Dosing & Uses
Dosing Form & Strengths
transdermal patch: Schedule III
- 5mcg/hr
- 7.5mcg/hr
- 10mcg/hr
- 15mcg/hr
- 20mcg/hr
Chronic Severe Pain
Indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate
Each patch is worn for 7 days (except during titration)
Opioid-naïve: Initiate with 5 mcg/hr patch; may supplement with prompt-acting opioid and nonopioid analgesic for break-through pain
Do not increase patch until patient has been exposed continually to previous dose for 72 hr
Based on requirement for supplemental short-acting analgesics, upward titration may be instituted with at a minimum interval of 72 hr
Do not exceed dose of one 20 mcg/hr transdermal system (risk of QT prolongation with higher doses)
Conversion from other opioids
- Oral morphine equivalent <30 mg/day: Initiate with 5 mcg/hr patch
- Oral morphine equivalent 30-80 mg/day: Initiate with 10 mcg/hr patch
- May supplement with prompt-acting opioid and nonopioid analgesic for break-through pain
- Use caution when prescribing to opioid-experienced patients requiring high doses of opioids (ie, >80 mg/day oral morphine equivalent); buprenorphine transdermal 20 mcg/hr may not provide adequate analgesia for patients previously on high-dose opioids
Opioid-tolerant definition
- Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression
- Patients who are opioid tolerant are those receiving, for 1 week or longer, at least 60 mg/day PO morphine, 25 mcg/hr transdermal fentanyl, 30 mg/day PO oxycodone, 8 mg/day PO hydromorphone, 25 mg/day PO oxymorphone, or an equianalgesic dose of another opioid
Limitations of use
- Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve for patients whom alternative treatment options (eg, nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain
- Not indicated as a PRN analgesic
Dosage Modification
Hepatic Impairment
- Only intended for 7-day application, consider use of an alternate analgesic that permits flexible dosing
- Mild-to-moderate: Initiate with 5 mcg/hr dose; titrate to provide adequate analgesia and tolerable adverse effects
- Severe: Not yet studied with severe hepatic impairment
<18 years: Safety and efficacy not established
Buprenorphine transdermal was evaluated in an open-label clinical trial in pediatric patients aged 7-16 yr requiring continuous, around-the-clock opioid treatment for moderate-to-severe chronic pain; however, definitive conclusions were not possible because of the small sample size
Although specific dose adjustments on the basis of advanced age are not required for pharmacokinetic reasons, use caution in the elderly population to ensure safe use
Clinical trials observed that some adverse effects (ie, respiratory depression, constipation, urinary retention) occur more frequently in elderly patients
Adverse Effects
>10%
Nausea (23%)
Dizziness (16%)
Headache (16%)
Pruritus at application site (15%)
Constipation (14%)
Somnolence (14%)
Vomiting (11%)
1-10%
Peripheral edema (7%)
Xerostomia (7%)
Erythema at application site (7%)
Rash at application site (6%)
Fatigue (5%)
Hyperhidrosis (4%)
Pruritus (4%)
Falls (4%)
Diarrhea (3%)
Pain in extremity (3%)
Insomnia (3%)
Dyspnea (3%)
Dyspepsia (3%)
Urinary tract infection (3%)
Back pain (3%)
Joint swelling (3%)
Hypoesthesia (2%)
Arthralgia (2%)
Stomach discomfort (2%)
Rash (2%)
Anorexia (2%)
Paraesthesia (2%)
Tremor (2%)
Confusional state (2%)
Warnings
Black Box Warnings
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 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
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
Contraindications
Hypersensitivity
Significant respiratory depression
Severe bronchial asthma
Paralytic ileus
Management of acute pain or opioid analgesia required for short period of time
Management of postoperative pain, including use after outpatient or day surgeries
Management of mild pain
Management of intermittent pain (not for PRN use)
Cautions
Respiratory depression is main hazard; may occur more frequently in elderly or debilitated patients, or in conditions associated with hypoxia or hypercapnia (even moderate therapeutic doses)
Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia; opioid use increases risk of CSA in a dose-dependent fashion; in patients who present with CSA, consider decreasing opioid dosage using best practices for opioid taper
CNS depression: May cause somnolence, dizziness, altered consciousness (including coma)
Coadministration with alcohol, other CNS depressants, and illicit drugs may cause hypotension, profound sedation, and coma or respiratory depression
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
Head injury: Respiratory depressant effects of opioids may include carbon dioxide retention and lead to elevated CSF pressure
Hypotensive effects: Can cause severe hypotension; caution with depleted blood volume or coadministration of drugs that that affect vasomotor tone (eg, phenothiazines), vasodilators, or antihypertensives
Misuse, abuse, diversion: Partial agonist at the mu opioid receptor and a Schedule III controlled opioids expose users to the risks of addiction, abuse, and misuse; there is a greater risk for overdose and death with extended-release opioids due to the larger amount of active opioid present (see Black Box Warnings)
Serious, life-threatening, or fatal respiratory depression reported (see Black Box Warnings)
Accidental exposure reported, including fatalities (see Black Box Warnings)
Neonatal opioid withdrawal syndrome reported with long-term use during pregnancy (see Black Box Warnings)
Do not abruptly discontinue buprenorphine in a patient physically dependent on opioids; when discontinuing therapy, in a physically dependent patient, gradually taper the dosage; rapid tapering in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain
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
Hepatoxicity: Although not observed in buprenorphine transdermal chronic pain clinical trials, cases of cytolytic hepatitis and hepatitis with jaundice observed in individuals receiving buprenorphine SL for opioid dependence treatment
Fever: If fever or increased core body temperature occurs following strenuous exertion, monitor for increased opioid adverse effects; adjust dose if necessary
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
May cause sphincter of Oddi spasm and aggravate abdominal conditions, including ileus
Not recommended for use within 14 days of MAO inhibitors; severe and unpredictable potentiation by MAO inhibitors reported
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 Risk Evaluation and Mitigation Strategy (REMS) for these products
- Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed; Use the following link to obtain the Patient Counseling Guide (PCG): www.fda.gov/OpioidAnalgesicREMSPCG
- Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them
- Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities
- 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
Pregnancy & Lactation
Pregnancy Category: C
Opioids cross the placenta and may produce respiratory depression and psychophysiologic effects in neonates; not recommended for use in women immediately prior to and during labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate
Neonates whose mothers have been taking opioids chronically may also exhibit withdrawal signs, either at birth and/or in the nursery, because they have developed physical dependence; neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening and should be treated according to protocols developed by neonatology experts
Lactation: Detected in low concentrations in human milk; breastfeeding not advised
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 the mu and delta opioid receptors in the CNS, and antagonistic effects at the kappa opioid receptor
Absorption
17 hr is the median time for 10mcg/hr to deliver quantifiable concentration (ie, >25 pg/mL)
Peak plasma concentration: 176 pg/mL (5 mcg/hr); 191 pg/mL (10 mcg/hr); 471 pg/mL (20 mcg/hr)
AUC: 12,087 pg•h/mL (5 mcg/hr); 27,035 pg•h/mL (10 mcg/hr); 54,294 pg•h/mL (20 mcg/hr)
Absolute bioavailability: 15%
Distribution
Vd: 430 L (after IV administration)
Protein bound: 96%
Metabolism
Metabolism: via hepatic metabolism, with subsequent biliary excretion and renal excretion of soluble metabolites
Pharmacokinetics
Half-life, terminal: 26 hr (after patch removal)
Clearance: 55 L/hr
Excretion (within 7 days): Feces (70%), urine (27%)
Administration
Transdermal Administration
Apply patch to hairless or nearly hairless skin site; if none available, clip hair at application site (do not shave)
Do not apply to irritated skin
Clean application site with water only; do not use soaps, alcohol, oils, lotions, or abrasive devices
Allow skin to dry completely before application
If problems with adhesion occur, may tape edges with first aid tape
If transdermal patch falls off during the 7 days, discard patch and apply new patch to different skin site
Rotate application site: after each patch removal, wait a minimum of 3 weeks before reapplying to same application site
When discontinuing patch, taper dose as part of comprehensive treatment plan; consider use of immediate-release opioid analgesics
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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.
