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standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(byoo pre NOR feen)
Generic Available (U.S.)
Yes: Excludes patch
Index Terms
Controlled Substance
C-III
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Butrans™: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM219146.pdf
Subutex®: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM285300.pdf
REMS Components
Butrans™: Elements to Assure Safe Use; Medication Guide
Subutex®: Elements to Assure Safe Use; Implementation System; Medication Guide
Prescribing and Access Restrictions
Prescribing of tablets for opioid dependence is limited to physicians who have met the qualification criteria and have received a DEA number specific to prescribing this product. Tablets will be available through pharmacies and wholesalers which normally provide controlled substances.
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Injection: Management of moderate-to-severe pain
Sublingual tablet: Treatment of opioid dependence
Transdermal patch: Management of moderate-to-severe chronic pain in patients requiring an around-the-clock opioid analgesic for an extended period of time
Use: Unlabeled
Injection: Management of opioid withdrawal in heroin-dependent hospitalized patients
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse effects have been observed in animal reproduction studies following buprenorphine subcutaneous and transdermal administration. In humans, withdrawal has been reported in infants of women receiving buprenorphine during pregnancy. Onset of symptoms ranged from day 1 to day 8 of life, most occurring on day 1.
Lactation
Enters breast milk/not recommended
Contraindications
Hypersensitivity to buprenorphine or any component of the formulation
Transdermal patch: Additional contraindications: Significant respiratory depression; severe asthma; known or suspected paralytic ileus; management of mild, acute, or intermittent pain; management of pain requiring short-term opioid analgesia; management of postoperative pain
Warnings/Precautions
Boxed warnings:
• Abuse/misuse/diversion: See “Other warnings/precautions” below.
• QT prolongation: See “Concerns related to adverse effects” below.
• Transdermal patches: See “Dosage form specific issues” below.
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Hepatic events: Hepatitis has been reported with buprenorphine use; hepatic events ranged from transient, asymptomatic transaminase elevations to hepatic failure; in many cases, patients had preexisting hepatic dysfunction. Monitor liver function tests in patients at increased risk for hepatotoxicity (eg, history of alcohol abuse, pre-existing hepatic dysfunction, I.V. drug abusers) prior to and during therapy.
• Hypersensitivity reactions: Hypersensitivity, including bronchospasm, angioneurotic edema, and anaphylactic shock, have been reported.
• Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics).
• QT prolongation: Transdermal patch: [U.S. Boxed Warning]: Do not exceed one 20 mcg/hour transdermal patch due to the risk of QTc-interval prolongation. Avoid using in patients with history of long QT syndrome or in patients with predisposing factors increasing the risk of QT abnormalities (eg, concurrent medications such as antiarrhythmics, hypokalemia, unstable heart failure, unstable atrial fibrillation).
Disease-related concerns:
• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.
• Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison's disease.
• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction; acute pancreatitis may cause constriction of sphincter of Oddi.
• Bowel obstruction: Use with caution in patients with a history of ileus or bowel obstruction.
• CNS depression/coma: Use with caution in patients with CNS depression or coma.
• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur.
• Hepatic impairment: Use with caution in patients with hepatic impairment. Dosage adjustments are recommended in hepatic impairment.
• Obesity: Use with caution in patients who are morbidly obese.
• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.
• Psychosis: Use with caution in patients with toxic psychosis.
• Renal impairment: Use with caution in patients with renal impairment.
• Respiratory disease: Use with extreme caution in patients with pre-existing respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function; critical respiratory depression may occur, even at therapeutic dosages.
• Seizure: Opioid therapy may lower seizure threshold; use caution in patients with a history of seizure disorders.
• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues:
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations:
• Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages.
• Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Decrease initial dose.
Dosage form specific issues:
• Transdermal patch: [U.S. Boxed Warning]: Indicated for the management of chronic moderate-to-severe pain when around the clock pain control is needed for an extended time period. Contraindicated in the management of pain requiring short-term opioid analgesia. [U.S. Boxed Warning]: Avoid exposure of application site and surrounding area to direct external heat sources. Buprenorphine release from the patch is temperature-dependent and may result in overdose. Patients who experience fever or increase in core temperature should be monitored closely. Application site reactions, including rare cases of severe reactions (eg, vesicles, discharge,“burns”), have been observed with use; onset varies from days to months after initiation; patients should be instructed to report severe reactions promptly. Therapy with the transdermal patch is not appropriate for use in the management of addictions.
Other warnings/precautions:
• Abuse/misuse/diversion: Transdermal patch: [U.S. Boxed Warning]: Healthcare provider should be alert to problems of abuse, misuse, and diversion.
• Optimal pain regimen: An opioid-containing analgesic regimen should be tailored to each patient's needs and based upon the type of pain being treated (acute versus chronic), the route of administration, degree of tolerance for opioids (naive versus chronic user), age, weight, and medical condition. The optimal analgesic dose varies widely among patients; doses should be titrated to pain relief/prevention.
• Withdrawal: Concurrent use of agonist/antagonist analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Abrupt discontinuation following prolonged use may also lead to withdrawal symptoms. Tablets, which are used for induction treatment of opioid dependence, should not be started until effects of withdrawal are evident.
Adverse Reactions
Injection:
>10%: Central nervous system: Sedation
1% to 10%:
Cardiovascular: Hypotension
Central nervous system: Respiratory depression, dizziness, headache
Gastrointestinal: Vomiting, nausea
Ocular: Miosis
Otic: Vertigo
Miscellaneous: Diaphoresis
<1%: Agitation, allergic reaction, apnea, appetite decreased, blurred vision, bradycardia, confusion, constipation, convulsion, coma, cyanosis, depersonalization, depression, diplopia, dyspnea, dysphoria, euphoria, fatigue, flatulence, flushing, hallucinations, hypertension, injection site reaction, malaise, nervousness, pallor, paresthesia, pruritus, psychosis, rash, slurred speech, tachycardia, tinnitus, tremor, urinary retention, urticaria, weakness, Wenckebach block, xerostomia
Tablet:
>10%:
Central nervous system: Headache (30%), pain (24%), insomnia (21% to 25%), anxiety (12%), depression (11%)
Gastrointestinal: Nausea (10% to 14%), abdominal pain (12%), constipation (8% to 11%)
Neuromuscular & skeletal: Back pain (14%), weakness (14%)
Respiratory: Rhinitis (11%)
Miscellaneous: Withdrawal syndrome (19%; placebo 37%), infection (12% to 20%), diaphoresis (12% to 13%)
1% to 10%:
Central nervous system: Chills (6%), nervousness (6%), somnolence (5%), dizziness (4%), fever (3%)
Gastrointestinal: Vomiting (5% to 8%), diarrhea (5%), dyspepsia (3%)
Ocular: Lacrimation (5%)
Respiratory: Cough (4%), pharyngitis (4%)
Miscellaneous: Flu-like syndrome (6%)
Transdermal patch:
>10%:
Central nervous system: Headache (16%), dizziness (16%), somnolence (14%),
Gastrointestinal: Nausea (23%), constipation (14%), vomiting (11%)
Local: Application site pruritus (15%)
1% to 10%:
Cardiovascular: Peripheral edema (7%), chest pain, hypertension
Central nervous system: Fatigue (5%), insomnia (3%), hypoesthesia (2%), anxiety, depression, fever, migraine
Dermatologic: Pruritus (4%), rash (2%)
Gastrointestinal: Xerostomia (7%), diarrhea (3%), abdominal discomfort (2%), anorexia (2%), upper abdominal pain
Genitourinary: Urinary tract infection (3%)
Local: Application site erythema (7%); application site rash (6%), application site irritation
Neuromuscular & skeletal: Pain in extremity (3%), back pain (3%), joint swelling (3%), paresthesia (2%), tremor (2%), muscles spasms, musculoskeletal pain, myalgia, neck pain, weakness
Respiratory: Dyspnea (3%), bronchitis, cough, nasopharyngitis, pharyngolaryngeal pain, sinusitis, upper respiratory tract infection
Miscellaneous: Hyperhydrosis (4%), fall (4%), flu-like syndrome
<1% (Limited to important or life-threatening): ALT increased, angina, angioedema, application site dermatitis, contact dermatitis, hypersensitivity, facial edema, hallucination, hypotension, ileus, loss of consciousness, mental status changes, miosis (dose-related), orthostatic hypotension, respiratory depression, respiratory distress, respiratory failure, syncope, tachycardia, urinary incontinence, urinary retention, visual disturbances, withdrawal syndrome
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP1A2 (weak), CYP2A6 (weak), CYP2C19 (weak), CYP2D6 (weak)
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alvimopan: Analgesics (Opioid) may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification
Ammonium Chloride: May increase the excretion of Analgesics (Opioid). Risk C: Monitor therapy
Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Risk C: Monitor therapy
Analgesics (Opioid): Mixed Agonist / Antagonist Opioids may diminish the analgesic effect of Analgesics (Opioid). Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Risk D: Consider therapy modification
Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Analgesics (Opioid). Risk C: Monitor therapy
Atazanavir: May increase the serum concentration of Buprenorphine. Buprenorphine may decrease the serum concentration of Atazanavir. Management: Avoid this combination in patients un-boosted atazanavir due to possible decreased atazanavir concentrations. This combination is not contraindicated in patients also receiving ritonavir, but monitoring for buprenorphine toxicity is recommended. Risk X: Avoid combination
Boceprevir: May decrease the serum concentration of Buprenorphine. Boceprevir may increase the serum concentration of Buprenorphine. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Efavirenz: May decrease serum concentrations of the active metabolite(s) of Buprenorphine. Efavirenz may decrease the serum concentration of Buprenorphine. Risk C: Monitor therapy
Etravirine: May decrease the serum concentration of Buprenorphine. Risk C: Monitor therapy
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MAO Inhibitors: Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors. Risk X: Avoid combination
Mixed Agonist / Antagonist Opioids: May diminish the analgesic effect of Analgesics (Opioid). Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Risk D: Consider therapy modification
Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: Analgesics (Opioid) may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk C: Monitor therapy
Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Risk C: Monitor therapy
Thiazide Diuretics: Analgesics (Opioid) may enhance the orthostatic hypotensive effect of Thiazide Diuretics. Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effect.
Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
Storage
Injection: Protect from excessive heat >40°C (>104°F). Protect from light.
Patch, tablet: Store at room temperature of 25°C (77°F).
Compatibility
Injection:
Y-site administration: Compatible: Acetaminophen, allopurinol, amifostine, aztreonam, cefepime, cisatracurium, cladribine, docetaxel, etoposide phosphate, filgrastim, gemcitabine, granisetron, linezolid, melphalan, oxaliplatin, pemetrexed, piperacillin/tazobactam, propofol, remifentanil, teniposide, thiotepa, vinorelbine. Incompatible: Amphotericin B cholesteryl sulfate complex, doxorubicin liposome.
Compatibility in syringe: Compatible: Bupivacaine, chlorpromazine, glycopyrrolate and haloperidol, heparin, midazolam.
Mechanism of Action
Buprenorphine exerts its analgesic effect via high affinity binding to μ opiate receptors in the CNS; displays partial mu agonist and weak kappa antagonist activity
Pharmacodynamics/Kinetics
Onset of action: Analgesic: I.M: Within 15 minutes
Peak effect: I.M.: ~1 hour; Transdermal patch: Steady state achieved by day 3
Duration: I.M.: ≥6 hours
Absorption: I.M., SubQ: 30% to 40%
Distribution: Vd: 97-187 L/kg
Protein binding: High (~96%, primarily to alpha- and beta globulin)
Metabolism: Primarily hepatic via N-dealkylation by CYP3A4 to norbuprenorphine (active metabolite), and to a lesser extent via glucuronidation by UGT1A1 and 2B7 to buprenorphine 3-O-glucuronide; the major metabolite, norbuprenorphine, also undergoes glucuronidation via UGT1A3; extensive first-pass effect
Bioavailability (relative to I.V. administration): I.M.: 70%; Sublingual tablet: 29%; Transdermal patch: ~15%
Half-life elimination: I.V.: 2.2-3 hours; Apparent terminal half-life: Sublingual tablet: ~37 hours; Transdermal patch: ~26 hours. Note: Extended elimination half-life for sublingual administration may be due to depot effect (Kuhlman, 1996).
Time to peak, plasma: Sublingual: 30 minutes to 1 hour (Kuhlman, 1996)
Excretion: Feces (~70%); urine (27% to 30%)
Dosage
I.M., I.V.: Acute pain (moderate-to-severe): Note: Long-term use is not recommended. The following recommendations are guidelines and do not represent the maximum doses that may be required in all patients. Doses should be titrated to pain relief/prevention. In high-risk patients (eg, elderly, debilitated, presence of respiratory disease) and/or concurrent CNS depressant use, reduce dose by one-half. Buprenorphine has an analgesic ceiling.
Children 2-12 years: I.M., slow I.V.: 2-6 mcg/kg every 4-6 hours
Children ≥13 years and Adults:
I.M.: Initial: Opiate-naive: 0.3 mg every 6-8 hours as needed; initial dose (up to 0.3 mg) may be repeated once in 30-60 minutes after the initial dose if needed; usual dosage range: 0.15-0.6 mg every 4-8 hours as needed
Slow I.V.: Initial: Opiate-naive: 0.3 mg every 6-8 hours as needed; initial dose (up to 0.3 mg) may be repeated once in 30-60 minutes after the initial dose if needed
Adults: I.V. infusion: Opiate withdrawal in heroin-dependent hospitalized patients (unlabeled): 0.3-0.9 mg (diluted in 50-100 mL of NS) over 20-30 minutes every 6-12 hours (Welsh, 2002)
Sublingual tablet: Children ≥16 years and Adults: Opioid dependence: Note: The combination product, buprenorphine and naloxone, is preferred therapy over buprenorphine monotherapy for induction treatment (and stabilization/maintenance treatment) for short-acting opioid dependence (U.S. Department of Health and Human Services, 2005).
Manufacturer's labeling:
Induction: Day 1: 8 mg; Day 2 and subsequent induction days: 16 mg; usual induction dosage range: 12-16 mg/day (induction usually accomplished over 3-4 days). Treatment should begin at least 4 hours after last use of heroin or other short-acting opioids, preferably when first signs of withdrawal appear. Titrating dose to clinical effectiveness should be done as rapidly as possible to prevent undue withdrawal symptoms and patient drop-out during the induction period. There is little controlled experience with induction in patients on methadone or other long-acting opioids; consult expert physician experienced with this procedure.
Maintenance: Target dose: 16 mg/day; in some patients 12 mg/day may be effective; patients should be switched to the buprenorphine/naloxone combination product for maintenance and unsupervised therapy
Transdermal patch: Adults: Chronic pain (moderate-to-severe):
Opioid-naive patients: Initial: 5 mcg/hour applied once every 7 days
Opioid-experienced patients (conversion from other opioids to buprenorphine): Taper the current around-the-clock opioid for up to 7 days to ≤30 mg/day of oral morphine or equivalent before initiating therapy. Short-acting analgesics as needed may be continued until analgesia with transdermal buprenorphine is attained. There is a potential for buprenorphine to precipitate withdrawal in patients already receiving opioids.
Patients who were receiving daily dose of <30 mg of oral morphine equivalents: Initial: 5 mcg/hour applied once every 7 days
Patients who were receiving daily dose of 30-80 mg of oral morphine equivalents: Initial: 10 mcg/hour applied once every 7 days
Dose titration (opioid-naive or opioid-experienced patients): May increase dose, based on patient's supplemental short-acting analgesic requirements, with a minimum titration interval of 72 hours (maximum dose: 20 mcg/hour applied once every 7 days; risk for QTc prolongation increases with doses ≥20 mcg/hour patch).
Discontinuation of therapy: Taper dose gradually to prevent withdrawal; consider initiating immediate-release opioids, if needed.
Elderly:
I.M., slow I.V.: 0.15 mg every 6 hours; elderly patients are more likely to suffer from confusion and drowsiness compared to younger patients
Transdermal patch: Chronic pain (moderate-to-severe): No specific dosage adjustments required; use caution due to potential for increased risk of adverse events. Refer to adult dosing.
Dosage adjustment in hepatic impairment:
Injection, sublingual tablet: Use caution due to extensive hepatic metabolism; dosage adjustments recommended although no specific recommendations are provided by the manufacturer.
Transdermal patch:
Mild-to-moderate impairment: Initial: 5 mcg/hour applied once every 7 days
Severe impairment: Not studied; consider alternative therapy with more flexibility for dosing adjustments
Administration: Oral
Sublingual: Tablet should be placed under the tongue until dissolved; should not be swallowed. If two or more tablets are needed per dose, all may be placed under the tongue at once, or two at a time. To ensure consistent bioavailability, subsequent doses should always be taken the same way.
Administration: I.M.
Administer via deep I.M. injection.
Administration: I.V.
Administer slowly, over at least 2 minutes. Administration over 20-30 minutes preferred when managing opioid withdrawal in heroin-dependent hospitalized patients (Welsh, 2002).
Administration: Other
Transdermal patch: Apply to patch to intact, nonirritated skin only. Apply to a hairless or nearly hairless skin site. If hairless site is not available, do not shave skin; hair at application site should be clipped. Prior to application, if the site must be cleaned, clean with clear water and allow to dry completely; do not use soaps, alcohol, lotions or abrasives due to potential for increased skin absorption. Do not use any patch that has been damaged, cut or manipulated in any way. Remove patch from protective pouch immediately before application. Remove the protective backing, and apply the sticky side of the patch to one of eight possible application sites (upper outer arm, upper chest, upper back, or the side of the chest [on either side of the body]). Firmly press patch in place and hold for ~15 seconds. Change patch every 7 days. Rotate patch application sites; wait ≥21 days before reapplying another patch to the same skin site. Avoid exposing application site to external heat sources (eg, heating pad, electric blanket, heat lamp, hot tub). If there is difficulty with patch adhesion, the edges of the system may be taped in place with first-aid tape. If the patch falls off during the 7-day dosing interval, dispose of the patch and apply a new patch to a different skin site.
Administration: I.V. Detail
pH: 3.5-5.5
Monitoring Parameters
Pain relief, respiratory and mental status, CNS depression, blood pressure; LFTs (prior to initiation and during therapy); symptoms of withdrawal; application site reactions (transdermal patch)
Patient Education
Apply transdermal patch to hairless site; if that is impossible, then clip hair; do not shave (as absorption from patch can be increased). Have patient avoid external heat sources (increases absorption from patch). Do not use alcohol, sedatives, tranquilizers, antihistamines, or pain medications without consulting prescriber. May cause dizziness, drowsiness, confusion, or blurred vision. You may experience nausea, vomiting, or constipation. If constipation is unresolved, consult prescriber about use of stool softeners and/or laxatives. Report unresolved nausea or vomiting, severe dizziness, respiratory difficulty or shortness of breath, excessive sedation or unusual weakness, or rapid heartbeat or palpitations.
Take with or without food once daily. May cause hypertension or headache. Report increase or changes in CNS symptoms (confusion, hallucinations, fatigue, aggressive reaction), chest pain or palpitations, dizziness or fainting, difficulty breathing or tightness in chest, or rash.
Geriatric Considerations
One postmarketing study found that elderly patients were more likely to suffer from confusion and drowsiness after buprenorphine as compared to younger patients. Use transdermal system with caution in the elderly. Respiratory depression occurs more frequently in the elderly. In clinical trials, the incidence of adverse events was higher in older subjects.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Buprenorphine has a longer duration of action than either morphine or meperidine. It may precipitate withdrawal in narcotic-dependent patients because the antagonist action at the kappa receptor prevails. Buprenorphine has a better safety profile than methadone because of its slow release from mu receptors, which limits withdrawal signs and symptoms. It is 25-40 times more potent than similar mg doses of morphine. Because it is a partial mu agonist, its analgesic effects plateau at higher doses and it then behaves like an antagonist. Buprenorphine is not readily reversed by naloxone.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Drowsiness is common; rare reports of euphoria
Mental Health: Effects on Psychiatric Treatment
Concurrent use with benzodiazepines or barbiturates may result in CNS or respiratory depression
Nursing: Physical Assessment/Monitoring
Monitor for effectiveness of pain relief. Monitor for possible respiratory depression prior to treatment and periodically throughout. For inpatients, implement safety measures to prevent falls. Assess patient's physical and/or psychological dependence. Discontinue slowly after prolonged use.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, solution: 0.3 mg/mL (1 mL)
Buprenex®: 0.3 mg/mL (1 mL)
Injection, solution [preservative free]: 0.3 mg/mL (1 mL)
Patch, transdermal:
Butrans®: 5 mcg/hr (4s) [total buprenorphine 5 mg]
Butrans®: 10 mcg/hr (4s) [total buprenorphine 10 mg]
Butrans®: 20 mcg/hr (4s) [total buprenorphine 20 mg]
Tablet, sublingual: 2 mg, 8 mg
Subutex®: 2 mg [DSC], 8 mg [DSC]
Pricing: U.S. (www.drugstore.com)
Patch weekly (Butrans)
20 mcg/hr (4): $380.00
Solution (Buprenex)
0.3 mg/mL (5): $55.99
Sublingual (Buprenorphine HCl)
2 mg (30): $75.99
8 mg (30): $99.99
Sublingual (Subutex)
2 mg (30): $193.99
8 mg (30): $357.01
References
Center for Substance Abuse Treatment, Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction, Treatment Improvement Protocol (TIP) Series 40. DHHS Publication No. (SMA) 04‐3939. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2004
“Drugs for Pain,” Med Lett Drugs Ther, 2000, 42(1085):73-8.
Gal TJ, “Naloxone Reversal of Buprenorphine-Induced Respiratory Depression,” Clin Pharmacol Ther, 1989, 45(1):66-71.
Harcus AH, Ward AE, and Smith DW, “Buprenorphine: Experience in an Elderly Population of 975 Patients During a Year's Monitored Release,” Br J Clin Pract, 1980, 34(5):144-6.
Jain PN and Shah SC, “Respiratory Depression Following Combination of Epidural Buprenorphine and Intramuscular Ketorolac,” Anaesthesia, 1993, 48(10):898-9.
Kuhlman JJ Jr, Lalani S, Magluilo J Jr, et al, “Human Pharmacokinetics of Intravenous, Sublingual and Buccal Buprenoprhine,” J Anal Toxicol, 1996, 20(6):369-78.
MacEvilly M and O'Carroll C, “Hallucinations After Epidural Buprenorphine,” Br Med J, 1989, 298(6678):928-9.
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
“Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain,” 6th ed, Glenview, IL: American Pain Society, 2008.
Sporer KA, “Buprenorphine: A Primer for Emergency Physicians,” Ann Emerg Med, 2004, 43(5):580-4.
Welsh CJ, Suman M, Cohen A, et al, “The Use of Intravenous Buprenorphine for the Treatment of Opioid Withdrawal in Medically Ill Hospitalized Patients,” Am J Addict, 2002, 11(2): 135-40.
International Brand Names
Lexi-Comp.com
Last full review/revision January 2012
Content last modified January 2012
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