FDA label 7af60e76-41ca-4324-8f44-c6cc00fdd694

5 WARNINGS AND PRECAUTIONS Acute Critical Illness: Potential benefit of treatment continuation should be weighed against the potential risk ( 5.1 ) Prader-Willi Syndrome in Children: Evaluate for signs of upper airway obstruction and sleep apnea before initiation of treatment for GHD. Discontinue treatment if these signs occur ( 5.2 ) Neoplasm: Monitor patients with preexisting tumors for progression or recurrence. Increased risk of a second neoplasm in childhood cancer survivors treated with somatropin - in particular meningiomas in patients treated with radiation to the head for their first neoplasm ( 5.3 ) Impaired Glucose Tolerance and Diabetes Mellitus: May be unmasked. Periodically monitor glucose levels in all patients. Doses of concurrent antihyperglycemic drugs in diabetics may require adjustment ( 5.4 ) Intracranial Hypertension: Exclude preexisting papilledema. May develop and is usually reversible after discontinuation or dose reduction ( 5.5 ) Fluid Retention (i.e., edema, arthralgia, carpal tunnel syndrome - especially in adults): May occur frequently. Reduce dose as necessary ( 5.6 ) Hypothyroidism: May first become evident or worsen ( 5.7 ) Slipped Capital Femoral Epiphysis: May develop. Evaluate children with the onset of a limp or hip/knee pain ( 5.8 ) Progression of Preexisting Scoliosis: May develop ( 5.9 ) 5.1 Acute Critical Illness Increased mortality in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure has been reported after treatment with pharmacologic amounts of somatropin [ see Contraindications (4.1) ]. The safety of continuing somatropin treatment in patients receiving replacement doses for approved indications who concurrently develop these illnesses has not been established. Therefore, the potential benefit of treatment continuation with somatropin in patients experiencing acute critical illnesses should be weighed against the potential risk. 5.2 Prader-Willi Syndrome in Children There have been reports of fatalities after initiating therapy with somatropin in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females. Patients with Prader-Willi syndrome should be evaluated for signs of upper airway obstruction and sleep apnea before initiation of treatment with somatropin. If, during treatment with somatropin, patients show signs of upper airway obstruction (including onset of or increased snoring) and/or new onset sleep apnea, treatment should be interrupted. All patients with Prader-Willi syndrome treated with somatropin should also have effective weight control and be monitored for signs of respiratory infection, which should be diagnosed as early as possible and treated aggressively [ see Contraindications (4.2) ]. Norditropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome. 5.3 Neoplasms Patients with preexisting tumors or GHD secondary to an intracranial lesion should be monitored routinely for progression or recurrence of the underlying disease process. In pediatric patients, clinical literature has revealed no relationship between somatropin replacement therapy and central nervous system (CNS) tumor recurrence or new extracranial tumors. However, in childhood cancer survivors, an increased risk of a second neoplasm has been reported in patients treated with somatropin after their first neoplasm. Intracranial tumors, in particular meningiomas, in patients treated with radiation to the head for their first neoplasm, were the most common of these second neoplasms. In adults, it is unknown whether there is any relationship between somatropin replacement therapy and CNS tumor recurrence. Patients should be monitored carefully for potential malignant transformation of skin lesions, i.e. increased growth of preexisting nevi. 5.4 Glucose Intolerance Treatment with somatropin may decrease insulin sensitivity, particularly at higher doses in susceptible patients. As a result, previously undiagnosed impaired glucose tolerance and overt diabetes mellitus may be unmasked during somatropin treatment. Therefore, glucose levels should be monitored periodically in all patients treated with somatropin, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. Patients with preexisting type 1 or type 2 diabetes mellitus or impaired glucose tolerance should be monitored closely during somatropin therapy. The doses of antihyperglycemic drugs (i.e., insulin or oral agents) may require adjustment when somatropin therapy is instituted in these patients. 5.5 Intracranial Hypertension Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea, and/or vomiting has been reported in a small number of patients treated with somatropin products. Symptoms usually occurred within the first eight (8) weeks after the initiation of somatropin therapy. In all reported cases, IH-associated signs and symptoms rapidly resolved after cessation of therapy or a reduction of the somatropin dose. Funduscopic examination should be performed routinely before initiating treatment with somatropin to exclude preexisting papilledema, and periodically during the course of somatropin therapy. If papilledema is observed by funduscopy during somatropin treatment, treatment should be stopped. If somatropin-induced IH is diagnosed, treatment with somatropin can be restarted at a lower dose after IH-associated signs and symptoms have resolved. Patients with Turner syndrome may be at increased risk for the development of IH. 5.6 Fluid Retention Fluid retention during somatropin replacement therapy in adults may frequently occur. Clinical manifestations of fluid retention are usually transient and dose dependent. 5.7 Hypothyroidism Undiagnosed/untreated hypothyroidism may prevent an optimal response to somatropin, in particular, the growth response in children. Patients with Turner syndrome have an inherently increased risk of developing autoimmune thyroid disease and primary hypothyroidism. In patients with GHD, central (secondary) hypothyroidism may first become evident or worsen during somatropin treatment. Therefore, patients treated with somatropin should have periodic thyroid function tests and thyroid hormone replacement therapy should be initiated or appropriately adjusted when indicated. In patients with hypopituitarism (multiple hormone deficiencies), standard hormonal replacement therapy should be monitored closely when somatropin therapy is administered. 5.8 Slipped Capital Femoral Epiphysis in Pediatric Patients Slipped capital femoral epiphysis may occur more frequently in patients with endocrine disorders (including GHD and Turner syndrome) or in patients undergoing rapid growth. Any pediatric patient with the onset of a limp or complaints of hip or knee pain during somatropin therapy should be carefully evaluated. 5.9 Progression of Preexisting Scoliosis in Pediatric Patients Progression of scoliosis can occur in patients who experience rapid growth. Because somatropin increases growth rate, patients with a history of scoliosis who are treated with somatropin should be monitored for progression of scoliosis. However, somatropin has not been shown to increase the occurrence of scoliosis. Skeletal abnormalities including scoliosis are commonly seen in untreated patients with Turner syndrome and Noonan syndrome. Scoliosis is also commonly seen in untreated patients with Prader-Willi syndrome. Physicians should be alert to these abnormalities, which may manifest during somatropin therapy. 5.10 Otitis Media and Cardiovascular Disorders in Turner Syndrome Patients with Turner syndrome should be evaluated carefully for otitis media and other ear disorders since these patients have an increased risk of ear and hearing disorders. Somatropin treatment may increase the occurrence of otitis media in patients with Turner syndrome. In addition, patients with Turner syndrome should be monitored closely for cardiovascular disorders (e.g., stroke, aortic aneurysm/dissection, hypertension) as these patients are also at risk for these conditions. 5.11 Confirmation of Childhood Onset Adult GHD Patients with epiphyseal closure who were treated with somatropin replacement therapy in childhood should be reevaluated according to the criteria in Indications and Usage ( 1.2 ) before continuation of somatropin therapy at the reduced dose level recommended for GH deficient adults. 5.12 Local and Systemic Reactions When somatropin is administered subcutaneously at the same site over a long period of time, tissue atrophy may result. This can be avoided by rotating the injection site [ see Dosage and Administration (2.3) ]. As with any protein, local or systemic allergic reactions may occur. Parents/Patients should be informed that such reactions are possible and that prompt medical attention should be sought if allergic reactions occur. 5.13 Laboratory Tests Serum levels of inorganic phosphorus, alkaline phosphatase, parathyroid hormone (PTH) and IGF-I may increase after somatropin therapy.

6 ADVERSE REACTIONS Other common somatropin-related adverse reactions include injection site reactions/rashes and lipoatrophy ( 6.1 ) and headaches ( 6.3 ). To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk at 1-888-NOVO-444 (1-888-668-6444) or FDA at 1-800-FDA-1088, or www.fda.gov/medwatch. 6.1 Most Serious and/or Most Frequently Observed Adverse Reactions This list presents the most serious b and/or most frequently observed a adverse reactions during treatment with somatropin: b Sudden death in pediatric patients with Prader-Willi syndrome with risk factors including severe obesity, history of upper airway obstruction or sleep apnea and unidentified respiratory infection [ see Contraindications (4.2) and Warnings and Precautions (5.2) ] b Intracranial tumors, in particular meningiomas, in teenagers/young adults treated with radiation to the head as children for a first neoplasm and somatropin [ see Contraindications (4.3) and Warnings and Precautions (5.3) ] a,b Glucose intolerance including impaired glucose tolerance/impaired fasting glucose as well as overt diabetes mellitus [ see Warnings and Precautions (5.4) ] b Intracranial hypertension [ see Warnings and Precautions (5.5) ] b Significant diabetic retinopathy [ see Contraindications (4.4) ] b Slipped capital femoral epiphysis in pediatric patients [ see Warnings and Precautions (5.8) ] b Progression of preexisting scoliosis in pediatric patients [ see Warnings and Precautions (5.9) ] a Fluid retention manifested by edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paraesthesias [ see Warnings and Precautions (5.6) ] a Unmasking of latent central hypothyroidism [ see Warnings and Precautions (5.7) ] a Injection site reactions/rashes and lipoatrophy (as well as rare generalized hypersensitivity reactions) [ see Warnings and Precautions (5.12) ] 6.2 Clinical Trials Experience Because clinical trials are conducted under varying conditions, adverse reaction rates observed during the clinical trials performed with one somatropin formulation cannot always be directly compared to the rates observed during the clinical trials performed with a second somatropin formulation, and may not reflect the adverse reaction rates observed in practice. Clinical Trials in Pediatric GHD Patients As with all protein drugs, a small percentage of patients may develop antibodies to the protein. GH antibodies with binding capacities lower than 2 mg/L have not been associated with growth attenuation. In a very small number of patients, when binding capacity was greater than 2 mg/L, interference with the growth response was observed. In clinical trials, patients receiving Norditropin for up to 12 months were tested for induction of antibodies, and 0/358 patients developed antibodies with binding capacities above 2 mg/L. Amongst these patients, 165 had previously been treated with other somatropin formulations, and 193 were previously untreated naive patients. Clinical Trials in Children with Noonan Syndrome Norditropin was studied in a two-year prospective, randomized, parallel dose group trial in 21 children, 3-14 years old, with Noonan syndrome. Doses were 0.033 and 0.066 mg/kg/day. After the initial two-year randomized trial, children continued Norditropin treatment until final height was achieved; randomized dose groups were not maintained. Final height and adverse event data were later collected retrospectively from 18 children; total follow-up was 11 years. An additional 6 children were not randomized, but followed the protocol and are included in this assessment of adverse events. Based on the mean dose per treatment group, no significant difference in the incidence of adverse events was seen between the two groups. The most frequent adverse events were the common infections of childhood, including upper respiratory infection, gastroenteritis, ear infection, and influenza. Cardiac disorders was the system organ class with the second most adverse events reported. However, congenital heart disease is an inherent component of Noonan syndrome, and there was no evidence of somatropin-induced ventricular hypertrophy or exacerbation of preexisting ventricular hypertrophy (as judged by echocardiography) during this study. Children who had baseline cardiac disease judged to be significant enough to potentially affect growth were excluded from the study; therefore the safety of Norditropin in children with Noonan syndrome and significant cardiac disease is not known. Among children who received 0.033 mg/kg/day, there was one adverse event of scoliosis; among children who received 0.066 mg/kg/day, there were four adverse events of scoliosis [ see Warnings and Precautions (5.9) ]. Mean serum IGF-I standard deviation score (SDS) levels did not exceed +1 in response to somatropin treatment. The mean serum IGF-I level was low at baseline and normalized during treatment. Clinical Trials in Children with Turner Syndrome In two clinical studies wherein children with Turner syndrome were treated until final height with various doses of Norditropin as described in Clinical Studies (14.2) , the most frequently reported adverse events were common childhood diseases including influenza-like illness, otitis media, upper respiratory tract infection, otitis externa, gastroenteritis and eczema. Otitis media adverse events in Study 1 were most frequent in the highest dose groups (86.4% in the 0.045-0.067-0.089 mg/kg/day group vs. 78.3% in the 0.045-0.067 mg/kg/day group vs. 69.6% in the 0.045 mg/kg/day group) suggesting a possible dose-response relationship. Of note, approximately 40-50% of these otitis media adverse events were designated as “serious” [ see Warnings and Precautions (5.10) ]. No patients in either study developed clearcut overt diabetes mellitus; however, in Study 1, impaired fasting glucose at Month 48 was more frequent in patients in the 0.045-0.067 mg/kg/day group (n=4/18) compared with the 0.045 mg/kg/day group (n=1/20). Transient episodes of fasting blood sugars between 100 and 126 mg/dL, and, on occasion, exceeding 126 mg/dL also occurred more often with larger doses of Norditropin in both studies [ see Warnings and Precautions (5.4) and Adverse Reactions (6.1) ]. Three patients withdrew from the 2 high dose groups in Study 1 because of concern about excessive growth of hands or feet. In addition, in Study 1, exacerbation of preexisting scoliosis was designated a serious adverse reaction in two patients in the 0.045 mg/kg/day group [see Warnings and Precautions (5.9) ]. Clinical Trials in Children Born Small for Gestational Age (SGA) with No Catch-up Growth by Age 2-4 Years Study 1 (Long-Term) In a multi-center, randomized, double-blind study, 53 non-GHD children with short stature born SGA with failure to catch-up were treated with 2 doses of Norditropin (0.033 or 0.067 mg/kg/day) to final height for up to 13 years (mean duration of treatment 7.9 and 9.5 years for girls and boys, respectively). The most frequently reported adverse events were common childhood diseases including influenza-like illness, upper respiratory tract infection, bronchitis, gastroenteritis, abdominal pain, otitis media, pharyngitis, arthralgia, and headache. Adverse events possibly/probably related to Norditropin were otitis media, arthralgia, headaches (no confirmed diagnoses of benign intracranial hypertension), gynecomastia, and increased sweating. One child treated with 0.067 mg/kg/day for 4 years was reported with disproportionate growth of the lower jaw, and another child treated with 0.067 mg/kg/day developed a melanocytic nevus [ see Warnings and Precautions (5.3) ]. There were no clear cut reports of exacerbation of preexisting scoliosis or slipped capital femoral epiphysis. No apparent differences between the treatment groups were observed. In addition, the timing of puberty was age-appropriate in boys and girls in both treatment groups. Therefore, it can be concluded that no novel adverse events potentially related to treatment with Norditropin were reported in long-term Study 1. Study 2 (Short-Term) In a multi-center, randomized, double-blind, parallel-group study, 98 Japanese non-GHD children with short stature born SGA with failure to catch-up were treated with 2 doses of Norditropin (0.033 or 0.067 mg/kg/day) for 2 years or were untreated for 1 year. The most frequently reported adverse events were common childhood diseases almost identical to those reported above for Study 1. Adverse events possibly/probably related to Norditropin were otitis media, arthralgia and impaired glucose tolerance. No apparent differences between the treatment groups were observed. However, arthralgia and transiently impaired glucose tolerance were only reported in the 0.067 mg/kg/day treatment group. Therefore, it can also be concluded that no novel adverse events potentially related to treatment with rhGH were reported in short-term Study 2. As with all protein drugs, some patients may develop antibodies to the protein. Eighteen of the 76 children (~24%) treated with Norditropin developed anti-rhGH antibodies. However, these antibodies did not appear to be neutralizing in that the change from baseline in height SDS at Year 2 was similar in antibody positive and antibody negative children by treatment group. In both Study 1 and Study 2, there were no clear cut cases of new onset diabetes mellitus, no children treated for hyperglycemia, and no adverse event withdrawals due to abnormalities in glucose tolerance. In Study 2, after treatment with either dose of Norditropin for 2 years, there were no children with consecutive fasting blood glucose levels between 100 and 126 mg/dL, or with fasting blood glucose levels > 126 mg/dL. Furthermore, mean hemoglobin A1c levels tended to decrease during long-term treatment in Study 1, and remained normal in Study 2. However, in Study 1, 4 children treated with 0.067 mg/kg/day of Norditropin and 2 children treated with 0.033 mg/kg/day of Norditropin shifted from normal fasting blood glucose levels at baseline to increased levels after 1 year of treatment (100 to 126 mg/dL or > 126 mg/dL). In addition, small increases in mean fasting blood glucose and insulin levels (within the normal reference range) after 1 and 2 years of Norditropin treatment appeared to be dose-dependent [see Warnings and Precautions (5.4) and Adverse Reactions (6.1)] . In both Study 1 and Study 2, there was no acceleration of bone maturation. A dose-dependent increase in mean serum IGF-I SDS levels within the reference range (but including a substantial number of children with serum IGF-1 SDS > +2) was observed after both long-term (Study 1) and short-term (Study 2) Norditropin treatment. Clinical Trials in Adult GHD Patients Adverse events with an incidence of ≥5% occurring in patients with AO GHD during the 6 month placebo-controlled portion of the largest of the six adult GHD Norditropin trials are presented in Table 1. Peripheral edema, other types of edema, arthralgia, myalgia, and paraesthesia were common in the Norditropin-treated patients, and reported much more frequently than in the placebo group. These types of adverse events are thought to be related to the fluid accumulating effects of somatropin. In general, these adverse events were mild and transient in nature. During the placebo-controlled portion of this study, approximately 5% of patients without preexisting diabetes mellitus treated with Norditropin were diagnosed with overt type 2 diabetes mellitus compared with none in the placebo group [ see Warnings and Precautions (5.4) and Adverse Reactions (6.1) ]. Anti-GH antibodies were not detected. Of note, the doses of Norditropin employed during this study (completed in the mid 1990s) were substantially larger than those currently recommended by the Growth Hormone Research Society, and, more than likely, resulted in a greater than expected incidence of fluid retention- and glucose intolerance-related adverse events. A similar incidence and pattern of adverse events were observed during the other three placebo-controlled AO GHD trials and during the two placebo-controlled CO GHD trials. Table 1 - Adverse Reactions with ≥5% Overall Incidence in Adult Onset Growth Hormone Deficient Patients Treated with Norditropin During a Six Month Placebo-Controlled Clinical Trial Norditropin (N=53) Placebo (N=52) Adverse Reactions n % n % Peripheral Edema 22 42 4 8 Edema 13 25 0 0 Arthralgia 10 19 8 15 Leg Edema 8 15 2 4 Myalgia 8 15 4 8 Infection (non-viral) 7 13 4 8 Paraesthesia 6 11 3 6 Skeletal Pain 6 11 1 2 Headache 5 9 3 6 Bronchitis 5 9 0 0 Flu-like symptoms 4 8 2 4 Hypertension 4 8 1 2 Gastroenteritis 4 8 4 8 Other Non-Classifiable Disorders (excludes accidental injury) 4 8 3 6 Increased sweating 4 8 1 2 Glucose tolerance abnormal 3 6 1 2 Laryngitis 3 6 3 6 The adverse event pattern observed during the open label phase of the study was similar to the one presented above. 6.3 Post-Marketing Surveillance Because these adverse events 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. The adverse events reported during post-marketing surveillance do not differ from those listed/discussed above in Sections 6.1 and 6.2 in children and adults. Leukemia has been reported in a small number of GH deficient children treated with somatropin, somatrem (methionylated rhGH) and GH of pituitary origin. It is uncertain whether these cases of leukemia are related to GH therapy, the pathology of GHD itself, or other associated treatments such as radiation therapy. On the basis of current evidence, experts have not been able to conclude that GH therapy per se was responsible for these cases of leukemia. The risk for children with GHD, if any, remains to be established [ see Contraindications (4.3) and Warnings and Precautions (5.3) ]. The following additional adverse reactions have been observed during the appropriate use of somatropin: headaches (children and adults), gynecomastia (children), and pancreatitis (children).

<table border="single" width="438.000" ID="id_3d104d64-b596-4fd2-aa4b-b74ea8e72e43"> <caption ID="id_f66f7907-9746-425a-a4a1-b43449a411c5">Table 1 - Adverse Reactions with &#x2265;5% Overall Incidence in Adult Onset Growth Hormone Deficient Patients Treated with Norditropin During a Six Month Placebo-Controlled Clinical Trial</caption> <col width="43.8%"/> <col width="13.7%"/> <col width="13.7%"/> <col width="15.1%"/> <col width="13.7%"/> <tbody> <tr ID="id_0daa6ff8-e7ee-4453-9039-0d2c2f335f9c"> <td align="left" valign="top" styleCode="Botrule Toprule Rrule Lrule"/> <td align="center" valign="top" colspan="2" styleCode="Botrule Rrule"> <paragraph>Norditropin</paragraph>(N=53)</td> <td align="center" valign="top" colspan="2" styleCode="Botrule Rrule"> <paragraph>Placebo</paragraph>(N=52)</td> </tr> <tr ID="id_daa0245e-bd9a-4304-ac3e-34c967b66638"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule">Adverse Reactions</td> <td align="center" valign="top" styleCode="Botrule Rrule">n</td> <td align="center" valign="top" styleCode="Botrule Rrule"> <paragraph>%</paragraph> </td> <td align="center" valign="top" styleCode="Botrule Rrule">n</td> <td align="center" valign="top" styleCode="Botrule Rrule">%</td> </tr> <tr ID="id_33126b37-76bf-4e71-9c4e-769e6c06e503"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule">Peripheral Edema</td> <td align="center" valign="top" styleCode="Botrule Rrule">22</td> <td align="center" valign="top" styleCode="Botrule Rrule">42</td> <td align="center" valign="top" styleCode="Botrule Rrule">4</td> <td align="center" valign="top" styleCode="Botrule Rrule">8</td> </tr> <tr ID="id_47095a4f-639d-4718-a04c-a0d6073b9be1"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule">Edema</td> <td align="center" valign="top" styleCode="Botrule Rrule">13</td> <td align="center" valign="top" styleCode="Botrule Rrule">25</td> <td align="center" valign="top" styleCode="Botrule Rrule">0</td> <td align="center" valign="top" styleCode="Botrule Rrule">0</td> </tr> <tr ID="id_ffb1d3e7-e6d9-4304-990d-8be7e8dd2807"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule">Arthralgia</td> <td align="center" valign="top" styleCode="Botrule Rrule">10</td> <td align="center" valign="top" styleCode="Botrule Rrule">19</td> <td align="center" valign="top" styleCode="Botrule Rrule">8</td> <td align="center" valign="top" styleCode="Botrule Rrule">15</td> </tr> <tr ID="id_d59fd3ae-35f2-43d7-a6da-78fbbd5bc382"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule">Leg Edema</td> <td align="center" valign="top" styleCode="Botrule Rrule">8</td> <td align="center" valign="top" styleCode="Botrule Rrule">15</td> <td align="center" valign="top" styleCode="Botrule Rrule">2</td> <td align="center" valign="top" styleCode="Botrule Rrule">4</td> </tr> <tr ID="id_4d09a4d6-b951-4620-90e6-bd987cbe3346"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule">Myalgia</td> <td align="center" valign="top" styleCode="Botrule Rrule">8</td> <td align="center" valign="top" styleCode="Botrule Rrule">15</td> <td align="center" valign="top" styleCode="Botrule Rrule">4</td> <td align="center" valign="top" styleCode="Botrule Rrule">8</td> </tr> <tr ID="id_3259ffcd-b2e4-4e9c-8a49-bb12192532bf"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule">Infection (non-viral) </td> <td align="center" valign="top" styleCode="Botrule Rrule">7</td> <td align="center" valign="top" styleCode="Botrule Rrule">13</td> <td align="center" valign="top" styleCode="Botrule Rrule">4</td> <td align="center" valign="top" styleCode="Botrule Rrule">8</td> </tr> <tr ID="id_4887ea94-413f-4922-a8e8-b17c7394acc0"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule">Paraesthesia</td> <td align="center" valign="top" styleCode="Botrule Rrule">6</td> <td align="center" valign="top" styleCode="Botrule Rrule">11</td> <td align="center" valign="top" styleCode="Botrule Rrule">3</td> <td align="center" valign="top" styleCode="Botrule Rrule">6</td> </tr> <tr ID="id_3698e60c-32a3-41a4-9115-86aa4744ecc2"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule">Skeletal Pain</td> <td align="center" valign="top" styleCode="Botrule Rrule">6</td> <td align="center" valign="top" styleCode="Botrule Rrule">11</td> <td align="center" valign="top" styleCode="Botrule Rrule">1</td> <td align="center" valign="top" styleCode="Botrule Rrule">2</td> </tr> <tr ID="id_d31c12e0-f835-41c7-80c3-f66e513519a4"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule">Headache</td> <td align="center" valign="top" styleCode="Botrule Rrule">5</td> <td align="center" valign="top" styleCode="Botrule Rrule">9</td> <td align="center" valign="top" styleCode="Botrule Rrule">3</td> <td align="center" valign="top" styleCode="Botrule Rrule">6</td> </tr> <tr ID="id_cf56b127-346e-4c91-a65d-ec6760397871"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule">Bronchitis</td> <td align="center" valign="top" styleCode="Botrule Rrule">5</td> <td align="center" valign="top" styleCode="Botrule Rrule">9</td> <td align="center" valign="top" styleCode="Botrule Rrule">0</td> <td align="center" valign="top" styleCode="Botrule Rrule">0</td> </tr> <tr ID="id_c28adb06-9745-4740-a7f7-61a17d618f31"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule">Flu-like symptoms</td> <td align="center" valign="top" styleCode="Botrule Rrule">4</td> <td align="center" valign="top" styleCode="Botrule Rrule">8</td> <td align="center" valign="top" styleCode="Botrule Rrule">2</td> <td align="center" valign="top" styleCode="Botrule Rrule">4</td> </tr> <tr ID="id_a01f9a70-67a9-4702-95ac-75aad123cb20"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule">Hypertension</td> <td align="center" valign="top" styleCode="Botrule Rrule">4</td> <td align="center" valign="top" styleCode="Botrule Rrule">8</td> <td align="center" valign="top" styleCode="Botrule Rrule">1</td> <td align="center" valign="top" styleCode="Botrule Rrule">2</td> </tr> <tr ID="id_95dcaf45-42af-476f-a8f4-34d807e6f909"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule">Gastroenteritis</td> <td align="center" valign="top" styleCode="Botrule Rrule">4</td> <td align="center" valign="top" styleCode="Botrule Rrule">8</td> <td align="center" valign="top" styleCode="Botrule Rrule">4</td> <td align="center" valign="top" styleCode="Botrule Rrule">8</td> </tr> <tr ID="id_22f84db8-4ca1-4af7-b2cd-496614c624e6"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule">Other Non-Classifiable Disorders (excludes accidental injury)</td> <td align="center" valign="top" styleCode="Botrule Rrule">4</td> <td align="center" valign="top" styleCode="Botrule Rrule">8</td> <td align="center" valign="top" styleCode="Botrule Rrule">3</td> <td align="center" valign="top" styleCode="Botrule Rrule">6</td> </tr> <tr ID="id_2c35d165-f55a-49a0-b5f2-04f37137fb4d"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule">Increased sweating</td> <td align="center" valign="top" styleCode="Botrule Rrule">4</td> <td align="center" valign="top" styleCode="Botrule Rrule">8</td> <td align="center" valign="top" styleCode="Botrule Rrule">1</td> <td align="center" valign="top" styleCode="Botrule Rrule">2</td> </tr> <tr ID="id_0311b940-9d0f-43fc-8036-af12fd9ec43f"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule">Glucose tolerance abnormal</td> <td align="center" valign="top" styleCode="Botrule Rrule">3</td> <td align="center" valign="top" styleCode="Botrule Rrule">6</td> <td align="center" valign="top" styleCode="Botrule Rrule">1</td> <td align="center" valign="top" styleCode="Botrule Rrule">2</td> </tr> <tr ID="id_57a9161b-49da-4447-84b5-cccbca22ceda"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule">Laryngitis</td> <td align="center" valign="top" styleCode="Rrule">3</td> <td align="center" valign="top" styleCode="Rrule">6</td> <td align="center" valign="top" styleCode="Rrule">3</td> <td align="center" valign="top" styleCode="Botrule Rrule">6</td> </tr> </tbody> </table>