buprenorphine (Rx)

>10%

Sedation (2/3 of patients)

1-10%

Dizziness

Headache

Hypotension

Hypoventilation

Miosis

Nausea

Sweating

Vertigo

Vomiting

<1%

Abdominal cramps

Amblyopia

Apnea

Blurred vision

Bradycardia

Coma

Confusion

Conjunctivitis

Constipation

Cyanosis

Depersonalization

Diplopia

Dreaming

Dry mouth

Dyspepsia

Dyspnea

Electrocardiographic (ECG) abnormalities

Euphoria

Fatigue

Flatulence

Hallucinations

Hypertension

Injection-site reactions

Malaise

Mental depression

Mydriasis

Nervousness

Paresthesia

Pruritus

Psychosis

Respiratory depression

Slurred speech

Tachycardia

Urticaria

Postmarketing Reports

Adrenal Insufficiency

Serotonin syndrome

Hepatotoxicity

Balck Box Warnings

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)

Associated with life-threatening respiratory depression and death; many, but not all, post-marketing reports regarding coma and death have involved misuse by self-injection or were associated with concomitant use of buprenorphine and benzodiazepines or other CNS depressants, including alcohol; warn patients of potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment

Interactions with CNS depressants (eg, alcohol, sedatives, anxiolytics, hypnotics, neuroleptics, other opioids) can cause additive effects and increase risk for respiratory depression, profound sedation, and hypotension

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

Caution in severe renal impairment

Severe hepatic impairment can cause increased buprenorphine plasma levels and prolonged half-life, but not in subjects with mild hepatic impairment; dose adjustment recommended in patients with moderate or severe hepatic; consider reducing the dose by half and closely monitor for signs and symptoms of toxicity and overdose (see Dosage Modifications)

May cause sphincter of Oddi spasm and aggravate abdominal conditions, including ileus (see Contraindications)

Respiratory sedation (dose-dependent; usual doses may depress respiration to same degree as 10 mg of parenteral morphine)

Similar to other opioids, may aggravate seizure disorders by lowering seizure threshold

Patients with cancer who have oral mucositis may absorb buprenorphine more rapidly than intended and have higher plasma levels of buprenorphine (see Dosage Modifications)

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

Chronic use of opioids may cause reduced fertility in females and males of reproductive potential; unknown whether effects on fertility are reversible

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 have 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

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

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

Bioavailability: 79%

Onset: IM, 15 min

Duration: 4-10 hr

Peak plasma time: <2 min

Peak plasma concentration: 18 ng/mL

Distribution

Protein bound: 96%

Vd: 97-187 L/kg

Metabolism

Liver (N-dealkylation)

Metabolized in liver via N-dealkylation

Metabolites: Norbuprenorphine (N-dealkylbuprenorphine)

Elimination

Half-life: 2.2 hr

Excretion: Urine, feces

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, by slow IV injection over ≥2 minutes, or by continuous IV infusion

Also may be given by epidural injection at concentration of 6-30 mcg/mL

Storage

Store at 15-30°C; protect from freezing

Protect from prolonged exposure to light