Turalio

WARNING: HEPATOTOXICITY TURALIO can cause serious and potentially fatal liver injury, including vanishing bile duct syndrome [see Warnings and Precautions (5.1) ] . Monitor liver tests prior to initiation of TURALIO and at specified intervals during treatment. Withhold and dose reduce or permanently discontinue TURALIO based on severity of hepatotoxicity. Monitoring and prompt cessation of TURALIO may not eliminate the risk of serious and potentially fatal liver injury [see Dosage and Administration (2.2) , Warnings and Precautions (5.1) ] . TURALIO is available only through a restricted program called the TURALIO Risk Evaluation and Mitigation Strategy (REMS) Program [see Warnings and Precautions (5.2) ] . WARNING: HEPATOTOXICITY See full prescribing information for complete boxed warning. TURALIO can cause serious and potentially fatal liver injury, including vanishing bile duct syndrome. ( 5.1 ) Monitor liver tests prior to initiation of TURALIO and at specified intervals during treatment. Withhold and dose reduce or permanently discontinue TURALIO based on severity of hepatotoxicity. Monitoring and prompt cessation of TURALIO may not eliminate the risk of serious and potentially fatal liver injury. ( 2.2 , 5.1 ) TURALIO is available only through a restricted program called the TURALIO Risk Evaluation and Mitigation Strategy (REMS) Program. ( 5.2 )

5 WARNINGS AND PRECAUTIONS Embryo-Fetal Toxicity : May cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use an effective non-hormonal method of contraception. ( 5.3 , 7.3 , 8.1 , 8.3 ) Potential Risks Associated with a High-Fat Meal : May increase incidence and severity of adverse reactions, including hepatotoxicity. Avoid taking TURALIO with a high-fat meal (approximately 55 to 65 grams of total fat). ( 2.1 , 5.4 ) 5.1 Hepatotoxicity TURALIO can cause serious and potentially fatal liver injury and is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) [see Warnings and Precautions (5.2) ]. Hepatotoxicity, including liver failure and life-threatening vanishing bile duct syndrome (VBDS), ductopenia, and symptomatic cholestasis (including severe pruritus) can occur in patients treated with TURALIO and can occur despite monitoring and prompt drug cessation. The mechanism of cholestatic hepatotoxicity is unknown and its occurrence cannot be predicted. It is unknown whether liver injury can also occur in the absence of increased transaminases. Of the first 609 patients who received TURALIO under the REMS program, 32 (5.3%) developed a liver injury event of concern (LIEC), defined as any serious liver-related outcome or any liver abnormality that triggers drug discontinuation per the US Prescribing Information [ see Dosage and Administration (2.2) ]. These 32 patients developed liver toxicity within 71 days of the first dose of TURALIO; ten required hospitalization, and two developed VBDS. Sixteen of the 32 patients had not fully recovered at the time of the analysis, including 6 patients followed for at least 6 months after discontinuation. Among 768 patients who received TURALIO in clinical trials, there were two irreversible cases of cholestatic liver injury. One patient with advanced cancer and ongoing liver toxicity died and one patient with a confirmed case of VBDS required a liver transplant. In ENLIVEN, 3 of 61 (5%) patients who received TURALIO developed signs of serious liver injury, defined as ALT or AST ≥3 × ULN with total bilirubin ≥2 × ULN. In these patients, peak ALT ranged from 6 to 9 × ULN, peak total bilirubin ranged from 2.5 to 15 × ULN, and alkaline phosphatase (ALP) was ≥2 × ULN. ALT, AST, and total bilirubin improved to <2 × ULN in these three patients 1 to 7 months after discontinuing TURALIO. Avoid TURALIO in patients with pre-existing increased serum transaminases; total bilirubin or direct bilirubin (>ULN); or active liver or biliary tract disease, including increased ALP. Monitor liver tests, including AST, ALT, total bilirubin, direct bilirubin, ALP, and gamma-glutamyl transferase (GGT) prior to initiation of TURALIO, weekly for the first 8 weeks, every 2 weeks for the next month and every 3 months thereafter. Withhold and dose reduce, or permanently discontinue TURALIO based on the severity of the hepatotoxicity [see Dosage and Administration (2.2) ] . Refer patients to a hepatologist if liver tests do not return to normal. Rechallenge with a reduced dose of TURALIO may result in a recurrence of increased serum transaminases, bilirubin, ALP., or other signs of liver injury. Monitor liver tests weekly for the first month after rechallenge. 5.2 TURALIO REMS Program TURALIO is only available through a restricted program under a REMS, because of the risk of hepatotoxicity [see Warnings and Precautions (5.1) ] . Notable requirements of the TURALIO REMS Program include the following: Prescribers must be certified with the program by enrolling and completing training. Patients must complete and sign an enrollment form for inclusion in a patient registry. Pharmacies must be certified with the program and must only dispense to patients who are authorized to receive TURALIO. Further information is available at www.TURALIOREMS.com or 1-833-887-2546. 5.3 Embryo-Fetal Toxicity Based on animal studies and its mechanism of action, TURALIO may cause fetal harm when administered to a pregnant woman. Oral administration of pexidartinib to pregnant rats and rabbits during the period of organogenesis resulted in malformations, increased post-implantation loss, and abortion at exposures approximately equal to the human exposure at the recommended dose based on area under the curve (AUC). Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective non-hormonal contraception, since TURALIO can render hormonal contraceptives ineffective, during treatment with TURALIO and for 1 month after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with TURALIO and for 1 week after the final dose [see Drug Interactions (7.3) , Use in Specific Populations (8.1 , 8.3) ] . 5.4 Potential Risks Associated with a High-Fat Meal Taking TURALIO with a high-fat meal increases pexidartinib concentrations, which may increase the incidence and severity of adverse reactions, including hepatotoxicity [see Clinical Pharmacology (12.2 , 12.3) ]. Instruct patients to take TURALIO with a low-fat meal (approximately 11 to 14 grams of total fat) and to avoid taking TURALIO with a high-fat meal (approximately 55 to 65 grams of total fat). Consider referring patients to a dietician as deemed necessary [see Dosage and Administration (2.1) , Warnings and Precautions (5.1) , Drug Interactions (7.2) ].

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hepatotoxicity [see Warnings and Precautions (5.1) ]. Most common adverse reactions (>20%) were increased lactate dehydrogenase, increased aspartate aminotransferase, hair color changes, fatigue, increased alanine aminotransferase, decreased neutrophils, increased cholesterol, increased alkaline phosphatase, decreased lymphocytes, eye edema, decreased hemoglobin, rash, dysgeusia, and decreased phosphate. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 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. The safety of TURALIO 250 mg orally twice daily administered with a low-fat meal has been established based on adequate and well-controlled studies of TURALIO 400 mg orally twice daily administered on an empty stomach and additional pharmacokinetic data that indicate there is no clinically significant difference in the relative exposure between the two dosages [see Clinical Pharmacology (12.3) ]. The safety of TURALIO was evaluated in ENLIVEN [see Clinical Studies (14.1) ] . ENLIVEN excluded patients with ALT, AST, or total bilirubin >1.5 × ULN; and known active or chronic infection with hepatitis B or C virus, or human immunodeficiency virus. Patients received TURALIO without food at a dose of 400 mg in the morning and 600 mg in the evening orally for 2 weeks followed by 400 mg orally twice daily until disease progression or unacceptable toxicity . Seventy-nine percent of patients received TURALIO for 6 months or longer and 66% for greater than one year. The median age of TURALIO-treated patients was 44 years (range: 22-75), 57% were females, and 85% were White. Serious adverse reactions were reported in 13% of patients who received TURALIO. Most frequent (occurring in >1 patient) serious adverse reactions included abnormal liver tests (3.3%) and hepatotoxicity (3.3%). Permanent discontinuation due to an adverse reaction occurred in 13% of patients who received TURALIO. Most frequent adverse reactions (occurring in >1 patient) requiring permanent discontinuation included increased ALT (4.9%), increased AST (4.9%) and hepatotoxicity (3.3%). Dose reductions or interruptions occurred in 38% of patients who received TURALIO. Most frequent adverse reactions (occurring in >1 patient) requiring a dosage reduction or interruption were increased ALT (13%), increased AST (13%), nausea (8%), increased ALP (7%), vomiting (4.9%), increased bilirubin (3.3%), increased GGT (3.3%), dizziness (3.3%), and abdominal pain (3.3%). The most common (>20%) adverse reactions, including laboratory abnormalities, in patients who received TURALIO were: increased lactate dehydrogenase (LDH), increased AST, hair color changes, fatigue, increased ALT, decreased neutrophils, increased cholesterol, increased ALP, decreased lymphocytes, eye edema, decreased hemoglobin, rash, dysgeusia, and decreased phosphate. Tables 4, 5, and 6 summarize the adverse reactions and laboratory abnormalities in ENLIVEN during the randomized phase (Week 25). Table 4: Adverse Reactions (≥10% All Grades or >2% Grade ≥ 3) in Patients Receiving TURALIO with a Difference Between Arms of >5% Compared to Placebo Through Week 25 in ENLIVEN TURALIO N=61 Placebo N=59 Adverse Reaction All Grades (%) Grade ≥ 3 (%) All Grades (%) Grade ≥ 3 (%) Skin and subcutaneous tissue Hair color changes 67 0 3.4 0 Rash Rash includes rash, maculo-papular rash, rash pruritic, urticaria, erythema, dermatitis acneiform, dermatitis allergic. 28 1.6 7 0 Pruritus Pruritis includes pruritus, pruritus generalized. 18 0 3.4 0 General Fatigue Fatigue includes fatigue, asthenia, malaise. 64 0 41 0 Peripheral edema Peripheral edema includes face edema, localized edema, edema peripheral, peripheral swelling. 20 0 7 0 Eye Eye edema Eye edema includes periorbital edema, eye edema, eyelid edema, papilledema. 30 1.6 5 0 Nervous system Dysgeusia Dysgeusia includes dysgeusia, ageusia. 26 0 1.7 0 Neuropathy Neuropathy includes neuropathy peripheral, paresthesia, hypoesthesia, burning sensation. 10 0 5 0 Gastrointestinal Vomiting 20 1.6 5 0 Constipation 12 0 5 0 Metabolism and nutrition Decreased appetite 16 0 10 0 Vascular Hypertension 15 4.9 10 0 Table 5: Hepatic Laboratory Abnormalities (≥10% All Grades or >2% Grade ≥ 3) Worsening from Baseline in Patients Receiving TURALIO with a Difference Between Arms of >5% Compared to Placebo Through Week 25 in ENLIVEN TURALIO Each test incidence is based on the number of patients who had both a baseline and at least one on-study measurement TURALIO (n=61) and placebo (n=59). Placebo Laboratory Abnormality Graded per NCI CTCAE v 4.03 Grade 1 (%) Grade 2 (%) Grade ≥ 3 (%) Grade 1 (%) Grade 2 (%) Grade ≥ 3 (%) ALT = alanine aminotransferase; AST = aspartate aminotransferase; ALP = alkaline phosphatase Liver Tests Increased AST 61 15 12 15 0 0 Increased ALT 31 13 20 22 0 0 Increased ALP 31 3.3 4.9 1.7 0 0 Increased bilirubin 3.3 3.3 3.3 0 0 0 Table 6: Other Laboratory Abnormalities Worsening from Baseline (≥10% All Grades or >2% of Grade ≥ 3) in Patients Receiving TURALIO with a Difference Between Arms of >5% Compared to Placebo Through Week 25 in ENLIVEN TURALIO Each test incidence is based on the number of patients who had both a baseline and at least one on-study measurement TURALIO (n = 61) and placebo (n = 58-59). Placebo Laboratory Abnormality Graded per NCI CTCAE v 4.03 except for LDH All Grades (%) Grade ≥3 (%) All Grades (%) Grade ≥3 (%) LDH=Lactate Dehydrogenase Chemistry Increased LDH LDH: Grade 1 >ULN to ≤2.5 × ULN; Grade 2 >2.5 to ≤5 × ULN; Grade 3 >5 to ≤20 × ULN; Grade 4 >20 × ULN 92 0 5 0 Increased cholesterol 44 4.9 25 0 Decreased phosphate 25 3.3 5 0 Hematology Decreased neutrophils 44 3.3 9 0 Decreased lymphocytes 38 1.6 3.4 0 Decreased hemoglobin 30 0 14 1.7 Decreased platelets 15 0 5 0 Clinically relevant adverse reactions occurring in <10% of patients were: Eye: blurred vision, photophobia, diplopia, reduced visual acuity Gastrointestinal: dry mouth, stomatitis, mouth ulceration General: pyrexia Hepatobiliary: cholangitis, hepatotoxicity, liver disorder Neurological: cognitive disorders (memory impairment, amnesia, confusional state, disturbance in attention, attention deficit/hyperactivity disorder) Skin and subcutaneous tissue: alopecia, skin pigment changes (hypopigmentation, depigmentation, discoloration, hyperpigmentation), photosensitivity reactions. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of TURALIO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Investigations: Blood creatine phosphokinase increased

<table width="90%" ID="table4"><caption>Table 4: Adverse Reactions (&#x2265;10% All Grades or &gt;2% Grade &#x2265; 3) in Patients Receiving TURALIO with a Difference Between Arms of &gt;5% Compared to Placebo Through Week 25 in ENLIVEN</caption><col width="28%" align="left" valign="top"/><col width="18%" align="center" valign="top"/><col width="18%" align="center" valign="top"/><col width="18%" align="center" valign="top"/><col width="18%" align="center" valign="top"/><thead><tr styleCode="Botrule"><th styleCode="Lrule Rrule"/><th styleCode="Rrule" colspan="2">TURALIO N=61</th><th styleCode="Rrule" colspan="2">Placebo N=59</th></tr><tr><th styleCode="Lrule Rrule" valign="middle">Adverse Reaction</th><th styleCode="Rrule">All Grades (%)</th><th styleCode="Rrule">Grade &#x2265; 3 (%)</th><th styleCode="Rrule">All Grades (%)</th><th styleCode="Rrule">Grade &#x2265; 3 (%)</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Skin and subcutaneous tissue </content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Hair color changes</td><td styleCode="Rrule">67</td><td styleCode="Rrule">0</td><td styleCode="Rrule">3.4</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Rash<footnote ID="foot41">Rash includes rash, maculo-papular rash, rash pruritic, urticaria, erythema, dermatitis acneiform, dermatitis allergic.</footnote></td><td styleCode="Rrule">28</td><td styleCode="Rrule">1.6</td><td styleCode="Rrule">7</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Pruritus<footnote ID="foot42">Pruritis includes pruritus, pruritus generalized.</footnote></td><td styleCode="Rrule">18</td><td styleCode="Rrule">0</td><td styleCode="Rrule">3.4</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">General </content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Fatigue<footnote ID="foot43">Fatigue includes fatigue, asthenia, malaise.</footnote></td><td styleCode="Rrule">64</td><td styleCode="Rrule">0</td><td styleCode="Rrule">41</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Peripheral edema<footnote ID="foot44">Peripheral edema includes face edema, localized edema, edema peripheral, peripheral swelling.</footnote></td><td styleCode="Rrule">20</td><td styleCode="Rrule">0</td><td styleCode="Rrule">7</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Eye </content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Eye edema<footnote ID="foot45">Eye edema includes periorbital edema, eye edema, eyelid edema, papilledema.</footnote></td><td styleCode="Rrule">30</td><td styleCode="Rrule">1.6</td><td styleCode="Rrule">5</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Nervous system </content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Dysgeusia<footnote ID="foot46">Dysgeusia includes dysgeusia, ageusia.</footnote></td><td styleCode="Rrule">26</td><td styleCode="Rrule">0</td><td styleCode="Rrule">1.7</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Neuropathy<footnote ID="foot47">Neuropathy includes neuropathy peripheral, paresthesia, hypoesthesia, burning sensation.</footnote></td><td styleCode="Rrule">10</td><td styleCode="Rrule">0</td><td styleCode="Rrule">5</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Gastrointestinal </content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Vomiting</td><td styleCode="Rrule">20</td><td styleCode="Rrule">1.6</td><td styleCode="Rrule">5</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Constipation</td><td styleCode="Rrule">12</td><td styleCode="Rrule">0</td><td styleCode="Rrule">5</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Metabolism and nutrition </content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Decreased appetite</td><td styleCode="Rrule">16</td><td styleCode="Rrule">0</td><td styleCode="Rrule">10</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Vascular </content></td></tr><tr><td styleCode="Lrule Rrule">Hypertension</td><td styleCode="Rrule">15</td><td styleCode="Rrule">4.9</td><td styleCode="Rrule">10</td><td styleCode="Rrule">0</td></tr></tbody></table>

<table width="90%" ID="table5"><caption>Table 5: Hepatic Laboratory Abnormalities (&#x2265;10% All Grades or &gt;2% Grade &#x2265; 3) Worsening from Baseline in Patients Receiving TURALIO with a Difference Between Arms of &gt;5% Compared to Placebo Through Week 25 in ENLIVEN</caption><col width="22%" align="left" valign="top"/><col width="13%" align="center" valign="top"/><col width="13%" align="center" valign="top"/><col width="13%" align="center" valign="top"/><col width="13%" align="center" valign="top"/><col width="13%" align="center" valign="top"/><col width="13%" align="center" valign="top"/><thead><tr styleCode="Botrule"><th styleCode="Lrule Rrule"/><th styleCode="Rrule" colspan="3">TURALIO<footnote ID="foot51">Each test incidence is based on the number of patients who had both a baseline and at least one on-study measurement TURALIO (n=61) and placebo (n=59).</footnote></th><th styleCode="Rrule" colspan="3">Placebo<footnoteRef IDREF="foot51"/></th></tr><tr><th styleCode="Lrule Rrule">Laboratory Abnormality<footnote ID="foot52">Graded per NCI CTCAE v 4.03</footnote></th><th styleCode="Rrule">Grade 1 (%)</th><th styleCode="Rrule">Grade 2 (%)</th><th styleCode="Rrule">Grade &#x2265; 3 (%)</th><th styleCode="Rrule">Grade 1 (%)</th><th styleCode="Rrule">Grade 2 (%)</th><th styleCode="Rrule">Grade &#x2265; 3 (%)</th></tr></thead><tfoot><tr><td colspan="7" align="left">ALT = alanine aminotransferase; AST = aspartate aminotransferase; ALP = alkaline phosphatase</td></tr></tfoot><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="7"><content styleCode="bold">Liver Tests</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Increased AST</td><td styleCode="Rrule">61</td><td styleCode="Rrule">15</td><td styleCode="Rrule">12</td><td styleCode="Rrule">15</td><td styleCode="Rrule">0</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Increased ALT</td><td styleCode="Rrule">31</td><td styleCode="Rrule">13</td><td styleCode="Rrule">20</td><td styleCode="Rrule">22</td><td styleCode="Rrule">0</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Increased ALP</td><td styleCode="Rrule">31</td><td styleCode="Rrule">3.3</td><td styleCode="Rrule">4.9</td><td styleCode="Rrule">1.7</td><td styleCode="Rrule">0</td><td styleCode="Rrule">0</td></tr><tr><td styleCode="Lrule Rrule">Increased bilirubin</td><td styleCode="Rrule">3.3</td><td styleCode="Rrule">3.3</td><td styleCode="Rrule">3.3</td><td styleCode="Rrule">0</td><td styleCode="Rrule">0</td><td styleCode="Rrule">0</td></tr></tbody></table>

<table width="90%" ID="table6"><caption>Table 6: Other Laboratory Abnormalities Worsening from Baseline (&#x2265;10% All Grades or &gt;2% of Grade &#x2265; 3) in Patients Receiving TURALIO with a Difference Between Arms of &gt;5% Compared to Placebo Through Week 25 in ENLIVEN</caption><col width="28%" align="left" valign="top"/><col width="18%" align="center" valign="top"/><col width="18%" align="center" valign="top"/><col width="18%" align="center" valign="top"/><col width="18%" align="center" valign="top"/><thead><tr styleCode="Botrule"><th styleCode="Lrule Rrule"/><th styleCode="Rrule" colspan="2">TURALIO<footnote ID="foot61">Each test incidence is based on the number of patients who had both a baseline and at least one on-study measurement TURALIO (n = 61) and placebo (n = 58-59).</footnote></th><th styleCode="Rrule" colspan="2">Placebo<footnoteRef IDREF="foot61"/></th></tr><tr><th styleCode="Lrule Rrule">Laboratory Abnormality<footnote ID="foot62">Graded per NCI CTCAE v 4.03 except for LDH</footnote></th><th styleCode="Rrule">All Grades (%)</th><th styleCode="Rrule">Grade &#x2265;3 (%)</th><th styleCode="Rrule">All Grades (%)</th><th styleCode="Rrule">Grade &#x2265;3 (%)</th></tr></thead><tfoot><tr><td colspan="5" align="left">LDH=Lactate Dehydrogenase</td></tr></tfoot><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Chemistry</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Increased LDH<footnote ID="foot63">LDH: Grade 1 &gt;ULN to &#x2264;2.5 &#xD7; ULN; Grade 2 &gt;2.5 to &#x2264;5 &#xD7; ULN; Grade 3 &gt;5 to &#x2264;20 &#xD7; ULN; Grade 4 &gt;20 &#xD7; ULN</footnote></td><td styleCode="Rrule">92</td><td styleCode="Rrule">0</td><td styleCode="Rrule">5</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Increased cholesterol</td><td styleCode="Rrule">44</td><td styleCode="Rrule">4.9</td><td styleCode="Rrule">25</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Decreased phosphate</td><td styleCode="Rrule">25</td><td styleCode="Rrule">3.3</td><td styleCode="Rrule">5</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="5"><content styleCode="bold">Hematology</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Decreased neutrophils</td><td styleCode="Rrule">44</td><td styleCode="Rrule">3.3</td><td styleCode="Rrule">9</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Decreased lymphocytes</td><td styleCode="Rrule">38</td><td styleCode="Rrule">1.6</td><td styleCode="Rrule">3.4</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Decreased hemoglobin</td><td styleCode="Rrule">30</td><td styleCode="Rrule">0</td><td styleCode="Rrule">14</td><td styleCode="Rrule">1.7</td></tr><tr><td styleCode="Lrule Rrule">Decreased platelets</td><td styleCode="Rrule">15</td><td styleCode="Rrule">0</td><td styleCode="Rrule">5</td><td styleCode="Rrule">0</td></tr></tbody></table>