Clinical Use of BuprenorphineFinding 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.

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

Introduction

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

AssessmentRecommended 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

AssessmentPossible 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.

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-Day 1

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 reappears-however 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

Buprenorphine Induction

Patient dependent on short-acting opioids?

Withdrawal symptomspresent 12-24 hrs

after last use of opioids?

Give buprenorphine2-4 mg, observe 1+ hrs

Withdrawal symptomscontinue or return?

Repeat dose up tomaximum 8 mg for first day

Withdrawal symptomsrelieved?

Manage withdrawalsymptomatically

Yes

Yes

No

Stop;not dependenton short-acting

opioids

No

Yes

Yes

Figure 1 Induction for Patient Physically DependentOn Short-acting Opioids, Day 1

Withdrawal symptomsreturn?

Daily dose established.GO TO SWITCH

DIAGRAM (Fig.4 )

No Daily dose established.GO TO SWITCH

DIAGRAM (Fig 4.)

No

Return next day forcontinued induction.

GO TO INDUCTION DAY 2DIAGRAM (Fig3.)

Yes

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

Buprenorphine InductionLong 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.

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

Induction for patients using long-acting opioids

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!

Buprenorphine Induction

Patient dependent on long-acting opioids?

24 hrs after last dose,give buprenorphine 2 mg

48 hrs after last dose,give buprenorphine 2 mg

Withdrawal symptoms present?

Give buprenorphine 2 mg

Repeat dose up to maximum 8 mg/24 hrs

Withdrawal symptoms relieved? Manage withdrawal symptomatically

No

Yes

Yes

Figure 2: Induction for Patient Physically DependentOn Long-acting Opioids, Day 1

If LAAM, taper to ≤ 40 mg forMonday/Wednesday dose

If methadone, taper to ≤ 30 mg per day

Yes

Dailydose

established

Dailydose

established

No

GO TO INDUCTION FOR PATIENTPHYSICALLY DEPENDENT DAY 2 DIAGRAM (Fig3.)

Withdrawal symptoms continue?

Yes

No

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

Buprenorphine Induction

Patient returns to office on 8 mg

Withdrawal symptomspresent since last dose?

Give buprenorphine10-12 mg

Withdrawal symptomscontinue?

Administer 2-4 mg doses upto maximum 16 mg (total)

for second day

Withdrawal symptomsrelieved?

Manage withdrawalsymptomatically

Yes

No

Maintain patient on8 mg per day.

GO TO SWITCHDIAGRAM (Fig 4).

No

Figure 3: Induction for Patient Physically DependentOn Short- or Long-acting Opioids, Days 2+

Withdrawal symptomsreturn?

Daily dose established.GO TO SWITCH

DIAGRAM (Fig. 4)

Yes

No

Yes

Yes

NoReturn next day for continued

induction; start with day 2total dose and increase by

2-4 mg increments.Maximum daily dose: 32 mg

Daily dose established. GO TO SWITCHDIAGRAM (Fig. 4)

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.

Buprenorphine Induction

Figure 4: Switch from Buprenorphine to Buprenorphine/naloxone

Patient on buprenorphine monotherapy(up to 32 mg/day)

Patient pregnant?

Yes

Yes

No No

Continue buprenorphinemonotherapy

Other compelling reasonto continue

buprenorphinemonotherapy?

Transfer tobuprenorphine/

naloxone therapy

InductionThe 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

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

Buprenorphine Induction and Stabilization

Figure 5: Induction/Stabilization

Continuedillicit

opioid use?

Withdrawalsymptomspresent?

Yes

No Induction phasecompleted?

Yes

Compulsionto use,

cravingspresent?

No Daily doseestablished

Continue adjusting dose up to 32/8 mg per day

No No

Continue illicit opioid use despite maximum dose?

YesYes

No Daily doseestablished

Yes

Maintain on buprenorphine/naloxonedose, increase intensity of

non-pharmacological treatments

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!

Buprenorphine Induction/Stabilization

Stabilization/Maintenance

Figure 6: Stabilization/maintenance

Continuedil licit

opioid use?

Withd rawalsymptomspresent?

Yes

No In duction phasecomp leted?

Yes

Compulsionto u se,

cravingspresent?

NoDaily doseestablished

Continue adju stin g do se u p to 32/8 mg p er day

No No

Continue il licit opioid use despite maximu m d ose?

YesYes

No Daily doseestablished

Yes

Maintain on buprenorphin e/naloxonedose, increase intensity o f

non -p harmacolog ical treatments

Buprenorphine/Naloxone Taperfor 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!!!