Transcript Pharmacodynamic Profile of Enadoline, A Selective Kappa (k

Clinical Use of Buprenorphine
Finding The Right Dose
Paul P. Casadonte MD
California Society of Addiction Medicine
2002
Clinical Case Presentation
• Janet T is a 37 year old single white female, head of an
Internet design corporation, seeking treatment for $
100/day IV heroin use. She is determined to stop, as she
is to be featured on the cover of a Women’s magazine in
several months.
• She met criteria for treatment, had no evidence of
medical disorder. Her screening udst was positive for
opiates and benzodiazepines prescribed for “panic
disorder.” She was advised to abstain from opiates for at
least 6 hours prior to the appointment.
Clinical Case
• She returned for induction, appeared in withdrawal and
was given a dose of 4 mg buprenorphine. 30 minutes
later she reported chills, anxiety, and was given another 4
mg. 10 later minutes she was retching and screaming. An
additional 8 mg was given, for a total of 16 mg in 40
minutes. The retching and panic continued for 30
minutes, as which point she became comfortable.She left
the Clinic after an hour of observation was given a
prescription for 16 mg a day for 3 days, and asked to
return for continued treatment.
Clinical Case
• She was stabilized on 16 mg a day, discontinued use,
udst negative for opiates,. She came for weekly visits and
medication for 6 weeks.
• She did not come at week 7, and when contacted
reported that she had resumed use at 3 bags/day. She
had learned to stop buprenorphine 8 hours before heroin
use, and to resume buprenorphine 6 hours after heroin.
• She continued reduced intermittent weekend heroin use
for several weeks, and insisted this was what kept her
functional.
Introduction
Buprenorphine presents a low risk of clinically significant problems
No reports of respiratory depression in clinical trials of buprenorphine
Overdose of buprenorphine combined with other drugs may cause
problems. Use special caution in patients using benzodiazepines
While buprenorphine has lower level of physical dependence, it may be
possible to precipitate withdrawal with opioid antagonist in
buprenorphine-maintained patients
Pre- Induction: Some thoughts
• Patient selection: who is a candidate?
• Office procedures: what changes do I make?
• Resources necessary: what do I need to do this task?
• Remember: You have 30 slots!!
• Keep in mind: The Law runs for 3 years-do not mess up!!
Pre-Induction: Assessment
• Telephone screen
• Clinical Interview
• Physical Examination
• ECG > 40
• Laboratory evaluations
• Urine Drug Screens
Assessment
Recommended Inclusion Criteria
For Private Off ice Treatment
Physically healthy
History of responsible behaviors
No pending legal charges
Lower level of Psychiatric disorders
Able to store medication
Limited Criminal history
Assessment
Possible Exclusion Factors
• Dependent on Alcohol
• Dependent on Benzodiazepines
• Stimulant abusers
• Circle of addict-only friends
• Ambivalent about treatment
Pre-Induction Tasks
• Complete medical and laboratory assessment
• Have patient sign a consent for treatment and contract
• Arrange an appointment for induction
• Advise not to drive alone to appointment
• Emphasize the need to abstain from opiates for 8-12
hours.
• Attempt to obtain the truth about amount of use
Pre-Induction
• Determine how and where you will start medication
• Be prepared for vomiting, pain, etc if you do not have a
patient in withdrawal at time of induction.
• Determine how comfortable you are with a sick patient.
• Try to avoid having other patients waiting while inducting.
Buprenorphine Induction-Day 1
Dependence on Heroin/pain medications
You will have instructed patient to abstain from any
opioid use for 8-12 hours (so they are in mild
withdrawal at time of first buprenorphine dose)
If patient is not in opioid withdrawal at time of arrival in
office, then assess time of last use and consider either
having him/her return another day or wait in the office.
Use standard withdrawal evaluations to assess.
Buprenorphine Induction
Advise on possible effects of buprenorphine
First dose: 2-4 mg sublingual buprenorphine
Advise on how the medication must be taken.
Monitor in office for 1-2 hours after first dose.
Re-dose if needed: if opioid withdrawal subsides then reappearshowever the withdrawal may be due to excess buprenorphine.
Recommended maximum first day dose of 8-12 mg.
May give a prescription for 2-3 days or have return the next day
Figure 1 Induction for Patient Physically Dependent
On Short-acting Opioids, Day 1
Patient dependent on short-acting opioids?
Yes
Withdrawal symptoms
present 12-24 hrs
after last use of opioids?
No
Yes
Stop;
not dependent
on short-acting
opioids
Give buprenorphine
2-4 mg, observe 1+ hrs
Withdrawal symptoms
continue or return?
No
Yes
Withdrawal symptoms
return?
No
Yes
Repeat dose up to
maximum 8 mg for first day
Withdrawal symptoms
relieved?
Yes
Daily dose established.
GO TO SWITCH
DIAGRAM (Fig.4 )
No
Manage withdrawal
symptomatically
Return next day for
continued induction.
GO TO INDUCTION DAY 2
DIAGRAM (Fig3.)
Daily dose established.
GO TO SWITCH
DIAGRAM (Fig 4.)
Buprenorphine Induction
May begin with buprenorphine monotherapy tablets (i.e.,
without naloxone) for first 2-3 days, then switch to
buprenorphine/naloxone combination tablets.
When switching to combination tablets, do direct switch
to same dose of buprenorphine (i.e., from 8 mg daily
go to 8/2 mg daily)
Buprenorphine Induction
If starting with combination tablets directly, you may use
same amount as mono buprenorphine.
It is safe and easy to begin on combo tablets.
The combo tablets will not produce withdrawal in 99% of
patients.
Buprenorphine Induction
Patients dependent on long-acting opioids:
Methadone
LAAM
Buprenorphine Induction
Long Acting Opioids
• Patients may be buying street methadone
• Amount of use is often not accurate
• Unlikely to be buying street LAAM
• If on a methadone program, advise need to discuss with
staff.
• If stable on methadone and wants simply to switch to
buprenorphine, assess benefits and risks.
Induction for patients using long-acting opioids
If using street methadone, advise he will be ill unless on
30 mg or less of methadone.
Begin induction 24 hours after last dose of methadone,
48 hours after last dose of LAAM
Assess for withdrawal before dosing.
Give no further methadone or LAAM once
buprenorphine induction is started
Buprenorphine Induction
First day dose of 8-12 mg sublingual buprenorphine
It may be difficult to determine if the withdrawal is due to
methadone or LAAM withdrawal or buprenorphine
precipitated withdrawal.
Need for active patient support
Need for nerves of steel!
Figure 2: Induction for Patient Physically Dependent
On Long-acting Opioids, Day 1
Patient dependent on long-acting opioids?
If LAAM, taper to ≤ 40 mg for
Monday/Wednesday dose
Yes
48 hrs after last dose,
give buprenorphine 2 mg
If methadone, taper to ≤ 30 mg
per day
24 hrs after last dose,
give buprenorphine 2 mg
Withdrawal symptoms present?
No
Yes
Daily
dose
established
Give buprenorphine 2 mg
No
Withdrawal symptoms continue?
Yes
Repeat dose up to maximum 8 mg/24 hrs
No
Withdrawal symptoms relieved?
Manage withdrawal symptomatically
Yes
Daily
dose
established
GO TO INDUCTION FOR PATIENT
PHYSICALLY DEPENDENT DAY 2 DIAGRAM (Fig3.)
Buprenorphine Induction
On second thru fourth day, have patient return to the
office for assessment, dosing, prescription
Adjust dose accordingly based on patient’s experiences
on first day (i.e., higher dose if there were withdrawal
symptoms after leaving your office; lower dose if
patient was over-medicated at end of first day)
Buprenorphine Induction
Continue adjusting dose by 2-4 mg increments until an
initial target dose of 12-16 mg is achieved for the
second day.
If continued dose increases are indicated after the
second day, have the patient return for further dose
induction (with a maximum daily dose of 32 mg)
This may not be possible, so use the telephone well
Figure 3: Induction for Patient Physically Dependent
On Short- or Long-acting Opioids, Days 2+
Patient returns to office on 8 mg
Yes
No
Withdrawal symptoms
present since last dose?
Yes
Maintain patient on
8 mg per day.
GO TO SWITCH
DIAGRAM (Fig 4).
Give buprenorphine
10-12 mg
Withdrawal symptoms
continue?
No
Withdrawal symptoms
return?
Yes
No
Daily dose established.
GO TO SWITCH
DIAGRAM (Fig. 4)
Administer 2-4 mg doses up
to maximum 16 mg (total)
for second day
Withdrawal symptoms
relieved?
No
Yes
Daily dose established. GO TO SWITCH
DIAGRAM (Fig. 4)
Manage withdrawal
symptomatically
Return next day for continued
induction; start with day 2
total dose and increase by
2-4 mg increments.
Maximum daily dose: 32 mg
Buprenorphine Induction
Conversion to buprenorphine/naloxone
If indicated, switch patient to buprenorphine/naloxone
combination tablets after 2-3 days of buprenorphine
monotherapy dosing.
Use mono product for pregnant women.
Figure 4: Switch from Buprenorphine to
Buprenorphine/naloxone
Patient on buprenorphine monotherapy
(up to 32 mg/day)
Patient pregnant?
Yes
No
Other compelling reason
to continue
buprenorphine
monotherapy?
Yes
Continue buprenorphine
monotherapy
No
Transfer to
buprenorphine/
naloxone therapy
Induction
The First Days
• Be prepared for continuous contact in early days
• Anxiety, fear, opiate use are common.
• Strongly discourage opiate use, it complicates all
• Advise that too much medication may cause withdrawal
• Give medication for several days.
• Advise not to increase without consultation.
• May use ancillary medications to cover withdrawal
Buprenorphine Induction and Stabilization
Increase dose to point of comfort
May take up to one week
Expect average daily dose will be somewhere between 8/2
and 32/8 mg of buprenorphine/naloxone
Higher daily doses more tolerable if taken sequentially
rather than all at once-use bid or t.i.d doses
Multiple doses are more reassuring early in treatment
Figure 5: Induction/Stabilization
No
Induction phase
completed?
Yes
Continued
illicit
opioid use?
Yes
No
Withdrawal
symptoms
present?
No
Compulsion
to use,
cravings
present?
Yes
No
Daily dose
established
Yes
Continue adjusting dose up to 32/8 mg per day
No
Continue illicit opioid use despite maximum dose?
Yes
Maintain on buprenorphine/naloxone
dose, increase intensity of
non-pharmacological treatments
Daily dose
established
Buprenorphine Induction/Stabilization
The patient should receive a daily dose until comfortable.
See as frequently as necessary.
Use additional medications for sleep or initiate
antidepressants
Once stabilized, the patient can shift to alternate day
dosing –but no rush!
Stabilization/Maintenance
Figure 6: Stabilization/maintenance
No
In duction phase
comp leted?
Yes
Continued
illicit
opioid use?
Yes
No
Withd rawal
sym ptom s
present?
No
Com pulsion
to u se,
cravings
present?
Yes
No
Daily dose
established
Yes
Continue adju stin g do se u p to 32/8 m g p er day
No
Continue illicit opioid use despite maximu m d ose?
Yes
Maintain on buprenor phin e/naloxone
dose, increase intensity o f
non -p harmacolog ical treatm ents
Daily dose
established
Buprenorphine/Naloxone Taper
for Maintained Patients
• Comprehensive treatment plan, patient desire and
acceptance.
• Ideally issues related to opiate use resolved.
• Taper can be over a period of days, weeks, months.
• Ancillary medications, psychological support, referral.
• Advise re-induction if relapse is an issue-but remember
30 patient limit.
Heroin Detoxification
• Assess the motivation and the reality of detoxification.
• Determine the length of time patient desires
• Work out a written schedule and agreement.
• Induct and Stabilize ( 3-7 days)
• Taper when use is discontinued
• No ideal taper schedule, many variables intrude
• Aftercare, ancillary medications, re-induction if relapse
Clinical Case Outcome
• Janet continued intermittent opiate use, alternating
buprenorphine with heroin for a period of 3 weeks with
medication she had saved. At one point she experienced
significant withdrawal and friends took her to an
emergency room. The doctor saw her as an addict and
she was given 10 mg IM methadone, which made her
very sick.
• She was discharged from the protocol. She is obtaining
buprenorophine from France at this time.
Summary
Carefully screen patients prior to induction.
Be prepared for patient and doctor anxiety.
Closely monitor patient during induction.
Best to keep patient at office for an hour on first day.
Give sufficient medication to allow dose changes by phone.
Buprenorphine works wonders and is effective and safe.
HAVE FUN!!!