TAZVERIK

5 WARNINGS AND PRECAUTIONS Secondary Malignancies : TAZVERIK increases the risk of developing secondary malignancies, including T-cell lymphoblastic lymphoma, myelodysplastic syndrome, acute myeloid leukemia, and B-cell acute lymphoblastic leukemia. Monitor patients long-term for the development of secondary malignancies. ( 5.1 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise patients of potential risk to a fetus and to use effective non-hormonal contraception. ( 5.2 ) 5.1 Secondary Malignancies The risk of developing secondary malignancies is increased following treatment with TAZVERIK. Across clinical trials of 758 adults who received TAZVERIK 800 mg twice daily as monotherapy, myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or B-cell acute lymphoblastic leukemia (B-ALL) occurred in 1.7% of patients. One pediatric patient developed T-cell lymphoblastic lymphoma (T-LBL). Monitor patients long-term for the development of secondary malignancies. 5.2 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, TAZVERIK can cause fetal harm when administered to pregnant women. There are no available data on TAZVERIK use in pregnant women to inform the drug-associated risk. Administration of tazemetostat to pregnant rats and rabbits during organogenesis resulted in dose-dependent increases in skeletal developmental abnormalities in both species beginning at maternal exposures approximately 1.5 times the adult human exposure (area under the plasma concentration time curve [AUC 0-45h ]) at the 800 mg twice daily dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAZVERIK and for 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with TAZVERIK and for 3 months after the final dose [see Use in Specific Populations ( 8.1 , 8.3 )] .

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in labeling: Secondary Malignancies [see Warnings and Precautions ( 5.1 )]. The most common (≥20%) adverse reactions in patients with epithelioid sarcoma are pain, fatigue, nausea, decreased appetite, vomiting, and constipation. ( 6.1 ) The most common (≥20%) adverse reactions in patients with follicular lymphoma are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Epizyme at 855-463-5127 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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Epithelioid Sarcoma The safety of TAZVERIK was evaluated in a cohort (Cohort 5) of Study EZH-202 that enrolled patients with epithelioid sarcoma [see Clinical Studies ( 14.1 )]. Patients received TAZVERIK 800 mg orally twice daily (n=62). Among patients who received TAZVERIK, 44% were exposed for 6 months or longer and 24% were exposed for greater than one year. Serious adverse reactions occurred in 37% of patients who received TAZVERIK. Serious adverse reactions in ≥3% of patients who received TAZVERIK were hemorrhage, pleural effusion, skin infection, dyspnea, pain, and respiratory distress. One patient (2%) permanently discontinued TAZVERIK due to an adverse reaction of altered mood. Dosage interruptions due to an adverse reaction occurred in 34% of patients who received TAZVERIK. The most frequent adverse reactions requiring dosage interruptions in ≥3% were hemorrhage, increased alanine aminotransferase (ALT), and increased aspartate aminotransferase (AST). Dose reduction due to an adverse reaction occurred in one (2%) patient who received TAZVERIK; the dose was reduced in this patient for decreased appetite. The most common adverse reactions (≥20%) were pain, fatigue, nausea, decreased appetite, vomiting, and constipation. Table 4 presents adverse reactions in patients with epithelioid sarcoma in Cohort 5 of Study EZH-202. Table 4. Adverse Reactions (≥10%) in Patients with Epithelioid Sarcoma Who Received TAZVERIK in Cohort 5 of Study EZH-202 Adverse Reaction TAZVERIK N=62 All Grades (%) Grade 3 or 4 (%) a Includes tumor pain, pain in extremity, non-cardiac chest pain, flank pain, back pain, arthralgia, bone pain, cancer pain, musculoskeletal pain, myalgia, neck pain b Includes fatigue and asthenia c Includes abdominal pain, gastrointestinal pain, abdominal pain lower d Includes dyspnea and dyspnea exertional e Includes wound hemorrhage, rectal hemorrhage, pulmonary hemorrhage, hemorrhage intracranial, cerebral hemorrhage, hemoptysis General Pain a 52 7 Fatigue b 47 1.6 Gastrointestinal Nausea 36 0 Vomiting 24 0 Constipation 21 0 Diarrhea 16 0 Abdominal pain c 13 1.6 Metabolism and nutrition Decreased appetite 26 4.8 Respiratory, thoracic and mediastinal Cough 18 0 Dyspnea d 16 4.8 Vascular Hemorrhage e 18 4.8 Nervous system Headache 18 0 Investigations Weight decreased 16 7 Table 5 summarizes select laboratory abnormalities in patients with epithelioid sarcoma in Cohort 5 of Study EZH-202. Table 5. Select Laboratory Abnormalities (≥ 10%) Worsening from Baseline in Patients with Epithelioid Sarcoma Who Received TAZVERIK in Cohort 5 of Study EZH-202 *The denominator used to calculate the rate varied from 39 to 61 based on the number of patients with a baseline value and at least one post-treatment value. Laboratory Abnormality TAZVERIK* All Grades (%) Grade 3 or 4 (%) Hematology Decreased hemoglobin 49 15 Decreased lymphocytes 36 13 Decreased white blood cell count 19 0 Chemistry Increased triglycerides 36 3.3 Increased glucose 33 1.6 Decreased sodium 30 1.7 Decreased phosphate 28 1.7 Decreased albumin 23 0 Increased alkaline phosphatase 23 1.7 Decreased potassium 20 1.7 Increased aspartate aminotransferase 18 3.5 Decreased calcium 16 0 Decreased glucose 16 0 Increased partial thromboplastin time 15 5 Increased alanine aminotransferase 14 3.4 Increased creatinine 12 0 Increased potassium 12 0 Relapsed or Refractory Follicular Lymphoma The safety of TAZVERIK was evaluated in two cohorts (Cohorts 4 and 5) of Study E7438-G000-101 that enrolled patients with relapsed or refractory follicular lymphoma [see Clinical Studies ( 14.2 )]. Patients received TAZVERIK 800 mg orally twice daily (n=99). Among patients who received TAZVERIK, 68% were exposed for 6 months or longer, 39% were exposed for 12 months or longer, and 21% were exposed for 18 months or longer. The median age was 62 years (range 36 to 87 years), 54% were male, and 95% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. The median number of prior therapies was 3 (range 1 to 11). Patients were required to have a creatinine clearance ≥40 mL/min per the Cockcroft and Gault formula. Serious adverse reactions occurred in 30% of patients who received TAZVERIK. Serious adverse reactions in ≥2% of patients who received TAZVERIK were general physical health deterioration, abdominal pain, pneumonia, sepsis, and anemia. Permanent discontinuation due to an adverse reaction occurred in 8% of patients who received TAZVERIK. Adverse reaction resulting in permanent discontinuation in ≥2% of patients was second primary malignancy. Dosage interruptions due to an adverse reaction occurred in 28% of patients who received TAZVERIK. Adverse reactions requiring dosage interruptions in ≥3% of patients were thrombocytopenia and fatigue. Dose reduction due to an adverse reaction occurred in 9% of patients who received TAZVERIK. The most common adverse reactions (≥20%) were fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain. Table 6 presents adverse reactions in patients with relapsed or refractory follicular lymphoma in Cohorts 4 and 5 of Study E7438-G000-101. Table 6. Adverse Reactions (≥10%) in Patients with Relapsed or Refractory Follicular Lymphoma Who Received TAZVERIK in Cohorts 4 and 5 of Study E7438-G000-101 Adverse Reaction TAZVERIK N=99 All Grades (%) Grade 3 or 4 (%) a Includes fatigue and asthenia b Includes laryngitis, nasopharyngitis, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection, viral upper respiratory tract infection c Includes bronchitis, lower respiratory tract infection, tracheobronchitis d Includes cystitis, urinary tract infection, urinary tract infection staphylococcal e Includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper f Includes back pain, limb discomfort, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, pain in extremity, pain in jaw, spinal pain g Includes erythema, rash, rash erythematous, rash generalized, rash maculo-papular, rash pruritic, rash pustular, skin exfoliation h Includes cough and productive cough i Includes headache, migraine, sinus headache General Fatigue a 36 5 Pyrexia 10 0 Infections Upper respiratory tract infection b 30 0 Lower respiratory tract infection c 17 0 Urinary tract infection d 11 2 Gastrointestinal Nausea 24 1 Abdominal pain e 20 3 Diarrhea 18 0 Vomiting 12 1 Musculoskeletal and connective tissue Musculoskeletal pain f 22 1 Skin and subcutaneous tissue Alopecia 17 0 Rash g 15 0 Respiratory and mediastinal system Cough h 17 0 Nervous system Headache i 13 0 Clinically relevant adverse reactions occurring in <10% of patients who received TAZVERIK included: Infection: sepsis (2%), pneumonia (2%), and herpes zoster (2%) Table 7 summarizes select laboratory abnormalities in patients with follicular lymphoma in Cohorts 4 and 5 of Study E7438-G000-101. Table 7. Select Laboratory Abnormalities (≥10%) Worsening from Baseline in Patients with Relapsed or Refractory Follicular Lymphoma Who Received TAZVERIK in Cohorts 4 and 5 of Study E7438-G000-101 Laboratory Abnormality TAZVERIK* All Grades (%) Grade 3 or 4 (%) *The denominator used to calculate the rate varied from 88 to 96 based on the number of patients with a baseline value and at least one post-treatment value. Hematology Decreased lymphocytes 57 18 Decreased hemoglobin 50 8 Decreased platelets 50 7 Decreased white blood cells 41 9 Decreased neutrophils 20 7 Chemistry Increased glucose 53 10 Increased aspartate aminotransferase 24 0 Increased alanine aminotransferase 21 2.3 Increased alkaline phosphatase 18 1.0 Increased creatinine 17 0

<table ID="t4" width="100%" styleCode="Noautorules"><caption>Table 4. Adverse Reactions (&#x2265;10%) in Patients with Epithelioid Sarcoma Who Received TAZVERIK in Cohort 5 of Study EZH-202</caption><col width="46.433%" align="left"/><col width="26.800%" align="left"/><col width="26.767%" align="left"/><thead><tr><th rowspan="2" align="left" valign="bottom" styleCode="Toprule Botrule Lrule Rrule">Adverse Reaction</th><th colspan="2" align="center" valign="top" styleCode="Toprule Botrule Rrule">TAZVERIK N=62</th></tr><tr><th align="center" valign="top" styleCode="Botrule Rrule">All Grades (%)</th><th align="center" valign="top" styleCode="Botrule Rrule">Grade 3 or 4 (%)</th></tr></thead><tfoot><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">a Includes tumor pain, pain in extremity, non-cardiac chest pain, flank pain, back pain, arthralgia, bone pain, cancer pain, musculoskeletal pain, myalgia, neck pain</paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">b Includes fatigue and asthenia</paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">c Includes abdominal pain, gastrointestinal pain, abdominal pain lower</paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">d Includes dyspnea and dyspnea exertional</paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">e Includes wound hemorrhage, rectal hemorrhage, pulmonary hemorrhage, hemorrhage intracranial, cerebral hemorrhage, hemoptysis</paragraph></td></tr></tfoot><tbody><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">General</td><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Pain^a</td><td align="center" valign="top" styleCode="Botrule Rrule">52</td><td align="center" valign="top" styleCode="Botrule Rrule">7</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Fatigue^b</td><td align="center" valign="top" styleCode="Botrule Rrule">47</td><td align="center" valign="top" styleCode="Botrule Rrule">1.6</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Gastrointestinal</td><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Nausea</td><td align="center" valign="top" styleCode="Botrule Rrule">36</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Vomiting</td><td align="center" valign="top" styleCode="Botrule Rrule">24</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Constipation</td><td align="center" valign="top" styleCode="Botrule Rrule">21</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Diarrhea</td><td align="center" valign="top" styleCode="Botrule Rrule">16</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Abdominal pain^c</td><td align="center" valign="top" styleCode="Botrule Rrule">13</td><td align="center" valign="top" styleCode="Botrule Rrule">1.6</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Metabolism and nutrition</td><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Decreased appetite</td><td align="center" valign="top" styleCode="Botrule Rrule">26</td><td align="center" valign="top" styleCode="Botrule Rrule">4.8</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Respiratory, thoracic and mediastinal</td><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Cough</td><td align="center" valign="top" styleCode="Botrule Rrule">18</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Dyspnea^d</td><td align="center" valign="top" styleCode="Botrule Rrule">16</td><td align="center" valign="top" styleCode="Botrule Rrule">4.8</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Vascular</td><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Hemorrhage^e</td><td align="center" valign="top" styleCode="Botrule Rrule">18</td><td align="center" valign="top" styleCode="Botrule Rrule">4.8</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Nervous system</td><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Headache</td><td align="center" valign="top" styleCode="Botrule Rrule">18</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Investigations</td><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Weight decreased</td><td align="center" valign="top" styleCode="Botrule Rrule">16</td><td align="center" valign="top" styleCode="Botrule Rrule">7</td></tr></tbody></table>

<table ID="t5" width="100%" styleCode="Noautorules"><caption>Table 5. Select Laboratory Abnormalities (&#x2265; 10%) Worsening from Baseline in Patients with Epithelioid Sarcoma Who Received TAZVERIK in Cohort 5 of Study EZH-202</caption><col width="46.600%" align="left"/><col width="26.700%" align="left"/><col width="26.700%" align="left"/><tfoot><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">*The denominator used to calculate the rate varied from 39 to 61 based on the number of patients with a baseline value and at least one post-treatment value.</paragraph></td></tr></tfoot><tbody><tr><td rowspan="2" align="left" valign="bottom" styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">Laboratory Abnormality</content></td><td colspan="2" align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">TAZVERIK*</content></td></tr><tr><td align="center" valign="top" styleCode="Botrule Rrule"><content styleCode="bold">All Grades (%)</content></td><td align="center" valign="top" styleCode="Botrule Rrule"><content styleCode="bold">Grade 3 or 4 (%)</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Hematology</td><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Decreased hemoglobin</td><td align="center" valign="top" styleCode="Botrule Rrule">49</td><td align="center" valign="top" styleCode="Botrule Rrule">15</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Decreased lymphocytes</td><td align="center" valign="top" styleCode="Botrule Rrule">36</td><td align="center" valign="top" styleCode="Botrule Rrule">13</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Decreased white blood cell count</td><td align="center" valign="top" styleCode="Botrule Rrule">19</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Chemistry</td><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Increased triglycerides</td><td align="center" valign="top" styleCode="Botrule Rrule">36</td><td align="center" valign="top" styleCode="Botrule Rrule">3.3</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Increased glucose</td><td align="center" valign="top" styleCode="Botrule Rrule">33</td><td align="center" valign="top" styleCode="Botrule Rrule">1.6</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Decreased sodium</td><td align="center" valign="top" styleCode="Botrule Rrule">30</td><td align="center" valign="top" styleCode="Botrule Rrule">1.7</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Decreased phosphate</td><td align="center" valign="top" styleCode="Botrule Rrule">28</td><td align="center" valign="top" styleCode="Botrule Rrule">1.7</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Decreased albumin</td><td align="center" valign="top" styleCode="Botrule Rrule">23</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Increased alkaline phosphatase</td><td align="center" valign="top" styleCode="Botrule Rrule">23</td><td align="center" valign="top" styleCode="Botrule Rrule">1.7</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Decreased potassium</td><td align="center" valign="top" styleCode="Botrule Rrule">20</td><td align="center" valign="top" styleCode="Botrule Rrule">1.7</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Increased aspartate aminotransferase</td><td align="center" valign="top" styleCode="Botrule Rrule">18</td><td align="center" valign="top" styleCode="Botrule Rrule">3.5</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Decreased calcium</td><td align="center" valign="top" styleCode="Botrule Rrule">16</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Decreased glucose</td><td align="center" valign="top" styleCode="Botrule Rrule">16</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Increased partial thromboplastin time</td><td align="center" valign="top" styleCode="Botrule Rrule">15</td><td align="center" valign="top" styleCode="Botrule Rrule">5</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Increased alanine aminotransferase</td><td align="center" valign="top" styleCode="Botrule Rrule">14</td><td align="center" valign="top" styleCode="Botrule Rrule">3.4</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Increased creatinine</td><td align="center" valign="top" styleCode="Botrule Rrule">12</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Increased potassium</td><td align="center" valign="top" styleCode="Botrule Rrule">12</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr></tbody></table>

<table ID="t6" width="100%" styleCode="Noautorules"><caption>Table 6. Adverse Reactions (&#x2265;10%) in Patients with Relapsed or Refractory Follicular Lymphoma Who Received TAZVERIK in Cohorts 4 and 5 of Study E7438-G000-101</caption><col width="46.667%" align="left"/><col width="26.700%" align="left"/><col width="26.633%" align="left"/><thead><tr><th rowspan="2" align="left" valign="bottom" styleCode="Toprule Botrule Lrule Rrule">Adverse Reaction</th><th colspan="2" align="center" valign="bottom" styleCode="Toprule Botrule Rrule">TAZVERIK N=99</th></tr><tr><th align="center" valign="bottom" styleCode="Botrule Rrule">All Grades (%)</th><th align="center" valign="bottom" styleCode="Botrule Rrule">Grade 3 or 4 (%)</th></tr></thead><tfoot><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">a Includes fatigue and asthenia</paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">b Includes laryngitis, nasopharyngitis, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection, viral upper respiratory tract infection</paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">c Includes bronchitis, lower respiratory tract infection, tracheobronchitis</paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">d Includes cystitis, urinary tract infection, urinary tract infection staphylococcal</paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">e Includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper</paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">f Includes back pain, limb discomfort, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, pain in extremity, pain in jaw, spinal pain</paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">g Includes erythema, rash, rash erythematous, rash generalized, rash maculo-papular, rash pruritic, rash pustular, skin exfoliation</paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">h Includes cough and productive cough</paragraph></td></tr><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">i Includes headache, migraine, sinus headache</paragraph></td></tr></tfoot><tbody><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">General</td><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Fatigue^a</td><td align="center" valign="top" styleCode="Botrule Rrule">36</td><td align="center" valign="top" styleCode="Botrule Rrule">5</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Pyrexia</td><td align="center" valign="top" styleCode="Botrule Rrule">10</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Infections</td><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Upper respiratory tract infection^b</td><td align="center" valign="top" styleCode="Botrule Rrule">30</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Lower respiratory tract infection^c</td><td align="center" valign="top" styleCode="Botrule Rrule">17</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Urinary tract infection^d</td><td align="center" valign="top" styleCode="Botrule Rrule">11</td><td align="center" valign="top" styleCode="Botrule Rrule">2</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Gastrointestinal</td><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Nausea</td><td align="center" valign="top" styleCode="Botrule Rrule">24</td><td align="center" valign="top" styleCode="Botrule Rrule">1</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Abdominal pain^e</td><td align="center" valign="top" styleCode="Botrule Rrule">20</td><td align="center" valign="top" styleCode="Botrule Rrule">3</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Diarrhea</td><td align="center" valign="top" styleCode="Botrule Rrule">18</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Vomiting</td><td align="center" valign="top" styleCode="Botrule Rrule">12</td><td align="center" valign="top" styleCode="Botrule Rrule">1</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Musculoskeletal and connective tissue</td><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Musculoskeletal pain^f</td><td align="center" valign="top" styleCode="Botrule Rrule">22</td><td align="center" valign="top" styleCode="Botrule Rrule">1</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Skin and subcutaneous tissue</td><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Alopecia</td><td align="center" valign="top" styleCode="Botrule Rrule">17</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Rash^g</td><td align="center" valign="top" styleCode="Botrule Rrule">15</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Respiratory and mediastinal system</td><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Cough^h</td><td align="center" valign="top" styleCode="Botrule Rrule">17</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule">Nervous system</td><td align="center" valign="top" styleCode="Botrule Rrule"/><td align="center" valign="top" styleCode="Botrule Rrule"/></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"> Headacheⁱ</td><td align="center" valign="top" styleCode="Botrule Rrule">13</td><td align="center" valign="top" styleCode="Botrule Rrule">0</td></tr></tbody></table>