Names and pronunciation
B rems (byoo-pre-nor′feen) Belbuca, Buprenex, Butrans, Probuphine, Sublocade
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Drug reference
B rems (byoo-pre-nor′feen) Belbuca, Buprenex, Butrans, Probuphine, Sublocade
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Func. class.: Opioid analgesic, partial agonist
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Chem. class.: Thebaine derivative Controlled Substance Schedule III
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ACTION: Depresses pain impulse transmission at the spinal cord level by interacting with opioid receptors, partial agonist at μ-opioid receptor
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USES: Moderate to severe pain, opiate agonist withdrawal/dependence
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Unlabeled uses: Cocaine withdrawal
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CONTRAINDICATIONS: Hyper- sensitivity, ileus, status asthmaticus
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Black Box Warning: Respiratory depres- sion Precautions: Pregnancy, breastfeeding, substance abuse/alcoholism, increased intracranial pressure, MI (acute), severe heart disease, respiratory depression, renal/hepatic/pulmonary disease, hypo- thyroidism, Addison’s disease, QT pro- longation, accidental exposure, neonatal opioid withdrawal syndrome Black Box Warning: Potential for over- dose/poisoning, substance abuse, IM, coadministration with other CNS depres- sants, implant insertion and removal Black Box Warning: Accidental expo- sure: keep away from children and pets; may be fatal • I&O ratio; check for decreasing out- put; may indicate urinary retention • Bowel pattern; severe constipation can occur • CNS changes, dizziness, drowsiness, hal- lucinations, euphoria, LOC, pupil reaction; withdrawal in opioid-dependent persons • Allergic reactions: rash, urticaria Black Box Warning: Respiratory dys- function: respiratory depression, char- acter, rate, rhythm; notify prescriber if respirations are <12/min, may be fatal Black Box Warning: Potential for over- dose may occur from chewing, swallow- ing, snorting, or injecting extracted product from TD formulation • QT prolongation: in those taking class Ia, III antidysrhythmics; patients with hy- pokalemia, cardiac instability (TD), max TD 20 mcg/hr q7day • Beers: avoid in older adults unless safer alternatives are not available, may cause impaired psychomotor function, syncope • Pregnancy/breastfeeding: avoid use in pregnancy and breastfeeding; in those using product and breastfeeding, watch infant for decreased respiration, lethargy, decreased heart rate Black Box Warning: That psychologic de- pendence leading to substance abuse may result when used for extended periods; that long-term use is not recommended • That product can cause serious breathing problems; call provider right away if feeling faint, dizzy, or if breath- ing gets much slower than normal • To avoid hazardous activities such as driving unless reaction is known • Do not start new meds/herbs without prescriber approval; do not double, skip doses • Start stool softener/laxatives to lessen constipation • SL route: to place under tongue and allow to dissolve • Transdermal route: how to apply and dispose of patch; not to use a heating pad or other heat source; do not cut
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SIDE EFFECTS CNS: Drowsiness, dizziness, confu- sion, headache, sedation, euphoria, hallucinations, strange dreams CV: Palpitations, QT prolongation, hypo/ hypertension EENT: Tinnitus, blurred vision, miosis, diplopia GI: Nausea, vomiting, anorexia, consti- pation, dry mouth, hepatotoxicity GU: Urinary retention INTEG: Rash, diaphoresis, pruritus RESP: Respiratory depression, bronchospasm MISC: Anaphylaxis, angioedema, dependency
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INTERACTIONS Increase: effect with other CNS depres- sants—alcohol, opioids, sedative/hyp- notics, antipsychotics, skeletal muscle relaxants, MAOIs Increase: buprenorphine effect— CYP3A4 inhibitors (erythromycin, indinavir, ketoconazole, ritonavir, saquinavir) Increase: QT prolongation—class IA, III antidysrhythmics Increase: serotonin syndrome 5-HT3 antagonists, linezolid, methylene blue, MAOIs, SSRIs, SNRIs, tricyclics Decrease: buprenorphine effect— CYP3A4 inducers (carBAMazepine, PHE- Nobarbital, phenytoin, rifampin) Drug/Herb Increase: CNS depression—chamomile, kava, St. John’s wort
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TREATMENT OF OVERDOSE: Naloxone 0.4 mg ampule diluted in 10 mL 0.9% NaCl given by direct IV push 0.02 mg q2min (adult)
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DOSAGE AND ROUTES Moderate/severe pain • Adult/child ≥13 yr: IM/IV 0.3 mg q4- 6hr as needed: TD each patch is worn for 7 days (moderate-severe pain); opioid- naive patients (those taking <30 mg of oral morphine or equivalent before begin- ning treatment with TD buprenorphine), 5 mcg/hr q7days, overestimating dose can be fatal; conversion from other opiate agonist therapy, titrate from other opi- oids for up to 7 days to no more than 30 mg oral morphine or equivalent before beginning TD therapy, begin with 5 mcg/hr q7days; for those with daily dose of 30-80 mg oral morphine or equivalent, start with 10 mcg/hr q7days; for those taking >80 mg oral morphine or equivalent, start with 20 mcg/hr q7days • Geriatric/debilitated patients: IM/IV 0.15 mg slowly • Child 2-12 yr: IM/IV 2-6 mcg/kg q4-8hr, give IV over ≥2 min Opioid dependence Adult: SL 8 mg on day 1 and 16 mg on day 2, titrate in increments of 2 or 4 mg up or down to needed, maintenance dose 4-24 mg SL daily Hepatic dose Adult TD (mild-moderate): 5 mcg/hr system initially disease): Buccal (severe hepatic decrease dose by 50%, titrate upward by 75 mcg q12hr ≥q4days
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Available forms: Injection 0.3 mg/mL (1-mL vials); SL tablet 2, 8 mg as base; TD system 5, 7.5, 10, 15, 20 mcg/hr (weekly); dissolving film (buccal) 75, 150, 300, 450, 600, 750, 900 mcg; solution for injection, extended release 100 mg/0.5 mL, 300 mg/1.5 mL; SD implant 74.2 mg/implant
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Administer: SL route • Do not chew; dissolve under tongue, use 2 or more at same time Transdermal route (REMS) • Apply to clean, dry, intact skin; each patch should be worn for 7 days, do not exceed dose, QTC prolongation may oc- cur; do not apply direct heat source to patch, will increase absorption of prod- uct, may use first-aid tape if edge of patch is not adhering • Apply to upper outer arm, upper chest/back, or side of chest Subcut route (extended-release injection—Sublocade) • Inject only in abdominal region. DO NOT use IM/IV • Visually inspect for particulate matter, discoloration before use; product is clear, colorless to yellow to amber solution • Give monthly with a minimum of 26 days between doses • Use only the syringe and safety needle included. Do not attach the needle until time of use • Do not inject into an area where skin is irritated, reddened, bruised, infected, or scarred • Do not rub area after injection • To avoid irritation, rotate injection site with each injection • Injection site should be examined for infection, evidence of tampering, or at- tempts to remove the depot • Storage: Store unopened prefilled syringes in the refrigerator in original packaging; do not freeze. Discard injec- tion if left at room temperature for lon- ger than 7 days Subdermal route (Probuphine) • Inserted in inner side of upper arm • Maintenance dose must be 8 mg/day or less • Use guideline from manufacturer • Available from REMS program (844- 859-6341), health care professional must complete training program • Inserts are removed after 6 mo, if other insert is not used, use transmucosal IM route • In deep muscle mass IV, direct route • Give undiluted over ≥2 min, titrate to patient response; rapid injection will in- crease side effects • With antiemetic if nausea, vomiting occur • When pain is beginning to return; de- termine dosage interval by patient re- sponse Y-site compatibilities: Acyclovir, alfent- anil, allopurinol, amifostine, amikacin, aminocaproic acid, amphotericin B lipo- some (AmBisome), anidulafungin, ascor- bic acid injection, atenolol, atracurium, atropine, aztreonam, benztropine, bivali- rudin, bleomycin, bumetanide, butorpha- nol, calcium chloride/gluconate, CARBOplatin, cefamandole, ceFAZolin, cefepime, cefotaxime, cefoTEtan, cefOXitin, cefTAZi- dime, ceftizoxime, cefTRIAXone, cefurox- ime, chloramphenicol, chlorproMAZINE, cimetidine, cisatracurium, CISplatin, cladribine, clindamycin, cyanocobalamin, cyclophosphamide, cycloSPORINE, cytara- bine, D5W-dextrose 5%, DACTINomycin, DAPTOmycin, dexamethasone, dexme- detomidine, digoxin, diltiazem, diphen- hydrAMINE, DOBUTamine, DOCEtaxel, DOPamine, doxacurium, DOXOrubicin HCl, doxycycline, enalaprilat, ePHEDrine, EPINEPHrine, epirubicin, epoetin alfa, eptifibatide, ertapenem, erythromycin, esmolol, etoposide, famotidine, fenoldo- pam, fentaNYL, filgrastim, fluconazole, fludarabine, gatifloxacin, gemcitabine, gentamicin, glycopyrrolate, granisetron, heparin, hydrocortisone, hydrOXYzine, IDArubicin, ifosfamide, imipenem-cila statin, inamrinone, insulin (regular), iri- notecan, isoproterenol, ketorolac, labet- alol, lactated Ringer’s injection, levofloxacin, lidocaine, linezolid, LORaz- epam, magnesium sulfate, mannitol, mechlorethamine, melphalan, meperi- dine, metaraminol, methicillin, metho- trexate, methoxamine, methyldopate, methylPREDNISolone, metoclopramide, metoprolol, metroNIDAZOLE, mezlocil- lin, miconazole, midazolam, milrinone, minocycline, mitoXANtrone, morphine, moxalactam, multiple vitamins injection, mycophenolate mofetil, nafcillin, nalbu- phine, naloxone, nesiritide, netilmicin, nitroglycerin, nitroprusside, norepineph- rine, octreotide, ondansetron, oxacillin, oxaliplatin, oxytocin, palonosetron, pami- dronate, pancuronium, papaverine, PEMEtrexed, penicillin G potassium/ sodium, pentamidine, pentazocine, phen- ylephrine, phytonadione, piperacillin, piperacillin-tazobactam, polymyxin B, potassium chloride, procainamide, pro- chlorperazine, promethazine, propofol, propranolol, protamine, pyridoxine, quiN- IDine, ranitidine, remifentanil, Ringer’s injection, riTUXimab, rocuronium, sodium acetate, succinylcholine, SUFent- anil, tacrolimus, teniposide, theophylline, thiamine, thiotepa, ticarcillin, ticarcillin- clavulanate, tigecycline, tirofiban, TNA (3-in-1), tobramycin, tolazoline, TPN, B trastuzumab, trimetaphan, urokinase, vancomycin, vasopressin, vecuronium, verapamil, vinCRIStine, vinorelbine, voriconazole
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Assess: • Pain: intensity, location, type before treatment, after 5, 15, 30 min (IV); need for pain medication, tolerance
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Evaluate: • Therapeutic response: decrease in pain, decreased withdrawal symptoms
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To report any symptoms of CNS changes, allergic reactions
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PHARMACOKINETICS Metabolized in liver by CYP3A4, excreted by kidneys and in feces, crosses placenta, excreted in breast milk, half-life 2½-3½ hr, 96% bound to plasma proteins IM: Onset 15 min, peak 1 hr, duration 6-10 hr SL: Onset, peak, duration unknown, half-life 37 hr IV: Onset 1 min, peak 5 min, duration 6 hr, half-life 2.2 hr TD: Half-life 26 hr Epidural: Duration dose dependent
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• Geriatric/debilitated patients: IM/IV 0.15 mg slowly
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