Butrans buprenorphine 7 day patch—15 mcg/hour dose

Do You Have Patients Like Scott, Nancy, David, Maria, or Kathy?

Patient Savings Program for Butrans

Choose from one of these 5 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.

Scott, Butrans hypothetical patient
Hypothetical patient

Medical history

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

 

Social history

  • Nonsmoker
  • No history of psychiatric illness or nonmedical use of medicine or illicit substances

 

Current therapy

  • Being treated with 100 mg of immediate-release tramadol taken 4 times a day (q6h) around the clock (ATC)
  • Patient reports he is still experiencing pain
  • His pain is a 6 on an 11-point scale (0–10)

 

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-experienced patients information to select the appropriate starting dose of Butrans for Scott.

Scott was previously taking 400 mg of tramadol, or between 30 and 80 mg oral morphine equivalents per day. According to the Full Prescribing Information, the recommended starting dose for Scott is Butrans 10 mcg/hour.

Continuing Scott's treatment

After initiating Scott on Butrans, you may decide to prescribe short-acting analgesics as needed until analgesic efficacy with Butrans is attained.

  • Follow up with Scott to ensure his dose of Butrans 10 mcg/hour is providing adequate analgesia with minimal adverse reactions
  • Once Scott is maintained at this dose (after 72 hours), he may still experience breakthrough pain. If Scott experiences breakthrough pain, he may require dose adjustment or rescue medication with an appropriate dose of an immediate-release opioid or non-opioid medication

During his follow-up, you learn he is still experiencing pain in his lower back. Once you confirm at least 3 days have passed since his last dosage adjustment and he is not experiencing any side effects, you decide to titrate his dose of Butrans to 20 mcg/hour. Consider continuing his immediate-release opioid or non-opioid medication for breakthrough pain, if needed.

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

Nancy, Butrans hypothetical patient
Hypothetical patient

Medical history

  • 62-year-old woman with chronic low back pain
  • Suffered an injury 4 years ago carrying groceries
  • Treated with chiropractic treatment and physiotherapy with
    no lasting effect
  • CAT scans show protrusion in the L3-L4 and L5-S1 discs
  • Has had one lower back surgery but still experiences pain
  • Limited range of motion during flexion of the back
  • Her pain is worse with movement and partially relieved when lying down

 

Social history

  • History of smoking
  • Does not drink alcohol
  • No history of psychiatric illness, or nonmedical use of medicine or illicit substances

 

Current therapy

  • Currently taking 5/325 mg of hydrocodone/acetaminophen taken 4 times a day (q6h) around the clock (ATC)
  • Patient reports she is still experiencing pain
  • Her pain is a 6 on an 11-point scale (0–10)

 

Determining the appropriate starting dose for Nancy

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

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

Nancy was previously taking 20 mg of hydrocodone, or between 30 and 80 mg oral morphine equivalents per day. According to the Full Prescribing Information, the recommended starting dose for Nancy is Butrans 10 mcg/hour.

Continuing Nancy's treatment

After initiating Nancy on Butrans, you may decide to prescribe short-acting analgesics as needed until analgesic efficacy with Butrans is attained.

  • Follow up with Nancy to ensure her dose of Butrans 10 mcg/hour is providing adequate analgesia with minimal adverse reactions
  • Once Nancy is maintained at this dose (after 72 hours), she may still experience breakthrough pain. If Nancy experiences breakthrough pain, she may require dose adjustment or rescue medication with an appropriate dose of an immediate-release opioid or non-opioid medication

During her follow-up, you learn she is still experiencing pain in her lower back. Once you confirm at least 3 days have passed since her last dosage adjustment and she is not experiencing any side effects, you decide to titrate her dose of Butrans to 20 mcg/hour. Also consider continuing her immediate-release opioid or non-opioid medication for breakthrough pain, if needed.

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

David, Butrans hypothetical patient
Hypothetical patient

Medical history

  • 58-year-old man with lower back pain due to nerve root entrapment
  • Pain radiates down to the lower extremities
  • Mild hypertension, being treated with a diuretic
  • Receiving chiropractic treatment
  • His pain is at its worst in the mornings and when climbing
    stairs or driving
  • Past visit to interventional pain specialist resulted in no
    long-term results

 

Social history

  • Nonsmoker
  • No history of psychiatric illness or nonmedical use of medicine or illicit substances

 

Current therapy

  • Currently being treated with 5/325 mg of oxycodone/acetaminophen taken every 4 hours (q4h) around the clock (ATC)
  • Currently taking a prn NSAID
  • Patient reports he is still experiencing pain
  • His pain is a 6 on an 11-point scale (0–10)

 

Determining the appropriate starting dose for David

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

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

David was previously taking 30 mg of oxycodone, or between 30 and 80 mg oral morphine equivalents per day. According to the Full Prescribing Information, the recommended starting dose for David is Butrans 10 mcg/hour.

Continuing David's treatment

After initiating David on Butrans, you may decide to prescribe short-acting analgesics as needed until analgesic efficacy with Butrans is attained.

  • Follow up with David to ensure his dose of Butrans 10 mcg/hour is providing adequate analgesia with minimal adverse reactions
  • Once David is maintained at this dose (after 72 hours), he may still experience breakthrough pain
  • If David experiences breakthrough pain, he may require dose adjustment or rescue medication with an appropriate dose of an immediate-release opioid or non-opioid medication

During his follow-up, you learn he is still experiencing pain in his lower back. Once you confirm at least 3 days have passed since his last dosage adjustment and he is not experiencing any side effects, you decide to titrate his dose of Butrans to 20 mcg/hour. Consider continuing his immediate-release opioid or non-opioid medication for breakthrough pain, if needed.

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

Maria, Butrans hypothetical patient
Hypothetical patient

Medical history

  • 45-year-old woman with low back pain due to intervertebral
    disc disease
  • Pain was induced by a moving injury 8 months ago
  • Has tried physical therapy
  • Is receiving chiropractic treatment
  • Mild renal impairment (serum creatinine of 1.4 mg/dL)
  • Cannot remain seated for long periods of time

 

Social history

  • Nonsmoker
  • No history of psychiatric illness or nonmedical use of medicine or illicit substances

 

Current therapy

  • Currently taking 200 mg ibuprofen about 6–8 times a day (1,200–1,600 mg ibuprofen per day)
  • Patient reports she is still experiencing pain
  • Maria's family is urging her to see her physician to appropriately treat her chronic pain
  • Her pain is a 7 on an 11-point scale (0–10)

 

Determining the appropriate starting dose for Maria

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

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

Maria was previously taking NSAIDs to treat her chronic pain. According to the Full Prescribing Information, the recommended starting dose for Maria is Butrans 5 mcg/hour.

Continuing Maria's treatment

  • Follow up with Maria to ensure her dose of Butrans 5 mcg/hour is providing adequate analgesia with minimal adverse reactions
  • Once Maria is maintained at this dose (after 72 hours), she may still experience breakthrough pain
  • If Maria experiences breakthrough pain, she may require dose adjustment or rescue medication with an appropriate dose of an immediate-release opioid or non-opioid medication, such as ibuprofen

If Maria's level of pain increases and she does not experience adverse effects, you may decide to titrate her dose of Butrans to 10 mcg/hour while continuing her immediate-release opioid or non-opioid medication for breakthrough pain, if needed.

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

Kathy, Butrans hypothetical patient
Hypothetical patient

Medical history

  • 44-year-old woman with 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

 

Social history

  • Nonsmoker
  • No history of psychiatric illness or nonmedical use of medicine or illicit substances

 

Current therapy

  • Currently taking 5/325 mg of hydrocodone/acetaminophen 4 times a day (p6h) around the clock (ATC)
  • Patient reports she is still experiencing pain
  • Her pain is a 6 on an 11-point scale (0–10)

 

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-experienced patients information to select the appropriate starting dose of Butrans for Kathy.

Kathy was previously taking 20/1300 mg of hydrocodone/acetaminophen, or between 30 and 80 mg oral morphine equivalents per day. According to the Full Prescribing Information, the recommended starting dose for Kathy is Butrans 10 mcg/hour.

Continuing Kathy's treatment

After initiating Kathy on Butrans, you may decide to prescribe short-acting analgesics as needed until analgesic efficacy with Butrans is attained.

  • After 3 days, as instructed, Kathy follows up with a phone call and reports her pain is inadequately controlled on Butrans 10 mcg/hour. If Kathy is not experiencing opioid-related adverse reactions, consider titrating Kathy’s dose of 10 mcg/hour to 15 mcg/hour to decrease the level of pain. Wait a minimum of 72 hours, or 3 days, before adjusting her dose. Butrans 15 mcg/hour provides flexibility when titrating from Butrans 10 mcg/hour
  • If Kathy experiences breakthrough pain, she may require a dose adjustment or rescue medication with an appropriate dose of an immediate-release opioid or non-opioid medication, such as acetaminophen

Follow-up visit

  • You find out a total dose of 15 mcg/hour of Butrans does not provide adequate analgesia and she does not experience opioid-related adverse events. Since it’s been longer than 3 days, you titrate Kathy’s dose to Butrans 20 mcg/hour

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

Butrans® (buprenorphine) is indicated for the management of moderate to severe chronic pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time.

Limitations of Use: Butrans is not for use: as an
as-needed (prn) analgesic; for pain that is mild or not expected to persist for an extended period of time; for acute pain; for postoperative pain unless the patient is already receiving chronic opioid therapy prior to surgery or if the postoperative pain is expected to be moderate to severe and persist for an extended period of time.

Please read Important Safety Information, including Boxed Warning.

IMPORTANT SAFETY INFORMATION

WARNING: ABUSE POTENTIAL,
LIFE-THREATENING RESPIRATORY DEPRESSION, and ACCIDENTAL EXPOSURE

Abuse Potential
Butrans contains buprenorphine, an opioid agonist and Schedule III controlled substance with an abuse liability similar to other Schedule III opioids, legal or illicit [see Warnings and Precautions (5.1)]. Assess each patient's risk for opioid abuse or addiction prior to prescribing Butrans. The risk for opioid abuse is increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (eg, major depressive disorder). Routinely monitor all patients receiving Butrans for signs of misuse, abuse, and addiction during treatment [see Drug Abuse and Dependence (9)].

Life-Threatening Respiratory Depression
Respiratory depression, including fatal cases, may occur with use of Butrans, even when the drug has been used as recommended and not misused or abused [see Warnings and Precautions (5.2)]. Proper dosing and titration are essential and Butrans should only be prescribed by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain. Monitor for respiratory depression, especially during initiation of Butrans or following a dose increase.

Accidental Exposure
Accidental exposure to Butrans, especially in children, can result in a fatal overdose of buprenorphine [see Warnings and Precautions (5.3)].

ADMINISTRATION OF BUTRANS

  • Butrans is for transdermal use (on intact skin) only. Each Butrans Transdermal System is intended to be worn for 7 days

  • Instruct patients not to use Butrans if the pouch seal is broken or the patch is cut, damaged, or changed in any way and not to cut Butrans

  • Instruct patients to apply immediately after removal from the individually sealed pouch

  • Apply Butrans to the upper outer arm, upper chest, upper back or the side of the chest. These 4 sites (each present on both sides of the body) provide 8 possible application sites. Rotate Butrans among the 8 described skin sites. After Butrans removal, wait a minimum of 21 days before reapplying to the same skin site

  • Apply Butrans to a hairless or nearly hairless skin site. If none are available, the hair at the site should be clipped, not shaven. Do not apply Butrans to irritated skin. If the application site must be cleaned, clean the site with water only. Do not use soaps, alcohol, oils, lotions, or abrasive devices. Allow the skin to dry before applying Butrans

  • If problems with adhesion of Butrans occur, the edges may be taped with first aid tape. If Butrans falls off during the 7 days dosing interval, dispose of the transdermal system properly and place a new Butrans Transdermal System on at a different skin site

  • If the buprenorphine-containing adhesive matrix accidentally contacts the skin, instruct patients or caregivers to wash the area with water and not to use soap, alcohol, or other solvents to remove the adhesive because they may enhance the absorption of the drug

  • See the Instructions for Use for step-by-step instructions for applying Butrans

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

  • Abuse Potential: Butrans contains buprenorphine, a Schedule III controlled substance that can be abused in a manner similar to other opioid agonists, legal or illicit. Assess each patient's risk for opioid abuse or addiction prior to prescribing Butrans. The risk for opioid abuse is 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). Patients at increased risk may still be appropriately treated with modified-release opioid formulations; however these patients will require intensive monitoring for signs of misuse, abuse, or addiction. Routinely monitor all patients receiving opioids for signs of abuse, misuse, and addiction because these drugs carry a risk for addiction even under appropriate medical use

  • Misuse or abuse of Butrans by chewing, swallowing, snorting or injecting buprenorphine extracted from the transdermal system will result in the uncontrolled delivery of the opioid and pose a significant risk that could result in overdose and death

  • Life-Threatening Respiratory Depression: Respiratory depression is the primary risk of Butrans. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Respiratory depression from opioids is manifested by a reduced urge to breathe and a decreased rate of respiration, often associated with a "sighing" pattern of breathing (deep breaths separated by abnormally long pauses). Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids

  • 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. Instruct patients against use by individuals other than the patient for whom Butrans was prescribed and to keep Butrans out of the reach of children, as such inappropriate use may result in fatal respiratory depression

  • 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. Respiratory depression has also been reported with use of modified-release opioids when used as recommended and not misused or abused

  • Accidental Exposure: Accidental exposure to Butrans, especially in children, can result in a fatal overdose of buprenorphine

  • Elderly, Cachectic, and Debilitated Patients: Respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients. Monitor such patients closely, particularly when initiating and titrating Butrans and when Butrans is given concomitantly with other drugs that depress respiration

  • Use in Patients with Chronic Pulmonary Disease: 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 for respiratory depression, particularly when initiating therapy and titrating with Butrans, as 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

  • Interactions with Alcohol, CNS Depressants, and Illicit Drugs: Hypotension, profound sedation, coma, or respiratory depression may result if Butrans is added to a regimen that includes other CNS depressants (eg, sedatives, anxiolytics, hypnotics, neuroleptics, muscle relaxants, other opioids). 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. Consider the patient's use, if any, of alcohol or illicit drugs that cause CNS depression

  • If Butrans therapy is to be initiated in a patient taking a CNS depressant, start with a lower Butrans dose than usual and monitor patients for signs of sedation and respiratory depression and consider using a lower dose of the concomitant CNS depressant

  • 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 Transdermal System dose of 10 mcg/hour; however, a Butrans Transdermal System 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 reduced blood volume or concurrent administration of certain CNS depressant drugs. 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 through 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. The buprenorphine in 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: The buprenorphine in 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

  • Avoidance of Withdrawal: Symptoms of withdrawal include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Significant fluid losses from vomiting and diarrhea can require intravenous fluid administration

  • When discontinuing Butrans, gradually taper the dose. Do not abruptly discontinue Butrans

  • 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. ©2013 Purdue Pharma L.P., Stamford, CT 06901-3431

Parentheses refer to sections in the Full Prescribing Information.

Important Safety Information

WARNING: ABUSE POTENTIAL, LIFE-THREATENING RESPIRATORY DEPRESSION, and ACCIDENTAL EXPOSURE

Abuse Potential
Butrans contains buprenorphine, an opioid agonist and Schedule III controlled substance with an abuse liability similar to other Schedule III opioids, legal or illicit [see Warnings and Precautions (5.1)]. Assess each patient's risk for opioid abuse or addiction prior to prescribing Butrans. The risk for opioid abuse is increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (eg, major depressive disorder). Routinely monitor all patients receiving Butrans for signs of misuse, abuse, and addiction during treatment [see Drug Abuse and Dependence (9)].

Life-Threatening Respiratory Depression
Respiratory depression, including fatal cases, may occur with use of Butrans, even when the drug has been used as recommended and not misused or abused [see Warnings and Precautions (5.2)]. Proper dosing and titration are essential and Butrans should only be prescribed by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain. Monitor for respiratory depression, especially during initiation of Butrans or following a dose increase.

Accidental Exposure
Accidental exposure to Butrans, especially in children, can result in a fatal overdose of buprenorphine [see Warnings and Precautions (5.3)].

Parentheses refer to sections in the Full Prescribing Information.

Administration of Butrans

  • Butrans is for transdermal use (on intact skin) only. Each Butrans Transdermal System is intended to be worn for 7 days

  • Instruct patients not to use Butrans if the pouch seal is broken or the patch is cut, damaged, or changed in any way and not to cut Butrans

  • Instruct patients to apply immediately after removal from the individually sealed pouch

  • Apply Butrans to the upper outer arm, upper chest, upper back or the side of the chest. These 4 sites (each present on both sides of the body) provide 8 possible application sites. Rotate Butrans among the 8 described skin sites. After Butrans removal, wait a minimum of 21 days before reapplying to the same skin site

  • Apply Butrans to a hairless or nearly hairless skin site. If none are available, the hair at the site should be clipped, not shaven. Do not apply Butrans to irritated skin. If the application site must be cleaned, clean the site with water only. Do not use soaps, alcohol, oils, lotions, or abrasive devices. Allow the skin to dry before applying Butrans

  • If problems with adhesion of Butrans occur, the edges may be taped with first aid tape. If Butrans falls off during the 7 days dosing interval, dispose of the transdermal system properly and place a new Butrans Transdermal System on at a different skin site

  • If the buprenorphine-containing adhesive matrix accidentally contacts the skin, instruct patients or caregivers to wash the area with water and not to use soap, alcohol, or other solvents to remove the adhesive because they may enhance the absorption of the drug

  • See the Instructions for Use for step-by-step instructions for applying Butrans

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

  • Abuse Potential: Butrans contains buprenorphine, a Schedule III controlled substance that can be abused in a manner similar to other opioid agonists, legal or illicit. Assess each patient's risk for opioid abuse or addiction prior to prescribing Butrans. The risk for opioid abuse is 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). Patients at increased risk may still be appropriately treated with modified-release opioid formulations; however these patients will require intensive monitoring for signs of misuse, abuse, or addiction. Routinely monitor all patients receiving opioids for signs of abuse, misuse, and addiction because these drugs carry a risk for addiction even under appropriate medical use

  • Misuse or abuse of Butrans by chewing, swallowing, snorting or injecting buprenorphine extracted from the transdermal system will result in the uncontrolled delivery of the opioid and pose a significant risk that could result in overdose and death

  • Life-Threatening Respiratory Depression: Respiratory depression is the primary risk of Butrans. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Respiratory depression from opioids is manifested by a reduced urge to breathe and a decreased rate of respiration, often associated with a "sighing" pattern of breathing (deep breaths separated by abnormally long pauses). Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids

  • 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. Instruct patients against use by individuals other than the patient for whom Butrans was prescribed and to keep Butrans out of the reach of children, as such inappropriate use may result in fatal respiratory depression

  • 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. Respiratory depression has also been reported with use of modified-release opioids when used as recommended and not misused or abused

  • Accidental Exposure: Accidental exposure to Butrans, especially in children, can result in a fatal overdose of buprenorphine

  • Elderly, Cachectic, and Debilitated Patients: Respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients. Monitor such patients closely, particularly when initiating and titrating Butrans and when Butrans is given concomitantly with other drugs that depress respiration

  • Use in Patients with Chronic Pulmonary Disease: 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 for respiratory depression, particularly when initiating therapy and titrating with Butrans, as 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

  • Interactions with Alcohol, CNS Depressants, and Illicit Drugs: Hypotension, profound sedation, coma, or respiratory depression may result if Butrans is added to a regimen that includes other CNS depressants (eg, sedatives, anxiolytics, hypnotics, neuroleptics, muscle relaxants, other opioids). 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. Consider the patient's use, if any, of alcohol or illicit drugs that cause CNS depression

  • If Butrans therapy is to be initiated in a patient taking a CNS depressant, start with a lower Butrans dose than usual and monitor patients for signs of sedation and respiratory depression and consider using a lower dose of the concomitant CNS depressant

  • 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 Transdermal System dose of 10 mcg/hour; however, a Butrans Transdermal System 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 reduced blood volume or concurrent administration of certain CNS depressant drugs. 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 through 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. The buprenorphine in 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: The buprenorphine in 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

  • Avoidance of Withdrawal: Symptoms of withdrawal include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Significant fluid losses from vomiting and diarrhea can require intravenous fluid administration

  • When discontinuing Butrans, gradually taper the dose. Do not abruptly discontinue Butrans

  • 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. ©2013 Purdue Pharma L.P., Stamford, CT 06901-3431