VIVIMUSTA

5 WARNINGS AND PRECAUTIONS • Myelosuppression : Delay or reduce dose, and restart treatment based on ANC and platelet count recovery. ( 5.1 ) • Infections : Monitor for fever and other signs of infection or reactivation of infections and treat promptly. ( 5.2 ) • Progressive multifocal leukoencephalopathy (PML) : Monitor for new or worsening neurological, cognitive or behavioral signs or symptoms suggestive of PML. ( 5.3 ) • Anaphylaxis and Infusion-Related Reactions : Severe anaphylactic reactions have occurred. Monitor clinically and discontinue drug for severe reactions. Pre-medicate in subsequent cycles for milder reactions. ( 5.4 ) • Tumor Lysis Syndrome : May lead to acute renal failure and death; anticipate and use supportive measures in patients at high risk. ( 5.5 ) • Skin Reactions : Discontinue for severe skin reactions. Cases of SJS, DRESS and TEN, some fatal, have been reported. ( 5.6 ). • Hepatotoxicity : Monitor liver chemistry tests prior to and during treatment. ( 5.7 ) • Other Malignancies : Pre-malignant and malignant diseases have been reported. ( 5.8 ) • Extravasation Injury : Take precautions to avoid extravasation, including monitoring intravenous infusion site during and after administration. ( 5.9 ) • Embryo-Fetal Toxicity : Can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of the potential risk to a fetus and to use an effective method of contraception. ( 5.10 , 8.1 , 8.3 ) 5.1 Myelosuppression VIVIMUSTA causes myelosuppression. Bendamustine hydrochloride caused severe myelosuppression (Grade 3-4) in 98% of patients in the two NHL studies [see Adverse Reactions ( 6.1 )] . Three patients (2%) died from myelosuppression-related adverse reactions; one each from neutropenic sepsis, diffuse alveolar hemorrhage with Grade 3 thrombocytopenia and pneumonia from an opportunistic infection (CMV). Monitor complete blood counts, including leukocytes, platelets, hemoglobin (Hgb), and neutrophils frequently. In the clinical trials, blood counts were monitored every week initially. Hematologic nadirs were observed predominantly in the third week of therapy. Myelosuppression may require dose delays and/or subsequent dose reductions if recovery to the recommended values has not occurred by the first day of the next scheduled cycle. Delay the next cycle of therapy if ANC less than 1 x 10 9 /L or platelet count less than 75 x 10 9 /L [see Dosage and Administration ( 2.1 , 2.2 )]. 5.2 Infections Infection, including pneumonia, sepsis, septic shock, hepatitis and death has occurred in adult and pediatric patients in clinical trials and in postmarketing reports for bendamustine hydrochloride [ see Adverse Reactions ( 6.1 , 6.2 ) ]. Patients with myelosuppression following treatment with bendamustine hydrochloride are more susceptible to infections. Advise patients with myelosuppression following VIVIMUSTA treatment to contact healthcare provider immediately if they have symptoms or signs of infection. Patients treated with VIVIMUSTA are at risk for reactivation of infections including (but not limited to) hepatitis B, cytomegalovirus, Mycobacterium tuberculosis, and herpes zoster. Implement appropriate measures (including clinical and laboratory monitoring, prophylaxis, and treatment) for infection and infection reactivation prior to administration. 5.3 Progressive Multifocal Leukoencephalopathy (PML) Progressive multifocal leukoencephalopathy (PML), including fatal cases, have occurred following treatment with bendamustine, primarily in combination with rituximab or obinutuzumab [see Adverse Reactions ( 6.2 )] . Consider PML in the differential diagnosis in patients with new or worsening neurological, cognitive or behavioral signs or symptoms. If PML is suspected, withhold VIVIMUSTA treatment and perform appropriate diagnostic evaluations. Consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML. 5.4 Anaphylaxis and Infusion-Related Reactions Infusion-related reactions to bendamustine hydrochloride have occurred commonly in clinical trials. Symptoms include fever, chills, pruritus and rash. In rare instances, severe anaphylactic and anaphylactoid reactions have occurred, particularly in the second and subsequent cycles of therapy. Monitor clinically and discontinue drug for severe reactions. Ask patients about symptoms suggestive of infusion-related reactions after their first cycle of therapy. Do not rechallenge patients who experienced Grade 3 or worse allergic-type reactions. Consider measures to prevent severe reactions, including antihistamines, antipyretics and corticosteroids in subsequent cycles in patients who have experienced Grade 1 or 2 infusion-related reactions. Discontinue VIVIMUSTA for patients with Grade 4 infusion-related reactions. Consider discontinuation for Grade 3 infusion-related reactions as clinically appropriate considering individual benefits, risks, and supportive care. 5.5 Tumor Lysis Syndrome Tumor lysis syndrome associated with bendamustine hydrochloride has occurred in patients in clinical trials and in postmarketing reports. The onset tends to be within the first treatment cycle of bendamustine hydrochloride and, without intervention, may lead to acute renal failure and death. Administer vigorous hydration and monitor blood chemistry, particularly potassium and uric acid levels at baseline and closely during treatment with VIVIMUSTA. Allopurinol has also been used during the beginning of bendamustine hydrochloride therapy. However, there may be an increased risk of severe skin toxicity when bendamustine hydrochloride and allopurinol are administered concomitantly [see Warnings and Precautions ( 5.6 )]. 5.6 Skin Reactions Fatal and serious skin reactions have been reported with bendamustine hydrochloride treatment in clinical trials and postmarketing safety reports, including toxic skin reactions [Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS)], bullous exanthema, and rash. Events occurred when bendamustine hydrochloride was given as a single agent and in combination with other anticancer agents or allopurinol. Where skin reactions occur, they may be progressive and increase in severity with further treatment. Monitor patients with skin reactions closely. If skin reactions are severe or progressive, withhold or discontinue VIVIMUSTA. 5.7 Hepatotoxicity Fatal and serious cases of liver injury have been reported with Bendamustine Hydrochloride Injection [see Adverse Reactions ( 6.1 )]. Combination therapy, progressive disease or reactivation of hepatitis B were confounding factors in some patients [see Warnings and Precautions ( 5.2 )]. Most cases were reported within the first three months of starting therapy. Monitor liver chemistry tests prior to and during treatment with VIVIMUSTA. 5.8 Other Malignancies Pre-malignant and malignant diseases have developed in patients who have been treated with bendamustine hydrochloride, including myelodysplastic syndrome, myeloproliferative disorders, acute myeloid leukemia, bronchial carcinoma, and non-melanoma skin cancer including basal cell carcinoma and squamous cell carcinoma [see Adverse Reactions ( 6.2 )] . Monitor patients for the development of secondary malignancies. Perform dermatologic evaluations during and after treatment with VIVIMUSTA. 5.9 Extravasation Injury Bendamustine hydrochloride extravasations have been reported in postmarketing resulting in hospitalizations from erythema, marked swelling, and pain. Assure good venous access prior to starting VIVIMUSTA infusion and monitor the intravenous infusion site for redness, swelling, pain, infection, and necrosis during and after administration of VIVIMUSTA. 5.10 Embryo-Fetal Toxicity Based on findings from animal reproduction studies and the drug's mechanism of action, VIVIMUSTA can cause fetal harm when administered to a pregnant woman. Single intraperitoneal doses of bendamustine (that approximated the maximum recommended human dose based on body surface area) to pregnant mice and rats during organogenesis caused adverse developmental outcomes, including an increase in resorptions, skeletal and visceral malformations, and decreased fetal body weights. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment with VIVIMUSTA and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with VIVIMUSTA and for 3 months after the last dose [see Use in Specific Populations ( 8.1 , 8.3 ) and Clinical Pharmacology ( 12.1 )].

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labelling: • Myelosuppression [see Warnings and Precautions ( 5.1 )] • Infections [see Warnings and Precautions ( 5.2 )] • Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions ( 5.3 )] • Anaphylaxis and Infusion-Related Reactions [see Warnings and Precautions ( 5.4 )] • Tumor Lysis Syndrome [see Warnings and Precautions ( 5.5 )] • Skin Reactions [see Warnings and Precautions ( 5.6 )] • Hepatotoxicity [see Warnings and Precautions ( 5.7 )] • Other Malignancies [see Warnings and Precautions ( 5.8 )] • Extravasation Injury [see Warnings and Precautions ( 5.9 )] • Adverse reactions (> 5%) during infusion and within 24 hours post-infusion are nausea, and fatigue. ( 6.1 ) • Most common adverse reactions (≥15%) for CLL are anemia, thrombocytopenia, neutropenia, lymphopenia, leukopenia, hyperbilirubinemia, pyrexia, nausea, vomiting. ( 6.1 ) • Most common adverse reactions (≥15%) for NHL are lymphopenia, leukopenia, anemia neutropenia, thrombocytopenia, nausea, fatigue, vomiting, diarrhea, pyrexia, constipation, anorexia, cough, headache, weight decreased dyspnea, rash, and stomatitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Slayback Pharma at 1-844-566-2505 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials 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. Chronic Lymphocytic Leukemia (CLL) The data described below reflect exposure to bendamustine hydrochloride in 153 patients. Bendamustine hydrochloride was studied in an active-controlled, randomized trial. The population was 45-77 years of age, 63% were male, 100% were White, and had treatment naïve CLL. All patients started the study at a dose of 100 mg/m2 intravenously over 30 minutes on Days 1 and 2 every 28 days. Adverse reactions were reported according to NCI CTC v.2.0. In the randomized CLL clinical study, non-hematologic adverse reactions (any grade) in the bendamustine hydrochloride group that occurred with a frequency greater than 15% were pyrexia (24%), nausea (20%), and vomiting (16%). Other adverse reactions seen frequently in one or more studies included asthenia, fatigue, malaise, and weakness; dry mouth; somnolence; cough; constipation; headache; mucosal inflammation and stomatitis. Worsening hypertension was reported in 4 patients treated with bendamustine hydrochloride and in none treated with chlorambucil. Three of these 4 adverse reactions were described as a hypertensive crisis and were managed with oral medications and resolved. The most frequent adverse reactions leading to study withdrawal for patients receiving bendamustine hydrochloride were hypersensitivity (2%) and pyrexia (1%). Table 2 summarizes the adverse reactions that were reported in ≥ 5% of patients in either treatment group in the randomized CLL clinical study. Table 2: Non-Hematologic Adverse Reactions that Occurred in at Least 5% of Patients Who Received Bendamustine Hydrochloride or Chlorambucil in the Randomized CLL Clinical Study Adverse Reaction Bendamustine Hydrochloride (N=153) Chlorambucil (N=143) All Grades n (%) Grade 3 or 4 n (%) All Grades n (%) Grade 3 or 4 n (%) Total number of patients with at least 1 adverse reaction 121 (79) 52 (34) 96 (67) 25 (17) Gastrointestinal disorders Nausea 31 (20) 1 (<1) 21 (15) 1 (<1) Vomiting 24 (16) 1 (<1) 9 (6) 0 Diarrhea 14 (9) 2 (1) 5 (3) 0 General disorders and administration site conditions Pyrexia 36 (24) 6 (4) 8 (6) 2 (1) Fatigue 14 (9) 2 (1) 8 (6) 0 Asthenia 13 (8) 0 6 (4) 0 Chills 9 (6) 0 1 (<1) 0 Immune system disorders Hypersensitivity 7 (5) 2 (1) 3 (2) 0 Infections and infestations Nasopharyngitis 10 (7) 0 12 (8) 0 Infection 9 (6) 3 (2) 1 (<1) 1 (<1) Herpes simplex 5 (3) 0 7 (5) 0 Investigations Weight decreased 11 (7) 0 5 (3) 0 Metabolism and nutrition disorders Hyperuricemia 11 (7) 3 (2) 2 (1) 0 Respiratory, thoracic and mediastinal disorders Cough 6 (4) 1 (<1) 7 (5) 1 (<1) Skin and subcutaneous tissue disorders Rash 12 (8) 4 (3) 7 (5) 3 (2) Pruritus 8 (5) 0 2 (1) 0 Hematology laboratory abnormalities are described in Table 3. Red blood cell transfusions were administered to 20% of patients receiving bendamustine hydrochloride compared with 6% of patients receiving chlorambucil. Bilirubin elevation occurred in 34% of patients, some without associated significant elevations in AST and ALT. Grade 3 or 4 increased bilirubin occurred in 3% of patients. Increases in AST and ALT of Grade 3 or 4 were limited to 1% and 3% of patients, respectively. Patients treated with bendamustine hydrochloride may also have changes in their creatinine levels. Table 3: Hematology Laboratory Abnormalities in Patients Who Received Bendamustine Hydrochloride or Chlorambucil in the Randomized CLL Clinical Study Laboratory Abnormality Bendamustine Hydrochloride (N=150) Chlorambucil (N=141) All Grades n (%) Grade 3 or 4 n (%) All Grades n (%) Grade 3 or 4 n (%) Hemoglobin Decreased 134 (89) 20 (13) 115 (82) 12 (9) Platelets Decreased 116 (77) 16 (11) 110 (78) 14 (10) Neutrophils Decreased 113 (75) 65 (43) 86 (61) 30 (21) Lymphocytes Decreased 102 (68) 70 (47) 27 (19) 6 (4) Leukocytes Decreased 92 (61) 42 (28) 26 (18) 4 (3) Non-Hodgkin Lymphoma (NHL) The data described below reflect exposure to bendamustine hydrochloride in 176 patients with indolent B-cell NHL treated in two single-arm studies. The population was 31-84 years of age; 60% were male; 89% were White, 7% were Black, 3% were Hispanic, 1% were other, and <1% were Asian. These patients received bendamustine hydrochloride at a dose of 120 mg/m 2 intravenously on Days 1 and 2 for up to eight 21-day cycles. In both studies, serious adverse reactions, were reported in 37% of patients receiving bendamustine hydrochloride. The most frequent serious adverse reactions occurring in ≥5% of patients were febrile neutropenia and pneumonia. Other important serious adverse reactions reported in clinical trials and/or postmarketing experience were acute renal failure, cardiac failure, hypersensitivity, skin reactions, pulmonary fibrosis, and myelodysplastic syndrome. Serious adverse reactions reported in clinical trials included myelosuppression, infection, pneumonia, tumor lysis syndrome and infusion-related reactions [see Warnings and Precautions ( 5 )]. Adverse reactions occurring less frequently but possibly related to bendamustine hydrochloride treatment were hemolysis, dysgeusia/taste disorder, atypical pneumonia, sepsis, herpes zoster, erythema, dermatitis, and skin necrosis. The most common non-hematologic adverse reactions (≥30%) were nausea (75%), fatigue (57%), vomiting (40%), diarrhea (37%) and pyrexia (34%). The most common non-hematologic Grade 3 or 4 adverse reactions (≥5%) were fatigue (11%), febrile neutropenia (6%), and pneumonia, hypokalemia and dehydration, each reported in 5% of patients. Non-hematologic adverse reactions are shown in Table 4. Table 4: Non-Hematologic Adverse Reactions that Occurred in at Least 5% of Patients who Received Bendamustine Hydrochloride in the NHL Studies Bendamustine Hydrochloride (N=176*) Adverse Reaction All Grades n(%) Grade 3 or 4 n(%) Total number of patients with at least 1 adverse reaction 176 (100) 94 (53) Cardiac Disorders Tachycardia 13 (7) 0 Gastrointestinal disorders Nausea 132 (75) 7 (4) Vomiting 71 (40) 5 (3) Diarrhea 65 (37) 6 (3) Constipation 51 (29) 1 (<1) Stomatitis 27 (15) 1 (<1) Abdominal pain 22 (13) 2 (1) Dyspepsia 20 (11) 0 Gastroesophageal reflux disease 18 (10) 0 Dry mouth 15 (9) 1 (<1) Abdominal pain upper 8 (5) 0 Abdominal distension 8 (5) 0 General disorders and administration site conditions Fatigue 101 (57) 19 (11) Pyrexia 59 (34) 3 (2) Chills 24 (14) 0 Edema peripheral 23 (13) 1 (<1) Asthenia 19 (11) 4 (2) Chest pain 11 (6) 1 (<1) Infusion site pain 11 (6) 0 Pain 10 (6) 0 Catheter site pain 8 (5) 0 Infections and infestations Herpes zoster 18 (10) 5 (3) Upper respiratory tract infection 18 (10) 0 Urinary tract infection 17 (10) 4 (2) Sinusitis 15 (9) 0 Pneumonia 14 (8) 9 (5) Febrile neutropenia 11 (6) 11 (6) Oral candidiasis 11 (6) 2 (1) Nasopharyngitis 11 (6) 0 Investigations Weight decreased 31 (18) 3 (2) Metabolism and nutrition disorders Anorexia 40 (23) 3 (2) Dehydration 24 (14) 8 (5) Decreased appetite 22 (13) 1 (<1) Hypokalemia 15 (9) 9 (5) Musculoskeletal and connective tissue disorders Back pain 25 (14) 5 (3) Arthralgia 11 (6) 0 Pain in extremity 8 (5) 2 (1) Bone pain 8 (5) 0 Nervous system disorders Headache 36 (21) 0 Dizziness 25 (14) 0 Dysgeusia 13 (7) 0 Psychiatric disorder Insomnia 23 (13) 0 Anxiety 14 (8) 1 (<1) Depression 10 (6) 0 Respiratory, thoracic and mediastinal disorders Cough 38 (22) 1 (<1) Dyspnea 28 (16) 3 (2) Pharyngolaryngeal pain 14 (8) 1 (<1) Wheezing 8 (5) 0 Nasal congestion 8 (5) 0 Skin and subcutaneous tissue disorders Rash 28 (16) 1 (<1) Pruritus 11 (6) 0 Dry skin 9 (5) 0 Night sweats 9 (5) 0 Hyperhidrosis 8 (5) 0 Vascular disorders Hypotension 10 (6) 2 (1) *Patients may have reported more than 1 adverse reaction. NOTE: Patients counted only once in each preferred term category and once in each body system category. Hematologic toxicities, based on laboratory values and CTC grade, in patients with NHL treated in both single arm studies combined are described in Table 5. Clinically important chemistry laboratory values that were new or worsened from baseline and occurred in >1% of patients at grade 3 or 4, in patients with NHL who were treated in both single arm studies combined were hyperglycemia (3%), elevated creatinine (2%), hyponatremia (2%), and hypocalcemia (2%). Table 5: Hematology Laboratory Abnormalities in Patients Who Received Bendamustine Hydrochloride in the NHL Studies Hematology Variable Bendamustine Hydrochloride All Grades (%) Grade 3 or 4 (%) Lymphocytes Decreased 99 94 Leukocytes Decreased 94 56 Hemoglobin Decreased 88 11 Neutrophils Decreased 86 60 Platelets Decreased 86 25 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of bendamustine hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and lymphatic systems disorders: Pancytopenia. Cardiovascular disorders: Atrial fibrillation, congestive heart failure (some fatal), myocardial infarction (some fatal), palpitation. General disorders and administration site conditions: Injection site reactions (including phlebitis, pruritus, irritation, pain, swelling), infusion site reactions (including phlebitis, pruritus, irritation, pain, swelling). Immune system disorders: Anaphylaxis. Infections and infestations: Pneumocystis jiroveci pneumonia, progressive multifocal leukoencephalopathy (PML). Renal and urinary disorders: Nephrogenic diabetes insipidus (NDI) Respiratory, thoracic and mediastinal disorders: Pneumonitis. Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and non-melanoma skin cancer (NMSC).

<table cellspacing="0" cellpadding="0" border="0" width="621"><colgroup><col width="29.6774193548387%"/><col width="16.6129032258065%"/><col width="16.7741935483871%"/><col width="18.2258064516129%"/><col width="18.7096774193548%"/></colgroup><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" rowspan="2" valign="top"><content styleCode="bold">Adverse Reaction</content> </td><td styleCode="Rrule" colspan="2" align="center" valign="middle"><content styleCode="bold">Bendamustine Hydrochloride</content> <content styleCode="bold">(N=153)</content> </td><td styleCode="Rrule" colspan="2" align="center" valign="middle"><content styleCode="bold">Chlorambucil</content> <content styleCode="bold">(N=143)</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" align="center" valign="middle"><content styleCode="bold">All Grades</content> <content styleCode="bold">n (%)</content> </td><td styleCode="Rrule" align="center" valign="middle"><content styleCode="bold">Grade 3 or 4</content> <content styleCode="bold">n (%)</content> </td><td styleCode="Rrule" align="center" valign="middle"><content styleCode="bold">All Grades</content> <content styleCode="bold">n (%)</content> </td><td styleCode="Rrule" align="center" valign="middle"><content styleCode="bold">Grade 3 or 4</content> <content styleCode="bold">n (%)</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Total number of patients with at least 1 adverse reaction</content> </td><td styleCode="Rrule" align="center" valign="middle"><content styleCode="bold"/> <content styleCode="bold">121 (79)</content> </td><td styleCode="Rrule" align="center" valign="middle"><content styleCode="bold"/> <content styleCode="bold">52 (34)</content> </td><td styleCode="Rrule" align="center" valign="middle"><content styleCode="bold"/> <content styleCode="bold">96 (67)</content> </td><td styleCode="Rrule" align="center" valign="middle"><content styleCode="bold"/> <content styleCode="bold">25 (17)</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Gastrointestinal disorders</content> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Nausea </td><td styleCode="Rrule" align="center" valign="middle">31 (20) </td><td styleCode="Rrule" align="center" valign="middle">1 (&lt;1) </td><td styleCode="Rrule" align="center" valign="middle">21 (15) </td><td styleCode="Rrule" align="center" valign="middle">1 (&lt;1) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Vomiting </td><td styleCode="Rrule" align="center" valign="middle">24 (16) </td><td styleCode="Rrule" align="center" valign="middle">1 (&lt;1) </td><td styleCode="Rrule" align="center" valign="middle">9 (6) </td><td styleCode="Rrule" align="center" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Diarrhea </td><td styleCode="Rrule" align="center" valign="middle">14 (9) </td><td styleCode="Rrule" align="center" valign="middle">2 (1) </td><td styleCode="Rrule" align="center" valign="middle">5 (3) </td><td styleCode="Rrule" align="center" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">General disorders and administration site conditions</content> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Pyrexia </td><td styleCode="Rrule" align="center" valign="middle">36 (24) </td><td styleCode="Rrule" align="center" valign="middle">6 (4) </td><td styleCode="Rrule" align="center" valign="middle">8 (6) </td><td styleCode="Rrule" align="center" valign="middle">2 (1) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Fatigue </td><td styleCode="Rrule" align="center" valign="middle">14 (9) </td><td styleCode="Rrule" align="center" valign="middle">2 (1) </td><td styleCode="Rrule" align="center" valign="middle">8 (6) </td><td styleCode="Rrule" align="center" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Asthenia </td><td styleCode="Rrule" align="center" valign="middle">13 (8) </td><td styleCode="Rrule" align="center" valign="middle">0 </td><td styleCode="Rrule" align="center" valign="middle">6 (4) </td><td styleCode="Rrule" align="center" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Chills </td><td styleCode="Rrule" align="center" valign="middle">9 (6) </td><td styleCode="Rrule" align="center" valign="middle">0 </td><td styleCode="Rrule" align="center" valign="middle">1 (&lt;1) </td><td styleCode="Rrule" align="center" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Immune system disorders</content> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Hypersensitivity </td><td styleCode="Rrule" align="center" valign="middle">7 (5) </td><td styleCode="Rrule" align="center" valign="middle">2 (1) </td><td styleCode="Rrule" align="center" valign="middle">3 (2) </td><td styleCode="Rrule" align="center" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Infections and infestations</content> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Nasopharyngitis </td><td styleCode="Rrule" align="center" valign="middle">10 (7) </td><td styleCode="Rrule" align="center" valign="middle">0 </td><td styleCode="Rrule" align="center" valign="middle">12 (8) </td><td styleCode="Rrule" align="center" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Infection </td><td styleCode="Rrule" align="center" valign="middle">9 (6) </td><td styleCode="Rrule" align="center" valign="middle">3 (2) </td><td styleCode="Rrule" align="center" valign="middle">1 (&lt;1) </td><td styleCode="Rrule" align="center" valign="middle">1 (&lt;1) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Herpes simplex </td><td styleCode="Rrule" align="center" valign="middle">5 (3) </td><td styleCode="Rrule" align="center" valign="middle">0 </td><td styleCode="Rrule" align="center" valign="middle">7 (5) </td><td styleCode="Rrule" align="center" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Investigations</content> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Weight decreased </td><td styleCode="Rrule" align="center" valign="middle">11 (7) </td><td styleCode="Rrule" align="center" valign="middle">0 </td><td styleCode="Rrule" align="center" valign="middle">5 (3) </td><td styleCode="Rrule" align="center" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Metabolism and nutrition disorders</content> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Hyperuricemia </td><td styleCode="Rrule" align="center" valign="middle">11 (7) </td><td styleCode="Rrule" align="center" valign="middle">3 (2) </td><td styleCode="Rrule" align="center" valign="middle">2 (1) </td><td styleCode="Rrule" align="center" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Cough </td><td styleCode="Rrule" align="center" valign="middle">6 (4) </td><td styleCode="Rrule" align="center" valign="middle">1 (&lt;1) </td><td styleCode="Rrule" align="center" valign="middle">7 (5) </td><td styleCode="Rrule" align="center" valign="middle">1 (&lt;1) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Skin and subcutaneous tissue disorders</content> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td><td styleCode="Rrule" align="center" valign="middle"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Rash </td><td styleCode="Rrule" align="center" valign="middle">12 (8) </td><td styleCode="Rrule" align="center" valign="middle">4 (3) </td><td styleCode="Rrule" align="center" valign="middle">7 (5) </td><td styleCode="Rrule" align="center" valign="middle">3 (2) </td></tr><tr><td styleCode="Lrule Rrule" valign="top">Pruritus </td><td styleCode="Rrule" align="center" valign="middle">8 (5) </td><td styleCode="Rrule" align="center" valign="middle">0 </td><td styleCode="Rrule" align="center" valign="middle">2 (1) </td><td styleCode="Rrule" align="center" valign="middle">0 </td></tr></tbody></table>

<table cellspacing="0" cellpadding="0" border="0" width="624"><colgroup><col width="20.48%"/><col width="20.48%"/><col width="20.48%"/><col width="20.48%"/><col width="18.08%"/></colgroup><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" rowspan="2" valign="top"><content styleCode="bold"> Laboratory</content> <content styleCode="bold">Abnormality</content> </td><td styleCode="Rrule" colspan="2" align="center" valign="middle"><content styleCode="bold">Bendamustine Hydrochloride </content> <content styleCode="bold">(N=150)</content> </td><td styleCode="Rrule" colspan="2" align="center" valign="middle"><content styleCode="bold">Chlorambucil </content> <content styleCode="bold">(N=141)</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" align="center" valign="middle"><content styleCode="bold">All Grades </content> <content styleCode="bold">n (%)</content> </td><td styleCode="Rrule" align="center" valign="middle"><content styleCode="bold">Grade 3 or 4 </content> <content styleCode="bold">n (%)</content> </td><td styleCode="Rrule" align="center" valign="middle"><content styleCode="bold">All Grades </content> <content styleCode="bold">n (%)</content> </td><td styleCode="Rrule" align="center" valign="middle"><content styleCode="bold">Grade 3 or 4 </content> <content styleCode="bold">n (%)</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Hemoglobin Decreased </td><td styleCode="Rrule" align="center" valign="middle">134 (89) </td><td styleCode="Rrule" align="center" valign="middle">20 (13) </td><td styleCode="Rrule" align="center" valign="middle">115 (82) </td><td styleCode="Rrule" align="center" valign="middle">12 (9) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Platelets Decreased </td><td styleCode="Rrule" align="center" valign="middle">116 (77) </td><td styleCode="Rrule" align="center" valign="middle">16 (11) </td><td styleCode="Rrule" align="center" valign="middle">110 (78) </td><td styleCode="Rrule" align="center" valign="middle">14 (10) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Neutrophils Decreased </td><td styleCode="Rrule" align="center" valign="middle">113 (75) </td><td styleCode="Rrule" align="center" valign="middle">65 (43) </td><td styleCode="Rrule" align="center" valign="middle">86 (61) </td><td styleCode="Rrule" align="center" valign="middle">30 (21) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top">Lymphocytes Decreased </td><td styleCode="Rrule" align="center" valign="middle">102 (68) </td><td styleCode="Rrule" align="center" valign="middle">70 (47) </td><td styleCode="Rrule" align="center" valign="middle">27 (19) </td><td styleCode="Rrule" align="center" valign="middle">6 (4) </td></tr><tr><td styleCode="Lrule Rrule" valign="top">Leukocytes Decreased </td><td styleCode="Rrule" align="center" valign="middle">92 (61) </td><td styleCode="Rrule" align="center" valign="middle">42 (28) </td><td styleCode="Rrule" align="center" valign="middle">26 (18) </td><td styleCode="Rrule" align="center" valign="middle">4 (3) </td></tr></tbody></table>

<table cellspacing="0" cellpadding="0" border="0" width="638"><colgroup><col width="56.5830721003135%"/><col width="22.5705329153605%"/><col width="20.846394984326%"/></colgroup><thead><tr><th styleCode="Lrule Rrule Toprule"> </th><th styleCode="Lrule Rrule Toprule" colspan="2"><content styleCode="bold">Bendamustine Hydrochloride (N=176*)</content> </th></tr><tr><th styleCode="Lrule Rrule Toprule"><content styleCode="bold">Adverse Reaction</content> </th><th styleCode="Lrule Rrule Toprule"><content styleCode="bold">All Grades n(%)</content> </th><th styleCode="Lrule Rrule Toprule"><content styleCode="bold">Grade</content><content styleCode="bold">3 or 4 n(%)</content> </th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Total number of patients with at least 1 adverse reaction</content> </td><td styleCode="Rrule" valign="middle">176 (100) </td><td styleCode="Rrule" valign="middle">94 (53) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Cardiac Disorders</content> </td><td styleCode="Rrule" valign="middle"> </td><td styleCode="Rrule" valign="middle"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Tachycardia </td><td styleCode="Rrule" valign="middle">13 (7) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3" valign="middle"><content styleCode="bold">Gastrointestinal disorders</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Nausea </td><td styleCode="Rrule" valign="middle">132 (75) </td><td styleCode="Rrule" valign="middle">7 (4) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Vomiting </td><td styleCode="Rrule" valign="middle">71 (40) </td><td styleCode="Rrule" valign="middle">5 (3) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Diarrhea </td><td styleCode="Rrule" valign="middle">65 (37) </td><td styleCode="Rrule" valign="middle">6 (3) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Constipation </td><td styleCode="Rrule" valign="middle">51 (29) </td><td styleCode="Rrule" valign="middle">1 (&lt;1) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Stomatitis </td><td styleCode="Rrule" valign="middle">27 (15) </td><td styleCode="Rrule" valign="middle">1 (&lt;1) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Abdominal pain </td><td styleCode="Rrule" valign="middle">22 (13) </td><td styleCode="Rrule" valign="middle">2 (1) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Dyspepsia </td><td styleCode="Rrule" valign="middle">20 (11) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Gastroesophageal reflux disease </td><td styleCode="Rrule" valign="middle">18 (10) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Dry mouth </td><td styleCode="Rrule" valign="middle">15 (9) </td><td styleCode="Rrule" valign="middle">1 (&lt;1) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Abdominal pain upper </td><td styleCode="Rrule" valign="middle">8 (5) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Abdominal distension </td><td styleCode="Rrule" valign="middle">8 (5) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3" valign="middle"><content styleCode="bold">General disorders and administration site conditions</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Fatigue </td><td styleCode="Rrule" valign="middle">101 (57) </td><td styleCode="Rrule" valign="middle">19 (11) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Pyrexia </td><td styleCode="Rrule" valign="middle">59 (34) </td><td styleCode="Rrule" valign="middle">3 (2) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Chills </td><td styleCode="Rrule" valign="middle">24 (14) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Edema peripheral </td><td styleCode="Rrule" valign="middle">23 (13) </td><td styleCode="Rrule" valign="middle">1 (&lt;1) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Asthenia </td><td styleCode="Rrule" valign="middle">19 (11) </td><td styleCode="Rrule" valign="middle">4 (2) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Chest pain </td><td styleCode="Rrule" valign="middle">11 (6) </td><td styleCode="Rrule" valign="middle">1 (&lt;1) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Infusion site pain </td><td styleCode="Rrule" valign="middle">11 (6) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Pain </td><td styleCode="Rrule" valign="middle">10 (6) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Catheter site pain </td><td styleCode="Rrule" valign="middle">8 (5) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Infections and infestations</content> </td><td styleCode="Rrule" colspan="2" valign="middle"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Herpes zoster </td><td styleCode="Rrule" valign="middle">18 (10) </td><td styleCode="Rrule" valign="middle">5 (3) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Upper respiratory tract infection </td><td styleCode="Rrule" valign="middle">18 (10) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Urinary tract infection </td><td styleCode="Rrule" valign="middle">17 (10) </td><td styleCode="Rrule" valign="middle">4 (2) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Sinusitis </td><td styleCode="Rrule" valign="middle">15 (9) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Pneumonia </td><td styleCode="Rrule" valign="middle">14 (8) </td><td styleCode="Rrule" valign="middle">9 (5) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Febrile neutropenia </td><td styleCode="Rrule" valign="middle">11 (6) </td><td styleCode="Rrule" valign="middle">11 (6) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Oral candidiasis </td><td styleCode="Rrule" valign="middle">11 (6) </td><td styleCode="Rrule" valign="middle">2 (1) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Nasopharyngitis </td><td styleCode="Rrule" valign="middle">11 (6) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Investigations</content> </td><td styleCode="Rrule" colspan="2" valign="middle"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Weight decreased </td><td styleCode="Rrule" valign="middle">31 (18) </td><td styleCode="Rrule" valign="middle">3 (2) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Metabolism and nutrition disorders</content> </td><td styleCode="Rrule" colspan="2" valign="middle"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Anorexia </td><td styleCode="Rrule" valign="middle">40 (23) </td><td styleCode="Rrule" valign="middle">3 (2) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Dehydration </td><td styleCode="Rrule" valign="middle">24 (14) </td><td styleCode="Rrule" valign="middle">8 (5) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Decreased appetite </td><td styleCode="Rrule" valign="middle">22 (13) </td><td styleCode="Rrule" valign="middle">1 (&lt;1) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Hypokalemia </td><td styleCode="Rrule" valign="middle">15 (9) </td><td styleCode="Rrule" valign="middle">9 (5) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Musculoskeletal and connective tissue disorders</content> </td><td styleCode="Rrule" colspan="2" valign="middle"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Back pain </td><td styleCode="Rrule" valign="middle">25 (14) </td><td styleCode="Rrule" valign="middle">5 (3) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Arthralgia </td><td styleCode="Rrule" valign="middle">11 (6) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Pain in extremity </td><td styleCode="Rrule" valign="middle">8 (5) </td><td styleCode="Rrule" valign="middle">2 (1) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Bone pain </td><td styleCode="Rrule" valign="middle">8 (5) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Nervous system disorders</content> </td><td styleCode="Rrule" colspan="2" valign="middle"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Headache </td><td styleCode="Rrule" valign="middle">36 (21) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Dizziness </td><td styleCode="Rrule" valign="middle">25 (14) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Dysgeusia </td><td styleCode="Rrule" valign="middle">13 (7) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Psychiatric disorder</content> </td><td styleCode="Rrule" colspan="2" valign="middle"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Insomnia </td><td styleCode="Rrule" valign="middle">23 (13) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Anxiety </td><td styleCode="Rrule" valign="middle">14 (8) </td><td styleCode="Rrule" valign="middle">1 (&lt;1) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Depression </td><td styleCode="Rrule" valign="middle">10 (6) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content> </td><td styleCode="Rrule" colspan="2" valign="middle"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Cough </td><td styleCode="Rrule" valign="middle">38 (22) </td><td styleCode="Rrule" valign="middle">1 (&lt;1) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Dyspnea </td><td styleCode="Rrule" valign="middle">28 (16) </td><td styleCode="Rrule" valign="middle">3 (2) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Pharyngolaryngeal pain </td><td styleCode="Rrule" valign="middle">14 (8) </td><td styleCode="Rrule" valign="middle">1 (&lt;1) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Wheezing </td><td styleCode="Rrule" valign="middle">8 (5) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Nasal congestion </td><td styleCode="Rrule" valign="middle">8 (5) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Skin and subcutaneous tissue disorders</content> </td><td styleCode="Rrule" colspan="2" valign="middle"> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Rash </td><td styleCode="Rrule" valign="middle">28 (16) </td><td styleCode="Rrule" valign="middle">1 (&lt;1) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Pruritus </td><td styleCode="Rrule" valign="middle">11 (6) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Dry skin </td><td styleCode="Rrule" valign="middle">9 (5) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Night sweats </td><td styleCode="Rrule" valign="middle">9 (5) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle">Hyperhidrosis </td><td styleCode="Rrule" valign="middle">8 (5) </td><td styleCode="Rrule" valign="middle">0 </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Vascular disorders</content> </td><td styleCode="Rrule" colspan="2" valign="middle"> </td></tr><tr><td styleCode="Lrule Rrule" valign="middle">Hypotension </td><td styleCode="Rrule" valign="middle">10 (6) </td><td styleCode="Rrule" valign="middle">2 (1) </td></tr></tbody></table>