Dosing & Uses
Dosage Forms & Strengths
injectable solution: Schedule III (Buprenex)
- 0.3mg/mL
tablet, sublingual: Schedule III (generic)
- 2mg
- 8mg
Moderate-to-Severe Pain
0.3 mg IV/IM q6hr; may be repeated once (up to 0.3 mg) if required 30-60 minutes after initial dose
Also see Administration
Opioid Dependence
Induction (sublingual tablet)
- 8 mg SL on day 1, then 16 mg SL on day 2; continued over 3-4 days
Maintenance (buprenorphine-naloxone combination)
- Switch to buprenorphine/naloxone combination for unsupervised maintenance
- For dosing, see drug monograph for buprenorphine/naloxone
Dosage Modifications
Renal impairment
- No differences in pharmacokinetics observed between 9 dialysis-dependent and 6 normal patients following IV administration of 0.3 mg buprenorphine
- Renal failure: Pharmacokinetics are unknown
Hepatic impairment
- SL use
- Mild: No dose adjustment is needed
- Moderate: No dose adjustment is necessary, closely monitor for signs and symptoms of toxicity or overdose
- Severe: Reducing starting and titration incremental dose by half, and monitor for signs and symptoms of toxicity or overdose
- IV/IM use
- Mild-to-moderate: No dosage adjustments provided
- Severe: No dosage adjustment provided; use with caution
Dosing Considerations
For prescriber qualifications, see prescribing information
Also given in combination with naloxone
Induction with SL tablets
- Patients dependent on heroin or other short-acting opioids
- At initiation, administer first dose of buprenorphine SL tablets only when signs/symptoms of moderate opioid withdrawal appear, and ≥4 hr after patient last used an opioid
- Titrate to clinical effectiveness achieved as rapidly as possible; dosing on the initial day of treatment may be given in 2-4 mg increments if preferred
- Patients dependent on methadone or other long-acting opioids
- Administer first dose of buprenorphine sublingual tablets should when clear signs/symptoms of moderate opioid withdrawal appear, and generally ≥24 hr after the patient last used a long-acting opioids
Dosage Forms & Strengths
injectable solution: Schedule III (Buprenex)
- 0.3mg/mL
Moderate-to-Severe Pain
0.15 mg IV/IM q6hr; titrate slowly due to increase risk of respiratory depression
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10% (SL)
Headache (29.1-30%)
Pain (18.4-24%)
Withdrawal syndrome (18.4-22%)
Insomnia (21.4%)
Infection (20%)
Asthenia (14%)
Back pain (7.8-14%)
Nausea (10-13.6%)
Sweating (12-12.6%)
Abdominal pain (11.7%)
Infection (11.7%)
Constipation (7.8-11%)
1-10% (IV/IM)
5-10%
- Nausea
- Dizziness/vertigo
1-5%
- Sweating
- Headache
- Hypotension
- Nausea/vomiting
- Hypoventilation
- Miosis
1-10% (SL)
Rhinitis (9.7%)
Chills (6-7.8%)
Vomiting (5-7.8%)
Flu syndrome (6%)
Nervousness (6%)
Runny eyes (5%)
Diarrhea (4.9-5%)
Asthenia (4.9%)
Vasodilation (3.9%)
Fever (3%)
Dyspepsia (3%)
Accidental injury (2-3%)
Abscess (2%)
<1%
Confusion, blurred vision, euphoria, weakness/fatigue, dry mouth, nervousness, depression, slurred speech, paresthesia
Hypertension, tachycardia, bradycardia
Constipation
Dyspnea, cyanosis
Pruritus
Diplopia, visual abnormalities
Injection site reaction, urinary retention, dreaming, flushing/warmth, chills/cold, tinnitus, conjunctivitis, Wenckebach block, and psychosis
Other effects observed infrequently include malaise, hallucinations, depersonalization, coma, dyspepsia, flatulence, apnea, rash, amblyopia, tremor, and pallor
Postmarketing Reports
Serotonin syndrome
Adrenal insufficiency
Anaphylaxis
Androgen deficiency
Glossodynia, glossitis, oral mucosal erythema, oral hypoesthesia, and stomatitis
Warnings
Black Box Warnings
Opioid analgesic risk evaluation and mitigation strategy (REMS)
- To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products; under requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers
- Healthcare providers are strongly encouraged to:
- Complete a REMS-compliant education program
- Counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products
- Emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist
- Consider other tools to improve patient, household, and community safety
- To obtain further information on opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com; the FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint
Addiction, abuse, and misuse
- Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death
- Assess each patient’s risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions
Life-threatening respiratory depression
- Serious, life-threatening, or fatal respiratory depression may occur
- Monitor for respiratory depression, especially during initiation or following a dose increase
Accidental exposure
- Accidental exposure of even 1 dose, especially by children, can result in a fatal overdose
Neonatal opioid withdrawal syndrome
- Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
- Syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight
- Onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn
- If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available
Risks from concomitant use with benzodiazepines or other CNS depressants
- Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; reserve concomitant use in patients for whom alternative treatment options are inadequate; limit dosages and durations to minimum required; and monitor for signs and symptoms of respiratory depression and sedation
Contraindications
Hypersensitivity
Significant respiratory depression
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
Known or suspected gastrointestinal obstruction, including paralytic ileus
Cautions
Partial agonist at the mu opioid receptor and a schedule III controlled opioid exposes users to the risks of addiction, abuse, and misuse; there is a greater risk for overdose and death with extended-release opioids owing to the larger amount of active opioid present (see Black Box Warnings)
Serious, life-threatening, or fatal respiratory depression reported; may occur more frequently in elderly or debilitated patients, or in conditions associated with hypoxia or hypercapnia (even moderate therapeutic doses) (see Black Box Warnings)
Neonatal opioid withdrawal syndrome reported with long-term use during pregnancy (see Black Box Warnings)
Accidental exposure reported, including fatalities (see Black Box Warnings)
May impair mental or physical abilities needed to perform potentially hazardous activities (eg, driving a car, operating machinery)
Risk of apnea in patients with chronic pulmonary disease; closely monitor these patients, when initiating and titrating therapy; alternatively, consider the use of alternative non-opioid analgesics in these patients (see Black Box Warnings and Contraindications)
QTc prolongation observed in healthy individuals at 40 mcg/hr; avoid in patients with history of long QT syndrome or coadministration with class IA (eg, quinidine, procainamide, disopyramide) or class III (eg, sotalol, amiodarone, dofetilide) antiarrhythmics
Respiratory depressant effects of opioids may include carbon dioxide retention and lead to elevated CSF pressure
Can cause severe hypotension; caution with depleted blood volume or coadministration of drugs that that affect vasomotor tone (eg, phenothiazines), vasodilators, or antihypertensives
Hypothyroidism, myxedema, adrenocortical insufficiency, alcohol intoxication, alcohol withdrawal syndrome, coma, geriatric or debilitated patients, delirium tremens, toxic psychoses, kyphoscoliosis, prostatic hypertrophy, urethral stricture, central nervous system (CNS) depression, biliary tract dysfunction, head injury, intracranial lesions, intracranial hypertension or conditions in which intracranial pressure may be increased
Cases of cytolytic hepatitis and hepatitis with jaundice observed in individuals receiving buprenorphine SL for opioid dependence treatment; increased risk for overdose with moderate or severe hepatic impairment (see Dosage Modifications)
Anaphylactic reactions reported
May cause sphincter of Oddi spasm and aggravate abdominal conditions, including ileus (see Contraindications)
Similar to other opioids, may aggravate seizure disorders by lowering seizure threshold
Special risk groups may experience increased adverse reactions; caution with alcoholism, delirium tremens, adrenocortical insufficiency, CNS depression, debilitation, kyphoscoliosis associated with respiratory compromise, myxedema or hypothyroidism, prostatic hypertrophy or urethral stricture, severe impairment of hepatic, pulmonary or renal function, and toxic psychosis
Prescribers should discuss with patients importance and benefits of management of opioid addiction throughout pregnancy
Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean patient off of opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers; other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency
Consider discontinuing therapy 24-36 hr prior anticipated need for surgical anesthesia to undergo elective surgery; may administer short-acting opioids during and/or after surgery; in patients unable to abruptly discontinue therapy may add full opioid to buprenorphine to maintain proper anesthesia; increased doses may be required to overcome buprenorphine receptor blockade; continuously monitor if opioid therapy required as part of anesthesia in an anesthesia care setting
Abrupt discontinuation following prolonged therapy may lead to withdrawal symptoms; not recommended; taper gradually
Use caution in patients who are morbidly obese
Avoid use in patients with impaired consciousness or coma; patients are susceptible to intracranial effects of CO2 retention
Use caution in patients with a history of ileus or bowel obstruction; contraindicated in patients with known or suspected GI obstruction including paralytic ileus
Chronic use of opioids may cause reduced fertility in females and males of reproductive potential; unknown whether effects on fertility are reversible (see Pregnancy)
Drug interactions overview
- Concomitant use of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose and death (See Black Box Warnings)
- Opioids may reduce efficacy of diuretics by inducing release of antidiuretic hormone
- Anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus; monitor for signs of urinary retention or reduced gastric motility when buprenorphine is concomitantly used with anticholinergics
- Serotonergic drugs
- Opioids may enhance serotonergic effect of drugs (eg, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors) that affect the serotonergic neurotransmitter system; which increases the risk of serotonin syndrome; if concomitant use is warranted, monitor; discontinue if serotonin syndrome is suspected
- Use of MAOIs with buprenorphine is not recommended during or within 14 days of discontinuing treatment
- CYP3A4 inhibitors
- Concomitant use of buprenorphine and CYP3A4 inhibitor may increase the plasma concentration of buprenorphine, resulting increased or prolonged opioid effects; specifically when adding a CYP3A4 inhibitor after achieving a stable buprenorphine dose
- CYP3A4 inducers
- Concomitant use of buprenorphine and CYP3A4 inducers may decrease plasma concentration of buprenorphine, potentially resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine
Pregnancy & Lactation
Pregnancy
Data in pregnancy are limited; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure; observational studies reported on congenital malformations among exposed pregnancies, but were also not designed appropriately to assess risk of congenital malformations specifically due to drug exposure
Dosage adjustments of buprenorphine may be required during pregnancy, even if patient was maintained on stable dose prior to pregnancy; withdrawal signs and symptoms should be monitored closely and the dose adjusted as necessary
Fetal/neonatal adverse reactions
- Neonatal opioid withdrawal syndrome may occur in newborn infants of mothers who are receiving treatment
Lactation
Data on two studies in 13 lactating women receiving therapy where the drug and it metabolite were present in low levels in human milk did not show adverse reactions in breastfed infants; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition
Advise breastfeeding women taking buprenorphine products to monitor infant for increased drowsiness and breathing difficulties
Pregnancy Categories
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Pharmacology
Mechanism of Action
Semisynthetic narcotic mixed agonist-antagonist analgesic; exerts agonistic effects at mu and delta opioid receptors in CNS and antagonistic effects at kappa opioid receptor
Absorption
Onset: 15 min (IM); ~1 hr (IV)
Duration: >6 hr (IM)
Peak plasma time: 1.84 hr (2-mg SL dose); 1.28 hr (8-mg SL dose); 1.42 hr (16-mg SL dose)
Peak plasma concentration: 1.25 ng/mL (2-mg SL dose); 2.88 ng/mL (8-mg SL dose); 4.7 ng/mL (16-mg SL dose)
AUC: 10.93 hr·ng/mL (2-mg SL dose); 28.39 hr·ng/mL (8-mg SL dose); 47.09 hr·ng/mL (16-mg SL dose)
Distribution
Protein bound: 96%, primarily to alpha and beta globulin
Metabolism
Buprenorphine undergoes both N-dealkylation to norbuprenorphine and glucuronidation
N-dealkylation pathway is mediated primarily by CYP3A4
Metabolites: Norbuprenorphine (N-dealkylbuprenorphine)
Elimination
Mean half-life: 2.2 hr (IV); 31-35 hr (SL)
Excretion: Urine (30%), feces (69%)
Administration
IV Incompatibilities
Additive: Floxacillin, furosemide
Y-site: Amphotericin B cholesteryl sulfate, doxorubicin liposomal
IV Compatibilities
Additive: Bupivacaine
Syringe: Heparin, midazolam
Y-site: Allopurinol, amifostine, aztreonam, cefepime, cisatracurium, cladribine, docetaxel, etoposide phosphate, filgrastim, gatifloxacin, gemcitabine, granisetron, linezolid, melphalan, piperacillin-tazobactam, propofol, remifentanil, teniposide, thiotepa, vinorelbine
IV Preparation
Solution: Dilute to final concentration of 15 mcg/mL in D5W, D5/NS, NS, or LR
Administer via controlled infusion device
IV/IM Administration
Administer by deep IM injection or by slow IV injection over ≥2 minutes
Storage
Injection: Store at 20-25°C (68-77°F)
SL tablets: Store at 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F)
Protect from prolonged exposure to light
Images
Patient Handout
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
