________________
Examination done by:
_____________________________
________________________ ____________
Physician’s Name
Physician’s Signature
Date
© 2008 Centre for Addiction and Mental Health, Toronto, Canada. Permission is granted for this document to be adapted as appropriate,
copied and distributed for use by health professionals in the treatment of opioid dependence. All other rights are reserved. This document
is available for download as part of the OpiATE Project Toolkit: please visit methadonesaveslives.ca.
9