Piasky

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS PIASKY, a complement inhibitor, increases the risk of serious infections caused by Neisseria meningitidis [see Warnings and Precautions (5.1) ] . Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early. Complete or update vaccination for meningococcal bacteria (for serogroups A, C, W, Y, and B) at least 2 weeks prior to the first dose of PIASKY, unless the risks of delaying therapy with PIASKY outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients receiving a complement inhibitor. See Warnings and Precautions (5.1) for additional guidance on the management of the risk of serious infections caused by meningococcal bacteria. Patients receiving PIASKY are at increased risk for invasive disease caused by N. meningitidis , even if they develop antibodies following vaccination. Monitor patients for early signs of serious meningococcal infections and evaluate immediately if infection is suspected. Because of the risk of serious meningococcal infections, PIASKY is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called PIASKY REMS [see Warnings and Precautions (5.2) ] . WARNING: SERIOUS MENINGOCOCCAL INFECTIONS See full prescribing information for complete boxed warning. PIASKY increases the risk of serious and life-threatening infections caused by Neisseria meningitidis . Complete or update meningococcal vaccination at least 2 weeks prior to the first dose of PIASKY, unless the risks of delaying PIASKY outweigh the risks of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients receiving a complement inhibitor ( 5.1 ). Patients receiving PIASKY are at increased risk for invasive disease caused by N. meningitidis , even if they develop antibodies following vaccination. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected ( 5.1 ). PIASKY is available only through a restricted program called the PIASKY REMS ( 5.2 )

5 WARNINGS AND PRECAUTIONS Type III hypersensitivity reactions: Monitor patients switching from another C5 inhibitor to PIASKY or from PIASKY to another C5 inhibitor as they are at risk of Type III hypersensitivity reactions related to the formation of drug-target-drug complexes ( 5.3 ) Other Infections: PIASKY can increase susceptibility to serious infections especially those caused by encapsulated bacteria. ( 5.4 ) Infusion- and Injection-Related Reactions: Monitor for these reactions and initiate medical management as needed ( 5.5 ) 5.1 Serious Meningococcal Infection PIASKY, a complement inhibitor, increases a patient's susceptibility to serious, life-threatening, or fatal infections caused by meningococcal bacteria (meningococcemia and/or meningitis) in any serogroup, including non-groupable strains. Life-threatening and fatal meningococcal infections have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors. The initiation of PIASKY is contraindicated in patients with a serious unresolved Neisseria meningitidis infection. Complete or update meningococcal vaccination (for serogroups A, C, W, Y, and B) at least 2 weeks prior to administration of the first dose of PIASKY, according to the current Advisory Committee on Immunization Practices (ACIP) recommendations for patients receiving a complement inhibitor. Revaccinate patients in accordance with ACIP recommendations considering the duration of PIASKY therapy. Note that ACIP recommends an administration schedule in patients receiving complement inhibitors that differs from the administration schedule in the vaccine prescribing information. If urgent PIASKY therapy is indicated in a patient who is not up to date with meningococcal vaccines according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer meningococcal vaccines as soon as possible. Various durations and regimens of antibacterial drug prophylaxis have been considered, but the optimal durations and drug regimens for prophylaxis and their efficacy have not been studied in unvaccinated or vaccinated patients receiving complement inhibitors, including PIASKY. The benefits and risks of treatment with PIASKY, as well as the benefits and risks of antibacterial drug prophylaxis in unvaccinated or vaccinated patients, must be considered against the known risks for serious infections caused by N. meningitidis . Vaccination does not eliminate the risk of meningococcal infections, despite development of antibodies following vaccination. Closely monitor patients for early signs and symptoms of meningococcal infection and evaluate patients immediately if infection is suspected. Inform patients of these signs and symptoms and instruct patients to seek immediate medical care if these signs and symptoms occur. Promptly treat known infections. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider interruption of PIASKY in patients who are undergoing treatment for serious meningococcal infection. PIASKY is available only through a restricted program under a REMS [see Warnings and Precautions (5.2) ] . 5.2 PIASKY REMS PIASKY is available only through a restricted program under a REMS called PIASKY REMS, because of the risk of serious meningococcal infections [see Warnings and Precautions (5.1) ] . Notable requirements of the PIASKY REMS include the following: Prescribers must enroll in the REMS. Prescribers must counsel patients about the risk of serious meningococcal infection. Prescribers must provide the patients with the REMS educational materials. Prescribers must assess patient vaccination status for meningococcal vaccines (against serogroups A, C, W, Y, and B) and vaccinate if needed according to current ACIP recommendations two weeks prior to the first dose of PIASKY. Prescribers must provide a prescription for antibacterial drug prophylaxis if treatment must be started urgently, and the patient is not up to date with both meningococcal vaccines according to current ACIP recommendations at least two weeks prior to the first dose of PIASKY. Healthcare settings and pharmacies that dispense PIASKY must be certified in the REMS and must verify prescribers are certified. Patients must receive counseling from the prescriber about the need to receive meningococcal vaccines per ACIP recommendations, the need to take antibiotics as directed by the prescriber, and the signs and symptoms of meningococcal infection. Patients must be instructed to carry the Patient Safety Card with them at all times during and for 11 months following treatment with PIASKY. Further information is available at www.PIASKYREMS.com or 1-866-4My-Skyy (469-7599). 5.3 Type III Hypersensitivity Reactions Related to Drug-Target-Drug Complexes Patients who are switching from another C5 inhibitor (e.g., eculizumab or ravulizumab) to PIASKY or from PIASKY to another C5 inhibitor are at risk of serious Type III hypersensitivity reactions related to the formation of drug-target-drug-complexes (DTDCs), because PIASKY and these other C5 inhibitors bind different epitopes of C5 [see Drug Interactions (7) ] . In clinical trials, Type III hypersensitivity reactions were reported in 39 of 201 patients (19%) who switched from eculizumab or ravulizumab to PIASKY. Four of these patients (10%) had not fully recovered from symptoms of Type III hypersensitivity reactions at the time of their last follow up visit. In addition, Type III hypersensitivity reactions were reported in 2 of 8 patients (25%) who switched from PIASKY to eculizumab or ravulizumab, including one patient who developed Grade 3 axonal neuropathy [see Adverse Reactions (6) ] . Symptoms of Type III hypersensitivity reactions that occurred in more than 2 patients were arthralgia, rash, pyrexia, myalgia, headache, fatigue, petechiae and abdominal pain. Among patients who experienced Type III hypersensitivity reactions, 8 (21%) had events that were considered serious due to hospitalization. Symptoms of serious Type III hypersensitivity reactions included pyrexia and arthralgia. Type III hypersensitivity reactions can also cause renal abnormalities. Healthcare providers should consider the benefits of the timing of switching C5 inhibitors vs. the risks of Type III hypersensitivity reactions. Patients are expected to no longer be at risk of Type III hypersensitivity reactions if the prior C5 inhibitor has been cleared from the body prior to starting PIASKY or if PIASKY has been cleared from the body prior to starting another C5 inhibitor. Therefore, initiating PIASKY sooner than 5.5 half-lives from the last dose of a C5 inhibitor (e.g., eculizumab or ravulizumab) or initiating a C5 inhibitor (e.g., eculizumab or ravulizumab) sooner than 5.5 half-lives from the last dose of PIASKY increases the risk of Type III hypersensitivity reactions. Based on time-to-onset of Type III hypersensitivity reactions observed in clinical trials, patients should be monitored for the first 30 days of the new therapy for the occurrence of symptoms of Type III hypersensitivity reactions. For mild or moderate Type III hypersensitivity reactions, administer symptomatic treatment, such as topical corticosteroids, antihistamines, antipyretics, and/or analgesics. For severe reactions, initiate and taper oral or systemic corticosteroid therapy as clinically indicated. 5.4 Other Infections Due to its mechanism of action, PIASKY may increase susceptibility to infections, especially with encapsulated bacteria, such as infections with Neisseria spp. but also Streptococcus pneumoniae, Haemophilus influenzae , and to a lesser extent, Neisseria gonorrhoeae . Children treated with PIASKY may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Vaccinate patients against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections according to ACIP recommendations. If PIASKY is administered to patients with active systemic infections, monitor closely for signs and symptoms of worsening infection. If the patient's infection worsens, consider whether to discontinue PIASKY. 5.5 Infusion- and Injection-Related Reactions Administration of PIASKY may cause infusion-related reactions or systemic injection-related reactions, depending on the route of administration [see Adverse Reactions (6) ] . These may include hypersensitivity reactions (including anaphylaxis) but also a range of other symptoms such as injection site pain, erythema, headache or myalgia. One patient experienced a serious infusion-related reaction that resolved 4 days after interruption of infusion with PIASKY. Instruct patients/caregivers to seek immediate medical attention if the patient develops symptoms of a serious hypersensitivity reaction and to report this reaction to their healthcare provider. If a serious hypersensitivity reaction (including anaphylaxis) occurs, discontinue PIASKY treatment immediately, institute appropriate treatment, per standard of care, and monitor until signs and symptoms are resolved. PIASKY is contraindicated in patients with a known serious hypersensitivity reaction to crovalimab or any of the excipients. 5.6 Monitoring PNH Manifestations after Discontinuation of PIASKY In case of PIASKY discontinuation, patients who do not switch to another treatment for PNH, must be closely monitored for at least 20 weeks for signs and symptoms of serious hemolysis, identified by elevated lactate dehydrogenase (LDH) levels, along with a sudden decrease in hemoglobin, or re-appearance of symptoms such as fatigue, hemoglobinuria, abdominal pain, dyspnea, major adverse vascular events (including thrombosis), dysphagia, erectile dysfunction or renal impairment. If signs and symptoms of hemolysis occur after discontinuation of PIASKY, consider restarting treatment with PIASKY, if appropriate, or initiating another treatment for PNH.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the label: Serious Meningococcal Infection [see Warnings and Precautions (5.1) ] Type III Hypersensitivity Reactions Related to Drug-Target-Drug Complexes [see Warnings and Precautions (5.3) ] Other Infections [see Warnings and Precautions (5.4) ] Infusion- and Injection-Related Reactions [see Warnings and Precautions (5.5) ] The most common adverse drug reactions (incidence ≥10%) were infusion-related reaction, respiratory tract infection, viral infection, and Type III hypersensitivity reactions. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Patients Who are Complement Inhibitor-Naïve The data described below reflect exposure of 204 patients with PNH who were complement inhibitor-naïve and who were randomized in COMMODORE 2 to receive PIASKY (n = 135) or eculizumab (n = 69) at the recommended dosing regimen for 24 weeks [see Clinical Studies (14) ] . Serious adverse reactions occurred in 6% of patients receiving PIASKY in the COMMODORE 2 study, including epistaxis and pneumonia, which occurred in 2 patients each, and infusion related reaction, pyelonephritis, COVID-19, and hypovolemic shock which were reported in 1 patient each. Table 4 lists adverse reactions that occurred at a rate of 5% or more among patients randomized to PIASKY treatment for 24 weeks in the COMMODORE 2 study. The most common adverse reactions (≥10%) in patients treated with PIASKY were infusion related reaction, respiratory tract infection, and viral infection. Table 4 Adverse Reactions Reported In 5% or More of Complement-Inhibitor Naïve Patients with PNH Randomized to PIASKY in COMMODORE 2 Adverse reactions PIASKY (N = 135) % ECULIZUMAB (N = 69) % Infusion-related reaction 16 13 Respiratory tract infection Grouped terms. Diarrhea includes diarrhea and diarrhea infectious. Headache includes headache and migraine. Injection-related reaction includes injection related reaction and injection site reaction. Respiratory tract infection includes nasopharyngitis, pharyngitis, rhinitis, rhinitis allergic, upper respiratory tract infection and pneumonia. Viral infection includes viral infection, COVID-19, influenza, herpes virus infection and oral herpes. 13 20 Viral infection 11 7 Hyperuricemia 8 9 Headache 8 6 Diarrhea 7 1 Injection-related reaction Injection-related reactions are only expected to occur in the PIASKY arm as eculizumab is not given by subcutaneous injection 6 0 Patients Previously Treated with a Complement C5 Inhibitor The data described below reflect exposure of 86 patients with PNH who received PIASKY (n=44) or eculizumab (n=42) at the recommended dosing regimen for 24 weeks in COMMODORE 1, an open-label, active-controlled, multicenter study conducted in patients switching from eculizumab. The median age was 47 years (range: 21 to 85); 52% were female, and race included White (73%), Asian (19%), unknown (5%), and Black/African-American (3%). The population ethnicities were 17% Hispanic or Latino and 76% not Hispanic or Latino. Serious adverse reactions in COMMODORE 1 were reported in 3 patients (7%) with PNH receiving PIASKY. Serious adverse reactions included pneumonia, nasopharyngitis, and urinary tract infection, which occurred in 1 patient each. Table 5 lists adverse reactions that occurred at a rate of 5% or more among patients randomized to PIASKY treatment for 24 weeks in the COMMODORE 1 study. The most common adverse reactions (≥10%) in patients treated with PIASKY were viral infections, respiratory tract infection, Type III hypersensitivity reaction, infusion-related reaction, peripheral edema, and headache. Table 5 Adverse Reactions Reported In 5% or More of Complement-Inhibitor Treated Patients with PNH Randomized to PIASKY in COMMODORE 1 Adverse reactions PIASKY (N = 44) % ECULIZUMAB (N = 42) % Viral infection Grouped terms Fatigue includes fatigue, malaise and asthenia. Injection-related reaction includes injection related reaction and injection site reaction. Rash includes rash and skin exfoliation. Peripheral edema includes edema peripheral and peripheral swelling. Respiratory tract infection includes respiratory tract infection, nasopharyngitis, pneumonia and upper respiratory tract infection. Viral infection includes viral infection, influenza, COVID-19, and respiratory syncytial virus infection 23 21 Respiratory tract infection 18 5 Type III hypersensitivity reaction Type III immune complex mediated reaction is only expected to occur in the PIASKY arm as patients in the eculizumab arm did not change C5 inhibitor treatment 16 0 Infusion-related reaction Infusion-related reactions are not expected to occur in the eculizumab arm as these patients tolerated eculizumab prior to study initiation 14 0 Peripheral edema 11 2 Headache 11 2 Injection-related reaction Injection-related reactions are only expected to occur in the PIASKY arm as eculizumab is not given by subcutaneous injection 9 0 Fatigue 9 12 Rash 9 0 Diarrhea 7 2 Nausea 7 5 Arthralgia 7 0 Type III Hypersensitivity Reactions Related to Drug-Target-Drug Complexes [see Warnings and Precautions (5.3) , and Drug Interactions (7) ] . Across the COMMODORE 1 and 2 studies, 39 out of 201 (19.4%) patients who switched from eculizumab or ravulizumab to PIASKY experienced a Type III hypersensitivity reaction (reported as Type III immune complex mediated reaction). A total of 6 patients had switched two times and of the 6 patients, 2 patients experienced a second episode of Type III hypersensitivity reaction after discontinuing PIASKY and switching to ravulizumab. One of these patients developed Grade 3 axonal neuropathy and a Type III hypersensitivity reaction could not be excluded and the other developed Grade 2 arthralgia and myalgia. These two events remained unresolved at the last follow up visit of the clinical studies (the duration of the events until last follow-up was 313 days for the event of Grade 3 axonal neuropathy and 142 days for the event of Grade 2 arthralgia and myalgia, respectively). Two additional patients who experienced Grade 3 rash and Grade 3 arthralgia, respectively, had unresolved Type III hypersensitivity reaction at the last follow-up visit. The median time to onset of Type III hypersensitivity reaction in patients who switched treatment from eculizumab or ravulizumab to PIASKY was 1.6 weeks (range: 0.7 – 4.4 weeks) and the median duration of Type III hypersensitivity reactions was 1.9 weeks (range 0.4 – 34.1 weeks). The majority of events were Grade 1-2. Grade 3 Type III hypersensitivity reaction occurred in 8% of patients who switched from eculizumab or ravulizumab to PIASKY. Out of 42 Type III hypersensitivity reactions, 37 (88%) resolved, including 1 (2.4%) that resolved with PIASKY discontinuation, 2 (4.8%) that resolved with PIASKY interruption and 34 (81%) that resolved without discontinuation, interruption, or dose change in PIASKY therapy. Axonal Neuropathy In COMMODORE 1 and 2, Grade 3 distal axonal demyelinating polyneuropathy and Grade 3 axonal neuropathy were reported, each in 1 patient who switched from another C5 inhibitor to PIASKY or from PIASKY to another C5 inhibitor. The Grade 3 distal axonal demyelinating polyneuropathy occurred 11 weeks after a patient switched from eculizumab to PIASKY (with first dose of PIASKY received 12 days after the last dose of eculizumab treatment) and was preceded by a bacterial respiratory tract infection. The Grade 3 axonal neuropathy occurred in a patient who had switched to ravulizumab treatment after 6 weeks of treatment with PIASKY, and previously received ravulizumab treatment prior to switching to treatment with PIASKY [see Warnings and Precautions (5.3) ] . Events associated with the axonal neuropathy included COVID-19, sepsis and administration of a fluoroquinolone. In both cases of axonal neuropathy, a Type III hypersensitivity reaction as a cause of, or contributor to, the axonal neuropathy could not be excluded. Both cases of axonal neuropathy remained unresolved at the last follow up visit of the clinical studies. Pediatric Population with PNH Treated with PIASKY Twelve pediatric patients with PNH (9 treatment-naïve patients and 3 patients who switched from another C5 inhibitor) were treated with PIASKY in COMMODORE 1 (n=2), COMMODORE 2 (n=7), and in a single-arm trial [(COMMODORE 3 (n=3)]. The safety profile of PIASKY appeared comparable between adult and pediatric patients, but conclusions are limited by the small number of pediatric patients.

<table width="90%" ID="Tb4"><caption>Table 4 Adverse Reactions Reported In 5% or More of Complement-Inhibitor Na&#xEF;ve Patients with PNH Randomized to PIASKY in COMMODORE 2</caption><col width="45%" align="left" valign="top"/><col width="30%" align="center" valign="top"/><col width="25%" align="center" valign="top"/><thead><tr><th styleCode="Lrule Rrule">Adverse reactions</th><th styleCode="Rrule"> PIASKY (N = 135) % </th><th styleCode="Rrule"> ECULIZUMAB (N = 69) % </th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Infusion-related reaction</td><td styleCode="Rrule">16</td><td styleCode="Rrule">13</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Respiratory tract infection<footnote ID="Tb4ft1">Grouped terms. Diarrhea includes diarrhea and diarrhea infectious. Headache includes headache and migraine. Injection-related reaction includes injection related reaction and injection site reaction. Respiratory tract infection includes nasopharyngitis, pharyngitis, rhinitis, rhinitis allergic, upper respiratory tract infection and pneumonia. Viral infection includes viral infection, COVID-19, influenza, herpes virus infection and oral herpes.</footnote></td><td styleCode="Rrule">13</td><td styleCode="Rrule">20</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Viral infection<footnoteRef IDREF="Tb4ft1"/></td><td styleCode="Rrule">11</td><td styleCode="Rrule">7</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Hyperuricemia</td><td styleCode="Rrule">8</td><td styleCode="Rrule">9</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Headache<footnoteRef IDREF="Tb4ft1"/></td><td styleCode="Rrule">8</td><td styleCode="Rrule">6</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Diarrhea<footnoteRef IDREF="Tb4ft1"/></td><td styleCode="Rrule">7</td><td styleCode="Rrule">1</td></tr><tr><td styleCode="Lrule Rrule">Injection-related reaction<footnote>Injection-related reactions are only expected to occur in the PIASKY arm as eculizumab is not given by subcutaneous injection</footnote></td><td styleCode="Rrule"> 6</td><td styleCode="Rrule">0</td></tr></tbody></table>

<table width="90%" ID="Tb5"><caption>Table 5 Adverse Reactions Reported In 5% or More of Complement-Inhibitor Treated Patients with PNH Randomized to PIASKY in COMMODORE 1</caption><col width="45%" align="left" valign="top"/><col width="30%" align="center" valign="top"/><col width="25%" align="center" valign="top"/><thead><tr><th styleCode="Lrule Rrule">Adverse reactions</th><th styleCode="Lrule Rrule"> PIASKY (N = 44) % </th><th styleCode="Lrule Rrule"> ECULIZUMAB (N = 42) % </th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Viral infection<footnote ID="Tb5ft1">Grouped terms Fatigue includes fatigue, malaise and asthenia. Injection-related reaction includes injection related reaction and injection site reaction. Rash includes rash and skin exfoliation. Peripheral edema includes edema peripheral and peripheral swelling. Respiratory tract infection includes respiratory tract infection, nasopharyngitis, pneumonia and upper respiratory tract infection. Viral infection includes viral infection, influenza, COVID-19, and respiratory syncytial virus infection</footnote></td><td styleCode="Lrule Rrule">23</td><td styleCode="Lrule Rrule">21</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Respiratory tract infection<footnoteRef IDREF="Tb5ft1"/></td><td styleCode="Lrule Rrule">18</td><td styleCode="Lrule Rrule">5</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Type III hypersensitivity reaction<footnote>Type III immune complex mediated reaction is only expected to occur in the PIASKY arm as patients in the eculizumab arm did not change C5 inhibitor treatment</footnote></td><td styleCode="Lrule Rrule">16</td><td styleCode="Lrule Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Infusion-related reaction<footnote>Infusion-related reactions are not expected to occur in the eculizumab arm as these patients tolerated eculizumab prior to study initiation</footnote></td><td styleCode="Lrule Rrule">14</td><td styleCode="Lrule Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Peripheral edema<footnoteRef IDREF="Tb5ft1"/></td><td styleCode="Lrule Rrule">11</td><td styleCode="Lrule Rrule">2</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Headache</td><td styleCode="Lrule Rrule">11</td><td styleCode="Lrule Rrule">2</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Injection-related reaction<footnote>Injection-related reactions are only expected to occur in the PIASKY arm as eculizumab is not given by subcutaneous injection</footnote></td><td styleCode="Lrule Rrule">9</td><td styleCode="Lrule Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Fatigue<footnoteRef IDREF="Tb5ft1"/></td><td styleCode="Lrule Rrule">9</td><td styleCode="Lrule Rrule">12</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Rash<footnoteRef IDREF="Tb5ft1"/></td><td styleCode="Lrule Rrule">9</td><td styleCode="Lrule Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Diarrhea</td><td styleCode="Lrule Rrule">7</td><td styleCode="Lrule Rrule">2</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Nausea</td><td styleCode="Lrule Rrule">7</td><td styleCode="Lrule Rrule">5</td></tr><tr><td styleCode="Lrule Rrule">Arthralgia</td><td styleCode="Lrule Rrule">7</td><td styleCode="Lrule Rrule">0</td></tr></tbody></table>