CNJ-016

WARNING: INTERACTIONS WITH GLUCOSE MONITORING SYSTEMS Blood glucose measurement in patients receiving VIGIV must be done with a glucose-specific method (monitor and test strips) to avoid interference by maltose contained in VIGIV. Glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) or glucose-dye-oxidoreductase method (monitor and test strips) must not be used for blood glucose testing in patients receiving VIGIV, since maltose in IGIV products has been shown to give falsely high blood glucose levels in these testing systems. This could result in the inappropriate administration of insulin, resulting in life-threatening hypoglycemia. Cases of true hypoglycemia may go untreated if the hypoglycemic state is masked by falsely elevated glucose readings. Carefully review the product information of the blood glucose testing system, including that of the test strips, to determine if the system is appropriate for use with maltose-containing parenteral products [see 5.3 Blood Glucose Monitoring ]. WARNING: INTERACTIONS WITH GLUCOSE MONITORING SYSTEMS See full prescribing information for complete boxed warning. Blood glucose measurement in patients receiving VIGIV (vaccinia immune globulin intravenous, human) must be done with a glucose-specific method (monitor and test strips) to avoid interference by maltose contained in VIGIV. Maltose in IGIV products may give falsely high blood glucose levels in certain types of blood glucose testing systems (for example those based on the GDH-PQQ or glucose-dye-oxidoreductase methods) resulting in inappropriate administration of insulin and life-threatening hypoglycemia. Cases of true hypoglycemia may go untreated if the hypoglycemic state is masked by falsely elevated glucose readings.

5 WARNINGS AND PRECAUTIONS • Hypersensitivity to human immune globulin (acute anaphylaxis) ( 5.1 ) • Acute renal dysfunction/failure ( 5.2 ) • Thrombosis may occur with immune globulin products, including VIGIV. For patients at risk of thrombosis, administer VIGIV at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity ( 5.4 ) • Hemolysis or hemolytic anemia ( 5.5 ) • Aseptic meningitis syndrome (AMS) ( 5.6 ) • Noncardiogenic pulmonary edema [Transfusion-Related Acute Lung Injury (TRALI)] ( 5.7 ) • Transmission of infectious agents from human plasma ( 5.8 ) • Monitor renal function and urine output in patients at risk of renal failure; check baseline blood viscosity in patients at risk of hyperviscosity; and conduct confirmatory tests if hemolysis or TRALI is suspected ( 5.9 ) 5.1 Hypersensitivity Severe immediate hypersensitivity reactions to plasma-derived products may occur, for example, in patients with IgA deficiency or hypersensitivity to human globulin. Although acute systemic allergic reactions were not seen in clinical trials with VIGIV [see 6.1 Clinical Trials Experience ], administer the product only in a setting where appropriate equipment and personnel trained in the management of acute anaphylaxis are available. In case of hypotension, allergic or anaphylactic reaction, discontinue the administration of VIGIV immediately and give supportive care as needed. In case of shock, observe the current medical standards for shock treatment. 5.2 Acute Renal Dysfunction/Failure Renal dysfunction, acute renal failure, osmotic nephropathy, proximal tubular nephropathy, and death may occur upon use of immune globulin intravenous (Human) (IGIV) products. Use VIGIV with caution in patients with pre-existing renal insufficiency and in patients at risk of developing renal insufficiency (including, but not limited to those with diabetes mellitus, age greater than 65 years, volume depletion, paraproteinemia, sepsis, and patients receiving known nephrotoxic drugs), and administer VIGIV at the minimum rate of infusion practicable. In these cases, it is important to ensure that patients are not volume depleted before VIGIV infusion. Do not exceed the recommended infusion rate and follow the infusion schedule closely [see 2.3 Administration ]. Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk of developing acute renal failure. Assess renal function, including measurement of blood urea nitrogen (BUN) and serum creatinine, before the initial infusion of VIGIV and at appropriate intervals thereafter. If renal function deteriorates, consider discontinuing VIGIV. Most cases of renal insufficiency following administration of IGIV have occurred in patients receiving total doses containing 400 mg/kg of sucrose or greater. VIGIV does not contain sucrose. No prospective data are currently available in patients with risk factors for renal insufficiency to identify a maximum safe dose, concentration, and/or rate of infusion for VIGIV. 5.3 Blood Glucose Monitoring Some types of blood glucose testing systems (for example those based on the glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) or glucose-dye-oxidoreductase methods) could falsely interpret the maltose contained in VIGIV as glucose [see BOXED WARNING ]. This could result in falsely elevated glucose readings and, consequently, in the inappropriate administration of insulin, resulting in life-threatening hypoglycemia. Also, cases of true hypoglycemia may go untreated if the hypoglycemic state is masked by falsely elevated glucose readings. Accordingly, when administering VIGIV or other parenteral maltose-containing products, measure blood glucose with a glucose-specific method. Carefully review the product information of the blood glucose testing system, including that of the test strips, to determine if the system is appropriate for use with maltose-containing parenteral products. If any uncertainty exists, contact the manufacturer of the testing system to determine if the system is appropriate for use with maltose-containing parenteral products. 5.4 Thrombosis Thrombotic events may occur in association with IGIV treatment. Patients at risk include those with a history of cardiovascular risk factors, advanced age, impaired cardiac output, hypercoagulable disorders, prolonged periods of immobilization, history of arterial or venous thrombosis, estrogen use, indwelling central vascular catheters, and/or known or suspected hyperviscosity. Weigh the potential risks and benefits of VIGIV against those of alternative therapies for all patients for whom VIGIV administration is being considered. Because of the potentially increased risk of thrombosis, consider baseline assessment of blood viscosity in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies. In patients where the benefits of VIGIV administration out-weigh the potential risks of thrombotic and thromboembolic events, administer VIGIV at the minimum concentration available and at the minimum rate of infusion practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. While there are currently no prospective data in patients with thrombosis/thromboembolism to identify a maximum safe dose, concentration, and/or rate of infusion for VIGIV, the maximum daily dose of VIGIV should not exceed 12,000 Units per kg in patients with thrombotic risk factors. 5.5 Hemolysis VIGIV may contain blood group antibodies which may act as hemolysins and induce in vivo coating of red blood cells with immune globulin, causing a positive direct antiglobulin reaction and hemolysis. Acute hemolysis, consistent with intravascular hemolysis, has been reported and hemolytic anemia can develop subsequent to IGIV therapy due to enhanced red blood cell sequestration. The following risk factors may be associated with the development of hemolysis following Immune Globulin Intravenous (Human) (IGIV) products: high doses, given either as a single administration or divided over several days, and non-O blood group ( 1 ). Other individual patient factors, such as an underlying inflammatory state (as may be reflected by, for example, elevated C-reactive protein or erythrocyte sedimentation rate), have been hypothesized to increase the risk of hemolysis following administration of IGIV ( 2 ), but their role is uncertain. Closely monitor VIGIV recipients for clinical signs and symptoms of hemolysis, particularly patients with risk factors noted above. Consider appropriate laboratory testing in higher risk patients, including measurement of hemoglobin or hematocrit prior to infusion and within approximately 36 to 96 hours post infusion. If signs and/or symptoms of hemolysis or a significant drop in hemoglobin or hematocrit have been observed after VIGIV infusion, perform additional confirmatory laboratory testing. If transfusion is indicated for patients who develop hemolysis with clinically compromising anemia after receiving VIGIV, perform adequate cross-matching to avoid exacerbating on-going hemolysis. 5.6 Aseptic Meningitis Syndrome (AMS) AMS may occur in association with IGIV administration. AMS usually begins within several hours to two days following IGIV treatment. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae. AMS is characterized by the following symptoms and signs: severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, and nausea and vomiting. Cerebrospinal fluid (CSF) studies are frequently positive with pleocytosis up to several thousand cells per cubic millimeter, predominately from the granulocytic series, and with elevated protein levels up to several hundred mg/dL, but negative culture results. Conduct a thorough neurological examination in patients exhibiting such symptoms and signs, including CSF studies, to rule out other causes of meningitis. AMS may occur more frequently in association with high total doses (2 g/kg) of IGIV treatment. For VIGIV, at the recommended dosage of 6000 Units per kg, a patient may be exposed to up to 0.18 g/kg protein after VIGIV administration. 5.7 Transfusion-related Acute Lung Injury (TRALI) Noncardiogenic pulmonary edema may occur in patients administered IGIV. TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever and typically occurs within one to six hours after transfusion. Patients with TRALI may be managed using oxygen therapy with adequate ventilatory support. Monitor VIGIV recipients for pulmonary adverse reactions. If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil antibodies in both the product and patient serum. 5.8 Transmissible Infectious Agents Because this product is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt‐Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt‐Jakob disease (CJD) agent. All infections thought to have been possibly transmitted by this product should be reported by the physician or other health care provider to Emergent BioSolutions Canada Inc. at 1 800-768-2304. 5.9 Monitoring: Laboratory Tests • Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk of developing acute renal failure. Assess renal function, including measurement of BUN and serum creatinine, before the initial infusion of VIGIV and at appropriate intervals thereafter. • Because of the potentially increased risk of thrombosis, consider baseline assessment of blood viscosity in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies. • If signs and/or symptoms of hemolysis are present after an infusion of VIGIV, perform appropriate laboratory testing for confirmation. • If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil antibodies in both the product and patient’s serum.

6 ADVERSE REACTIONS The adverse drug reactions to VIGIV treatment in clinical trials (>10%) include headache, nausea, rigors and dizziness. The adverse drug reactions to VIGIV treatment in clinical trials (>10%) include headache, nausea, rigors and dizziness. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Emergent BioSolutions Canada Inc. at 1-800-768-2304 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. In a safety/pharmacokinetics study, 60 healthy male and female volunteers received a single intravenous dose of either 6000 Units per kg or 9000 Units per kg VIGIV. The population consisted of vaccinia vaccination-naïve subjects, ages 18 to 32, with both males and females enrolled in an approximate 50:50 ratio. In a pharmacodynamic study, 32 healthy male and female volunteers were randomized to receive vaccinia vaccination (n=10), VIGIV (9000 Units per kg) 4 days prior to vaccinia vaccination (n=10), or VIGIV (9000 Units per kg) concurrent with vaccinia vaccination (n=12). The population consisted of vaccinia vaccination-naïve subjects, ages 18 to 32, with both male and female enrolled in a 75:25 ratio. The ethnic background of patients included those of Caucasian, African American, Asian and Hispanic descent, with the majority of them being Caucasian. In an additional pharmacodynamic clinical study, 50 healthy male and female volunteers were randomized to receive VIGIV at 9000 Units per kg (n=20) or at 24,000 Units per kg (n=20) or placebo (n=10) 4 days prior to vaccinia vaccination (n=30) or placebo (n=20). The population consisted of vaccinia vaccination-naïve male and female subjects, ages 18 to 33, in a 60:40 ratio. The ethnic background of patients included those of Caucasian, African American, and Hispanic descent, with the majority of them being African American. The most frequently reported adverse reactions related to VIGIV administration in all three clinical studies were headache, nausea, rigors, and dizziness. Table 1 describes the adverse reactions that were temporally related to VIGIV or placebo administration that occurred during or within three days of product infusion with a frequency of 5% or higher in any one treatment group. Table 1 Adverse Drug Reactions that Occurred Temporally* During or Following VIGIV Administration (≥5%) *Adverse events that occurred during or within 3 days of VIGIV or placebo administration. a 0.9% NaCl infused at 2 mL/min. b Infusion rate: 4 mL/min; subjects were fasted. c Infusion rate: 4 mL/min or 2 mL/min; subjects were fasted. d Infusion rate: 2 mL/min; subjects were not fasted. SYSTEM ORGAN CLASS PREFERRED TERM VIGIV (%) 6000 U/kg b N=31 VIGIV (%) 9000 U/kg c N=39 VIGIV (%) 9000 U/kg d N=20 VIGIV (%) 24,000 U/kg d N=20 PLACEBO a N=32 (%) All Body System All Preferred Terms 19 (61.3) 30 (76.9) 2 (10.0) 5 (25.0) 4 (12.5) Gastrointestinal Disorders Nausea 4 (12.9) 11 (28.2) 0 (0.0) 0 (0.0) 1 (3.1) Vomiting NOS 1 (3.2) 3 (7.7) 0 (0.0) 0 (0.0) 0 (0.0) General Disorders and Administration Site Conditions Rigors 7 (22.6) 7 (17.9) 0 (0.0) 0 (0.0) 0 (0.0) -- Feeling cold 4 (12.9) 6 (15.4) 0 (0.0) 0 (0.0) 0 (0.0) -- Pain NOS 1 (3.2) 5 (12.8) 0 (0.0) 0 (0.0) 0 (0.0) -- Feeling hot 3 (9.7) 1 (2.6) 0 (0.0) 0 (0.0) 0 (0.0) -- Asthenia 2 (6.5) 2 (5.1) 0 (0.0) 0 (0.0) 1 (3.1) -- Pyrexia 2 (6.5) 1 (2.6) 0 (0.0) 0 (0.0) 0 (0.0) -- Fatigue 0 (0.0) 2 (5.1) 0 (0.0) 0 (0.0) 1 (3.1) -- Edema peripheral 0 (0.0) 0 (0.0) 0 (0.0) 1 (5.0) 0 (0.0) Metabolism and Nutrition Disorders Appetite decreased NOS 2 (6.5) 2 (5.1) 0 (0.0) 0 (0.0) 0 (0.0) Musculoskeletal and Connective Tissue Disorders Muscle spasm 2 (6.5) 2 (5.1) 0 (0.0) 1 (5.0) 0 (0.0) -- Back pain 2 (6.5) 2 (5.1) 0 (0.0) 0 (0.0) 0 (0.0) Nervous System Disorders Headache 17 (54.8) 23 (59.0) 1 (5.0) 4 (20.0) 3 (9.4) -- Dizziness 5 (16.1) 7 (17.9) 1 (5.0) 0 (0.0) 1 (3.1) -- Paraesthesia 2 (6.5) 1 (2.6) 0 (0.0) 0 (0.0) 0 (0.0) -- Tremor 1 (3.2) 2 (5.1) 0 (0.0) 0 (0.0) 0 (0.0) Skin and Subcutaneous Tissue Disorders Sweating increased 3 (9.7) 2 (5.1) 0 (0.0) 0 (0.0) 0 (0.0) Vascular Disorders Pallor 1 (3.2) 3 (7.7) 0 (0.0) 0 (0.0) 0 (0.0) Most adverse reactions were of mild intensity (defined in study protocols as awareness of a sign or symptom but subject can tolerate). One subject in the 9000 Units per kg dosage group experienced syncope. There was a lower incidence of adverse reactions when VIGIV (9000 Units per kg) was infused at 2 mL/min than 4 mL/min. There was a higher incidence of adverse reactions after administration of VIGIV in fasted subjects compared to subjects that were not fasted overnight. There were no serious adverse reactions or adverse reactions of severe intensity in the clinical studies. There were no instances of VIGIV discontinuation due to an adverse event, or reduction in dose or infusion rate. 6.2 Post-marketing Experience Because post-marketing adverse 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 exposure to the product. Severe vaccinia infection that developed possible intravascular hemolysis and transient renal injury has been reported. As VIGIV may contain blood group antigens that may have hemolysins, VIGIV doses may have contributed to the hemolysis. However, the hemolysis did not reoccur with continued VIGIV dosing. Mild and transient chest pain that occurred the same day of VIGIV infusion has been reported. The following are adverse reactions listed by body system that have been identified and reported during the post-approval use of other IGIV products: • Cardiovascular : Cardiac arrest, tachycardia • Hematologic and Lymphatic : Neutropenia, leukopenia, anemia, lymphadenopathy • Integumentary : Stevens-Johnson syndrome, epidermolysis, erythema multiforme, dermatitis (e.g., bullous dermatitis), urticaria or other skin reactions • Gastrointestinal : Hepatic dysfunction, abdominal pain, diarrhea • Muscular: Myalgia, arthralgia • Neurological : Coma, loss of consciousness, seizures • Renal : Acute kidney injury, osmotic nephropathy • Respiratory : Apnea, Acute Respiratory Distress Syndrome (ARDS), cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm, wheezing • General/Body as a Whole : Malaise, chest discomfort

<table ID="_Ref201152624" width="100%"><caption>Table 1 Adverse Drug Reactions that Occurred Temporally* During or Following VIGIV Administration (&#x2265;5%)</caption><col width="18%"/><col width="14%"/><col width="13%"/><col width="13%"/><col width="13%"/><col width="14%"/><col width="14%"/><tfoot><tr><td align="left" colspan="7" valign="top">*Adverse events that occurred during or within 3 days of VIGIV or placebo administration.</td></tr><tr><td align="left" colspan="7" valign="top">^a 0.9% NaCl infused at 2 mL/min.</td></tr><tr><td align="left" colspan="7" valign="top">^b Infusion rate: 4 mL/min; subjects were fasted. </td></tr><tr><td align="left" colspan="7" valign="top">^c Infusion rate: 4 mL/min or 2 mL/min; subjects were fasted. </td></tr><tr><td align="left" colspan="7" valign="top">^d Infusion rate: 2 mL/min; subjects were not fasted.</td></tr></tfoot><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">SYSTEM ORGAN CLASS</content></paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">PREFERRED TERM</content></paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">VIGIV (%) 6000 U/kg^b N=31</content></paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">VIGIV (%) 9000 U/kg^c N=39</content></paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">VIGIV (%) 9000 U/kg^d N=20</content></paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">VIGIV (%) 24,000 U/kg^d N=20</content></paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">PLACEBO^a N=32 (%)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>All Body System</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>All Preferred Terms</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>19 (61.3)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>30 (76.9)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2 (10.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>5 (25.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>4 (12.5)</paragraph></td></tr><tr><td rowspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Gastrointestinal Disorders</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Nausea</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>4 (12.9)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>11 (28.2)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (3.1)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Vomiting NOS</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (3.2)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3 (7.7)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>General Disorders and Administration Site Conditions</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Rigors</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>7 (22.6)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>7 (17.9)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>--</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Feeling cold</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>4 (12.9)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6 (15.4)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>--</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Pain NOS</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (3.2)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>5 (12.8)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>--</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Feeling hot</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3 (9.7)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (2.6)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>--</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Asthenia</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2 (6.5)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2 (5.1)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (3.1)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>--</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Pyrexia</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2 (6.5)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (2.6)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>--</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Fatigue</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2 (5.1)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (3.1)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>--</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Edema peripheral</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (5.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Metabolism and Nutrition Disorders</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Appetite decreased NOS</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2 (6.5)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2 (5.1)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Musculoskeletal and Connective Tissue Disorders</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Muscle spasm</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2 (6.5)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2 (5.1)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (5.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>--</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Back pain</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2 (6.5)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2 (5.1)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Nervous System Disorders</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Headache</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>17 (54.8)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>23 (59.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (5.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>4 (20.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3 (9.4)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>--</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Dizziness</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>5 (16.1)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>7 (17.9)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (5.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (3.1)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>--</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Paraesthesia</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2 (6.5)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (2.6)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>--</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Tremor</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1 (3.2)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2 (5.1)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Skin and Subcutaneous Tissue Disorders</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Sweating increased</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3 (9.7)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2 (5.1)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Vascular Disorders</paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Pallor</paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>1 (3.2)</paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>3 (7.7)</paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0 (0.0)</paragraph></td><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr></tbody></table>