FDA label 1a3dc4fa-db69-ab55-e063-6394a90aed0e

WARNING: SERIOUS AND SOMETIMES FATAL INFECTIONS OR BLEEDING Serious and sometimes fatal infections and bleeding occur very rarely following spontaneous, surgical, and medical abortions, including following Mifepristone tablets, 200 mg use. No causal relationship between the use of Mifepristone tablets, 200 mg and misoprostol and these events has been established. Atypical Presentation of Infection. Patients with serious bacterial infections (e.g., Clostridium sordellii ) and sepsis can present without fever, bacteremia, or significant findings on pelvic examination following an abortion. Very rarely, deaths have been reported in patients who presented without fever, with or without abdominal pain, but with leukocytosis with a marked left shift, tachycardia, hemoconcentration, and general malaise. A high index of suspicion is needed to rule out serious infection and sepsis [see Warnings and Precautions ( 5.1 )] Bleeding. Prolonged heavy bleeding may be a sign of incomplete abortion or other complications and prompt medical or surgical intervention may be needed. Advise patients to seek immediate medical attention if they experience prolonged heavy vaginal bleeding [see Warnings and Precautions ( 5.2 )]. Because of the risks of serious complications described above, Mifepristone tablets, 200mg is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Mifepristone REMS Program [see Warnings and Precautions ( 5.3 )]. Before prescribing mifepristone, inform the patient about the risk of these serious events. Ensure that the patient knows whom to call and what to do, including going to an Emergency Room if none of the provided contacts are reachable, if they experience sustained fever, severe abdominal pain, prolonged heavy bleeding, or syncope, or if they experience abdominal pain or discomfort, or general malaise (including weakness, nausea, vomiting or diarrhea) for more than 24 hours after taking misoprostol. WARNING: SERIOUS AND SOMETIMES FATAL INFECTIONS OR BLEEDING See full prescribing information for complete boxed warning. Serious and sometimes fatal infections and bleeding occur very rarely following spontaneous, surgical, and medical abortions, including following Mifepristone tablets, 200 mg use. Atypical Presentation of Infection. Patients with serious bacterial infections and sepsis can present without fever, bacteremia or significant findings on pelvic examination. A high index of suspicion is needed to rule out serious infection and sepsis. ( 5.1 ) Bleeding. Prolonged heavy bleeding may be a sign of incomplete abortion or other complications and prompt medical or surgical intervention may be needed. ( 5.2 ) Mifepristone tablets, 200 mg is only available through a restricted program called the mifepristone REMS Program ( 5.3 ). Before prescribing Mifepristone tablets, 200 mg, inform the patient about these risks. Ensure the patient knows whom to call and what to do if they experience sustained fever, severe abdominal pain, prolonged heavy bleeding, or syncope, or if they experience abdominal pain or discomfort or general malaise for more than 24 hours after taking misoprostol.

WARNING MISOPROSTOL ADMINISTRATION TO WOMEN WHO ARE PREGNANT CAN CAUSE BIRTH DEFECTS, ABORTION, OR PREMATURE BIRTH. UTERINE RUPTURE HAS BEEN REPORTED WHEN MISOPROSTOL TABLETS WERE ADMINISTERED IN PREGNANT WOMEN TO INDUCE LABOR OR TO INDUCE ABORTION BEYOND THE EIGHTH WEEK OF PREGNANCY (see also PRECAUTIONS and LABOR AND DELIVERY ). MISOPROSTOL TABLETS SHOULD NOT BE TAKEN BY PREGNANT WOMEN TO REDUCE THE RISK OF ULCERS INDUCED BY NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs) (see CONTRAINDICATIONS, WARNINGS , and PRECAUTIONS ). PATIENTS MUST BE ADVISED OF THE ABORTIFACIENT PROPERTY AND WARNED NOT TO GIVE THE DRUG TO OTHERS. Misoprostol Tablets should not be used for reducing the risk of NSAID-induced ulcers in women of childbearing potential unless the patient is at high risk of complications from gastric ulcers associated with use of the NSAID, or is at high risk of developing gastric ulceration. In such patients, Misoprostol Tablets may be prescribed if the patient has had a negative serum pregnancy test within 2 weeks prior to beginning therapy. is capable of complying with effective contraceptive measures. has received both oral and written warnings of the hazards of Misoprostol Tablets, the risk of possible contraception failure, and the danger to other women of childbearing potential should the drug be taken by mistake. will begin Misoprostol Tablets only on the second or third day of the next normal menstrual period.

Cardiovascular Thrombotic Events Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use [see Warnings and Precautions ]. Ibuprofen tablets are contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see Contraindications and Warnings ]. Gastrointestinal Risk NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events (see WARNINGS ).

WARNINGS See boxed WARNINGS . For hospital use only if misoprostol were to be used for cervical ripening, induction of labor, or for the treatment of serious post-partum hemorrhage, which are outside of the approved indication.

WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses. To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as ibuprofen, increases the risk of serious gastrointestinal (GI) events [ see Warnings ]. Status Post Coronary Artery Bypass Graft (CABG) Surgery Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG [ see Contraindications ]. Post-MI Patients Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up. Avoid the use of ibuprofen tablets in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If ibuprofen tablets are used in patients with a recent MI, monitor patients for signs of cardiac ischemia. Hypertension NSAIDs including ibuprofen tablets, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including ibuprofen tablets, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy. Heart Failure and Edema The Coxib and traditional NSAID Trialists’ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death. Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of ibuprofen may blunt the CV effects of several therapeutic agents used to treat these medical conditions [e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers (ARBs)] [see Drug Interactions ]. Avoid the use of ibuprofen tablets in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If ibuprofen tablets are used in patients with severe heart failure, monitor patients for signs of worsening heart failure. Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation p>NSAIDs, including ibuprofen tablets, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3 to 6 months, and in about 2 to 4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk. NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients treated with neither of these risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population. To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulcerations and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high-risk patients, alternate therapies that do not involve NSAIDs should be considered. Renal Effects Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. Advanced Renal Disease No information is available from controlled clinical studies regarding the use of ibuprofen tablets in patients with advanced renal disease. Therefore, treatment with ibuprofen tablets is not recommended in these patients with advanced renal disease. If ibuprofen tablet therapy must be initiated, close monitoring of the patients renal function is advisable. Anaphylactoid Reactions As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to ibuprofen tablets. Ibuprofen tablets should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS , Preexisting Asthma ). Emergency help should be sought in cases where an anaphylactoid reaction occurs. Skin Reactions NSAIDs, including ibuprofen tablets, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as ibuprofen tablets. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue ibuprofen tablets and evaluate the patient immediately. Fetal Toxicity Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs, including ibuprofen tablets, in pregnant women at about 30 weeks gestation and later. NSAIDs including ibuprofen tablets, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age. Oligohydramnios/Neonatal Renal Impairment: Use of NSAIDs, including ibuprofen tablets, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required. If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit ibuprofen tablets use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if ibuprofen tablets treatment extends beyond 48 hours. Discontinue ibuprofen tablets if oligohydramnios occurs and follow up according to clinical practice [ see PRECAUTIONS; Pregnancy ] .

5 WARNINGS AND PRECAUTIONS Ectopic pregnancy: Exclude before treatment. ( 5.4 ) Rhesus immunization: Prevention needed as for surgical abortion. ( 5.5 ) 5.1 Infection and Sepsis As with other types of abortion, cases of serious bacterial infection, including very rare cases of fatal septic shock, have been reported following the use of Mifepristone tablets, 200 mg [see Boxed Warning ]. Healthcare providers evaluating a patient who is undergoing a medical abortion should be alert to the possibility of this rare event. A sustained (>4 hours) fever of 100.4°F or higher, severe abdominal pain, or pelvic tenderness in the days after a medical abortion may be an indication of infection. A high index of suspicion is needed to rule out sepsis (e.g., from Clostridium sordellii ) if a patient reports abdominal pain or discomfort or general malaise (including weakness, nausea, vomiting or diarrhea) more than 24 hours after taking misoprostol. Very rarely, deaths have been reported in patients who presented without fever, with or without abdominal pain, but with leukocytosis with a marked left shift, tachycardia, hemoconcentration, and general malaise. No causal relationship between Mifepristone tablets, 200 mg and misoprostol use and an increased risk of infection or death has been established. Clostridium sordellii infections have also been reported very rarely following childbirth (vaginal delivery and caesarian section), and in other gynecologic and non-gynecologic conditions. 5.2 Uterine Bleeding Uterine bleeding occurs in almost all patients during a medical abortion. Prolonged heavy bleeding (soaking through two thick full-size sanitary pads per hour for two consecutive hours) may be a sign of incomplete abortion or other complications and prompt medical or surgical intervention may be needed to prevent the development of hypovolemic shock. Counsel patients to seek immediate medical attention if they experience prolonged heavy vaginal bleeding following a medical abortion [see Boxed Warning ]. Women should expect to experience vaginal bleeding or spotting for an average of 9 to 16 days. Women report experiencing heavy bleeding for a median duration of 2 days. Up to 8% of all subjects may experience some type of bleeding for 30 days or more. In general, the duration of bleeding and spotting increased as the duration of the pregnancy increased. Decreases in hemoglobin concentration, hematocrit, and red blood cell count may occur in patients who bleed heavily. Excessive uterine bleeding usually requires treatment by uterotonics, vasoconstrictor drugs, surgical uterine evacuation, administration of saline infusions, and/or blood transfusions. Based on data from several large clinical trials, vasoconstrictor drugs were used in 4.3% of all subjects, there was a decrease in hemoglobin of more than 2 g/dL in 5.5% of subjects, and blood transfusions were administered to ≤0.1% of subjects. Because heavy bleeding requiring surgical uterine evacuation occurs in about 1% of patients, special care should be given to patients with hemostatic disorders, hypocoagulability, or severe anemia. 5.3 Mifepristone REMS Program Mifepristone tablets, 200 mg is available only through a restricted program under a REMS called the mifepristone REMS Program, because of the risks of serious complications [see Warnings and Precautions ( 5.1 , 5.2 )] Notable requirements of the mifepristone REMS Program include the following: Prescribers must be certified with the program by completing the Prescriber Agreement Form Patients must sign a Patient Agreement Form Mifepristone tablets, 200 mg must be dispensed to patients by or under the supervision of a certified prescriber, or by certified pharmacies on prescriptions issued by certified prescribers Further information is available at 1-855-MIFEINFO (1-855-643-3463). 5.4 Ectopic Pregnancy Mifepristone tablets, 200 mg is contraindicated in patients with a confirmed or suspected ectopic pregnancy because mifepristone is not effective for terminating ectopic pregnancies [see Contraindications ( 4 )]. Healthcare providers should remain alert to the possibility that a patient who is undergoing a medical abortion could have an undiagnosed ectopic pregnancy because some of the expected symptoms experienced with a medical abortion (abdominal pain, uterine bleeding) may be similar to those of a ruptured ectopic pregnancy. The presence of an ectopic pregnancy may have been missed even if the patient underwent ultrasonography prior to being prescribed Mifepristone tablets, 200 mg. Patients who became pregnant with an IUD in place should be assessed for ectopic pregnancy. 5.5 Rhesus Immunization The use of Mifepristone tablets, 200 mg is assumed to require the same preventive measures as those taken prior to and during surgical abortion to prevent rhesus immunization.

5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions, Including Anaphylaxis and Bronchospasm : Discontinue ondansetron if suspected. Monitor and treat promptly per standard of care until signs and symptoms resolve. ( 5.1 ) QT Interval Prolongation and Torsade de Pointes : Avoid ondansetron in patients with congenital long QT syndrome; monitor with electrocardiograms (ECGs) if concomitant electrolyte abnormalities, cardiac failure or arrhythmias, or use of other QT prolonging drugs. ( 5.2 ) Serotonin Syndrome : Reported with 5-HT 3 receptor antagonists alone but particularly with concomitant use of serotonergic drugs. If such symptoms occur, discontinue ondansetron and initiate supportive treatment. If concomitant use of ondansetron with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome. ( 5.3 ) Myocardial Ischemia : Monitor or advise patients for signs and symptoms of myocardial ischemia after oral administration. ( 5.4 ) Masking of Progressive Ileus and/or Gastric Distension Following Abdominal Surgery or Chemotherapy-Induced Nausea and Vomiting : Monitor for decreased bowel activity, particularly in patients with risk factors for gastrointestinal obstruction. ( 5.5 ) Phenylketonuria: Patients should be informed that ondansetron orally disintegrating tablets contain phenylalanine (a component of aspartame). Each 4 mg orally disintegrating tablet contains 1.68 mg phenylalanine and 8 mg orally disintegrating tablet contains 3.37 mg phenylalanine. ( 5.6 ) 5.1 Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis and bronchospasm, have been reported in patients who have exhibited hypersensitivity to other selective 5-HT 3 receptor antagonists. If hypersensitivity reactions occur, discontinue use of ondansetron; treat promptly per standard of care and monitor until signs and symptoms resolve [see Contraindications (4) ] . 5.2 QT Prolongation Electrocardiogram (ECG) changes, including QT interval prolongation have been seen in patients receiving ondansetron. In addition, postmarketing cases of Torsade de Pointes have been reported in patients using ondansetron. Avoid ondansetron in patients with congenital long QT syndrome. ECG monitoring is recommended in patients with electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, bradyarrhythmias, or patients taking other medicinal products that lead to QT prolongation [see Clinical Pharmacology (12.2) ] . 5.3 Serotonin Syndrome The development of serotonin syndrome has been reported with 5-HT 3 receptor antagonists alone. Most reports have been associated with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and intravenous methylene blue). Some of the reported cases were fatal. Serotonin syndrome occurring with overdose of ondansetron alone has also been reported. The majority of reports of serotonin syndrome related to 5-HT 3 receptor antagonist use occurred in a post-anesthesia care unit or an infusion center. Symptoms associated with serotonin syndrome may include the following combination of signs and symptoms: mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, with or without gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of ondansetron and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue ondansetron and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if ondansetron is used concomitantly with other serotonergic drugs [see Drug Interactions (7.1) , Overdosage (10) ] . 5.4 Myocardial Ischemia Myocardial ischemia has been reported in patients treated with ondansetron. In some cases, predominantly during intravenous administration, the symptoms appeared immediately after administration but resolved with prompt treatment. Coronary artery spasm appears to be the most common underlying cause. Therefore, monitor or advise patients for signs or symptoms of myocardial ischemia after oral administration of ondansetron [see Adverse Reactions (6.2) ]. 5.5 Masking of Progressive Ileus and Gastric Distension The use of ondansetron in patients following abdominal surgery or in patients with chemotherapy-induced nausea and vomiting may mask a progressive ileus and/or gastric distension. Monitor for decreased bowel activity, particularly in patients with risk factors for gastrointestinal obstruction. Ondansetron is not a drug that stimulates gastric or intestinal peristalsis. It should not be used instead of nasogastric suction. 5.6 Phenylketonuria Phenylketonuric patients should be informed that ondansetron orally disintegrating tablets contain phenylalanine (a component of aspartame). Each 4 mg orally disintegrating tablet contains 1.68 mg phenylalanine and 8 mg orally disintegrating tablet contains 3.37 mg phenylalanine.

<table width="85%"><tbody><tr><td align="center" styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold">Adverse Reaction</content></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold"># US studies </content></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold">Number of Evaluable Women </content></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold">Range of frequency (%) </content></td><td align="center" styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold">Upper Gestational Age of Studies Reporting Outcome </content></td></tr><tr><td align="center" styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold">Nausea</content></td><td align="center" styleCode="Botrule Lrule Rrule Toprule">3</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">1,248</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">51-75%</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">70 days</td></tr><tr><td align="center" styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold">Weakness</content></td><td align="center" styleCode="Botrule Lrule Rrule Toprule">2</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">630</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">55-58%</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">63 days</td></tr><tr><td align="center" styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold">Fever/chills</content></td><td align="center" styleCode="Botrule Lrule Rrule Toprule">1</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">414</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">48%</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">63 days</td></tr><tr><td align="center" styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold">Vomiting</content></td><td align="center" styleCode="Botrule Lrule Rrule Toprule">3</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">1,248</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">37-48%</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">70 days</td></tr><tr><td align="center" styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold">Headache</content></td><td align="center" styleCode="Botrule Lrule Rrule Toprule">2</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">630</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">41-44%</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">63 days</td></tr><tr><td align="center" styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold">Diarrhea</content></td><td align="center" styleCode="Botrule Lrule Rrule Toprule">3</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">1,248</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">18-43%</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">70 days</td></tr><tr><td align="center" styleCode="Botrule Lrule Rrule Toprule"><content styleCode="bold">Dizziness</content></td><td align="center" styleCode="Botrule Lrule Rrule Toprule">2</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">630</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">39-41%</td><td align="center" styleCode="Botrule Lrule Rrule Toprule">63 days</td></tr></tbody></table>

<table width="85%"><tfoot><tr><td align="left" colspan="3" valign="top"><paragraph>NR= Not reported</paragraph><paragraph>^*This outcome represents a single patient who experienced death related to sepsis. </paragraph></td></tr></tfoot><tbody><tr><td align="center" rowspan="2" styleCode="Rrule Lrule Toprule Botrule "><content styleCode="bold">Adverse Reaction </content></td><td align="center" styleCode="Rrule Lrule Toprule Botrule "><content styleCode="bold">US </content></td><td align="center" colspan="5" styleCode="Rrule Lrule Toprule Botrule "><content styleCode="bold">Non-US</content></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule "><content styleCode="bold"># of studies</content></td><td align="center" styleCode="Rrule Lrule Toprule Botrule "><content styleCode="bold">Number of Evaluable Women</content></td><td align="center" styleCode="Rrule Lrule Toprule Botrule "><content styleCode="bold">Range of frequency (%) </content></td><td align="center" styleCode="Rrule Lrule Toprule Botrule "><content styleCode="bold"># of studies </content></td><td align="center" styleCode="Rrule Lrule Toprule Botrule "><content styleCode="bold">Number of Evaluable Women </content></td><td align="center" styleCode="Rrule Lrule Toprule Botrule "><content styleCode="bold">Range of frequency (%) </content></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule "><content styleCode="bold">Transfusion</content></td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">4</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">17,774</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">0.03-0.5%</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">3</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">12,134</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">0-0.1%</td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule "><content styleCode="bold">Sepsis</content></td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">1</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">629</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">0.2%</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">1</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">11,155</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">&lt;0.01% ^*</td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule "><content styleCode="bold">ER visit</content></td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">2</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">1,043</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">2.9-4.6%</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">1</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">95</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">0</td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule "><content styleCode="bold">Hospitalization Related to Medical Abortion </content></td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">3</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">14,339</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">0.04-0.6%</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">3</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">1,286</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">0-0.7%</td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule "><content styleCode="bold">Infection without sepsis </content></td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">1</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">216</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">0</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">1</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">11,155</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">0.2%</td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule "><content styleCode="bold">Hemorrhage</content></td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">NR</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">NR</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">NR</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">1</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">11,155</td><td align="center" styleCode="Rrule Lrule Toprule Botrule ">0.1%</td></tr></tbody></table>

<table border="0" cellpadding="0" cellspacing="0" width="100%"><caption>Table 3: Most Common Adverse Reactions in Adults ^a for the Prevention of Nausea and Vomiting Associated With Moderately Emetogenic Chemotherapy [Primarily Cyclophosphamide-based Regimens] </caption><col width="27.42%"/><col width="36.3%"/><col width="36.28%"/><tfoot><tr><td colspan="3">^a Reported in greater than or equal to 5% of patients treated with ondansetron orally disintegrating tablets and at a rate that exceeded placebo. </td></tr></tfoot><tbody><tr styleCode="Botrule"><td align="center" styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Adverse Reaction</content> </td><td align="center" styleCode="Rrule" valign="middle"><content styleCode="bold">Ondansetron Orally </content> <content styleCode="bold">Disintegrating Tablets </content> <content styleCode="bold">8 mg Twice Daily</content> <content styleCode="bold">(n</content><content styleCode="bold"> = 242)</content> </td><td align="center" styleCode="Rrule" valign="middle"><content styleCode="bold">Placebo</content> <content styleCode="bold">(n</content><content styleCode="bold"> = 262)</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> Headache </td><td align="center" styleCode="Rrule" valign="middle">58 (24%) </td><td align="center" styleCode="Rrule" valign="middle">34 (13%) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> Malaise/Fatigue </td><td align="center" styleCode="Rrule" valign="middle">32 (13%) </td><td align="center" styleCode="Rrule" valign="middle">6 (2%) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> Constipation </td><td align="center" styleCode="Rrule" valign="middle">22 (9%) </td><td align="center" styleCode="Rrule" valign="middle">1 (&lt; 1%) </td></tr><tr><td styleCode="Lrule Rrule" valign="middle"> Diarrhea </td><td align="center" styleCode="Rrule" valign="middle">15 (6%) </td><td align="center" styleCode="Rrule" valign="middle">10 (4%) </td></tr></tbody></table>

<table border="0" cellpadding="0" cellspacing="0" width="98%"><caption>Table 4: Most Common Adverse Reactions in Adults ^a for the Prevention of Postoperative Nausea and Vomiting </caption><col width="32.58%"/><col width="33.7%"/><col width="33.7%"/><tfoot><tr><td colspan="3">^a Reported in greater than or equal to 5% of patients treated with ondansetron orally disintegrating tablets and at a rate that exceeded placebo. </td></tr></tfoot><tbody><tr styleCode="Botrule"><td align="center" styleCode="Lrule Rrule" valign="middle"><content styleCode="bold">Adverse Reaction</content> </td><td align="center" styleCode="Rrule" valign="middle"><content styleCode="bold">Ondansetron Orally </content> <content styleCode="bold">Disintegrating Tablets </content> <content styleCode="bold"/><content styleCode="bold">16 mg as a Single Dose</content> <content styleCode="bold">(n</content><content styleCode="bold"> = 550)</content> </td><td align="center" styleCode="Rrule" valign="middle"><content styleCode="bold">Placebo </content> <content styleCode="bold"/><content styleCode="bold"> (n</content><content styleCode="bold"> = 531)</content> </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Headache </td><td align="center" styleCode="Rrule" valign="top">49 (9%) </td><td align="center" styleCode="Rrule" valign="top">27 (5%) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Hypoxia </td><td align="center" styleCode="Rrule" valign="top">49 (9%) </td><td align="center" styleCode="Rrule" valign="top">35 (7%) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Pyrexia </td><td align="center" styleCode="Rrule" valign="top">45 (8%) </td><td align="center" styleCode="Rrule" valign="top">34 (6%) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Dizziness </td><td align="center" styleCode="Rrule" valign="top">36 (7%) </td><td align="center" styleCode="Rrule" valign="top">34 (6%) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Gynecological disorder </td><td align="center" styleCode="Rrule" valign="top">36 (7%) </td><td align="center" styleCode="Rrule" valign="top">33 (6%) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Anxiety/Agitation </td><td align="center" styleCode="Rrule" valign="top">33 (6%) </td><td align="center" styleCode="Rrule" valign="top">29 (5%) </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="top"> Urinary retention </td><td align="center" styleCode="Rrule" valign="top">28 (5%) </td><td align="center" styleCode="Rrule" valign="top">18 (3%) </td></tr><tr><td styleCode="Lrule Rrule" valign="top"> Pruritus </td><td align="center" styleCode="Rrule" valign="top">27 (5%) </td><td align="center" styleCode="Rrule" valign="top">20 (4%) </td></tr></tbody></table>