Mycophenolic Acid

WARNING: EMBRYO-FETAL TOXICITY, MALIGNANCIES, AND SERIOUS INFECTIONS Use during pregnancy is associated with increased risks of pregnancy loss and congenital malformations. Avoid if safer treatment options are available. Females of reproductive potential must be counseled regarding pregnancy prevention and planning [see Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.1 , 8.3 )] . Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe mycophenolic acid delayed-release tablets. Patients receiving mycophenolic acid delayed-release tablets should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient [see Warnings and Precautions ( 5.2 )] . Increased risk of development of lymphoma and other malignancies, particularly of the skin, due to immunosuppression [see Warnings and Precautions ( 5.3 )] . Increased susceptibility to bacterial, viral, fungal, and protozoal infections, including opportunistic infections [see Warnings and Precautions ( 5.4 , 5.5 )] . WARNING: EMBRYO-FETAL TOXICITY, MALIGNANCIES, and SERIOUS INFECTIONS See full prescribing information for complete boxed warning Use during pregnancy is associated with increased risks of pregnancy loss and congenital malformations. Avoid if safer treatment options are available. Females of reproductive potential must be counseled regarding pregnancy prevention and planning. ( 5.1 , 8.1 , 8.3 ) Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe mycophenolic acid delayed-release tablets. ( 5.2 ) Increased risk of development of lymphoma and other malignancies, particularly of the skin, due to immunosuppression. ( 5.3 ) Increased susceptibility to bacterial, viral, fungal, and protozoal infections, including opportunistic infections. ( 5.4 , 5.5 )

5 WARNINGS AND PRECAUTIONS New or Reactivated Viral Infections: Consider reducing immunosuppression. ( 5.5 ) Blood Dyscrasias, including Pure Red Cell Aplasia (PRCA): Monitor for neutropenia or anemia; consider treatment interruption or dose reduction. ( 5.6 ) Serious GI Tract Complications (gastrointestinal bleeding, perforations and ulcers): Administer with caution to patients with active digestive system disease. ( 5.7 ) Hypersensitivity Reactions: Discontinue mycophenolic acid delayed-release tablets; treat and monitor until signs and symptoms resolve. ( 5.9 ) Immunizations: Avoid live attenuated vaccines. ( 5.10 ) Patients with Hereditary Deficiency of Hypoxanthine-guanine Phosphoribosyl-transferase (HGPRT): May cause exacerbation of disease symptoms; avoid use. ( 5.11 ) Blood Donation: Avoid during therapy and for 6 weeks thereafter. ( 5.12 ) Semen Donation: Avoid during therapy and for 90 days thereafter. ( 5.13 ) 5.1 Embryo-Fetal Toxicity Use of mycophenolic acid delayed-release tablets during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations, especially external ear and other facial abnormalities, including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney, and nervous system. Females of reproductive potential must be aware of these risks and must be counseled regarding pregnancy prevention and planning. Avoid use of mycophenolic acid delayed-release tablets during pregnancy if safer treatment options are available [see Use in Specific Populations ( 8.1 , 8.3 )] . 5.2 Management of Immunosuppression Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe mycophenolic acid delayed-release tablets. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physicians responsible for maintenance therapy should have complete information requisite for the follow-up of the patient [see Boxed Warning] . 5.3 Lymphoma and Other Malignancies Patients receiving immunosuppressants, including mycophenolic acid delayed-release tablets, are at increased risk of developing lymphomas and other malignancies, particularly of the skin [see Adverse Reactions ( 6 )] . The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent. As usual for patients with increased risk for skin cancer, exposure to sunlight and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen with a high protection factor. Post-transplant lymphoproliferative disorder (PTLD) has been reported in immunosuppressed organ transplant recipients. The majority of PTLD events appear related to Epstein-Barr Virus (EBV) infection. The risk of PTLD appears greatest in those individuals who are EBV seronegative, a population which includes many young children. 5.4 Serious Infections Patients receiving immunosuppressants, including mycophenolic acid delayed-release tablets, are at increased risk of developing bacterial, viral, fungal, and protozoal infections, and new or reactivated viral infections, including opportunistic infections [see Warnings and Precautions ( 5.5 )] . These infections may lead to serious, including fatal outcomes. Because of the danger of oversuppression of the immune system which can increase susceptibility to infection, combination immunosuppressant therapy should be used with caution. 5.5 New or Reactivated Viral Infections Polyomavirus associated nephropathy (PVAN), JC virus-associated progressive multifocal leukoencephalopathy (PML), cytomegalovirus (CMV) infections, reactivation of hepatitis B (HBV) or hepatitis C (HCV), SARS-CoV-2 infection, have been reported in patients treated with immunosuppressants, including MPA derivatives mycophenolic acid delayed-release tablets and MMF. Reduction in immunosuppression should be considered for patients who develop evidence of new or reactivated viral infections. Physicians should also consider the risk that reduced immunosuppression represents to the functioning allograft. PVAN, especially due to BK virus infection, is associated with serious outcomes, including deteriorating renal function and renal graft loss. Patient monitoring may help detect patients at risk for PVAN. PML, which is sometimes fatal, commonly presents with hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia. Risk factors for PML include treatment with immunosuppressant therapies and impairment of immune function. In immunosuppressed patients, physicians should consider PML in the differential diagnosis in patients reporting neurological symptoms and consultation with a neurologist should be considered as clinically indicated. The risk of CMV viremia and CMV disease is highest among transplant recipients seronegative for CMV at time of transplant who receive a graft from a CMV seropositive donor. Therapeutic approaches to limiting CMV disease exist and should be routinely provided. Patient monitoring may help detect patients at risk for CMV disease [see Adverse Reactions ( 6.1 )] . Viral reactivation has been reported in patients infected with HBV or HCV. Monitoring infected patients for clinical and laboratory signs of active HBV or HCV infection is recommended. 5.6 Blood Dyscrasias, Including Pure Red Cell Aplasia Cases of pure red cell aplasia (PRCA) have been reported in patients treated with MPA derivatives in combination with other immunosuppressive agents. The mechanism for MPA derivatives induced PRCA is unknown; the relative contribution of other immunosuppressants and their combinations in an immunosuppressive regimen is also unknown. In some cases, PRCA was found to be reversible with dose reduction or cessation of therapy with MPA derivatives. In transplant patients, however, reduced immunosuppression may place the graft at risk. Changes to mycophenolic acid delayed-release tablets therapy should only be undertaken under appropriate supervision in transplant recipients in order to minimize the risk of graft rejection. Patients receiving mycophenolic acid delayed-release tablets should be monitored for blood dyscrasias (e.g., neutropenia or anemia). The development of neutropenia may be related to mycophenolic acid delayed-release tablets itself, concomitant medications, viral infections, or some combination of these reactions. Complete blood count should be performed weekly during the first month, twice monthly for the second and the third month of treatment, then monthly through the first year. If blood dyscrasias occur [neutropenia develops (ANC<1.3×10 3 /mcL) or anemia], dosing with mycophenolic acid delayed-release tablets should be interrupted or the dose reduced, appropriate tests performed, and the patient managed accordingly. 5.7 Serious GI Tract Complications Gastrointestinal bleeding (requiring hospitalization), intestinal perforations, gastric ulcers, and duodenal ulcers have been reported in patients treated with mycophenolic acid delayed-release tablets. Mycophenolic acid delayed-release tablets should be administered with caution in patients with active serious digestive system disease. 5.8 Acute Inflammatory Syndrome Associated with Mycophenolate Products Acute inflammatory syndrome (AIS) has been reported with the use of mycophenolate products, and some cases have resulted in hospitalization. AIS is a paradoxical pro-inflammatory reaction characterized by fever, arthralgias, arthritis, muscle pain and elevated inflammatory markers including, C-reactive protein and erythrocyte sedimentation rate, without evidence of infection or underlying disease recurrence. Symptoms occur within weeks to months of initiation of treatment or a dose increase. After discontinuation, improvement of symptoms and inflammatory markers are usually observed within 24 to 48 hours. Monitor patients for symptoms and laboratory parameters of AIS when starting treatment with mycophenolate products or when increasing the dosage. Discontinue treatment and consider other treatment alternatives based on the risk and benefit for the patient. 5.9 Hypersensitivity Reactions Postmarketing cases of hypersensitivity reactions, including angioedema and anaphylaxis, have been reported with mycophenolic acid delayed-release tablets. These reactions generally occurred within hours to the next day after initiating mycophenolic acid delayed-release tablets. If signs or symptoms of a hypersensitivity reaction occur, discontinue mycophenolic acid delayed-release tablets; treat and monitor until signs and symptoms resolve [see Contraindications ( 4 )] . 5.10 Immunizations During treatment with mycophenolic acid delayed-release tablets, the use of live attenuated vaccines should be avoided and patients should be advised that vaccinations may be less effective. Advise patients to discuss with the physician before seeking any immunizations. 5.11 Rare Hereditary Deficiencies Mycophenolic acid delayed-release tablets are an inosine monophosphate dehydrogenase inhibitor (IMPDH inhibitor). Mycophenolic acid delayed-release tablets should be avoided in patients with rare hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT), such as Lesch-Nyhan and Kelley-Seegmiller syndromes because it may cause an exacerbation of disease symptoms characterized by the overproduction and accumulation of uric acid leading to symptoms associated with gout, such as acute arthritis, tophi, nephrolithiasis or urolithiasis, and renal disease, including renal failure. 5.12 Blood Donation Patients should not donate blood during therapy and for at least 6 weeks following discontinuation of mycophenolic acid delayed-release tablets because their blood or blood products might be administered to a female of reproductive potential or a pregnant woman. 5.13 Semen Donation Based on animal data, men should not donate semen during therapy and for 90 days following discontinuation of mycophenolic acid delayed-release tablets [see Use in Specific Populations ( 8.3 )] .

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label. Embryo-Fetal Toxicity [see Boxed Warning, Warnings and Precautions ( 5.1 )] Lymphomas and Other Malignancies [see Boxed Warning, Warnings and Precautions ( 5.3 )] Serious Infections [see Boxed Warning, Warnings and Precautions ( 5.4 )] New or Reactivated Viral Infections [see Warnings and Precautions ( 5.5 )] Blood Dyscrasias, Including Pure Red Cell Aplasia [see Warnings and Precautions ( 5.6 )] Serious GI Tract Complications [see Warnings and Precautions ( 5.7 )] Acute Inflammatory Syndrome Associated with Mycophenolate Products [see Warnings and Precautions ( 5.8 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.9 )] Rare Hereditary Deficiencies [see Warnings and Precautions ( 5.11 )] Most common adverse reactions (≥20%): anemia, leukopenia, constipation, nausea, diarrhea, vomiting, dyspepsia, urinary tract infection, CMV infection, insomnia, and postoperative pain. ( 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Slate Run Pharmaceuticals, LLC at 1-888-341-9214 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies 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 data described below derive from two randomized, comparative, active-controlled, double-blind, double-dummy trials in prevention of acute rejection in de novo and converted stable kidney transplant patients. In the de novo trial, patients were administered either mycophenolic acid delayed-release tablets 1.44 grams per day (N=213) or MMF 2 grams per day (N=210) within 48 hours post-transplant for 12 months in combination with cyclosporine, USP MODIFIED and corticosteroids. Forty-one percent of patients also received antibody therapy as induction treatment. In the conversion trial, renal transplant patients who were at least 6 months post-transplant and receiving 2 grams per day MMF in combination with cyclosporine USP MODIFIED, with or without corticosteroids for at least two weeks prior to entry in the trial were randomized to mycophenolic acid delayed-release tablets 1.44 grams per day (N=159) or MMF 2 grams per day (N=163) for 12 months. The average age of patients in both studies was 47 years and 48 years ( de novo study and conversion study, respectively), ranging from 22 to 75 years. Approximately 66% of patients were male; 82% were white, 12% were black, and 6% other races. About 40% of patients were from the United States and 60% from other countries. In the de novo trial, the overall incidence of discontinuation due to adverse reactions was 18% (39/213) and 17% (35/210) in the mycophenolic acid delayed-release tablets and MMF arms, respectively. The most common adverse reactions leading to discontinuation in the mycophenolic acid delayed-release tablets arm were graft loss (2%), diarrhea (2%), vomiting (1%), renal impairment (1%), CMV infection (1%), and leukopenia (1%). The overall incidence of patients reporting dose reduction at least once during the 0- to 12-month study period was 59% and 60% in the mycophenolic acid delayed-release tablets and MMF arms, respectively. The most frequent reasons for dose reduction in the mycophenolic acid delayed-release tablets arm were adverse reactions (44%), dose reductions according to protocol guidelines (17%), dosing errors (11%) and missing data (2%). The most common adverse reactions (≥20%) associated with the administration of mycophenolic acid delayed-release tablets were anemia, leukopenia, constipation, nausea, diarrhea, vomiting, dyspepsia, urinary tract infection, CMV infection, insomnia, and postoperative pain. The adverse reactions reported in ≥10% of patients in the de novo trial are presented in Table 2 below. Table 2: Adverse Reactions (%) Reported in ≥10% of De novo Kidney Transplant Patients in Either Treatment Group **The trial was not designed to support comparative claims for mycophenolic acid delayed-release tablets for the adverse reactions reported in this table. De novo Renal Trial** System organ class adverse drug reactions Mycophenolic Acid Delayed-Release Tablets 1.44 grams per day (n=213) (%) Mycophenolate mofetil (MMF) 2 grams per day (n=210) (%) Blood and lymphatic system disorders Anemia 22 22 Leukopenia 19 21 Gastrointestinal system disorders Constipation 38 40 Nausea 29 27 Diarrhea 24 25 Vomiting 23 20 Dyspepsia 23 19 Abdominal pain upper 14 14 Flatulence 10 13 General and administrative site disorders Edema 17 18 Edema lower limb 16 17 Pyrexia 13 19 Investigations Increased blood creatinine 15 10 Infections and infestations Urinary tract infection 29 33 CMV infection 20 18 Metabolism and nutrition disorders Hypocalcemia 11 15 Hyperuricemia 13 13 Hyperlipidemia 12 10 Hypokalemia 13 9 Hypophosphatemia 11 9 Musculoskeletal, connective tissue and bone disorders Back pain 12 6 Arthralgia 7 11 Nervous system disorder Insomnia 24 24 Tremor 12 14 Headache 13 11 Vascular disorders Hypertension 18 18 Table 3 summarizes the incidence of opportunistic infections in de novo transplant patients. Table 3: Viral and Fungal Infections (%) Reported Over 0 to 12 Months De novo Renal Trial Mycophenolic Acid Delayed-Release Tablets 1.44 grams per day (n=213) (%) Mycophenolate mofetil (MMF) 2 grams per day (n=210) (%) Any cytomegalovirus 22 21 - Cytomegalovirus disease 5 4 Herpes simplex 8 6 Herpes zoster 5 4 Any fungal infection 11 12 - Candida NOS 6 6 - Candida albicans 2 4 Lymphoma developed in 2 de novo patients (1%), (1 diagnosed 9 days after treatment initiation) and in 2 conversion patients (1%) receiving mycophenolic acid delayed-release tablets with other immunosuppressive agents in the 12-month controlled clinical trials. Nonmelanoma skin carcinoma occurred in 1% de novo and 12% conversion patients. Other types of malignancy occurred in 1% de novo and 1% conversion patients [see Warnings and Precautions ( 5.3 )] . The adverse reactions reported in less than 10% of de novo or conversion patients treated with mycophenolic acid delayed-release tablets in combination with cyclosporine and corticosteroids are listed in Table 4. Table 4: Adverse Reactions Reported in <10% of Patients Treated with Mycophenolic Acid Delayed-Release Tablets in Combination With Cyclosporine* and Corticosteroids *USP MODIFIED. Blood and lymphatic disorders Lymphocele, thrombocytopenia Cardiac disorder Tachycardia Eye disorder Vision blurred Gastrointestinal disorders Abdominal pain, abdominal distension, gastroesophageal reflux disease, gingival hyperplasia General Disorders and administration-site conditions Fatigue, peripheral edema Infections and infestations Nasopharyngitis, herpes simplex, upper respiratory infection, oral candidiasis, herpes zoster, sinusitis, influenza, wound infection, implant infection, pneumonia, sepsis Investigations Hemoglobin decrease, liver function tests abnormal Metabolism and nutrition disorders Hypercholesterolemia, hyperkalemia, hypomagnesemia, diabetes mellitus, hyperglycemia Musculoskeletal and connective tissue disorders Arthralgia, pain in limb, peripheral swelling, muscle cramps, myalgia Nervous system disorders Dizziness (excluding vertigo) Psychiatric disorders Anxiety Renal and urinary disorders Renal tubular necrosis, renal impairment, hematuria, urinary retention Respiratory, thoracic and mediastinal disorders Cough, dyspnea, dyspnea exertional Skin and subcutaneous tissue disorders Acne, pruritus, rash Vascular disorders Hypertension aggravated, hypotension The following additional adverse reactions have been associated with the exposure to MPA when administered as a sodium salt or as mofetil ester: Gastrointestinal : Intestinal perforation, gastrointestinal hemorrhage, gastric ulcers, duodenal ulcers [see Warnings and Precautions ( 5.7 )] , colitis (including CMV colitis), pancreatitis, esophagitis, and ileus. Infections : Serious life-threatening infections, such as meningitis and infectious endocarditis, tuberculosis, and atypical mycobacterial infection [see Warnings and Precautions ( 5.4 )] . Respiratory : Interstitial lung disorders, including fatal pulmonary fibrosis. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of mycophenolic acid delayed-release tablets or other MPA derivatives. 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: Congenital malformations, including ear, facial, cardiac and nervous system malformations and an increased incidence of first trimester pregnancy loss have been reported following exposure to MMF during pregnancy [see Boxed Warning, Warnings and Precautions ( 5.1 )] . Infections [see Warnings and Precautions ( 5.4 , 5.5 )] Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal. Polyomavirus associated nephropathy (PVAN), especially due to BK virus infection, associated with serious outcomes, including deteriorating renal function and renal graft loss. Viral reactivation in patients infected with HBV or HCV. Cases of pure red cell aplasia (PRCA) have been reported in patients treated with MPA derivatives in combination with other immunosuppressive agents [see Warnings and Precautions ( 5.6 )]. Hypersensitivity reactions, including anaphylaxis and angioedema [see Warnings and Precautions ( 5.9 )]. The following additional adverse reactions have been identified during post-approval use of mycophenolic acid delayed-release tablets: agranulocytosis, asthenia, osteomyelitis, lymphadenopathy, lymphopenia, wheezing, dry mouth, gastritis, peritonitis, anorexia, alopecia, pulmonary edema, Kaposi’s sarcoma, de novo purine synthesis inhibitors-associated acute inflammatory syndrome.

<table><caption>Table 2: Adverse Reactions (%) Reported in &#x2265;10% of De novo Kidney Transplant Patients in Either Treatment Group</caption><col width="350"/><col width="150"/><col width="250"/><tfoot><tr styleCode="First Last"><td colspan="3"> **The trial was not designed to support comparative claims for mycophenolic acid delayed-release tablets for the adverse reactions reported in this table.</td></tr></tfoot><tbody><tr><td styleCode="Toprule"/><td colspan="2" align="center" styleCode="Toprule" valign="bottom"><content styleCode="bold"><content styleCode="italics">De novo </content></content><content styleCode="bold">Renal Trial**</content></td></tr><tr><td align="left" styleCode="Botrule Toprule" valign="top"><paragraph/><paragraph><content styleCode="bold">System organ class</content></paragraph><paragraph><content styleCode="bold"> adverse drug reactions</content></paragraph></td><td align="center" styleCode="Toprule"><content styleCode="bold">Mycophenolic Acid Delayed-Release Tablets 1.44 grams per day (n=213) (%) </content></td><td align="center" styleCode="Toprule"><paragraph/><paragraph><content styleCode="bold">Mycophenolate mofetil (MMF)</content></paragraph><paragraph/><paragraph><content styleCode="bold">2 grams per day (n=210) (%) </content></paragraph></td></tr><tr><td colspan="3" align="left" styleCode="Toprule"><content styleCode="bold"> Blood and lymphatic system disorders</content></td></tr><tr><td> Anemia</td><td align="center">22</td><td align="center">22</td></tr><tr><td> Leukopenia</td><td align="center">19</td><td align="center">21</td></tr><tr><td colspan="3" align="left"><content styleCode="bold"> Gastrointestinal system disorders</content></td></tr><tr><td> Constipation</td><td align="center">38</td><td align="center">40</td></tr><tr><td> Nausea</td><td align="center">29</td><td align="center">27</td></tr><tr><td> Diarrhea</td><td align="center">24</td><td align="center">25</td></tr><tr><td> Vomiting</td><td align="center">23</td><td align="center">20</td></tr><tr><td> Dyspepsia</td><td align="center">23</td><td align="center">19</td></tr><tr><td> Abdominal pain upper</td><td align="center">14</td><td align="center">14</td></tr><tr><td> Flatulence</td><td align="center">10</td><td align="center">13</td></tr><tr><td colspan="3" align="left"><content styleCode="bold"> General and administrative site disorders</content></td></tr><tr><td> Edema</td><td align="center">17</td><td align="center">18</td></tr><tr><td> Edema lower limb</td><td align="center">16</td><td align="center">17</td></tr><tr><td> Pyrexia</td><td align="center">13</td><td align="center">19</td></tr><tr><td colspan="3" align="left"><content styleCode="bold"> Investigations</content></td></tr><tr><td> Increased blood creatinine</td><td align="center">15</td><td align="center">10</td></tr><tr><td colspan="3" align="left"><content styleCode="bold"> Infections and infestations</content></td></tr><tr><td> Urinary tract infection</td><td align="center">29</td><td align="center">33</td></tr><tr><td> CMV infection</td><td align="center">20</td><td align="center">18</td></tr><tr><td colspan="3" align="left"><content styleCode="bold"> Metabolism and nutrition disorders</content></td></tr><tr><td> Hypocalcemia</td><td align="center">11</td><td align="center">15</td></tr><tr><td> Hyperuricemia</td><td align="center">13</td><td align="center">13</td></tr><tr><td> Hyperlipidemia</td><td align="center">12</td><td align="center">10</td></tr><tr><td> Hypokalemia</td><td align="center">13</td><td align="center">9</td></tr><tr><td> Hypophosphatemia</td><td align="center">11</td><td align="center">9</td></tr><tr><td colspan="3" align="left"><content styleCode="bold"> Musculoskeletal, connective tissue and bone disorders</content></td></tr><tr><td> Back pain</td><td align="center">12</td><td align="center">6</td></tr><tr><td> Arthralgia</td><td align="center">7</td><td align="center">11</td></tr><tr><td colspan="3" align="left"><content styleCode="bold"> Nervous system disorder</content></td></tr><tr><td> Insomnia</td><td align="center">24</td><td align="center">24</td></tr><tr><td> Tremor</td><td align="center">12</td><td align="center">14</td></tr><tr><td> Headache</td><td align="center">13</td><td align="center">11</td></tr><tr><td colspan="3" align="left"><content styleCode="bold"> Vascular disorders</content></td></tr><tr><td> Hypertension</td><td align="center">18</td><td align="center">18</td></tr></tbody></table>

<table><caption>Table 3: Viral and Fungal Infections (%) Reported Over 0 to 12 Months</caption><col width="350"/><col width="150"/><col width="250"/><tbody><tr><td styleCode="Botrule Toprule"/><td colspan="2" align="center" styleCode="Botrule Toprule"><content styleCode="bold"><content styleCode="italics">De novo </content></content><content styleCode="bold">Renal Trial</content></td></tr><tr><td styleCode="Botrule Toprule"/><td align="center" styleCode="Botrule Toprule"><content styleCode="bold">Mycophenolic Acid Delayed-Release Tablets 1.44 grams per day (n=213) (%) </content></td><td align="center" styleCode="Botrule Toprule"><paragraph/><paragraph><content styleCode="bold">Mycophenolate mofetil (MMF)</content></paragraph><paragraph/><paragraph><content styleCode="bold">2 grams per day (n=210) (%) </content></paragraph></td></tr><tr><td align="left"> Any cytomegalovirus</td><td align="center">22</td><td align="center">21</td></tr><tr><td align="left"> - Cytomegalovirus disease</td><td align="center">5</td><td align="center">4</td></tr><tr><td align="left"> Herpes simplex</td><td align="center">8</td><td align="center">6</td></tr><tr><td align="left"> Herpes zoster</td><td align="center">5</td><td align="center">4</td></tr><tr><td align="left"> Any fungal infection</td><td align="center">11</td><td align="center">12</td></tr><tr><td align="left"> - <content styleCode="italics">Candida NOS</content></td><td align="center">6</td><td align="center">6</td></tr><tr><td align="left" styleCode="Botrule"> - <content styleCode="italics">Candida albicans</content></td><td align="center" styleCode="Botrule">2</td><td align="center" styleCode="Botrule">4</td></tr></tbody></table>

<table><caption>Table 4: Adverse Reactions Reported in &lt;10% of Patients Treated with Mycophenolic Acid Delayed-Release Tablets in Combination With Cyclosporine* and Corticosteroids</caption><col width="375"/><col width="375"/><tfoot><tr styleCode="First Last"><td colspan="2"> *USP MODIFIED.</td></tr></tfoot><tbody><tr><td styleCode="Rrule Toprule"> Blood and lymphatic disorders</td><td styleCode="Toprule">Lymphocele, thrombocytopenia</td></tr><tr><td styleCode="Rrule Toprule"> Cardiac disorder</td><td styleCode="Toprule">Tachycardia</td></tr><tr><td styleCode="Rrule Toprule"> Eye disorder</td><td styleCode="Toprule">Vision blurred</td></tr><tr><td styleCode="Rrule Toprule"> Gastrointestinal disorders</td><td styleCode="Toprule"><paragraph>Abdominal pain, abdominal distension, gastroesophageal reflux disease, gingival hyperplasia</paragraph></td></tr><tr><td styleCode="Rrule Toprule"> General Disorders and administration-site conditions</td><td styleCode="Toprule">Fatigue, peripheral edema</td></tr><tr><td styleCode="Rrule Toprule"> Infections and infestations</td><td styleCode="Toprule"><paragraph>Nasopharyngitis, herpes simplex, upper respiratory infection, oral candidiasis, herpes zoster, sinusitis, influenza, wound infection, implant infection, pneumonia, sepsis</paragraph></td></tr><tr><td styleCode="Rrule Toprule"> Investigations</td><td styleCode="Toprule">Hemoglobin decrease, liver function tests abnormal</td></tr><tr><td styleCode="Rrule Toprule"> Metabolism and nutrition disorders</td><td styleCode="Toprule"><paragraph>Hypercholesterolemia, hyperkalemia, hypomagnesemia, diabetes mellitus, hyperglycemia</paragraph></td></tr><tr><td styleCode="Rrule Toprule"> Musculoskeletal and connective tissue disorders</td><td styleCode="Toprule"><paragraph>Arthralgia, pain in limb, peripheral swelling, muscle cramps, myalgia</paragraph></td></tr><tr><td styleCode="Rrule Toprule"> Nervous system disorders</td><td styleCode="Toprule">Dizziness (excluding vertigo)</td></tr><tr><td styleCode="Rrule Toprule"> Psychiatric disorders</td><td styleCode="Toprule">Anxiety</td></tr><tr><td styleCode="Rrule Toprule"> Renal and urinary disorders</td><td styleCode="Toprule"><paragraph>Renal tubular necrosis, renal impairment, hematuria, urinary retention</paragraph></td></tr><tr><td styleCode="Rrule Toprule"> Respiratory, thoracic and mediastinal disorders</td><td styleCode="Toprule">Cough, dyspnea, dyspnea exertional</td></tr><tr><td styleCode="Rrule Toprule"> Skin and subcutaneous tissue disorders</td><td styleCode="Toprule">Acne, pruritus, rash</td></tr><tr><td styleCode="Rrule Toprule"> Vascular disorders</td><td styleCode="Toprule">Hypertension aggravated, hypotension</td></tr></tbody></table>