FDA label 3acfb583-827d-11e2-9e96-0800200c9a66

WARNING: RISK OF RESPIRATORY DEPRESSION, MEDICATION ERRORS, ABUSE POTENTIAL RESPIRATORY DEPRESSION Fatal respiratory depression has occurred in patients treated with immediate-release transmucosal fentanyl, including following use in opioid non-tolerant patients and improper dosing. The substitution of ONSOLIS for any other fentanyl product may result in fatal overdose. Due to the risk of respiratory depression, ONSOLIS is contraindicated in the management of acute or postoperative pain including headache/migraine and in opioid non-tolerant patients. [ see Contraindications ( 4 )] ONSOLIS must be kept out of reach of children. [See Patient Counseling Information ( 17.1 ) and How Supplied/Storage and Handling( 16.1 )] The concomitant use of ONSOLIS with CYP3A4 inhibitors may result in an increase in fentanyl plasma concentrations, and may cause potentially fatal respiratory depression [see Drug Interactions ( 7 )]. MEDICATION ERRORS Substantial differences exist in the pharmacokinetic profile of ONSOLIS compared to other fentanyl products that result in clinically important differences in the extent of absorption of fentanyl that could result in fatal overdose. – When prescribing, do not convert patients on a mcg per mcg basis from any other fentanyl products to ONSOLIS. ( 2.1 ) – When dispensing, do not substitute an ONSOLIS prescription for other fentanyl products. ABUSE POTENTIAL ONSOLIS contains fentanyl, an opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics. ONSOLIS can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing ONSOLIS in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion. Because of the risk for misuse, abuse, addiction, and overdose, Onsolis is available only through a restricted program required by the Food and Drug Administration, called a Risk Evaluation and Mitigation Strategy (REMS). Under the Transmucosal Immediate Release Fentanyl (TIRF) REMS Access program, outpatients, healthcare professionals who prescribe to outpatients, pharmacies, and distributors must enroll in the program [see Warnings and Precautions ( 5.10 )]. Further information is available at www.TIRFREMSAccess.com or by calling 1-866-822-1483. WARNING: RISK OF RESPIRATORY DEPRESSION, MEDICATION ERRORS, ABUSE POTENTIAL See full prescribing information for complete boxed warning. Due to the risk of fatal respiratory depression, ONSOLIS is contraindicated in opioid non-tolerant patients ( 1 ) and in management of acute or postoperative pain, including headache/migraines. ( 4 ) Keep out of reach of children ( 5.3 ) Use with CYP3A4 inhibitors may cause fatal respiratory depression ( 7 ) When prescribing, do not convert patients on a mcg per mcg basis from any other oral transmucosal fentanyl product to ONSOLIS ( 2.1 , 5.2 ) When dispensing, do not substitute with any other fentanyl products ( 5.2 ) Contains fentanyl, a Schedule II controlled substance with abuse liability similar to other opioid analgesics. ( 9.1 ) Onsolis is available only through a restricted program called the TIRF REMS Access program. Outpatients, healthcare professionals who prescribe to outpatients, pharmacies, and distributors are required to enroll in the Program ( 5.10 )

5 WARNINGS AND PRECAUTIONS See Boxed Warning - WARNING: RISK OF RESPIRATORY DEPRESSION, MEDICATION ERRORS, ABUSE POTENTIAL Clinically significant respiratory and CNS depression can occur. Monitor patients accordingly. ( 5.1 , 5.4 ) Onsolis films contain medicine that can be fatal to a child. Ensure proper storage and disposal. ( 5.3 , 16.2 ) Use with other CNS depressants or CYP3A4 inhibitors may increase depressant effects including hypoventilation, hypotension, and profound sedation. Consider dosage adjustments if warranted. ( 5.4 , 7 ) Onsolis may impair ability for the performance of potentially dangerous tasks (e.g., driving a car or operating machinery). ( 5.5 ) Titrate Onsolis cautiously in patients with chronic obstructive pulmonary disease or preexisting medical conditions predisposing them to hypoventilation and in patients susceptible to intracranial effects of CO 2 retention. ( 5.6 , 5.7 ) 5.1 Respiratory Depression (Hypoventilation) Respiratory depression is the chief hazard of opioid agonists, including fentanyl, the active ingredient in Onsolis. Respiratory depression is more likely to occur in patients with underlying respiratory disorders and elderly or debilitated patients, usually following large initial doses in opioid non-tolerant patients, or when opioids are given in conjunction with other drugs that depress respiration. Respiratory depression from opioids is manifested by a reduced urge to breathe and a decreased rate of respiration, often associated with the “sighing” pattern of breathing (deep breaths separated by abnormally long pauses). Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. This makes overdoses involving drugs with sedative properties and opioids especially dangerous. 5.2 Onsolis Dispensing When dispensing, do not substitute an Onsolis prescription for any other fentanyl product. Substantial differences exist in the pharmacokinetic profile of Onsolis compared to other fentanyl products (e.g., see Figure 1 ) that result in clinically important differences in the extent of absorption of fentanyl. As a result of these differences, the substitution of Onsolis for any other fentanyl product may result in fatal overdose. Onsolis is NOT a generic version of any other transmucosal fentanyl product. 5.3 Patient/Caregiver Instructions Patients and their caregivers must be instructed that Onsolis contains a medicine in an amount which can be fatal in children, in individuals for whom it is not prescribed, and in those who are not opioid-tolerant. Patients and their caregivers must be instructed to keep Onsolis out of the reach of children. [see How Supplied ( 16.3 ), Storage and Handling ( 16.1 ), and Patient Counseling Information ( 17 )]. Physicians and dispensing pharmacists must specifically question patients or caregivers about the presence of children in the home (on a full time or visiting basis) and counsel them regarding the dangers to children from inadvertent exposure. 5.4 Additive CNS Depressant Effects The concomitant use of Onsolis with other CNS depressants, including other opioids, sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, skeletal muscle relaxants, sedating antihistamines, and alcoholic beverages may produce increased depressant effects (e.g., hypoventilation, hypotension, and profound sedation). Concomitant use with inhibitors of the cytochrome P450 3A4 (CYP3A4) isoform (e.g., erythromycin, ketoconazole, and certain protease inhibitors) may increase fentanyl levels, resulting in increased depressant effects [see Drug Interactions ( 7 )]. Patients on concomitant CNS depressants must be monitored for a change in opioid effects. Consideration should be given to adjusting the dose of Onsolis if warranted. 5.5 Effects on Ability to Drive and Use Machines Opioid analgesics impair the mental and/or physical ability required for the performance of potentially dangerous tasks (e.g., driving a car or operating machinery). Warn patients taking Onsolis of these dangers and counsel them accordingly. 5.6 Chronic Pulmonary Disease Because potent opioids can cause respiratory depression, titrate Onsolis with caution in patients with chronic obstructive pulmonary disease or pre-existing medical conditions predisposing them to hypoventilation. In such patients, even normal therapeutic doses of Onsolis may further decrease respiratory drive to the point of respiratory failure. 5.7 Head Injuries and Increased Intracranial Pressure Administer Onsolis with extreme caution in patients who may be particularly susceptible to the intracranial effects of CO 2 retention such as those with evidence of increased intracranial pressure or impaired consciousness. Opioids may obscure the clinical course of a patient with a head injury and should be used only if clinically warranted. 5.8 Cardiac Disease Intravenous fentanyl may produce bradycardia. Therefore, use Onsolis with caution in patients with bradyarrhythmias. 5.9 MAO Inhibitors Onsolis is not recommended for use in patients who have received MAO inhibitors within 14 days because severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. 5.10 Transmucosal Immediate Release Fentanyl (TIRF) Risk Evaluation and Mitigation Strategy (REMS) Access Program Because of the risk for misuse, abuse, addiction, and overdose [see Drug Abuse and Dependence ( 9 )], Onsolis is available only through a restricted program called the TIRF REMS Access program. Under the TIRF REMS Access program, outpatients, prescribers who prescribe to outpatients, pharmacies, and distributors must enroll in the program. For inpatient administration (e.g. hospitals, hospices, and long-term care facilities that prescribe for inpatient use) of Onsolis, patient and prescriber enrollment is not required. Required components of the TIRF REMS Access program are: Healthcare professionals who prescribe Onsolis must review the prescriber educational materials for the TIRF REMS Access program, enroll in the program, and comply with the REMS requirements. To receive Onsolis, outpatients must understand the risks and benefits and sign a Patient-Prescriber Agreement. Pharmacies that dispense Onsolis must enroll in the program and agree to comply with the REMS requirements. Wholesalers and distributors that distribute Onsolis must enroll in the program and distribute only to authorized pharmacies. Further information, including a list of qualified pharmacies/distributors, is available at www.TIRFREMSAccess.com or by calling 1-866-822-1483.

6 ADVERSE REACTIONS Most common adverse reactions (frequency ≥10%): nausea, vomiting, dizziness, dehydration, dyspnea, and somnolence. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Meda Pharmaceuticals Inc. at 1-800-526-3840 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Studies Experience The safety of Onsolis has been evaluated in 306 opioid tolerant patients with breakthrough cancer pain in the efficacy study and an open-label safety study. The mean duration of therapy was 115 days, with 32 patients treated for more than 1 year. The adverse reactions seen with Onsolis are typical opioid side effects in a population with cancer. Frequently, opioid-associated adverse reactions will cease or decrease in intensity with continued use of Onsolis. Expect opioid side effects and manage them accordingly. The most serious adverse reactions associated with all opioids including Onsolis are respiratory depression (potentially leading to apnea or respiratory arrest), circulatory depression, hypotension, and shock. Follow all patients for symptoms of respiratory depression. Because the clinical trials of Onsolis were designed to evaluate safety and efficacy in treating patients with breakthrough pain associated with cancer, all patients were also taking concomitant opioids, such as sustained-release morphine, sustained-release oxycodone or transdermal fentanyl, for their persistent cancer pain. The adverse event data presented here reflect the actual percentage of patients experiencing each adverse event among patients who received Onsolis for breakthrough cancer pain along with a concomitant opioid for persistent cancer pain. There has been no attempt to correct for concomitant use of other opioids, duration of Onsolis therapy, or cancer-related symptoms. Adverse reactions are included regardless of severity. Because clinical trials are conducted under widely varying conditions, adverse event 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. Table 1 lists, by maximum dose received, adverse reactions with an overall frequency of 5% or greater that occurred during titration. The ability to assign a dose-response relationship to these adverse reactions is limited by the titration schedules used in these studies. Adverse reactions are listed in descending order of frequency within each body system. Table 1 Adverse Reactions Which Occurred During Titration at a Frequency of ≥5% Onsolis Dose (mcg) System Organ Class, 200 400 600 800 1200 >1200 Total Preferred Term, n (%) (N=303) (N=257) (N=207) (N=138) (N=79) (N=9) (N=306) Gastrointestinal Disorders Nausea 16 (5) 12 (5) 6 (3) 5 (4) 4 (5) 0 42 (14) Vomiting 7 (2) 9 (4) 8 (4) 2 (1) 0 0 26 (8) Nervous System Disorders Dizziness 5 (2) 5 (2) 6 (3) 2 (1) 4 (5) 0 22 (7) Somnolence 6 (2) 2 (1) 4 (2) 2 (1) 4 (5) 1 (11) 17 (6) Table 2 lists, by successful dose, adverse reactions with an overall frequency of ≥5% that occurred during long-term treatment (i.e., the double-blind or open-label maintenance periods). Table 2 Adverse Reactions Which Occurred During Long-Term Treatment at a Frequency of ≥5% Onsolis Dose (mcg) System Organ Class, 200 400 600 800 1200 >1200 Total Preferred Term, n (%) (N=23) (N=59) (N=79) (N=91) (N=81) (N=28) (N=213) Gastrointestinal Nausea 2 (9) 6 (10) 8 (10) 12 (13) 26 (32) 4 (14) 56 (26) Vomiting 1 (4) 5 (8) 9 (11) 8 (9) 23 (28) 3 (11) 45 (21) Constipation 2 (9) 4 (7) 4 (5) 4 (4) 6 (7) 4 (14) 23 (11) Diarrhea 1 (4) 1 (2) 4 (5) 4 (4) 10 (12) 0 19 (9) Dry mouth 1 (4) 4 (7) 3 (4) 2 (2) 3 (4) 1 (4) 14 (7) Abdominal pain 0 0 3 (4) 1 (1) 7 (9) 1 (4) 11 (5) General/administration site Asthenia 0 6 (10) 3 (4) 8 (9) 7 (9) 4 (14) 28 (13) Fatigue 2 (9) 6 (10) 1 (1) 7 (8) 7 (9) 3 (11) 25 (12) Investigations Weight decreased 3 (13) 0 2 (3) 5 (5) 5 (6) 1 (4) 15 (7) Metabolism/nutrition Dehydration 1 (4) 4 (7) 6 (8) 5 (5) 10 (12) 3 (11) 28 (13) Decreased appetite 0 4 (7) 4 (5) 6 (7) 2 (2) 2 (7) 18 (8) Anorexia 2 (9) 1 (2) 3 (4) 4 (4) 6 (7) 1 (4) 17 (8) Nervous system Dizziness 2 (9) 4 (7) 2 (3) 3 (3) 10 (12) 2 (7) 23 (11) Headache 2 (9) 1 (2) 3 (4) 9 (10) 7 (9) 0 20 (9) Somnolence 2 (9) 0 4 (5) 2 (2) 3 (4) 3 (11) 14 (7) Psychiatric Confusional state 1 (4) 0 4 (5) 4 (4) 6 (7) 4 (14) 18 (8) Depression 0 3 (5) 1 (1) 4 (4) 7 (9) 3 (11) 18 (8) Insomnia 0 2 (3) 2 (3) 3 (3) 4 (5) 2 (7) 12 (6) Anxiety 1 (4) 1 (2) 2 (3) 3 (3) 3 (4) 1 (4) 11 (5) Respiratory Dyspnea 3 (13) 4 (7) 3 (4) 8 (9) 6 (7) 3 (11) 26 (12) Cough 1 (4) 0 3 (4) 5 (5) 6 (7) 1 (4) 15 (7) Vascular Hypotension 0 3 (5) 3 (4) 1 (1) 3 (4) 1 (4) 11 (5) In a mucositis study, a group of patients (n=7) with Grade 1 oral mucositis and a matched group of control patients (n=7) without oral mucositis were included in a clinical trial designed to support the safety of Onsolis. The adverse event profile was similar in both subsets of patients. There was no evidence that Onsolis caused or worsened oral mucosal irritation or pain in either study group. The duration of exposure to Onsolis varied greatly, and included open-label and double-blind studies. The adverse reactions listed below represent those that were reported by ≥1% of patients from two clinical trials (the titration and post-titration periods) while receiving Onsolis. Events are classified by system organ class. Cardiac disorders: tachycardia Eye disorders: vision blurred, diplopia Gastrointestinal disorders: nausea, vomiting, constipation, diarrhea, dry mouth, abdominal pain, dyspepsia, dysphagia, abdominal distension, intestinal obstruction, flatulence General disorders and administration site conditions: asthenia, fatigue, malaise Injury, poisoning and procedural complications: fall, contusion Investigations: weight decreased, blood pressure increased Metabolism and nutrition disorders: dehydration, decreased appetite, anorexia Nervous system disorders: dizziness, somnolence, headache, lethargy, amnesia, sedation Psychiatric disorders: confusional state, depression, insomnia, anxiety, hallucination, agitation, mental status changes Renal and urinary disorders: urinary retention Respiratory, thoracic and mediastinal disorders: dyspnea, cough Skin and subcutaneous tissue disorders: pruritus, rash Vascular disorders: hypotension, hot flush, deep vein thrombosis, hypertension

<table width="750"> <caption>Adverse Reactions Which Occurred During Titration at a Frequency of &#x2265;5%</caption> <tbody> <tr> <td styleCode="Toprule Lrule"/> <td align="center" colspan="6" styleCode="Lrule Rrule Botrule"> <content styleCode="bold"> Onsolis Dose (mcg)</content> </td> <td styleCode="Rrule"/> </tr> <tr> <td styleCode="Lrule" valign="bottom"> <content styleCode="bold">System Organ Class,</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">200</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">400</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">600</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">800</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">1200</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">&gt;1200</content> </td> <td align="center" styleCode="Lrule Rrule"> <content styleCode="bold">Total</content> </td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> <content styleCode="bold">Preferred Term, n (%)</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">(N=303)</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">(N=257)</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">(N=207)</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">(N=138)</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">(N=79)</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">(N=9)</content> </td> <td align="center" styleCode="Lrule Rrule"> <content styleCode="bold">(N=306)</content> </td> </tr> <tr> <td colspan="8" styleCode="Lrule Rrule Botrule"> <content styleCode="bold">Gastrointestinal Disorders</content> </td> </tr> <tr> <td styleCode="Lrule Botrule">Nausea</td> <td align="center" styleCode="Lrule Botrule">16 (5)</td> <td align="center" styleCode="Lrule Botrule">12 (5)</td> <td align="center" styleCode="Lrule Botrule">6 (3)</td> <td align="center" styleCode="Lrule Botrule">5 (4)</td> <td align="center" styleCode="Lrule Botrule">4 (5)</td> <td align="center" styleCode="Lrule Botrule">0</td> <td align="center" styleCode="Lrule Rrule Botrule">42 (14)</td> </tr> <tr> <td styleCode="Lrule Botrule">Vomiting</td> <td align="center" styleCode="Lrule Botrule">7 (2)</td> <td align="center" styleCode="Lrule Botrule">9 (4)</td> <td align="center" styleCode="Lrule Botrule">8 (4)</td> <td align="center" styleCode="Lrule Botrule">2 (1)</td> <td align="center" styleCode="Lrule Botrule">0</td> <td align="center" styleCode="Lrule Botrule">0</td> <td align="center" styleCode="Lrule Rrule Botrule">26 (8)</td> </tr> <tr> <td colspan="8" styleCode="Lrule Rrule Botrule"> <content styleCode="bold">Nervous System Disorders</content> </td> </tr> <tr> <td styleCode="Lrule Botrule">Dizziness</td> <td align="center" styleCode="Lrule Botrule">5 (2)</td> <td align="center" styleCode="Lrule Botrule">5 (2)</td> <td align="center" styleCode="Lrule Botrule">6 (3)</td> <td align="center" styleCode="Lrule Botrule">2 (1)</td> <td align="center" styleCode="Lrule Botrule">4 (5)</td> <td align="center" styleCode="Lrule Botrule">0</td> <td align="center" styleCode="Lrule Rrule Botrule">22 (7)</td> </tr> <tr> <td styleCode="Lrule">Somnolence</td> <td align="center" styleCode="Lrule">6 (2)</td> <td align="center" styleCode="Lrule">2 (1)</td> <td align="center" styleCode="Lrule">4 (2)</td> <td align="center" styleCode="Lrule">2 (1)</td> <td align="center" styleCode="Lrule">4 (5)</td> <td align="center" styleCode="Lrule">1 (11)</td> <td align="center" styleCode="Lrule Rrule">17 (6)</td> </tr> </tbody> </table>

<table width="750"> <caption>Adverse Reactions Which Occurred During Long-Term Treatment at a Frequency of &#x2265;5%</caption> <tbody> <tr> <td styleCode="Toprule Lrule"/> <td align="center" colspan="6" styleCode="Lrule Rrule Botrule"> <content styleCode="bold"> Onsolis Dose (mcg)</content> </td> <td styleCode="Rrule"/> </tr> <tr> <td styleCode="Lrule" valign="bottom"> <content styleCode="bold">System Organ Class,</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">200</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">400</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">600</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">800</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">1200</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">&gt;1200</content> </td> <td align="center" styleCode="Lrule Rrule"> <content styleCode="bold">Total</content> </td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> <content styleCode="bold">Preferred Term, n (%)</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">(N=23)</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">(N=59)</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">(N=79)</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">(N=91)</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">(N=81)</content> </td> <td align="center" styleCode="Lrule"> <content styleCode="bold">(N=28)</content> </td> <td align="center" styleCode="Lrule Rrule"> <content styleCode="bold">(N=213)</content> </td> </tr> <tr> <td colspan="8" styleCode="Lrule Rrule Botrule"> <content styleCode="bold">Gastrointestinal</content> </td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Nausea</td> <td align="center" styleCode="Lrule">2 (9)</td> <td align="center" styleCode="Lrule">6 (10)</td> <td align="center" styleCode="Lrule">8 (10)</td> <td align="center" styleCode="Lrule">12 (13)</td> <td align="center" styleCode="Lrule">26 (32)</td> <td align="center" styleCode="Lrule">4 (14)</td> <td align="center" styleCode="Lrule Rrule">56 (26)</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Vomiting</td> <td align="center" styleCode="Lrule">1 (4)</td> <td align="center" styleCode="Lrule">5 (8)</td> <td align="center" styleCode="Lrule">9 (11)</td> <td align="center" styleCode="Lrule">8 (9)</td> <td align="center" styleCode="Lrule">23 (28)</td> <td align="center" styleCode="Lrule">3 (11)</td> <td align="center" styleCode="Lrule Rrule">45 (21)</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Constipation</td> <td align="center" styleCode="Lrule">2 (9)</td> <td align="center" styleCode="Lrule">4 (7)</td> <td align="center" styleCode="Lrule">4 (5)</td> <td align="center" styleCode="Lrule">4 (4)</td> <td align="center" styleCode="Lrule">6 (7)</td> <td align="center" styleCode="Lrule">4 (14)</td> <td align="center" styleCode="Lrule Rrule">23 (11)</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Diarrhea</td> <td align="center" styleCode="Lrule">1 (4)</td> <td align="center" styleCode="Lrule">1 (2)</td> <td align="center" styleCode="Lrule">4 (5)</td> <td align="center" styleCode="Lrule">4 (4)</td> <td align="center" styleCode="Lrule">10 (12)</td> <td align="center" styleCode="Lrule">0</td> <td align="center" styleCode="Lrule Rrule">19 (9)</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Dry mouth</td> <td align="center" styleCode="Lrule">1 (4)</td> <td align="center" styleCode="Lrule">4 (7)</td> <td align="center" styleCode="Lrule">3 (4)</td> <td align="center" styleCode="Lrule">2 (2)</td> <td align="center" styleCode="Lrule">3 (4)</td> <td align="center" styleCode="Lrule">1 (4)</td> <td align="center" styleCode="Lrule Rrule">14 (7)</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Abdominal pain</td> <td align="center" styleCode="Lrule">0</td> <td align="center" styleCode="Lrule">0</td> <td align="center" styleCode="Lrule">3 (4)</td> <td align="center" styleCode="Lrule">1 (1)</td> <td align="center" styleCode="Lrule">7 (9)</td> <td align="center" styleCode="Lrule">1 (4)</td> <td align="center" styleCode="Lrule Rrule">11 (5)</td> </tr> <tr> <td colspan="8" styleCode="Lrule Rrule Botrule"> <content styleCode="bold">General/administration site</content> </td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Asthenia</td> <td align="center" styleCode="Lrule">0</td> <td align="center" styleCode="Lrule">6 (10)</td> <td align="center" styleCode="Lrule">3 (4)</td> <td align="center" styleCode="Lrule">8 (9)</td> <td align="center" styleCode="Lrule">7 (9)</td> <td align="center" styleCode="Lrule">4 (14)</td> <td align="center" styleCode="Lrule Rrule">28 (13)</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Fatigue</td> <td align="center" styleCode="Lrule">2 (9)</td> <td align="center" styleCode="Lrule">6 (10)</td> <td align="center" styleCode="Lrule">1 (1)</td> <td align="center" styleCode="Lrule">7 (8)</td> <td align="center" styleCode="Lrule">7 (9)</td> <td align="center" styleCode="Lrule">3 (11)</td> <td align="center" styleCode="Lrule Rrule">25 (12)</td> </tr> <tr> <td colspan="8" styleCode="Lrule Rrule Botrule"> <content styleCode="bold">Investigations</content> </td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Weight decreased</td> <td align="center" styleCode="Lrule">3 (13)</td> <td align="center" styleCode="Lrule">0</td> <td align="center" styleCode="Lrule">2 (3)</td> <td align="center" styleCode="Lrule">5 (5)</td> <td align="center" styleCode="Lrule">5 (6)</td> <td align="center" styleCode="Lrule">1 (4)</td> <td align="center" styleCode="Lrule Rrule">15 (7)</td> </tr> <tr> <td colspan="8" styleCode="Lrule Rrule Botrule"> <content styleCode="bold">Metabolism/nutrition</content> </td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Dehydration</td> <td align="center" styleCode="Lrule">1 (4)</td> <td align="center" styleCode="Lrule">4 (7)</td> <td align="center" styleCode="Lrule">6 (8)</td> <td align="center" styleCode="Lrule">5 (5)</td> <td align="center" styleCode="Lrule">10 (12)</td> <td align="center" styleCode="Lrule">3 (11)</td> <td align="center" styleCode="Lrule Rrule">28 (13)</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Decreased appetite</td> <td align="center" styleCode="Lrule">0</td> <td align="center" styleCode="Lrule">4 (7)</td> <td align="center" styleCode="Lrule">4 (5)</td> <td align="center" styleCode="Lrule">6 (7)</td> <td align="center" styleCode="Lrule">2 (2)</td> <td align="center" styleCode="Lrule">2 (7)</td> <td align="center" styleCode="Lrule Rrule">18 (8)</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Anorexia</td> <td align="center" styleCode="Lrule">2 (9)</td> <td align="center" styleCode="Lrule">1 (2)</td> <td align="center" styleCode="Lrule">3 (4)</td> <td align="center" styleCode="Lrule">4 (4)</td> <td align="center" styleCode="Lrule">6 (7)</td> <td align="center" styleCode="Lrule">1 (4)</td> <td align="center" styleCode="Lrule Rrule">17 (8)</td> </tr> <tr> <td colspan="8" styleCode="Lrule Rrule Botrule"> <content styleCode="bold">Nervous system</content> </td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Dizziness</td> <td align="center" styleCode="Lrule">2 (9)</td> <td align="center" styleCode="Lrule">4 (7)</td> <td align="center" styleCode="Lrule">2 (3)</td> <td align="center" styleCode="Lrule">3 (3)</td> <td align="center" styleCode="Lrule">10 (12)</td> <td align="center" styleCode="Lrule">2 (7)</td> <td align="center" styleCode="Lrule Rrule">23 (11)</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Headache</td> <td align="center" styleCode="Lrule">2 (9)</td> <td align="center" styleCode="Lrule">1 (2)</td> <td align="center" styleCode="Lrule">3 (4)</td> <td align="center" styleCode="Lrule">9 (10)</td> <td align="center" styleCode="Lrule">7 (9)</td> <td align="center" styleCode="Lrule">0</td> <td align="center" styleCode="Lrule Rrule">20 (9)</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Somnolence</td> <td align="center" styleCode="Lrule">2 (9)</td> <td align="center" styleCode="Lrule">0</td> <td align="center" styleCode="Lrule">4 (5)</td> <td align="center" styleCode="Lrule">2 (2)</td> <td align="center" styleCode="Lrule">3 (4)</td> <td align="center" styleCode="Lrule">3 (11)</td> <td align="center" styleCode="Lrule Rrule">14 (7)</td> </tr> <tr> <td colspan="8" styleCode="Lrule Rrule Botrule"> <content styleCode="bold">Psychiatric</content> </td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Confusional state</td> <td align="center" styleCode="Lrule">1 (4)</td> <td align="center" styleCode="Lrule">0</td> <td align="center" styleCode="Lrule">4 (5)</td> <td align="center" styleCode="Lrule">4 (4)</td> <td align="center" styleCode="Lrule">6 (7)</td> <td align="center" styleCode="Lrule">4 (14)</td> <td align="center" styleCode="Lrule Rrule">18 (8)</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Depression</td> <td align="center" styleCode="Lrule">0</td> <td align="center" styleCode="Lrule">3 (5)</td> <td align="center" styleCode="Lrule">1 (1)</td> <td align="center" styleCode="Lrule">4 (4)</td> <td align="center" styleCode="Lrule">7 (9)</td> <td align="center" styleCode="Lrule">3 (11)</td> <td align="center" styleCode="Lrule Rrule">18 (8)</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Insomnia</td> <td align="center" styleCode="Lrule">0</td> <td align="center" styleCode="Lrule">2 (3)</td> <td align="center" styleCode="Lrule">2 (3)</td> <td align="center" styleCode="Lrule">3 (3)</td> <td align="center" styleCode="Lrule">4 (5)</td> <td align="center" styleCode="Lrule">2 (7)</td> <td align="center" styleCode="Lrule Rrule">12 (6)</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Anxiety</td> <td align="center" styleCode="Lrule">1 (4)</td> <td align="center" styleCode="Lrule">1 (2)</td> <td align="center" styleCode="Lrule">2 (3)</td> <td align="center" styleCode="Lrule">3 (3)</td> <td align="center" styleCode="Lrule">3 (4)</td> <td align="center" styleCode="Lrule">1 (4)</td> <td align="center" styleCode="Lrule Rrule">11 (5)</td> </tr> <tr> <td colspan="8" styleCode="Lrule Rrule Botrule"> <content styleCode="bold">Respiratory</content> </td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Dyspnea</td> <td align="center" styleCode="Lrule">3 (13)</td> <td align="center" styleCode="Lrule">4 (7)</td> <td align="center" styleCode="Lrule">3 (4)</td> <td align="center" styleCode="Lrule">8 (9)</td> <td align="center" styleCode="Lrule">6 (7)</td> <td align="center" styleCode="Lrule">3 (11)</td> <td align="center" styleCode="Lrule Rrule">26 (12)</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Cough</td> <td align="center" styleCode="Lrule">1 (4)</td> <td align="center" styleCode="Lrule">0</td> <td align="center" styleCode="Lrule">3 (4)</td> <td align="center" styleCode="Lrule">5 (5)</td> <td align="center" styleCode="Lrule">6 (7)</td> <td align="center" styleCode="Lrule">1 (4)</td> <td align="center" styleCode="Lrule Rrule">15 (7)</td> </tr> <tr> <td colspan="8" styleCode="Lrule Rrule Botrule"> <content styleCode="bold">Vascular</content> </td> </tr> <tr> <td styleCode="Lrule"> Hypotension</td> <td align="center" styleCode="Lrule">0</td> <td align="center" styleCode="Lrule">3 (5)</td> <td align="center" styleCode="Lrule">3 (4)</td> <td align="center" styleCode="Lrule">1 (1)</td> <td align="center" styleCode="Lrule">3 (4)</td> <td align="center" styleCode="Lrule">1 (4)</td> <td align="center" styleCode="Lrule Rrule">11 (5)</td> </tr> </tbody> </table>