Indications
IM, IV: Management of moderate to severe acute pain.
Buccal, Transdermal: Pain that is severe enough to require
daily, around-the-clock long-term opioid treatment
and for which alternative treatment options (e.g. nonopioid
analgesics or immediate-release opioids) are inadequate.
SL: Treatment of opioid dependence (preferred
for induction only); suppresses withdrawal
symptoms in opioid detoxification. Subdermal: Maintenance
treatment of opioid dependence in patients who
have achieved and sustained prolonged (3 mo) clinical
stability on low-to-moderate doses of a transmucosal buprenorphine-
containing product (8 mg/day).
Action
Binds to opiate receptors in the CNS. Alters the perception
of and response to painful stimuli while producing
generalized CNS depression. Has partial antagonist
properties that may result in opioid withdrawal in physically
dependent patients when used as an analgesic.
Therapeutic Effects: IM, IV, Transdermal: Decreased
severity of pain. SL: Suppression of withdrawal
symptoms during detoxification and maintenance from
heroin or other opioids. Produces a relatively mild
withdrawal compared to other agents. Subdermal:
Continued cessation of opioid use.
Pharmacokinetics
Absorption: Well absorbed after IM and SL use; 46–
65% absorbed with buccal use; 15% of transdermal dose absorbed through skin; IV administration results
in complete bioavailability.
Distribution: Crosses the placenta; enters breast
milk. CNS concentration is 15–25% of plasma.
Protein Binding: 96%.
Metabolism and Excretion: Mostly metabolized
by the liver mostly via the CYP3A4 enzyme system; one
metabolite is active; 70% excreted in feces; 27% excreted
in urine.
Half-life: 2–3 hr (parenteral); 27 hr (buccal); 26 hr
(transdermal); 37 hr (SL); 24–48 hr (subdermal).
TIME/ACTION PROFILE (analgesia)
ROUTE ONSET PEAK DURATION
IM 15 min 60 min 6 hr†
IV rapid less than 60
min
6 hr†
SL unknown unknown unknown
Transdermal unknown unknown 7 days
Buccal unknown unknown unknown
Subdermal unknown unknown unknown
†4–5 hr in children.
Contraindications/Precautions
Contraindicated in: Hypersensitivity; Significant
respiratory depression (transdermal, buccal); Acute or
severe bronchial asthma (transdermal, buccal); Paralytic
ileus (transdermal, buccal); Acute, mild, intermittent,
or postoperative pain (transdermal); Long QT syndrome
(transdermal, buccal); Concurrent use of class I
or III antiarrhythmics (transdermal); Lactation: Enters
breast milk; avoid use or discontinue nursing.
Use Cautiously in:qintracranial pressure; Severe
renal or pulmonary disease; Moderate or severe hepatic
disease (dosepneeded for severe impairment);
Hypothyroidism; Seizure disorders; Adrenal insufficiency;
Alcoholism; Biliary tract disease; Acute pancreatitis;
Debilitated patients (doseprequired); Oral mucositis
(doseprequired) (buccal); Undiagnosed
abdominal pain; Hypokalemia, hypomagnesemia, unstable
atrial fibrillation, symptomatic bradycardia, unstable
HF, or myocardial ischemia (transdermal, buccal);
Prostatic hyperplasia; OB: Safety not established;
prolonged use of buccal, transdermal, subdermal, or
SL buprenorphine during pregnancy can result in neonatal
opioid withdrawal syndrome; Pedi: Safety not established
in children (SL and transdermal) or children
2 yr (parenteral); Geri:qrisk of respiratory depression
(doseprequired).
Adverse Reactions/Side Effects
CNS: confusion, dysphoria, hallucinations, sedation,
dizziness, euphoria, floating feeling, headache, unusual
dreams. EENT: blurred vision, diplopia, miosis (high
doses). Resp: RESPIRATORY DEPRESSION. CV: hypertension,
hypotension, palpitations, QT interval prolongation
(transdermal). Endo: adrenal insufficiency.
GI: HEPATOTOXICITY, nausea, constipation, dry mouth,
ileus, vomiting. GU: urinary retention. Derm: sweating,
clammy feeling, erythema, pruritus, rash. Misc:
HYPERSENSITIVITY REACTIONS (including anaphylaxis, angioedema,
and bronchospasm), physical dependence,
psychological dependence, tolerance.
Interactions
Drug-Drug: Concurrent use with class Ia antiarrhythmics,
class III antiarrhythmics, or other QT
interval prolonging medications mayqrisk of QT
interval prolongation; avoid concurrent use. Use with
benzodiazepines or other CNS depressants including
other opioids, non-benzodiazepine sedative/
hypnotics, anxiolytics, general anesthetics, muscle
relaxants, antipsychotics, and alcohol may
cause profound sedation, respiratory depression,
coma, and death; reserve concurrent use for when alternative
treatment options are inadequate. Use with extreme
caution in patients receiving MAO inhibitors
(qCNS and respiratory depression and hypotension—
pbuprenorphine dose by 50%; may need topMAO inhibitor
dose; do not use transdermal formulation
within 14 days of MAO inhibitor). Maypeffectiveness
of other opioid analgesics. Inhibitors of the CYP3A4
enzyme system including itraconazole, ketoconazole,
erythromycin, ritonavir, indinavir, saquinavir,
atazanavir, or fosamprenavir mayqblood levels
and effects; may need topbuprenorphine dose.
Inducers of the CYP3A4 enzyme system including carbamazepine,
rifampin, or phenytoin maypblood
levels and effects; buprenorphine dose modification
may be necessary during concurrent use. Concurrent
abuse of buprenorphine and benzodiazepines may
result in coma and death. Drugs that affect serotonergic
neurotransmitter systems, including tricyclic antidepressants,
SSRIs, SNRIs, MAO inhibitors, TCAs,
tramadol, trazodone, mirtazapine, 5–HT3 receptor
antagonists, linezolid, methylene blue, and
triptansqrisk of serotonin syndrome.
Drug-Natural Products: Concomitant use of
kava-kava, valerian, chamomile, or hops canq
CNS depression.
Route/Dosage
Analgesia
IM, IV (Adults): 0.3 mg every 4–6 hr as needed. May
repeat initial dose after 30 min (up to 0.3 mg every 4 hr
or 0.6 mg every 6 hr); 0.6-mg doses should be given
only IM.
IM, IV (Children 2–12 yr): 2–6 mcg (0.002–0.006
mg)/kg every 4–6 hr.
Transdermal (Adults): Opioid-naı¨ve—Transdermal
system delivering 5–20 mcg/hr applied every 7
days. Initiate with 5 mcg/hr system; each dose titration
may occur after 72 hr; do not exceed dose of 20 mcg/
hr (due toqrisk of QT interval prolongation); Previously
taking 30 mg/day of morphine or equivalent—
Initiate with 5 mcg/hr system; each dose titration
may occur after 72 hr; do not exceed dose of 20
mcg/hr (due toqrisk of QT interval prolongation); apply patch every 7 days; Previously taking 30–80 mg/
day of morphine or equivalent—Initiate with 10
mcg/hr system; each dose titration may occur after 72
hr; do not exceed dose of 20 mcg/hr (due toqrisk of
QT interval prolongation); apply patch every 7 days;
Previously taking 80 mg/day of morphine or equivalent—
Consider use of alternate analgesic.
Buccal (Adults): Opioid-naı¨ve—Initiate therapy
with 75 mcg once daily or every 12 hr for 4 days, then
qdose to 150 mcg every 12 hr; may then titrate dose in
increments of 150 mcg every 12 hr no more frequently
than every 4 days; do not exceed dose of 450 mcg every
12 hr (based on clinical studies); Previously taking
30 mg/day of morphine or equivalent—Initiate
therapy with 75 mcg once daily or every 12 hr for 4
days, thenqdose to 150 mcg every 12 hr; may then titrate
dose in increments of 150 mcg every 12 hr no
more frequently than every 4 days; do not exceed dose
of 900 mcg every 12 hr (due toqrisk of QT interval
prolongation); Previously taking 30–89 mg/day of
morphine or equivalent—Initiate therapy with 150
mcg every 12 hr for 4 days; may then titrate dose in
increments of 150 mcg every 12 hr no more frequently
than every 4 days; do not exceed dose of 900 mcg every
12 hr (due toqrisk of QT interval prolongation); Previously
taking 90–160 mg/day of morphine or
equivalent—Initiate therapy with 300 mcg every 12 hr
for 4 days; may then titrate dose in increments of 150
mcg every 12 hr no more frequently than every 4 days;
do not exceed dose of 900 mcg every 12 hr (due toq
risk of QT interval prolongation); Previously taking
160 mg/day of morphine or equivalent—Consider
use of alternate analgesic; Patients with oral mucositis—
pinitial dose by 50% then titrate dose in increments
of 75 mcg every 12 hr no more frequently than
every 4 days.
Hepatic Impairment
Transdermal (Adults): Mild to moderate hepatic
impairment—Initiate with 5 mcg/hr system.
Hepatic Impairment
Buccal (Adults): Severe hepatic impairment—p
initial dose by 50% then titrate dose in increments of 75
mcg every 12 hr no more frequently than every 4 days.
Treatment of opioid dependence
SL (Adults): Induction—8 mg once daily on Day 1,
then 16 mg once daily on Day 2–4; Maintenance—
Patients should preferably be transitioned to buprenorphine/
naloxone; if patient cannot tolerate naloxone,
then can use buprenorphine (dose can beqorpby 2–
4 mg, as needed to prevent signs/symptoms of opioid
withdrawal).
Hepatic Impairment
SL (Adults): Severe hepatic impairment—pinitial
dose and adjustment dose by 50%.
Subdermal (Adults): Insert 4 implants in inner side of
upper arm and then remove at end of 6 mo.
Availability (generic available)
Sublingual tablets: 2 mg, 8 mg. Injection (Buprenex):
300 mcg (0.3 mg)/mL. Transdermal system
(Butrans): 5 mcg/hr, 7.5 mcg/hr, 10 mcg/hr, 15 mcg/
hr, 20 mcg/hr. Buccal film (Belbuca): 75 mcg, 150
mcg, 300 mcg, 450 mcg, 600 mcg, 750 mcg, 900 mcg.
Implant: 74.2 mg/implant. In combination with:
naloxone (Bunavail, Suboxone, Zubsolv). See
Appendix B.
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