FDA label 4e96a24d-5ee7-48b9-a9f0-8a40f8fba46f

Immunosuppression may lead to increased susceptibility to infection and possible development of lymphoma. Only physicians experienced in immunosuppressive therapy and management of renal, cardiac or hepatic transplant patients should use mycophenolate mofetil capsules and mycophenolate mofetil tablets. Patients receiving the drug 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. Female users of childbearing potential must use contraception. Use of mycophenolate mofetil during pregnancy is associated with increased risk of pregnancy loss and congenital malformations.

WARNINGS (See boxed WARNING.) Lymphoma and Malignancy Patients receiving immunosuppressive regimens involving combinations of drugs, including mycophenolate mofetil, as part of an immunosuppressive regimen are at increased risk of developing lymphomas and other malignancies, particularly of the skin (see ADVERSE REACTIONS ). 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 sunscreen with a high protection factor. Lymphoproliferative disease or lymphoma developed in 0.4% to 1% of patients receiving mycophenolate mofetil (2 g or 3 g) with other immunosuppressive agents in controlled clinical trials of renal, cardiac, and hepatic transplant patients (see ADVERSE REACTIONS ). In pediatric patients, no other malignancies besides lymphoproliferative disorder (2/148 patients) have been observed (see ADVERSE REACTIONS ). Combination With Other Immunosuppressive Agents Mycophenolate mofetil has been administered in combination with the following agents in clinical trials: antithymocyte globulin, OKT3, cyclosporine, and corticosteroids. The efficacy and safety of the use of mycophenolate mofetil in combination with other immunosuppressive agents have not been determined. Infections Oversuppression of the immune system can also increase susceptibility to infection, including opportunistic infections, fatal infections, and sepsis. In patients receiving mycophenolate mofetil (2 g or 3 g) in controlled studies for prevention of renal, cardiac or hepatic rejection, fatal infection/sepsis occurred in approximately 2% of renal and cardiac patients and in 5% of hepatic patients (see ADVERSE REACTIONS ). Latent Viral infections Immunosuppressed patients are at risk for opportunistic infections, including activation of latent viral infections. These include cases of progressive multifocal leukoencephalopathy (PML) and BK virus-associated nephropathy (BKVAN) which have been observed in patients receiving immunosuppressants, including mycophenolate mofetil capsules or mycophenolate mofetil tablets. Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal, have been reported in patients treated with mycophenolate mofetil. Hemiparesis, apathy, confusion, cognitive deficiencies and ataxia were the most frequent clinical features observed. The reported cases generally had risk factors for PML, including 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. Consideration should be given to reducing the amount of immunosuppression in patients who develop PML. In transplant patients, physicians should also consider the risk that reduced immunosuppression represents to the graft. BKVAN is associated with serious outcomes, including deteriorating renal function and renal graft loss (see ADVERSE REACTIONS: Postmarketing Experience ). Patient monitoring may help detect patients at risk for BK virus-associated nephropathy. Reduction in immunosuppression should be considered for patients who develop evidence of BK virus-associated nephropathy. Pregnancy Teratogenic Effects Pregnancy category D Mycophenolate mofetil (MMF) can cause fetal harm when administered to a pregnant woman. Use of MMF 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, and kidney. In the National Transplantation Pregnancy Registry (NTPR), there were data on 33 MMF-exposed pregnancies in 24 transplant patients; there were 15 spontaneous abortions (45%) and 18 live-born infants. Four of these 18 infants had structural malformations (22%). In postmarketing data (collected 1995 to 2007) on 77 women exposed to systemic MMF during pregnancy, 25 had spontaneous abortions and 14 had a malformed infant or fetus. Six of 14 malformed offspring had ear abnormalities. Because these postmarketing data are reported voluntarily, it is not always possible to reliably estimate the frequency of particular adverse outcomes. These malformations seen in offspring were similar to findings in animal reproductive toxicology studies. For comparison, the background rate for congenital anomalies in the United States is about 3%, and NTPR data show a rate of 4 to 5% among babies born to organ transplant patients using other immunosuppressive drugs. In animal reproductive toxicology studies, there were increased rates of fetal resorptions and malformations in the absence of maternal toxicity. Female rats and rabbits received mycophenolate mofetil (MMF) doses equivalent to 0.02 to 0.9 times the recommended human dose for renal and cardiac transplant patients, based on body surface area conversions. In rat offspring, malformations included anophthalmia, agnathia, and hydrocephaly. In rabbit offspring, malformations included ectopia cordis, ectopic kidneys, diaphragmatic hernia, and umbilical hernia. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. In certain situations, the patient and her healthcare practitioner may decide that the maternal benefits outweigh the risks to the fetus. Women using mycophenolate mofetil capsules or mycophenolate mofetil tablets at any time during pregnancy should be encouraged to enroll in the National Transplantation Pregnancy Registry. Pregnancy Exposure Prevention Women of childbearing potential should have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 1 week prior to beginning therapy. Mycophenolate mofetil therapy should not be initiated until a negative pregnancy test report is obtained. Women of childbearing potential (including pubertal girls and peri-menopausal women) taking mycophenolate mofetil must receive contraceptive counseling and use effective contraception. The patient should begin using her two chosen methods of contraception 4 weeks prior to starting mycophenolate mofetil therapy, unless abstinence is the chosen method. She should continue contraceptive use during therapy and for 6 weeks after stopping mycophenolate mofetil. Patients should be aware that mycophenolate mofetil reduces blood levels of the hormones in the oral contraceptive pill and could theoretically reduce its effectiveness (see PRECAUTIONS : Information for patients and PRECAUTIONS : Drug Interactions : Oral Contraceptives). Neutropenia Severe neutropenia [absolute neutrophil count (ANC) < 0.5 x 103/µL] developed in up to 2.0% of renal, up to 2.8% of cardiac, and up to 3.6% of hepatic transplant patients receiving mycophenolate mofetil 3 g daily (see ADVERSE REACTIONS ). Patients receiving mycophenolate mofetil should be monitored for neutropenia (see PRECAUTIONS : Laboratory tests ). The development of neutropenia may be related to mycophenolate mofetil itself, concomitant medications, viral infections, or some combination of these causes. If neutropenia develops (ANC < 1.3 x 103/µL), dosing with mycophenolate mofetil should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately (see DOSAGE AND ADMINISTRATION ). Neutropenia has been observed most frequently in the period from 31 to 180 days posttransplant in patients treated for prevention of renal, cardiac, and hepatic rejection. Patients receiving mycophenolate mofetil should be instructed to report immediately any evidence of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression. Pure Red Cell Aplasia (PRCA) Cases of pure red cell aplasia (PRCA) have been reported in patients treated with mycophenolate mofetil capsules or mycophenolate mofetil tablets in combination with other immunosuppressive agents. The mechanism for mycophenolate mofetil induced PRCA is unknown; the relative contribution of other immunosuppressants and their combinations in an immunosuppression regimen are also unknown. In some cases, PRCA was found to be reversible with dose reduction or cessation of mycophenolate mofetil capsules or mycophenolate mofetil tablets therapy. In transplant patients, however, reduced immunosuppression may place the graft at risk. CAUTION: MYCOPHENOLATE MOFETIL INTRAVENOUS SOLUTION SHOULD NEVER BE ADMINISTERED BY RAPID OR BOLUS INTRAVENOUS INJECTION.

ADVERSE REACTIONS The principal adverse reactions associated with the administration of mycophenolate mofetil include diarrhea, leukopenia, sepsis, vomiting, and there is evidence of a higher frequency of certain types of infections, e.g., opportunistic infection (see WARNINGS : Infections ). The adverse event profile associated with the administration of mycophenolate mofetil intravenous has been shown to be similar to that observed after administration of oral dosage forms of mycophenolate mofetil. Geriatrics Elderly patients (≥ 65 years), particularly those who are receiving mycophenolate mofetil as part of a combination immunosuppressive regimen, may be at increased risk of certain infections (including cytomegalovirus [CMV] tissue invasive disease) and possibly gastrointestinal hemorrhage and pulmonary edema, compared to younger individuals (see PRECAUTIONS ). Safety data are summarized below for all active-controlled trials in renal (2 trials), cardiac (1 trial), and hepatic (1 trial) transplant patients. Approximately 53% of the renal patients, 65% of the cardiac patients, and 48% of the hepatic patients have been treated for more than 1 year. Adverse events reported in ≥ 20% of patients in the mycophenolate mofetil treatment groups are presented below. Table 8: Adverse Events in Controlled Studies in Prevention of Renal, Cardiac or Hepatic Allograft Rejectionn (Reported in ≥20% of Patients in the Mycophenolate Mofetil Group) Renal Studies Cardiac Study Hepatic Study MMF Capsules or MMF Tablets 2 g/day MMF Capsules or MMF Tablets 3 g/day Azathioprine 1 to 2 mg/kg/day or 100 to 150 mg/day MMF Capsules or MMF Tablets 3 g/day Azathioprine 1.5 to 3 mg/kg/day MMF Capsules or MMF Tablets 3 g/day Azathioprine 1 to 2 mg/kg/day (n = 336) (n = 330) (n = 326) (n = 289) (n = 289) (n = 277) (n = 287) % % % % % % % Body as a Whole Pain 33.0 31.2 32.2 75.8 74.7 74.0 77.7 Abdominal pain 24.7 27.6 23.0 33.9 33.2 62.5 51.2 Fever 21.4 23.3 23.3 47.4 46.4 52.3 56.1 Headache 21.1 16.1 21.2 54.3 51.9 53.8 49.1 Infection 18.2 20.9 19.9 25.6 19.4 27.1 25.1 Sepsis – – – – – 27.4 26.5 Asthenia – – – 43.3 36.3 35.4 33.8 Chest pain – – – 26.3 26.0 – – Back pain – – – 34.6 28.4 46.6 47.4 Ascites – – – – – 24.2 22.6 Hematologic and Lymphatic Anemia 25.6 25.8 23.6 42.9 43.9 43.0 53.0 Leukopenia 23.2 34.5 24.8 30.4 39.1 45.8 39.0 Thrombocytopenia – – – 23.5 27.0 38.3 42.2 Hypochromic anemia – – – 24.6 23.5 – – Leukocytosis – – – 40.5 35.6 22.4 21.3 Urogenital Urinary tract infection 37.2 37.0 33.7 – – – – Kidney function abnormal – – – 21.8 26.3 25.6 28.9 Cardiovascular Hypertension 32.4 28.2 32.2 77.5 72.3 62.1 59.6 Hypotension – – – 32.5 36.0 – – Cardiovascular disorder – – – 25.6 24.2 – – Tachycardia – – – 20.1 18.0 22.0 15.7 Metabolic and Nutritional Peripheral edema 28.6 27.0 28.2 64.0 53.3 48.4 47.7 Hyper-cholesteremia – – – 41.2 38.4 – – Edema – – – 26.6 25.6 28.2 28.2 Hypokalemia – – – 31.8 25.6 37.2 41.1 Hyperkalemia – – – – – 22.0 23.7 Hyperglycemia – – – 46.7 52.6 43.7 48.8 Creatinine increased – – – 39.4 36.0 – – BUN increased – – – 34.6 32.5 – – Lactic dehydrogenase increased – – – 23.2 17.0 – – Hypomagnesemia – – – – – 39.0 37.6 Hypocalcemia – – – – – 30.0 30.0 Digestive Diarrhea 31.0 36.1 20.9 45.3 34.3 51.3 49.8 Constipation 22.9 18.5 22.4 41.2 37.7 37.9 38.3 Nausea 19.9 23.6 24.5 54.0 54.3 54.5 51.2 Dyspepsia – – – – – 22.4 20.9 Vomiting – – – 33.9 28.4 32.9 33.4 Anorexia – – – – – 25.3 17.1 Liver function tests abnormal – – – – – 24.9 19.2 Respiratory Infection 22.0 23.9 19.6 37.0 35.3 – – Dyspnea – – – 36.7 36.3 31.0 30.3 Cough increased – – – 31.1 25.6 – – Lung disorder – – – 30.1 29.1 22.0 18.8 Sinusitis – – – 26.0 19.0 – – Pleural effusion – – – – – 34.3 35.9 Skin and Appendages Rash – – – 22.1 18.0 – – Nervous System Tremor – – – 24.2 23.9 33.9 35.5 Insomnia – – – 40.8 37.7 52.3 47.0 Dizziness – – – 28.7 27.7 – – Anxiety – – – 28.4 23.9 – – Paresthesia – – – 20.8 18.0 – – The placebo-controlled renal transplant study generally showed fewer adverse events occurring in ≥ 20% of patients. In addition, those that occurred were not only qualitatively similar to the azathioprine-controlled renal transplant studies, but also occurred at lower rates, particularly for infection, leukopenia, hypertension, diarrhea and respiratory infection. The above data demonstrate that in three controlled trials for prevention of renal rejection, patients receiving 2 g/day of mycophenolate mofetil had an overall better safety profile than did patients receiving 3 g/day of mycophenolate mofetil. The above data demonstrate that the types of adverse events observed in multicenter controlled trials in renal, cardiac, and hepatic transplant patients are qualitatively similar except for those that are unique to the specific organ involved. Sepsis, which was generally CMV viremia, was slightly more common in renal transplant patients treated with mycophenolate mofetil compared to patients treated with azathioprine. The incidence of sepsis was comparable in mycophenolate mofetil and in azathioprine-treated patients in cardiac and hepatic studies. In the digestive system, diarrhea was increased in renal and cardiac transplant patients receiving mycophenolate mofetil compared to patients receiving azathioprine, but was comparable in hepatic transplant patients treated with mycophenolate mofetil or azathioprine. Patients receiving mycophenolate mofetil alone or as part of an immunosuppressive regimen are at increased risk of developing lymphomas and other malignancies, particularly of the skin (see WARNINGS : Lymphoma and Malignancy ). The incidence of malignancies among the 1483 patients treated in controlled trials for the prevention of renal allograft rejection who were followed for ≥ 1 year was similar to the incidence reported in the literature for renal allograft recipients. Lymphoproliferative disease or lymphoma developed in 0.4% to 1% of patients receiving mycophenolate mofetil (2 g or 3 g daily) with other immunosuppressive agents in controlled clinical trials of renal, cardiac, and hepatic transplant patients followed for at least 1 year (see WARNINGS : Lymphoma and Malignancy ). Non-melanoma skin carcinomas occurred in 1.6% to 4.2% of patients, other types of malignancy in 0.7% to 2.1% of patients. Three-year safety data in renal and cardiac transplant patients did not reveal any unexpected changes in incidence of malignancy compared to the 1 year data. In pediatric patients, no other malignancies besides lymphoproliferative disorder (2/148 patients) have been observed. Severe neutropenia (ANC < 0.5 x 103/µL) developed in up to 2.0% of renal transplant patients, up to 2.8% of cardiac transplant patients and up to 3.6% of hepatic transplant patients receiving mycophenolate mofetil 3 g daily (see WARNINGS : Neutropenia , PRECAUTIONS : Laboratory tests and DOSAGE AND ADMINISTRATION ). All transplant patients are at increased risk of opportunistic infections. The risk increases with total immunosuppressive load (see WARNINGS : Infections ). Table 9 shows the incidence of opportunistic infections that occurred in the renal, cardiac, and hepatic transplant populations in the azathioprine-controlled prevention trials: Table 9: Viral and Fungal Infections in Controlled Studies in Prevention of Renal, Cardiac or Hepatic Transplant Rejection Viral and Fungal Infections in Controlled Studies in Prevention of Renal, Cardiac or Hepatic Transplant Rejection Renal Studies Cardiac Study Hepatic Study MMF Capsules or MMF Tablets 2 g/day MMF Capsules or MMF Tablets 3 g/day Azathioprine 1 to 2 mg/kg/day or 100 to 150 mg/day MMF Capsules or MMF Tablets 3 g/day Azathioprine 1.5 to 3 mg/kg/day MMF Capsules or MMF Tablets 3 g/day Azathioprine 1 to 2 mg/kg/day (n = 336) (n = 330) (n = 326) (n = 289) (n = 289) (n = 277) (n = 287) % % % % % % % Herpes simplex 16.7 20.0 19.0 20.8 14.5 10.1 5.9 CMV – Viremia/syndrome 13.4 12.4 13.8 12.1 10.0 14.1 12.2 – Tissue invasive disease 8.3 11.5 6.1 11.4 8.7 5.8 8.0 Herpes zoster 6.0 7.6 5.8 10.7 5.9 4.3 4.9 – Cutaneous disease 6.0 7.3 5.5 10.0 5.5 4.3 4.9 Candida 17.0 17.3 18.1 18.7 17.6 22.4 24.4 – Mucocutaneous 15.5 16.4 15.3 18.0 17.3 18.4 17.4 The following other opportunistic infections occurred with an incidence of less than 4% in mycophenolate mofetil patients in the above azathioprine-controlled studies: Herpes zoster, visceral disease; Candida, urinary tract infection, fungemia/disseminated disease, tissue invasive disease; Cryptococcosis; Aspergillus/Mucor; Pneumocystis carinii. In the placebo-controlled renal transplant study, the same pattern of opportunistic infection was observed compared to the azathioprine-controlled renal studies, with a notably lower incidence of the following: Herpes simplex and CMV tissue-invasive disease. In patients receiving mycophenolate mofetil (2 g or 3 g) in controlled studies for prevention of renal, cardiac or hepatic rejection, fatal infection/sepsis occurred in approximately 2% of renal and cardiac patients and in 5% of hepatic patients (see WARNINGS, Infections). In cardiac transplant patients, the overall incidence of opportunistic infections was approximately 10% higher in patients treated with mycophenolate mofetil than in those receiving azathioprine, but this difference was not associated with excess mortality due to infection/sepsis among patients treated with mycophenolate mofetil. The following adverse events were reported with 3% to < 20% incidence in renal, cardiac, and hepatic transplant patients treated with mycophenolate mofetil, in combination with cyclosporine and corticosteroids. Table 10: Adverse Events Reported in 3% to < 20% of Patients Treated With Mycophenolate Mofetil in Combination With Cyclosporine and Corticosteroids Body System Body as a Whole abdomen enlarged, abscess, accidental injury, cellulitis, chills occurring with fever, cyst, face edema, flu syndrome, hemorrhage, hernia, lab test abnormal, malaise, neck pain, pelvic pain, peritonitis Hematologic and Lymphatic coagulation disorder, ecchymosis, pancytopenia, petechia, polycythemia, prothrombin time increased, thromboplastin time increased Urogenital acute kidney failure, albuminuria, dysuria, hydronephrosis, hematuria, impotence, kidney failure, kidney tubular necrosis, nocturia, oliguria, pain, prostatic disorder, pyelonephritis, scrotal edema, urine abnormality, urinary frequency, urinary incontinence, urinary retention, urinary tract disorder Cardiovascular angina pectoris, arrhythmia, arterial thrombosis, atrial fibrillation, atrial flutter, bradycardia, cardiovascular disorder, congestive heart failure, extrasystole, heart arrest, heart failure, hypotension, pallor, palpitation, pericardial effusion, peripheral vascular disorder, postural hypotension, pulmonary hypertension, supraventricular tachycardia, supraventricular extrasystoles, syncope, tachycardia, thrombosis, vasodilatation, vasospasm, ventricular extrasystole, ventricular tachycardia, venous pressure increased Metabolic and Nutritional abnormal healing, acidosis, alkaline phosphatase increased, alkalosis, bilirubinemia, creatinine increased, dehydration, gamma glutamyl transpeptidase increased, generalized edema, gout, hypercalcemia, hypercholesteremia, hyperlipemia, hyperphosphatemia, hyperuricemia, hypervolemia, hypocalcemia, hypochloremia, hypoglycemia, hyponatremia, hypophosphatemia, hypoproteinemia, hypovolemia, hypoxia, lactic dehydrogenase increased, respiratory acidosis, SGOT increased, SGPT increased, thirst, weight gain, weight loss Digestive anorexia, cholangitis, cholestatic jaundice, dysphagia, esophagitis, flatulence, gastritis, gastroenteritis, gastrointestinal disorder, gastrointestinal hemorrhage, gastrointestinal moniliasis, gingivitis, gum hyperplasia, hepatitis, ileus, infection, jaundice, liver damage, liver function tests abnormal, melena, mouth ulceration, nausea and vomiting, oral moniliasis, rectal disorder, stomach ulcer, stomatitis Respiratory apnea, asthma, atelectasis, bronchitis, epistaxis, hemoptysis, hiccup, hyperventilation, lung edema, lung disorder, neoplasm, pain, pharyngitis, pleural effusion, pneumonia, pneumothorax, respiratory disorder, respiratory moniliasis, rhinitis, sinusitis, sputum increased, voice alteration Skin and Appendages acne, alopecia, fungal dermatitis, hemorrhage, hirsutism, pruritus, rash, skin benign neoplasm, skin carcinoma, skin disorder, skin hypertrophy, skin ulcer, sweating, vesiculobullous rash Nervous agitation, anxiety, confusion, convulsion, delirium, depression, dry mouth, emotional lability, hallucinations, hypertonia, hypesthesia, nervousness, neuropathy, paresthesia, psychosis, somnolence, thinking abnormal, vertigo Endocrine Cushing’s syndrome, diabetes mellitus, hypothyroidism, parathyroid disorder Musculoskeletal arthralgia, joint disorder, leg cramps, myalgia, myasthenia, osteoporosis Special Senses abnormal vision, amblyopia, cataract (not specified), conjunctivitis, deafness, ear disorder, ear pain, eye hemorrhage, tinnitus, lacrimation disorder Pediatrics The type and frequency of adverse events in a clinical study in 100 pediatric patients 3 months to 18 years of age dosed with mycophenolate mofetil oral suspension 600 mg/m2 bid (up to 1 g bid) were generally similar to those observed in adult patients dosed with mycophenolate mofetil capsules at a dose of 1 g bid with the exception of abdominal pain, fever, infection, pain, sepsis, diarrhea, vomiting, pharyngitis, respiratory tract infection, hypertension, leukopenia, and anemia, which were observed in a higher proportion in pediatric patients. Mycophenolate Mofetil Intravenous The adverse event profile of mycophenolate mofetil intravenous was determined from a single, double-blind, controlled comparative study of the safety of 2 g/day of intravenous and oral mycophenolate mofetil in renal transplant patients in the immediate posttransplant period (administered for the first 5 days). The potential venous irritation of mycophenolate mofetil intravenous was evaluated by comparing the adverse events attributable to peripheral venous infusion of mycophenolate mofetil intravenous with those observed in the intravenous placebo group; patients in this group received active medication by the oral route. Adverse events attributable to peripheral venous infusion were phlebitis and thrombosis, both observed at 4% in patients treated with mycophenolate mofetil intravenous. In the active controlled study in hepatic transplant patients, 2 g/day of mycophenolate mofetil intravenous were administered in the immediate posttransplant period (up to 14 days). The safety profile of intravenous mycophenolate mofetil was similar to that of intravenous azathioprine. Postmarketing Experience Congenital Disorders: Congenital malformations including ear malformations have been reported in offspring of patients exposed to mycophenolate mofetil during pregnancy (see WARNINGS : Pregnancy ). Digestive: Colitis (sometimes caused by cytomegalovirus), pancreatitis, isolated cases of intestinal villous atrophy. Infections: Serious life-threatening infections such as meningitis and infectious endocarditis have been reported occasionally and there is evidence of a higher frequency of certain types of serious infections such as tuberculosis and atypical mycobacterial infection. Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal, have been reported in patients treated with mycophenolate mofetil capsules and mycophenolate mofetil tablets. The reported cases generally had risk factors for PML, including treatment with immunosuppressant therapies and impairment of immune function. BK virus-associated nephropathy has been observed in patients receiving immunosuppressants, including mycophenolate mofetil capsules and mycophenolate mofetil tablets. This infection is associated with serious outcomes, including deteriorating renal function and renal graft loss. Respiratory: Interstitial lung disorders, including fatal pulmonary fibrosis, have been reported rarely and should be considered in the differential diagnosis of pulmonary symptoms ranging from dyspnea to respiratory failure in posttransplant patients receiving mycophenolate mofetil.

<table ID="_Refid_de2bbb1a-c2d7-41c0-941c-fa34b719e" width="100%"> <caption>Table 8: Adverse Events in Controlled Studies in Prevention of Renal, Cardiac or Hepatic Allograft Rejectionn (Reported in &#x2265;20% of Patients in the Mycophenolate Mofetil Group) </caption> <col width="19%"/> <col width="10%"/> <col width="10%"/> <col width="14%"/> <col width="10%"/> <col width="14%"/> <col width="10%"/> <col width="14%"/> <tbody> <tr> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"/> <td align="center" colspan="3" styleCode="Rrule Botrule Toprule " valign="top"> <paragraph>Renal Studies</paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="top"> <paragraph>Cardiac Study</paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="top"> <paragraph>Hepatic Study</paragraph> </td> </tr> <tr> <td rowspan="3" styleCode="Rrule Lrule Botrule " valign="top"/> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>MMF Capsules or MMF Tablets 2 g/day</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>MMF Capsules or MMF Tablets 3 g/day</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>Azathioprine 1 to 2 mg/kg/day or 100 to 150 mg/day</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>MMF Capsules or MMF Tablets 3 g/day</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>Azathioprine 1.5 to 3 mg/kg/day</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>MMF Capsules or MMF Tablets 3 g/day</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>Azathioprine 1 to 2 mg/kg/day</paragraph> </td> </tr> <tr> <td align="center" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>(n = 336)</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>(n = 330)</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>(n = 326)</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>(n = 289)</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>(n = 289)</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>(n = 277)</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>(n = 287)</paragraph> </td> </tr> <tr> <td align="center" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>%</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>%</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>%</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>%</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>%</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>%</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>%</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Body as a Whole </paragraph> </td> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Pain</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>33.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>31.2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>32.2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>75.8</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>74.7</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>74.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>77.7</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Abdominal pain</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>24.7</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>27.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>23.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>33.9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>33.2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>62.5</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>51.2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Fever</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>21.4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>23.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>23.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>47.4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>46.4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>52.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>56.1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Headache</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>21.1</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>16.1</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>21.2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>54.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>51.9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>53.8</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>49.1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Infection</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>18.2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>20.9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>19.9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>25.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>19.4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>27.1</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>25.1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Sepsis</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>27.4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>26.5</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Asthenia</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>43.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>36.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>35.4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>33.8</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Chest pain</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>26.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>26.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Back pain</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>34.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>28.4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>46.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>47.4</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Ascites</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>24.2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>22.6</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Hematologic and Lymphatic </paragraph> </td> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Anemia</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>25.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>25.8</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>23.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>42.9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>43.9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>43.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>53.0</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Leukopenia</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>23.2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>34.5</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>24.8</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>30.4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>39.1</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>45.8</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>39.0</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Thrombocytopenia</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>23.5</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>27.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>38.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>42.2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Hypochromic anemia</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>24.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>23.5</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Leukocytosis</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>40.5</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>35.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>22.4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>21.3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Urogenital </paragraph> </td> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Urinary tract infection</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>37.2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>37.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>33.7</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Kidney function abnormal</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>21.8</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>26.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>25.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>28.9</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Cardiovascular </paragraph> </td> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Hypertension</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>32.4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>28.2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>32.2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>77.5</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>72.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>62.1</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>59.6</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Hypotension</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>32.5</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>36.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Cardiovascular disorder</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>25.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>24.2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Tachycardia</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>20.1</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>18.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>22.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>15.7</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Metabolic and Nutritional </paragraph> </td> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Peripheral edema</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>28.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>27.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>28.2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>64.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>53.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>48.4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>47.7</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Hyper-cholesteremia</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>41.2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>38.4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Edema</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>26.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>25.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>28.2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>28.2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Hypokalemia</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>31.8</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>25.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>37.2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>41.1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Hyperkalemia</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>22.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>23.7</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Hyperglycemia</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>46.7</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>52.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>43.7</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>48.8</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Creatinine increased</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>39.4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>36.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>BUN increased</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>34.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>32.5</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Lactic dehydrogenase increased</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>23.2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>17.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Hypomagnesemia</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>39.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>37.6</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Hypocalcemia</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>30.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>30.0</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Digestive </paragraph> </td> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Diarrhea</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>31.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>36.1</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>20.9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>45.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>34.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>51.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>49.8</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Constipation</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>22.9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>18.5</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>22.4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>41.2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>37.7</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>37.9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>38.3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Nausea</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>19.9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>23.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>24.5</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>54.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>54.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>54.5</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>51.2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Dyspepsia</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>22.4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>20.9</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Vomiting</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>33.9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>28.4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>32.9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>33.4</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Anorexia</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>25.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>17.1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Liver function tests abnormal</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>24.9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>19.2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Respiratory </paragraph> </td> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Infection</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>22.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>23.9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>19.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>37.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>35.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Dyspnea</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>36.7</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>36.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>31.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>30.3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Cough increased</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>31.1</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>25.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Lung disorder</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>30.1</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>29.1</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>22.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>18.8</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Sinusitis</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>26.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>19.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Pleural effusion</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>34.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>35.9</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Skin and Appendages </paragraph> </td> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Rash</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>22.1</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>18.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Nervous System </paragraph> </td> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> <td styleCode="Rrule Botrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Tremor</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>24.2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>23.9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>33.9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>35.5</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Insomnia</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>40.8</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>37.7</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>52.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>47.0</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Dizziness</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>28.7</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>27.7</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Anxiety</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>28.4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>23.9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule Lrule " valign="top"> <paragraph>Paresthesia</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>20.8</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>18.0</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013;</paragraph> </td> </tr> </tbody> </table>

<table ID="_Refid_0f8fe950-a5eb-4d97-abe8-6e688a445" width="100%"> <caption>Table 9: Viral and Fungal Infections in Controlled Studies in Prevention of Renal, Cardiac or Hepatic Transplant Rejection</caption> <col width="19%"/> <col width="10%"/> <col width="10%"/> <col width="14%"/> <col width="10%"/> <col width="14%"/> <col width="10%"/> <col width="14%"/> <tbody> <tr> <td align="center" colspan="8" styleCode="Toprule " valign="top"> <paragraph>Viral and Fungal Infections in Controlled Studies in Prevention of Renal, Cardiac or Hepatic Transplant Rejection</paragraph> </td> </tr> <tr> <td rowspan="4" styleCode="Rrule Botrule " valign="top"> <paragraph> </paragraph> </td> <td align="center" colspan="3" styleCode="Rrule Botrule " valign="top"> <paragraph>Renal Studies</paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"> <paragraph>Cardiac Study</paragraph> </td> <td align="center" colspan="2" styleCode="Botrule " valign="top"> <paragraph>Hepatic Study</paragraph> </td> </tr> <tr> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>MMF Capsules or MMF Tablets 2 g/day</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>MMF Capsules or MMF Tablets 3 g/day</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>Azathioprine 1 to 2 mg/kg/day or 100 to 150 mg/day</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>MMF Capsules or MMF Tablets 3 g/day</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>Azathioprine 1.5 to 3 mg/kg/day</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>MMF Capsules or MMF Tablets 3 g/day</paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>Azathioprine 1 to 2 mg/kg/day</paragraph> </td> </tr> <tr> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>(n = 336) </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>(n = 330) </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>(n = 326) </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>(n = 289) </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>(n = 289) </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>(n = 277) </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>(n = 287) </paragraph> </td> </tr> <tr> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>% </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>% </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>% </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>% </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>% </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>% </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>% </paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule " valign="top"> <paragraph>Herpes simplex </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>16.7 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>20.0 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>19.0 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>20.8 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>14.5 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>10.1 </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>5.9 </paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule " valign="top"> <paragraph>CMV </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph> </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph> </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph> </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph> </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph> </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph> </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013; Viremia/syndrome </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>13.4 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>12.4 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>13.8 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>12.1 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>10.0 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>14.1 </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>12.2 </paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013; Tissue invasive disease </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>8.3 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>11.5 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>6.1 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>11.4 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>8.7 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>5.8 </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>8.0 </paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule " valign="top"> <paragraph>Herpes zoster </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>6.0 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>7.6 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>5.8 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>10.7 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>5.9 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>4.3 </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>4.9 </paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013; Cutaneous disease </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>6.0 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>7.3 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>5.5 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>10.0 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>5.5 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>4.3 </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>4.9 </paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule " valign="top"> <paragraph>Candida </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>17.0 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>17.3 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>18.1 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>18.7 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>17.6 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>22.4 </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>24.4 </paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule " valign="top"> <paragraph>&#x2013; Mucocutaneous </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>15.5 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>16.4 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>15.3 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>18.0 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>17.3 </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>18.4 </paragraph> </td> <td align="center" styleCode="Botrule " valign="top"> <paragraph>17.4 </paragraph> </td> </tr> </tbody> </table>

<table ID="_Refid_bd5b8edd-4f83-497d-b2cf-4a8cff9c8" width="100%"> <caption>Table 10: Adverse Events Reported in 3% to &lt; 20% of Patients Treated With Mycophenolate Mofetil in Combination With Cyclosporine and Corticosteroids</caption> <col width="20%"/> <col width="80%"/> <tbody> <tr> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>Body System </paragraph> </td> <td styleCode="Rrule Botrule Toprule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Body as a Whole</paragraph> </td> <td styleCode="Rrule Botrule " valign="top"> <paragraph>abdomen enlarged, abscess, accidental injury, cellulitis, chills occurring with fever, cyst, face edema, flu syndrome, hemorrhage, hernia, lab test abnormal, malaise, neck pain, pelvic pain, peritonitis</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Hematologic and Lymphatic</paragraph> </td> <td styleCode="Rrule Botrule " valign="top"> <paragraph>coagulation disorder, ecchymosis, pancytopenia, petechia, polycythemia, prothrombin time increased, thromboplastin time increased</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Urogenital</paragraph> </td> <td styleCode="Rrule Botrule " valign="top"> <paragraph>acute kidney failure, albuminuria, dysuria, hydronephrosis, hematuria, impotence, kidney failure, kidney tubular necrosis, nocturia, oliguria, pain, prostatic disorder, pyelonephritis, scrotal edema, urine abnormality, urinary frequency, urinary incontinence, urinary retention, urinary tract disorder</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Cardiovascular</paragraph> </td> <td styleCode="Rrule Botrule " valign="top"> <paragraph>angina pectoris, arrhythmia, arterial thrombosis, atrial fibrillation, atrial flutter, bradycardia, cardiovascular disorder, congestive heart failure, extrasystole, heart arrest, heart failure, hypotension, pallor, palpitation, pericardial effusion, peripheral vascular disorder, postural hypotension, pulmonary hypertension, supraventricular tachycardia, supraventricular extrasystoles, syncope, tachycardia, thrombosis, vasodilatation, vasospasm, ventricular extrasystole, ventricular tachycardia, venous pressure increased</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Metabolic and Nutritional</paragraph> </td> <td styleCode="Rrule Botrule " valign="top"> <paragraph>abnormal healing, acidosis, alkaline phosphatase increased, alkalosis, bilirubinemia, creatinine increased, dehydration, gamma glutamyl transpeptidase increased, generalized edema, gout, hypercalcemia, hypercholesteremia, hyperlipemia, hyperphosphatemia, hyperuricemia, hypervolemia, hypocalcemia, hypochloremia, hypoglycemia, hyponatremia, hypophosphatemia, hypoproteinemia, hypovolemia, hypoxia, lactic dehydrogenase increased, respiratory acidosis, SGOT increased, SGPT increased, thirst, weight gain, weight loss</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Digestive</paragraph> </td> <td styleCode="Rrule Botrule " valign="top"> <paragraph>anorexia, cholangitis, cholestatic jaundice, dysphagia, esophagitis, flatulence, gastritis, gastroenteritis, gastrointestinal disorder, gastrointestinal hemorrhage, gastrointestinal moniliasis, gingivitis, gum hyperplasia, hepatitis, ileus, infection, jaundice, liver damage, liver function tests abnormal, melena, mouth ulceration, nausea and vomiting, oral moniliasis, rectal disorder, stomach ulcer, stomatitis</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Respiratory</paragraph> </td> <td styleCode="Rrule Botrule " valign="top"> <paragraph>apnea, asthma, atelectasis, bronchitis, epistaxis, hemoptysis, hiccup, hyperventilation, lung edema, lung disorder, neoplasm, pain, pharyngitis, pleural effusion, pneumonia, pneumothorax, respiratory disorder, respiratory moniliasis, rhinitis, sinusitis, sputum increased, voice alteration</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Skin and Appendages</paragraph> </td> <td styleCode="Rrule Botrule " valign="top"> <paragraph>acne, alopecia, fungal dermatitis, hemorrhage, hirsutism, pruritus, rash, skin benign neoplasm, skin carcinoma, skin disorder, skin hypertrophy, skin ulcer, sweating, vesiculobullous rash</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Nervous</paragraph> </td> <td styleCode="Rrule Botrule " valign="top"> <paragraph>agitation, anxiety, confusion, convulsion, delirium, depression, dry mouth, emotional lability, hallucinations, hypertonia, hypesthesia, nervousness, neuropathy, paresthesia, psychosis, somnolence, thinking abnormal, vertigo</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Endocrine</paragraph> </td> <td styleCode="Rrule Botrule " valign="top"> <paragraph>Cushing&#x2019;s syndrome, diabetes mellitus, hypothyroidism, parathyroid disorder</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Musculoskeletal</paragraph> </td> <td styleCode="Rrule Botrule " valign="top"> <paragraph>arthralgia, joint disorder, leg cramps, myalgia, myasthenia, osteoporosis</paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule Lrule " valign="top"> <paragraph>Special Senses</paragraph> </td> <td styleCode="Rrule Botrule " valign="top"> <paragraph>abnormal vision, amblyopia, cataract (not specified), conjunctivitis, deafness, ear disorder, ear pain, eye hemorrhage, tinnitus, lacrimation disorder</paragraph> </td> </tr> </tbody> </table>