DOSAGE AND ADMINISTRATION
Initial Dosing
BUTRANS should be prescribed only by healthcare
professionals who are knowledgeable in the use of potent opioids for
the management of chronic pain.
BUTRANS doses of 7.5, 10, 15, and 20 mcg/hour
are for opioid-experienced patients only.
Initiate the dosing regimen
for each patient individually; take into account the patient's prior
analgesic treatment experience and risk factors for addiction, abuse,
and misuse [see Warnings and Precautions ]. Monitor patients closely
for respiratory depression, especially within the first 24-72 hours
of initiating therapy with BUTRANS [see Warnings and Precautions].
BUTRANS is for transdermal use (on intact skin) only. Each BUTRANS
patch is intended to be worn for 7 days.
Instruct patients
not to use BUTRANS if the pouch seal is broken or the patch is cut,
damaged, or changed in any way and not to cut BUTRANS.
Use of BUTRANS as the First Opioid Analgesic
Initiate treatment with BUTRANS with a 5 mcg/hour patch.
Conversion from Other Opioids to BUTRANS
Discontinue all other around-the-clock opioid drugs when BUTRANS
therapy is initiated.
There is a potential for
buprenorphine to precipitate withdrawal in patients who are already
on opioids.
Prior Total Daily Dose of Opioid Less
than 30 mg of Oral Morphine Equivalents per Day:
Initiate treatment with BUTRANS 5 mcg/hour at the next dosing interval
(see Table 1 below, middle column).
Prior Total Daily
Dose of Opioid Between 30 mg to 80 mg of Oral Morphine Equivalents
per Day:
Taper the patient’s current around-the-clock
opioids for up to 7 days to no more than 30 mg of morphine or equivalent
per day before beginning treatment with BUTRANS. Then initiate treatment
with BUTRANS 10 mcg/hour at the next dosing interval (see Table 1
below, right column). Patients may use short-acting analgesics as
needed until analgesic efficacy with BUTRANS is attained.
Prior
Total Daily Dose of Opioid Greater than 80 mg of Oral Morphine Equivalents
per Day:
BUTRANS 20 mcg/hour may not provide adequate
analgesia for patients requiring greater than 80 mg/day oral morphine
equivalents. Consider the use of an alternate analgesic.
Table 1: Initial
BUTRANS Dose
Previous
Opioid Analgesic Daily Dose
(Oral Morphine Equivalent) |
<30 mg |
30-80 mg |
|
|
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Recommended
BUTRANS Starting Dose
|
5 mcg/hour
|
10 mcg/hour
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Conversion from Methadone to BUTRANS
Close monitoring
is of particular importance when converting from methadone to other
opioid agonists. The ratio between methadone and other opioid agonists
may vary widely as a function of previous dose exposure. Methadone
has a long half-life and can accumulate in the plasma.
Titration and Maintenanceof Therapy
Individually titrate BUTRANS to a dose that provides adequate analgesia
and minimizes adverse reactions. Continually reevaluate patients receiving
BUTRANS to assess the maintenance of pain control and the relative
incidence of adverse reactions, and monitor for the development of
addiction, abuse, or misuse. Frequent communication is important
among the prescriber, other members of healthcare team, the patient,
and the caregiver/family during periods of changing analgesic requirements,
including initial titration. During chronic therapy, periodically
reassess the continued need for opioid analgesics.
The minimum BUTRANS titration
interval is 72 hours, based on the pharmacokinetic profile and time
to reach steady state levels [see Clinical Pharmacology ].
The maximum BUTRANS dose is 20 mcg/hour. Do not exceed
a dose of one 20 mcg/hour BUTRANS system due to the risk of QTc interval
prolongation. In a clinical trial, BUTRANS 40 mcg/hour (given
as two BUTRANS 20 mcg/hour systems) resulted in prolongation of the
QTc interval [see Warnings and Precautions and Clinical Pharmacology].
If the level of pain increases, attempt
to identify the source of increased pain, while adjusting the BUTRANS
dose to decrease the level of pain. Because steady-state plasma concentrations
are achieved within 72 hours, BUTRANS dosage may be adjusted every
3 days. Dose adjustments may be made in 5 mcg/hour, 7.5 mcg/hour,
or 10 mcg/hour increments by using no more than two patches of the
5 mcg/hour, 7.5 mcg/hour, or 10 mcg/hour system(s). The total dose
from both patches should not exceed 20 mcg/hour. For the use of two
patches, patients should be instructed to remove their current patch,
and apply the two new patches at the same time, adjacent to one another
at a different application site [see Dosage and Administration ].
Patients who experience breakthrough pain may require dosage adjustment
increase of BUTRANS, or may need rescue medication with an appropriate
dose of an immediate-release analgesic. If the level of pain increases
after dose stabilization, attempt to identify the source of increased
pain before increasing the BUTRANS dose.
If unacceptable opioid-related
adverse reactions are observed, the subsequent doses may be reduced.
Adjust the dose to obtain an appropriate balance between the management
of pain and opioid-related adverse reactions.
Cessation of Therapy
When the patient no longer requires therapy
with BUTRANS, use a gradual downward titration of the dose every 7
days to prevent signs and symptoms of withdrawal in the physically
dependent patient; consider introduction of an appropriate immediate-release
opioid medication. Do not abruptly discontinue BUTRANS.
Patients with HepaticImpairment
BUTRANS has not
been evaluated in patients with severe hepatic impairment. As BUTRANS
is only intended for 7-day application, consider use of an alternate
analgesic that may permit more flexibility with the dosing in patients
with severe hepatic impairment [see Warnings and Precautions
(5.10), Use in Specific Populations
(8.6), and Clinical Pharmacology].
Administration ofBUTRANS
Instruct patients to apply immediately after removal from the individually
sealed pouch. Instruct patients not to use BUTRANS if the pouch seal
is broken or the patch is cut, damaged, or changed in any way. See
the Instructions for Use for step-by-step instructions for applying
BUTRANS.
Apply BUTRANS to the upper outer arm, upper chest, upper back or
the side of the chest. These 4 sites (each present on both sides
of the body) provide 8 possible application sites. Rotate BUTRANS
among the 8 described skin sites. After BUTRANS removal, wait a minimum
of 21 days before reapplying to the same skin site [see Clinical
Pharmacology ].
Apply BUTRANS
to a hairless or nearly hairless skin site. If none are available,
the hair at the site should be clipped, not shaven. Do not apply
BUTRANS to irritated skin. If the application site must be cleaned,
clean the site with water only. Do not use soaps, alcohol, oils, lotions,
or abrasive devices. Allow the skin to dry before applying BUTRANS.
Incidental
exposure of the BUTRANS patch to water, such as while bathing or showering
is acceptable based on experience during clinical studies.
If problems
with adhesion of BUTRANS occur, the edges may be taped with first
aid tape. If problems with lack of adhesion continue, the patch may
be covered with waterproof or semipermeable adhesive dressings suitable
for 7 days of wear.
If BUTRANS falls off during the 7-day
dosing interval, dispose of the transdermal system properly and place
a new BUTRANS patch on at a different skin site.
When changing
the system, instruct patients to remove BUTRANS and dispose of it
properly [see Dosage and Administration].
If the buprenorphine-containing
adhesive matrix accidentally contacts the skin, instruct patients
or caregivers to wash the area with water and not to use soap, alcohol,
or other solvents to remove the adhesive because they may enhance
the absorption of the drug.
Disposal Instructions
Patients should refer to
the Instructions for Use for proper disposal of BUTRANS. Dispose of
used and unused patches by following the instructions on the Patch-Disposal
Unit that is packaged with the BUTRANS patches.
Alternatively, patients can dispose of used patches by folding the
adhesive side of the patch to itself, then flushing the patch down
the toilet immediately upon removal. Unused patches should be removed
from their pouches, the protective liners removed, the patches folded
so that the adhesive side of the patch adheres to itself, and immediately
flushed down the toilet.
Patients should dispose
of any patches remaining from a prescription as soon as they are no
longer needed.
DOSAGE FORMS AND STRENGTHS
BUTRANS is a rectangular or square, beige-colored
system consisting of a protective liner and functional layers. BUTRANS
is available in five strengths:
- BUTRANS 5 mcg/hour Transdermal System (dimensions: 45 mm
by 45 mm)
- BUTRANS 7.5 mcg/hour Transdermal System (dimensions: 58
mm by 45 mm)
- BUTRANS 10 mcg/hour Transdermal System (dimensions: 45 mm
by 68 mm)
- BUTRANS 15 mcg/hour Transdermal System (dimensions: 59 mm
by 72 mm)
- BUTRANS 20 mcg/hour Transdermal System (dimensions: 72 mm
by 72 mm)
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