Butrans 7 day patch

Do You Have Patients Like Scott,
Kathy or Pam?

Choose from one of these 3 hypothetical patient profiles to view selection, initiation, and titration information for that patient. Remember, these are sample patient summaries and may not necessarily include all the elements of a thorough patient assessment. Or try our Build-a-Patient Tool to customize the patient profile.

Kathy, Butrans hypothetical patient
Hypothetical patient

Medical history

  • 44-year-old woman with chronic low back pain due to intervertebral disc disease
  • Has tried lifestyle changes, like increased physical activity and weight reduction
  • Experiences restrictions in functional mobility due to pain

 

Current therapy

  • Currently taking ibuprofen 800 mg, 1 tablet q6h around the clock (ATC)
  • Patient reports she is still experiencing pain
  • Her pain is a 6 on an 11-point scale (0–10)

 

Coverage

  • Has commercial insurance coverage

 

Determining the appropriate starting dose for Kathy

Take into consideration the Indication, Contraindications, Warnings, and Precautions, and further guidance from the Full Prescribing Information, to determine if Kathy is an appropriate candidate for Butrans.

After determining Kathy is appropriate for Butrans, review the initial dosing and initiation in opioid-naïve patients information to select the appropriate starting dose of Butrans for Kathy.

Kathy is currently taking ibuprofen 800 mg, 1 tablet every 6 hours, to treat her chronic pain. According to the Full Prescribing Information, the recommended starting dose for Kathy is Butrans 5 mcg/hour.

Continuing Kathy's treatment

Continually reevaluate patients receiving Butrans to assess the maintenance of pain control and the relative incidence of adverse reactions, and monitor for the development of addiction, abuse, or misuse

  • Individually titrate Butrans to a dose that provides adequate analgesia and minimizes adverse reactions
  • The minimum Butrans titration interval is 72 hours, based on the pharmacokinetic profile and time to reach steady state levels
  • If Kathy experiences breakthrough pain, she may require a dosage adjustment increase of Butrans or may need rescue medication with an appropriate dose of an immediate-release analgesic (opioid or non-opioid). If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the Butrans dose
  • The maximum Butrans dose is 20 mcg/hour. Do not exceed a dose of one 20 mcg/hour Butrans system due to the risk of QTc interval prolongation

Follow-up visit

  • Follow up with Kathy to ensure her dose of Butrans 5 mcg/hour is providing adequate analgesia with minimal adverse reactions
  • During her follow-up, you learn that she is still experiencing pain in her lower back. Once you confirm that at least 3 days have passed since starting Butrans, you decide to titrate her dose of Butrans to 10 mcg/hour. You should also consider prescribing an immediate-release analgesic (opioid or non-opioid) for breakthrough pain, if needed
  • To titrate Kathy’s dose of Butrans to 10 mcg/hour, you also have the option of using 2 of her remaining 5 mcg/hour patches
  • For the use of two 5 mcg/hour patches, Kathy should be instructed to remove her current patch, and apply the 2 new patches at the same time, adjacent to one another at a different application site

See the titration and maintenance of therapy section for more information regarding continuing a patient's treatment with Butrans.

See the administration of Butrans section.

Scott, Butrans hypothetical patient
Hypothetical patient

Medical history

  • 54-year-old man with chronic low back pain due to osteoarthritis
  • Undergoing physical therapy
  • Physical examination indicates moderate restrictions in his functional mobility

 

Current therapy

  • Being treated with 50 mg of immediate-release tramadol taken 6 times a day (q4h) around the clock (ATC)
  • Patient reports he is still experiencing pain, as well as intolerable side effects
  • His pain is a 6 on an 11-point scale (0–10)

 

Coverage

  • Has commercial insurance coverage

 

Determining the appropriate starting dose for Scott

Take into consideration the Indication, Contraindications, Warnings and Precautions, and further guidance from the Full Prescribing Information, to determine if Scott is an appropriate candidate for Butrans.

After determining Scott is appropriate for Butrans, review the initial dosing and initiation in opioid-naïve patients information to select the appropriate starting dose of Butrans for Scott.

Scott is currently taking 300 mg of tramadol per day or between 30 and 80 mg of oral morphine equivalents per day. According to the Full Prescribing Information, the recommended starting dose for Scott is Butrans 10 mcg/hour. Scott is initiated on this dose after his ATC tramadol therapy is discontinued.

There is a potential for buprenorphine to precipitate withdrawal in patients who are already on opioids.

Continuing Scott's treatment

  • Continually reevaluate patients receiving Butrans to assess the maintenance of pain control and the relative incidence of adverse reactions, and monitor for the development of addiction, abuse, or misuse
  • Individually titrate Butrans to a dose that provides adequate analgesia and minimizes adverse reactions
  • The minimum Butrans titration interval is 72 hours, based on the pharmacokinetic profile and time to reach steady state levels
  • If Scott experiences breakthrough pain, he may require a dosage adjustment increase of Butrans or may need rescue medication with an appropriate dose of an immediate-release analgesic (opioid or non-opioid). If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the Butrans dose
  • The maximum Butrans dose is 20 mcg/hour. Do not exceed a dose of one 20 mcg/hour Butrans system due to the risk of QTc interval prolongation

Follow-up visit

Follow up with Scott to ensure that his dose of Butrans 10 mcg/hour is providing adequate analgesia with minimal adverse reactions

  • During his follow-up, you learn he is still experiencing pain in his lower back. Once you confirm that at least 3 days have passed since starting Butrans, you decide to titrate his dose of Butrans to 15 mcg/hour. You should also consider prescribing an immediate-release analgesic (opioid or non-opioid) for breakthrough pain, if needed

See the titration and maintenance of therapy section for more information regarding continuing a patient's treatment with Butrans.

See the administration of Butrans section.

Pam, Butrans hypothetical patient
Hypothetical patient

Medical history

  • 71-year-old woman with chronic low back pain due to osteoarthritis
  • Chronic low back pain has intensified over the last 9 months
  • Pain is not being adequately controlled. Physical examination
    indicates moderate restriction in her functional mobility
  • Moderate renal impairment

 

Current therapy

  • Currently taking celecoxib 200 mg, 1 capsule q12h, around the clock (ATC)
  • Pain is inadequately controlled on current therapy
  • Her pain at the worst is an 8 on an 11-point scale; average pain ranks as a 6
  • Her pain is worse in the mornings and after being sedentary for periods of time

 

Coverage

  • Has Medicare Part D Prescription coverage

 

Determining the appropriate starting dose for Pam

Take into consideration the Indication, Contraindications, Warnings and Precautions, and further guidance from the Full Prescribing Information, to determine if Pam is an appropriate candidate for Butrans.

After determining Pam is appropriate for Butrans, review the initial dosing and initiation in opioid-naïve patients information to select the appropriate dose of Butrans for Pam.

Pam is currently taking celecoxib 200 mg, 1 capsule every 12 hours, to treat her chronic pain. According to the Full Prescribing Information, the recommended starting dose for Pam is Butrans 5 mcg/hour.

Continuing Pam's treatment

  • Continually reevaluate patients receiving Butrans to assess the maintenance of pain control and the relative incidence of adverse reactions, and monitor for the development of addiction, abuse, or misuse
  • Individually titrate Butrans to a dose that provides adequate analgesia and minimizes adverse reactions
  • The minimum Butrans titration interval is 72 hours, based on the pharmacokinetic profile and time to reach steady state levels
  • If Pam experiences breakthrough pain, she may require a dosage adjustment increase of Butrans, or may need rescue medication with an appropriate dose of an immediate-release analgesic (opioid or non-opioid). If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the Butrans dose
  • The maximum Butrans dose is 20 mcg/hour. Do not exceed a dose of one 20 mcg/hour Butrans system due to the risk of QTc interval prolongation

Follow-up phone call

  • Follow up with Pam to ensure Butrans 5 mcg/hour is providing adequate analgesia with minimal adverse reactions. During a follow-up phone call, you learn that Pam is still experiencing pain in her lower back
  • Once you confirm that at least 3 days have passed since starting Butrans, you decide to titrate her dose of Butrans to 10 mcg/hour by using 2 of her remaining 5 mcg/hour patches
  • You instruct her to remove the current patch and apply two 5 mcg/hour patches at the same time, adjacent to one another at a different application site, as explained in the Instructions for Use
  • You also consider prescribing an immediate-release analgesic (opioid or non-opioid) for breakthrough pain, if needed.

See the titration and maintenance of therapy section for more information regarding continuing a patient's treatment with Butrans.

See the administration of Butrans section.


Use in Specific Populations

Geriatric Use

  • Of the total number of subjects in the clinical trials (5,415), Butrans was administered to 1,377 patients aged 65 years and older. Of those, 457 patients were 75 years of age and older. In the clinical program, the incidences of selected Butrans-related AEs were higher in older subjects. The incidences of application site AEs were slightly higher among subjects <65 years of age than those ≥65 years of age for both Butrans and placebo treatment groups
  • In a single-dose study of healthy elderly and healthy young subjects treated with Butrans 10 mcg/hour, the pharmacokinetics were similar. In a separate dose-escalation safety study, the pharmacokinetics in the healthy elderly and hypertensive elderly subjects taking thiazide diuretics were similar to those in the healthy young adults. In the elderly groups evaluated, adverse event rates were similar to or lower than rates in healthy young adult subjects, except for constipation and urinary retention, which were more common in the elderly. 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

 

Renal Impairment

  • No dose adjustments for patients with renal impairment are noted in the Full Prescribing Information
  • No studies in patients with renal impairment have been performed with Butrans. However, no notable relationship was observed between estimated creatinine clearance rates and steady-state buprenorphine concentrations among patients during Butrans therapy
  • In an independent study, the effect of impaired renal function on buprenorphine pharmacokinetics after IV bolus and after continuous IV infusion administrations was evaluated. It was found that plasma buprenorphine concentrations were similar in patients with normal renal function and in patients with impaired renal function or renal failure
  • In a separate investigation of the effect of intermittent hemodialysis on buprenorphine plasma concentrations in chronic pain patients with end-stage renal disease who were treated with a transdermal buprenorphine product (marketed outside the US) up to 70 mcg/hour, no signifi cant differences in buprenorphine plasma concentrations before or after hemodialysis were observed

 

Hepatic Impairment

  • In a study utilizing intravenous buprenorphine, peak plasma levels (Cmax) and exposure (AUC) of buprenorphine in patients with mild and moderate hepatic impairment did not increase as compared to those observed in subjects with normal hepatic function. Butrans has not been evaluated in patients with severe hepatic impairment. As Butrans is only intended for 7-day application, consider use of an alternate analgesic that may permit more flexibility with the dosing in patients with severe hepatic impairment

Butrans® (buprenorphine) Transdermal System is 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.

Limitations of Use: Because of the risks of addiction, abuse and misuse with opioids, even at recommended doses, and because of the greater risk of overdose and death with extended-release opioid formulations, reserve Butrans for use in patients for whom alternative treatment options (eg, non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Butrans is not indicated as an as-needed (prn) analgesic.

Please read Important Safety Information, including Boxed Warning.

IMPORTANT SAFETY INFORMATION

WARNING: ADDICTION, ABUSE and MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL EXPOSURE; and NEONATAL OPIOID WITHDRAWAL SYNDROME

Addiction, Abuse, and Misuse
Butrans exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing Butrans, and monitor all patients regularly for the development of these behaviors or conditions [see Warnings and Precautions (5.1) and Overdosage (10)].

Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of Butrans. Monitor for respiratory depression, especially during initiation of Butrans or following a dose increase. Misuse or abuse of Butrans by chewing, swallowing, snorting or injecting buprenorphine extracted from the transdermal system will result in the uncontrolled delivery of buprenorphine and pose a significant risk of overdose and death [see Warnings and Precautions (5.2)].

Accidental Exposure
Accidental exposure to even one dose of Butrans, especially by children, can result in a fatal overdose of buprenorphine [see Warnings and Precautions (5.2)].

Neonatal Opioid Withdrawal Syndrome
Prolonged use of Butrans 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. 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 [see Warnings and Precautions (5.3)].

CONTRAINDICATIONS

  • Butrans is contraindicated in patients with: significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; known or suspected paralytic ileus; hypersensitivity (eg, anaphylaxis) to buprenorphine

WARNINGS AND PRECAUTIONS

Addiction, Abuse, and Misuse

  • Butrans contains buprenorphine, a Schedule III controlled substance. Butrans exposes users to the risks of opioid addiction, abuse, and misuse. As modified-release products such as Butrans deliver the opioid over an extended period of time, there is a greater risk for overdose and death, due to the larger amount of buprenorphine present
  • Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Butrans and in those who obtain the drug illicitly. Addiction can occur at recommended doses and if the drug is misused or abused
  • Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing Butrans, and monitor all patients receiving Butrans for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (eg, major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed modified-release opioid formulations such as Butrans, but use in such patients necessitates intensive counseling about the risks and proper use of Butrans, along with intensive monitoring for signs of addiction, abuse, or misuse
  • Abuse or misuse of Butrans by placing it in the mouth, chewing it, swallowing it, or using it in ways other than indicated may cause choking, overdose and death
  • Opioid agonists such as Butrans are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing Butrans. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug

Life-Threatening Respiratory Depression

  • Serious, life-threatening, or fatal respiratory depression has been reported with the use of modified-release opioids, even when used as recommended, and if not immediately recognized and treated, may lead to respiratory arrest and death
  • While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of Butrans, the risk is greatest during the initiation of therapy or following a dose increase. Closely monitor patients for respiratory depression when initiating therapy with Butrans and following dose increases
  • To reduce the risk of respiratory depression, proper dosing and titration of Butrans are essential. Overestimating the Butrans dose when converting patients from another opioid product can result in fatal overdose with the first dose
  • Accidental exposure to Butrans, especially in children, can result in respiratory depression and death due to an overdose of buprenorphine

Neonatal Opioid Withdrawal Syndrome

  • Prolonged use of Butrans during pregnancy can result in withdrawal signs in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. 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

Interactions With Central Nervous System Depressants

  • Hypotension, profound sedation, coma, respiratory depression, and death may result if Butrans is used concomitantly with other CNS depressants (eg, sedatives, anxiolytics, hypnotics, neuroleptics, other opioids). When considering the use of Butrans in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient's response, including the degree of tolerance that has developed to CNS depression. Additionally, evaluate the patient's use of alcohol or illicit drugs that cause CNS depression. If the decision to begin Butrans therapy is made, start with Butrans 5 mcg/hour patch, monitor patients for signs of sedation and respiratory depression and consider using a lower dose of the concomitant CNS depressant

Use in Elderly, Cachectic, and Debilitated Patients

  • Closely monitor elderly, cachectic, and debilitated patients, since life-threatening respiratory depression is more likely to occur due to altered pharmacokinetics or clearance, particularly when initiating and titrating Butrans and when given concomitantly with other drugs that depress respiration

Use in Patients With Chronic Pulmonary Disease

  • When initiating therapy and titrating with Butrans, monitor patients with significant chronic obstructive pulmonary disease or cor pulmonale, and patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression. In these patients, even usual therapeutic doses of Butrans may decrease respiratory drive to the point of apnea. Consider the use of alternative non-opioid analgesics in these patients if possible

QTc Prolongation

  • A positive-controlled study of the effects of Butrans on the QTc interval in healthy subjects demonstrated no clinically meaningful effect at a Butrans dose of 10 mcg/hour; however, a Butrans dose of 40 mcg/hour (given as two Butrans 20 mcg/hour Transdermal Systems) was observed to prolong the QTc interval
  • Consider these observations in clinical decisions when prescribing Butrans to patients with hypokalemia or clinically unstable cardiac disease, including: unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, or active myocardial ischemia. Avoid the use of Butrans in patients with a history of Long QT Syndrome or an immediate family member with this condition, or those taking Class IA antiarrhythmic medications (eg, quinidine, procainamide, disopyramide) or Class III antiarrhythmic medications (eg, sotalol, amiodarone, dofetilide)

Hypotensive Effects

  • Butrans may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration with certain CNS depressant drugs (eg, phenothiazines or general anesthetics). Monitor these patients for signs of hypotension after initiating or titrating the dose of Butrans

Use in Patients With Head Injury or Increased Intracranial Pressure

  • Monitor patients taking Butrans who may be susceptible to the intracranial effects of CO2 retention (eg, those with evidence of increased intracranial pressure or brain tumors) for signs of sedation and respiratory depression, particularly when initiating therapy with Butrans. Butrans may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of Butrans in patients with impaired consciousness or coma

Hepatotoxicity

  • Although not observed in Butrans chronic pain clinical trials, cases of cytolytic hepatitis and hepatitis with jaundice have been observed in individuals receiving sublingual buprenorphine for the treatment of opioid dependence, both in clinical trials and in post-marketing adverse event reports. For patients at increased risk of hepatotoxicity, obtain baseline liver enzyme levels and monitor periodically and during treatment with Butrans

Application Site Skin Reactions

  • In rare cases, severe application site skin reactions with signs of marked inflammation including "burn," "discharge," and "vesicles" have occurred. Time of onset varies, ranging from days to months following the initiation of Butrans treatment. Instruct patients to promptly report the development of severe application site reactions and discontinue therapy

Anaphylactic/Allergic Reactions

  • Cases of acute and chronic hypersensitivity to buprenorphine have been reported both in clinical trials and in the post-marketing experience. The most common signs and symptoms include rashes, hives, and pruritus. Cases of bronchospasm, angioneurotic edema, and anaphylactic shock have been reported. A history of hypersensitivity to buprenorphine is a contraindication to the use of Butrans

Application of External Heat

  • Advise patients and their caregivers to avoid exposing the Butrans application site and surrounding area to direct external heat sources, such as heating pads or electric blankets, heat or tanning lamps, saunas, hot tubs, and heated water beds while wearing the system because an increase in absorption of buprenorphine may occur. Advise patients against exposure of the Butrans application site and surrounding area to hot water or prolonged exposure to direct sunlight. There is a potential for temperature-dependent increases in buprenorphine released from the system resulting in possible overdose and death

Patients With Fever

  • Monitor patients wearing Butrans systems who develop fever or increased core body temperature due to strenuous exertion for opioid side effects and adjust the Butrans dose if signs of respiratory or central nervous system depression occur

Use in Patients With Gastrointestinal Conditions

  • Butrans is contraindicated in patients with paralytic ileus. Avoid the use of Butrans in patients with other GI obstruction. Butrans may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. Opioids may cause increases in the serum amylase

Use in Patients With Convulsive or Seizure Disorders

  • Butrans may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings. Monitor patients with a history of seizure disorders for worsened seizure control during Butrans therapy

Driving and Operating Machinery

  • Butrans may impair the mental and physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of Butrans and know how they will react to the medication

Use in Addiction Treatment

  • Butrans has not been studied and is not approved for use in the management of addictive disorders

ADVERSE REACTIONS

  • Most common adverse reactions (≥5%) reported by patients treated with Butrans in clinical trials were nausea, headache, application site pruritus, dizziness, constipation, somnolence, vomiting, application site erythema, dry mouth, and application site rash

Please read the Full Prescribing Information, including Boxed Warning.

To report SUSPECTED ADVERSE REACTIONS, contact Purdue Pharma L.P. at 1-888-726-7535 or FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch.
Intended for healthcare professionals of the United States of America only. ©2015 Purdue Pharma L.P., Stamford, CT 06901-3431

Important Safety Information

WARNING: ADDICTION, ABUSE and MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL EXPOSURE; and NEONATAL OPIOID WITHDRAWAL SYNDROME

Addiction, Abuse, and Misuse
Butrans exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing Butrans, and monitor all patients regularly for the development of these behaviors or conditions [see Warnings and Precautions (5.1) and Overdosage (10)].

Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of Butrans. Monitor for respiratory depression, especially during initiation of Butrans or following a dose increase. Misuse or abuse of Butrans by chewing, swallowing, snorting or injecting buprenorphine extracted from the transdermal system will result in the uncontrolled delivery of buprenorphine and pose a significant risk of overdose and death [see Warnings and Precautions (5.2)].

Accidental Exposure
Accidental exposure to even one dose of Butrans, especially by children, can result in a fatal overdose of buprenorphine [see Warnings and Precautions (5.2)].

Neonatal Opioid Withdrawal Syndrome
Prolonged use of Butrans 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. 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 [see Warnings and Precautions (5.3)].

CONTRAINDICATIONS

  • Butrans is contraindicated in patients with: significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; known or suspected paralytic ileus; hypersensitivity (eg, anaphylaxis) to buprenorphine

WARNINGS AND PRECAUTIONS

Addiction, Abuse, and Misuse

  • Butrans contains buprenorphine, a Schedule III controlled substance. Butrans exposes users to the risks of opioid addiction, abuse, and misuse. As modified-release products such as Butrans deliver the opioid over an extended period of time, there is a greater risk for overdose and death, due to the larger amount of buprenorphine present
  • Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Butrans and in those who obtain the drug illicitly. Addiction can occur at recommended doses and if the drug is misused or abused
  • Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing Butrans, and monitor all patients receiving Butrans for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (eg, major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed modified-release opioid formulations such as Butrans, but use in such patients necessitates intensive counseling about the risks and proper use of Butrans, along with intensive monitoring for signs of addiction, abuse, or misuse
  • Abuse or misuse of Butrans by placing it in the mouth, chewing it, swallowing it, or using it in ways other than indicated may cause choking, overdose and death
  • Opioid agonists such as Butrans are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing Butrans. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug

Life-Threatening Respiratory Depression

  • Serious, life-threatening, or fatal respiratory depression has been reported with the use of modified-release opioids, even when used as recommended, and if not immediately recognized and treated, may lead to respiratory arrest and death
  • While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of Butrans, the risk is greatest during the initiation of therapy or following a dose increase. Closely monitor patients for respiratory depression when initiating therapy with Butrans and following dose increases
  • To reduce the risk of respiratory depression, proper dosing and titration of Butrans are essential. Overestimating the Butrans dose when converting patients from another opioid product can result in fatal overdose with the first dose
  • Accidental exposure to Butrans, especially in children, can result in respiratory depression and death due to an overdose of buprenorphine

Neonatal Opioid Withdrawal Syndrome

  • Prolonged use of Butrans during pregnancy can result in withdrawal signs in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. 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

Interactions With Central Nervous System Depressants

  • Hypotension, profound sedation, coma, respiratory depression, and death may result if Butrans is used concomitantly with other CNS depressants (eg, sedatives, anxiolytics, hypnotics, neuroleptics, other opioids). When considering the use of Butrans in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient's response, including the degree of tolerance that has developed to CNS depression. Additionally, evaluate the patient's use of alcohol or illicit drugs that cause CNS depression. If the decision to begin Butrans therapy is made, start with Butrans 5 mcg/hour patch, monitor patients for signs of sedation and respiratory depression and consider using a lower dose of the concomitant CNS depressant

Use in Elderly, Cachectic, and Debilitated Patients

  • Closely monitor elderly, cachectic, and debilitated patients, since life-threatening respiratory depression is more likely to occur due to altered pharmacokinetics or clearance, particularly when initiating and titrating Butrans and when given concomitantly with other drugs that depress respiration

Use in Patients With Chronic Pulmonary Disease

  • When initiating therapy and titrating with Butrans, monitor patients with significant chronic obstructive pulmonary disease or cor pulmonale, and patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression. In these patients, even usual therapeutic doses of Butrans may decrease respiratory drive to the point of apnea. Consider the use of alternative non-opioid analgesics in these patients if possible

QTc Prolongation

  • A positive-controlled study of the effects of Butrans on the QTc interval in healthy subjects demonstrated no clinically meaningful effect at a Butrans dose of 10 mcg/hour; however, a Butrans dose of 40 mcg/hour (given as two Butrans 20 mcg/hour Transdermal Systems) was observed to prolong the QTc interval
  • Consider these observations in clinical decisions when prescribing Butrans to patients with hypokalemia or clinically unstable cardiac disease, including: unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, or active myocardial ischemia. Avoid the use of Butrans in patients with a history of Long QT Syndrome or an immediate family member with this condition, or those taking Class IA antiarrhythmic medications (eg, quinidine, procainamide, disopyramide) or Class III antiarrhythmic medications (eg, sotalol, amiodarone, dofetilide)

Hypotensive Effects

  • Butrans may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration with certain CNS depressant drugs (eg, phenothiazines or general anesthetics). Monitor these patients for signs of hypotension after initiating or titrating the dose of Butrans

Use in Patients With Head Injury or Increased Intracranial Pressure

  • Monitor patients taking Butrans who may be susceptible to the intracranial effects of CO2 retention (eg, those with evidence of increased intracranial pressure or brain tumors) for signs of sedation and respiratory depression, particularly when initiating therapy with Butrans. Butrans may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of Butrans in patients with impaired consciousness or coma

Hepatotoxicity

  • Although not observed in Butrans chronic pain clinical trials, cases of cytolytic hepatitis and hepatitis with jaundice have been observed in individuals receiving sublingual buprenorphine for the treatment of opioid dependence, both in clinical trials and in post-marketing adverse event reports. For patients at increased risk of hepatotoxicity, obtain baseline liver enzyme levels and monitor periodically and during treatment with Butrans

Application Site Skin Reactions

  • In rare cases, severe application site skin reactions with signs of marked inflammation including "burn," "discharge," and "vesicles" have occurred. Time of onset varies, ranging from days to months following the initiation of Butrans treatment. Instruct patients to promptly report the development of severe application site reactions and discontinue therapy

Anaphylactic/Allergic Reactions

  • Cases of acute and chronic hypersensitivity to buprenorphine have been reported both in clinical trials and in the post-marketing experience. The most common signs and symptoms include rashes, hives, and pruritus. Cases of bronchospasm, angioneurotic edema, and anaphylactic shock have been reported. A history of hypersensitivity to buprenorphine is a contraindication to the use of Butrans

Application of External Heat

  • Advise patients and their caregivers to avoid exposing the Butrans application site and surrounding area to direct external heat sources, such as heating pads or electric blankets, heat or tanning lamps, saunas, hot tubs, and heated water beds while wearing the system because an increase in absorption of buprenorphine may occur. Advise patients against exposure of the Butrans application site and surrounding area to hot water or prolonged exposure to direct sunlight. There is a potential for temperature-dependent increases in buprenorphine released from the system resulting in possible overdose and death

Patients With Fever

  • Monitor patients wearing Butrans systems who develop fever or increased core body temperature due to strenuous exertion for opioid side effects and adjust the Butrans dose if signs of respiratory or central nervous system depression occur

Use in Patients With Gastrointestinal Conditions

  • Butrans is contraindicated in patients with paralytic ileus. Avoid the use of Butrans in patients with other GI obstruction. Butrans may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. Opioids may cause increases in the serum amylase

Use in Patients With Convulsive or Seizure Disorders

  • Butrans may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings. Monitor patients with a history of seizure disorders for worsened seizure control during Butrans therapy

Driving and Operating Machinery

  • Butrans may impair the mental and physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of Butrans and know how they will react to the medication

Use in Addiction Treatment

  • Butrans has not been studied and is not approved for use in the management of addictive disorders

ADVERSE REACTIONS

  • Most common adverse reactions (≥5%) reported by patients treated with Butrans in clinical trials were nausea, headache, application site pruritus, dizziness, constipation, somnolence, vomiting, application site erythema, dry mouth, and application site rash

Please read the Full Prescribing Information, including Boxed Warning.

To report SUSPECTED ADVERSE REACTIONS, contact Purdue Pharma L.P. at 1-888-726-7535 or FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch.
Intended for healthcare professionals of the United States of America only. ©2015 Purdue Pharma L.P., Stamford, CT 06901-3431