FDA label e77e80f1-60e9-4034-a2bc-d19592c754a2

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 (e.g., 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 )] . WARNING: ABUSE POTENTIAL, LIFE-THREATENING RESPIRATORY DEPRESSION, and ACCIDENTAL EXPOSURE See full prescribing information for complete boxed warning. BUTRANS contains buprenorphine, a Schedule III controlled substance. Monitor for signs of misuse, abuse, and addiction during BUTRANS therapy ( 5.1 , 9 ). Fatal respiratory depression may occur, with highest risk at initiation and with dose increases. Instruct patients on proper administration of BUTRANS to reduce the risk ( 5.2 ). Accidental exposure to BUTRANS can result in fatal overdose of buprenorphine, especially in children ( 5.3 ).

5 WARNINGS AND PRECAUTIONS Elderly, cachectic, and debilitated patients, and patients with chronic pulmonary disease: Monitor closely because of increased risk of respiratory depression. ( 5.4 , 5.5 ) Interaction with CNS depressants, especially benzodiazepines: Consider dose reduction of one or both drugs because of additive effects. ( 5.6 , 7.2 , 7.3 ) Avoid in patients with Long QT Syndrome, family history of Long QT Syndrome, or those taking Class IA or Class III antiarrhythmic medications. ( 5.7 , 12.2 ) Hypotensive effects: Monitor during dose initiation and titration. ( 5.8 ) Patients with head injury or increased intracranial pressure: Monitor for sedation and respiratory depression and avoid use of BUTRANS in patients with impaired consciousness or coma susceptible to intracranial effects of CO 2 retention. ( 5.9 ) 5.1 Abuse Potential BUTRANS contains buprenorphine, a partial agonist at the mu opioid receptor and a Schedule III controlled substance. Buprenorphine can be abused in a manner similar to other opioid agonists, legal or illicit. Opioid agonists are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing BUTRANS in situations where there is concern about increased risks of misuse, abuse, or diversion. Concerns about abuse, addiction, and diversion should not, however, prevent the proper management of pain. 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 (e.g., 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 misuse, abuse, 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 [see Overdosage ( 10 )] . Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product. 5.2 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 (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see Overdosage ( 10 )] . 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 [see Dosage and Administration ( 2.1 , 2.2 )] . 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. To further reduce the risk of respiratory depression, consider the following: 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. BUTRANS is contraindicated in patients with respiratory depression and in patients with conditions that increase the risk of life-threatening respiratory depression [see Contraindications ( 4 )] . 5.3 Accidental Exposure Accidental exposure to BUTRANS, especially in children, can result in a fatal overdose of buprenorphine. 5.4 Elderly, Cachectic, and Debilitated Patients Respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics due to poor fat stores, muscle wasting, or altered clearance compared to younger, healthier patients. Therefore, monitor such patients closely, particularly when initiating and titrating BUTRANS and when BUTRANS is given concomitantly with other drugs that depress respiration [see Warnings and Precautions ( 5.2 )] . 5.5 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 [see Warnings and Precautions ( 5.2 )] . Consider the use of alternative non-opioid analgesics in these patients if possible. 5.6 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 (e.g., sedatives, anxiolytics, hypnotics, neuroleptics, muscle relaxants, 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, 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 [see Drug Interactions ( 7.3 )] . 5.7 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 [see Clinical Pharmacology ( 12.2 )] . 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 (e.g., quinidine, procainamide, disopyramide) or Class III antiarrhythmic medications (e.g., sotalol, amiodarone, dofetilide). 5.8 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 already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see Drug Interactions ( 7.3 )]. Monitor these patients for signs of hypotension after initiating or titrating the dose of BUTRANS. 5.9 Use in Patients with Head Injury or Increased Intracranial Pressure Monitor patients taking BUTRANS who may be susceptible to the intracranial effects of CO 2 retention (e.g., 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 CO 2 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. 5.10 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. The spectrum of abnormalities ranges from transient asymptomatic elevations in hepatic transaminases to case reports of hepatic failure, hepatic necrosis, hepatorenal syndrome, and hepatic encephalopathy. In many cases, the presence of pre-existing liver enzyme abnormalities, infection with hepatitis B or hepatitis C virus, concomitant usage of other potentially hepatotoxic drugs, and ongoing injection drug abuse may have played a causative or contributory role. For patients at increased risk of hepatotoxicity (e.g., patients with a history of excessive alcohol intake, intravenous drug abuse or liver disease), obtain baseline liver enzyme levels and monitor periodically and during treatment with BUTRANS. 5.11 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. 5.12 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. 5.13 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 [see Clinical Pharmacology ( 12.3 )] . 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. 5.14 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. 5.15 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. 5.16 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. 5.17 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 [see Dosage and Administration ( 2.3 )] . Do not abruptly discontinue BUTRANS. 5.18 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. 5.19 Use in Addiction Treatment BUTRANS has not been studied and is not approved for use in the management of addictive disorders.

6 ADVERSE REACTIONS The following adverse reactions described elsewhere in the labeling include: Respiratory Depression [see Warnings and Precautions ( 5.2 )] QTc Prolongation [see Warnings and Precautions ( 5.7 )] Hypotensive Effects [see Warnings and Precautions ( 5.8 )] Application Site Skin Reactions [see Warnings and Precautions ( 5.11 )] Anaphylactic/Allergic Reactions [see Warnings and Precautions ( 5.12 )] Gastrointestinal Effects [see Warnings and Precautions ( 5.15 )] Seizures [see Warnings and Precautions ( 5.16 )] Most common adverse reactions (≥ 5%) include: nausea, headache, application site pruritus, dizziness, constipation, somnolence, vomiting, application site erythema, dry mouth, and application site rash. ( 6.1 ) 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/medwatch . 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 5,415 patients were treated with BUTRANS in controlled and open-label chronic pain clinical trials. Nine hundred twenty-four subjects were treated for approximately six months and 183 subjects were treated for approximately one year. The clinical trial population consisted of patients with persistent moderate to severe pain. The most common serious adverse drug reactions (all <0.1%) occurring during clinical trials with BUTRANS were: chest pain, abdominal pain, vomiting, dehydration, and hypertension/blood pressure increased. The most common adverse events (≥ 2%) leading to discontinuation were: nausea, dizziness, vomiting, headache, and somnolence. The most common adverse reactions (≥ 5%) reported by patients in clinical trials comparing BUTRANS 10 or 20 mcg/hour to placebo are shown in Table 2, and comparing BUTRANS 20 mcg/hour to BUTRANS 5 mcg/hour are shown in Table 3 below: Table 2: Adverse Reactions Reported in ≥ 5% of Patients during the Open-Label Titration Period and Double-Blind Treatment Period: Opioid-Naïve Patients Open-Label Titration Period BUTRANS Double-Blind BUTRANS Treatment Period Placebo MedDRA Preferred Term (N = 1024) (N = 256) (N = 283) Nausea 23% 13% 10% Dizziness 10% 4% 1% Headache 9% 5% 5% Application site pruritus 8% 4% 7% Somnolence 8% 2% 2% Vomiting 7% 4% 1% Constipation 6% 4% 1% Table 3: Adverse Reactions Reported in ≥ 5% of Patients during the Open-Label Titration Period and Double-Blind Treatment Period: Opioid-Experienced Patients Open-Label Titration Period BUTRANS Double-Blind BUTRANS 20 Treatment Period BUTRANS 5 MedDRA Preferred Term (N = 1160) (N = 219) (N = 221) Nausea 14% 11% 6% Application site pruritus 9% 13% 5% Headache 9% 8% 3% Somnolence 6% 4% 2% Dizziness 5% 4% 2% Constipation 4% 6% 3% Application site erythema 3% 10% 5% Application site rash 3% 8% 6% Application site irritation 2% 6% 2% The following table lists adverse reactions that were reported in at least 2.0% of patients in four placebo/active-controlled titration-to-effect trials. Table 4: Adverse Reactions Reported in Titration-to-Effect Placebo/Active-Controlled Clinical Trials with Incidence ≥ 2% MedDRA Preferred Term BUTRANS (N = 392) Placebo (N = 261) Nausea 21% 6% Application site pruritus 15% 12% Dizziness 15% 7% Headache 14% 9% Somnolence 13% 4% Constipation 13% 5% Vomiting 9% 1% Application site erythema 7% 2% Application site rash 6% 6% Dry mouth 6% 2% Fatigue 5% 1% Hyperhidrosis 4% 1% Peripheral edema 3% 1% Pruritus 3% 0% Stomach discomfort 2% 0% The adverse reactions seen in controlled and open-label studies are presented below in the following manner: most common (≥ 5%), common (≥ 1% to < 5%), and less common (< 1%). The most common adverse reactions (≥ 5%) reported by patients treated with BUTRANS in the clinical trials were nausea, headache, application site pruritus, dizziness, constipation, somnolence, vomiting, application site erythema, dry mouth, and application site rash. The common (≥ 1% to < 5%) adverse reactions reported by patients treated with BUTRANS in the clinical trials organized by MedDRA (Medical Dictionary for Regulatory Activities) System Organ Class were: Gastrointestinal disorders: diarrhea, dyspepsia, and upper abdominal pain General disorders and administration site conditions: fatigue, peripheral edema, application site irritation, pain, pyrexia, chest pain, and asthenia Infections and infestations: urinary tract infection, upper respiratory tract infection, nasopharyngitis, influenza, sinusitis, and bronchitis Injury, poisoning and procedural complications: fall Metabolism and nutrition disorders: anorexia Musculoskeletal and connective tissue disorders: back pain, arthralgia, pain in extremity, muscle spasms, musculoskeletal pain, joint swelling, neck pain, and myalgia Nervous system disorders: hypoesthesia, tremor, migraine, and paresthesia Psychiatric disorders: insomnia, anxiety, and depression Respiratory, thoracic and mediastinal disorders: dyspnea, pharyngolaryngeal pain, and cough Skin and subcutaneous tissue disorders: pruritus, hyperhidrosis, rash, and generalized pruritus Vascular disorders: hypertension Other less common adverse reactions, including those known to occur with opioid treatment, that were seen in < 1% of the patients in the BUTRANS trials include the following in alphabetical order: Abdominal distention, abdominal pain, accidental injury, affect lability, agitation, alanine aminotransferase increased, angina pectoris, angioedema, apathy, application site dermatitis, asthma aggravated, bradycardia, chills, confusional state, contact dermatitis, coordination abnormal, dehydration, depersonalization, depressed level of consciousness, depressed mood, disorientation, disturbance in attention, diverticulitis, drug hypersensitivity, drug withdrawal syndrome, dry eye, dry skin, dysarthria, dysgeusia, dysphagia, euphoric mood, face edema, flatulence, flushing, gait disturbance, hallucination, hiccups, hot flush, hyperventilation, hypotension, hypoventilation, ileus, insomnia, libido decreased, loss of consciousness, malaise, memory impairment, mental impairment, mental status changes, miosis, muscle weakness, nervousness, nightmare, orthostatic hypotension, palpitations, psychotic disorder, respiration abnormal, respiratory depression, respiratory distress, respiratory failure, restlessness, rhinitis, sedation, sexual dysfunction, syncope, tachycardia, tinnitus, urinary hesitation, urinary incontinence, urinary retention, urticaria, vasodilatation, vertigo, vision blurred, visual disturbance, weight decreased, and wheezing.

<table ID="t11561322" border="0" width="80%"> <colgroup> <col/> <col/> <col/> <col/> </colgroup> <tbody> <tr> <td> </td> <td align="center"> <content styleCode="bold">Open-Label Titration Period BUTRANS</content> </td> <td align="center"> <content styleCode="bold">Double-Blind BUTRANS</content> </td> <td align="center"> <content styleCode="bold">Treatment Period Placebo</content> </td> </tr> <tr> <td styleCode="Toprule Botrule"> <content styleCode="bold">MedDRA Preferred Term</content> </td> <td styleCode="Toprule Botrule" align="center"> <content styleCode="bold">(N = 1024)</content> </td> <td styleCode="Toprule Botrule" align="center"> <content styleCode="bold">(N = 256)</content> </td> <td styleCode="Toprule Botrule" align="center"> <content styleCode="bold">(N = 283)</content> </td> </tr> <tr> <td>Nausea</td> <td align="center">23%</td> <td align="center">13%</td> <td align="center">10%</td> </tr> <tr> <td>Dizziness</td> <td align="center">10%</td> <td align="center">4%</td> <td align="center">1%</td> </tr> <tr> <td>Headache</td> <td align="center">9%</td> <td align="center">5%</td> <td align="center">5%</td> </tr> <tr> <td>Application site pruritus</td> <td align="center">8%</td> <td align="center">4%</td> <td align="center">7%</td> </tr> <tr> <td>Somnolence</td> <td align="center">8%</td> <td align="center">2%</td> <td align="center">2%</td> </tr> <tr> <td>Vomiting</td> <td align="center">7%</td> <td align="center">4%</td> <td align="center">1%</td> </tr> <tr> <td>Constipation</td> <td align="center">6%</td> <td align="center">4%</td> <td align="center">1%</td> </tr> </tbody> </table>

<table ID="t12545822" border="0" width="80%"> <colgroup> <col/> <col/> <col/> <col/> </colgroup> <tbody> <tr> <td> </td> <td align="center"> <content styleCode="bold">Open-Label Titration Period BUTRANS</content> </td> <td align="center"> <content styleCode="bold">Double-Blind BUTRANS 20</content> </td> <td align="center"> <content styleCode="bold">Treatment Period BUTRANS 5</content> </td> </tr> <tr> <td styleCode="Toprule Botrule"> <content styleCode="bold">MedDRA Preferred Term</content> </td> <td styleCode="Toprule Botrule" align="center"> <content styleCode="bold">(N = 1160)</content> </td> <td styleCode="Toprule Botrule" align="center"> <content styleCode="bold">(N = 219)</content> </td> <td styleCode="Toprule Botrule" align="center"> <content styleCode="bold">(N = 221)</content> </td> </tr> <tr> <td>Nausea</td> <td align="center">14%</td> <td align="center">11%</td> <td align="center">6%</td> </tr> <tr> <td>Application site pruritus</td> <td align="center">9%</td> <td align="center">13%</td> <td align="center">5%</td> </tr> <tr> <td>Headache</td> <td align="center">9%</td> <td align="center">8%</td> <td align="center">3%</td> </tr> <tr> <td>Somnolence</td> <td align="center">6%</td> <td align="center">4%</td> <td align="center">2%</td> </tr> <tr> <td>Dizziness</td> <td align="center">5%</td> <td align="center">4%</td> <td align="center">2%</td> </tr> <tr> <td>Constipation</td> <td align="center">4%</td> <td align="center">6%</td> <td align="center">3%</td> </tr> <tr> <td>Application site erythema</td> <td align="center">3%</td> <td align="center">10%</td> <td align="center">5%</td> </tr> <tr> <td>Application site rash</td> <td align="center">3%</td> <td align="center">8%</td> <td align="center">6%</td> </tr> <tr> <td>Application site irritation</td> <td align="center">2%</td> <td align="center">6%</td> <td align="center">2%</td> </tr> </tbody> </table>

<table ID="t13568222" border="1" width="80%"> <colgroup> <col width="33*"/> <col width="33*"/> <col width="33*"/> </colgroup> <tbody> <tr> <td> <content styleCode="bold">MedDRA Preferred Term</content> </td> <td align="center"> <content styleCode="bold">BUTRANS (N = 392)</content> </td> <td align="center"> <content styleCode="bold">Placebo (N = 261)</content> </td> </tr> <tr> <td>Nausea</td> <td align="center">21%</td> <td align="center">6%</td> </tr> <tr> <td>Application site pruritus</td> <td align="center">15%</td> <td align="center">12%</td> </tr> <tr> <td>Dizziness</td> <td align="center">15%</td> <td align="center">7%</td> </tr> <tr> <td>Headache</td> <td align="center">14%</td> <td align="center">9%</td> </tr> <tr> <td>Somnolence</td> <td align="center">13%</td> <td align="center">4%</td> </tr> <tr> <td>Constipation</td> <td align="center">13%</td> <td align="center">5%</td> </tr> <tr> <td>Vomiting</td> <td align="center">9%</td> <td align="center">1%</td> </tr> <tr> <td>Application site erythema</td> <td align="center">7%</td> <td align="center">2%</td> </tr> <tr> <td>Application site rash</td> <td align="center">6%</td> <td align="center">6%</td> </tr> <tr> <td>Dry mouth</td> <td align="center">6%</td> <td align="center">2%</td> </tr> <tr> <td>Fatigue</td> <td align="center">5%</td> <td align="center">1%</td> </tr> <tr> <td>Hyperhidrosis</td> <td align="center">4%</td> <td align="center">1%</td> </tr> <tr> <td>Peripheral edema</td> <td align="center">3%</td> <td align="center">1%</td> </tr> <tr> <td>Pruritus</td> <td align="center">3%</td> <td align="center">0%</td> </tr> <tr> <td>Stomach discomfort</td> <td align="center">2%</td> <td align="center">0%</td> </tr> </tbody> </table>