Boxed WARNINGS: Cardiomyopathy- Trastuzumab products administration can result in sub-clinical and clinical cardiac failure.
The incidence and severity was highest in patients receiving trastuzumab with anthracycline-containing chemotherapy regimens

• Evaluate left ventricular function in all patients prior to and during treatment with KANJINTI^®. Discontinue KANJINTI^® treatment in patients receiving adjuvant therapy and withhold KANJINTI^® in patients with metastatic disease for clinically significant decrease in left ventricular function

Infusion Reactions; Pulmonary Toxicity- Trastuzumab products administration can result in serious and fatal infusion reactions and pulmonary toxicity. Symptoms usually occur during or within 24 hours of administration. Interrupt KANJINTI^® infusion for dyspnea or clinically significant hypotension. Monitor patients until symptoms completely resolve. Discontinue KANJINTI^® for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome

Embryo-Fetal Toxicity- Exposure to trastuzumab products during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception

Additional Important Safety Information

Cardiomyopathy

• Administration of trastuzumab products can result in sub-clinical and clinical cardiac failure. The incidence and severity was highest in patients receiving trastuzumab with anthracycline-containing chemotherapy regimens. In a pivotal adjuvant breast cancer trial, one patient who developed CHF died of cardiomyopathy
• Trastuzumab products can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death
• Trastuzumab products can also cause asymptomatic decline in left ventricular ejection fraction (LVEF)
• Discontinue KANJINTI^® treatment in patients receiving adjuvant breast cancer therapy and withhold KANJINTI^® in patients with metastatic disease for clinically significant decrease in left ventricular function

Cardiac Monitoring

• Evaluate cardiac function prior to and during treatment. For adjuvant breast cancer therapy, also evaluate cardiac function after completion of KANJINTI^®
• Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan
• Monitor frequently for decreased left ventricular function during and after KANJINTI^® treatment
• Monitor more frequently if KANJINTI^® is withheld for significant left ventricular cardiac dysfunction

Infusion Reactions

• KANJINTI^® administration can result in serious and fatal infusion reactions
• Symptoms usually occur during or within 24 hours of KANJINTI^® administration
• Interrupt KANJINTI^® infusion for dyspnea or clinically significant hypotension
• Monitor patients until symptoms completely resolve
• Discontinue KANJINTI^® for infusion reactions manifesting as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. Strongly consider permanent discontinuation in all patients with severe infusion reactions
• Infusion reactions consist of a symptom complex characterized by fever and chills, and on occasion include nausea, vomiting, pain (in some cases at tumor sites), headache, dizziness, dyspnea, hypotension, rash, and asthenia

Embryo-Fetal Toxicity

• Exposure to trastuzumab products during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception
• Verify the pregnancy status of females of reproductive potential prior to the initiation of KANJINTI^®
• Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of KANJINTI^®. Advise female patients to contact their healthcare provider with a known or suspected pregnancy
• Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for KANJINTI^® treatment and any potential adverse effects on the breastfed child from KANJINTI^® or from the underlying maternal condition

Pulmonary Toxicity

• Trastuzumab products can result in serious and fatal pulmonary toxicity, which includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, noncardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as sequelae of infusion reactions
• Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity
• Discontinue KANJINTI^® in patients experiencing pulmonary toxicity

Exacerbation of Chemotherapy-Induced Neutropenia

• In randomized, controlled clinical trials, the per-patient incidences of NCI-CTC Grade 3-4 neutropenia and of febrile neutropenia were higher in patients receiving trastuzumab in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was similar among patients who received trastuzumab and those who did not

Most Common Adverse Reactions

• The most common adverse reactions associated with trastuzumab products in breast cancer were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia
• The most common adverse reactions associated with trastuzumab products in metastatic gastric cancer were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Amgen at 1-800-772-6436.

Please see full Prescribing Information, including Boxed WARNINGS.

Serious adverse reactions (Warnings and Precautions)

• Serious and sometimes fatal adverse reactions with increased incidence in the bevacizumab-treated arm vs chemotherapy arm included:

• Gastrointestinal (GI) perforation ranged from 0.3% to 3% of patients across clinical studies
• Non-GI fistulae (<1% to 1.8%, highest in patients with cervical cancer)
• Arterial thromboembolic events (Grade ≥3, 5%, highest in patients with GBM)
• The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in MVASI^®-treated patients
• Hemorrhage (Grade 3-5) ranged from 0.4% to 7% of patients across clinical studies
• Renal injury and proteinuria

• Grade 3-4 proteinuria ranged from 0.7% to 7% in clinical studies
• Nephrotic syndrome (<1%)

• Additional serious adverse reactions with increased incidence in the bevacizumab-treated arm vs chemotherapy arm included:

• Venous thromboembolism (Grade ≥3, 11% seen in GOG-0240)
• Hypertension (Grade 3-4, 5%-18%)
• Posterior reversible encephalopathy syndrome (PRES) (<0.5%)
• Congestive heart failure (CHF): Grade ≥3 left ventricular dysfunction (1%)

• Infusion-related reactions, including but not limited to anaphylactoid/anaphylactic reactions, have occurred. In clinical studies, iInfusion-related reactions with the first dose of bevacizumab occurred in <3% of patients, and severe reactions occurred in 0.4% of patients

• Avoid use in patients with ovarian cancer who have evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction

• Inform females of reproductive potential of the risk of ovarian failure prior to initiating treatment with MVASI^®

Pregnancy warning

• Based on the mechanism of action and animal studies, MVASI^® may cause fetal harm
• Advise female patients that MVASI^® may cause fetal harm, and to inform their healthcare provider of a known or suspected pregnancy
• Advise females of reproductive potential to use effective contraception during treatment with MVASI^® and for 6 months after the last dose of MVASI^®
• Advise nursing women not to breastfeed during treatment with MVASI^® and for 6 months following their last dose of treatment
• MVASI^® may impair fertility

Most common adverse reactions

• Across studies, the most common adverse reactions observed in bevacizumab patients at a rate >10% were:

• Epistaxis
• Headache
• Hypertension
• Rhinitis

• Proteinuria
• Taste alteration
• Dry skin
• Hemorrhage

• Lacrimation disorder
• Back pain
• Exfoliative dermatitis

Indication-specific adverse reactions

• In CC, Grade 3 or 4 adverse reactions in Study GOG-0240, occurring at a higher incidence (≥2%) in 218 patients receiving bevacizumab plus chemotherapy compared to 222 patients receiving chemotherapy alone, were abdominal pain (12% vs 10%), diarrhea (6% vs 3%), anal fistula (4% vs 0%), proctalgia (3% vs 0%), urinary tract infection (8% vs 6%), cellulitis (3% vs 0.5%), fatigue (14% vs 10%), hypertension (11% vs 0.5%), thrombosis (8% vs 3%), hypokalemia (7% vs 4%), hyponatremia (4% vs 1%), dehydration (4% vs 0.5%), neutropenia (8% vs 4%), lymphopenia (6% vs 3%), back pain (6% vs 3%), and pelvic pain (6% vs 1%)
• In mRCC, the most common Grade 3-5 adverse reactions in AVOREN, occurring at a >2% higher incidence in bevacizumab-treated patients vs controls, were fatigue (13% vs 8%), asthenia (10% vs 7%), proteinuria (7% vs 0%), hypertension (6% vs 1%, including hypertension and hypertensive crisis), and hemorrhage (3% vs 0.3%; including epistaxis, small intestinal hemorrhage, aneurysm ruptured, gastric ulcer hemorrhage, gingival bleeding, hemoptysis, hemorrhage intracranial, large intestinal hemorrhage, respiratory tract hemorrhage, and traumatic hematoma)
• In rGBM Study EORTC 26101, the incidence of Grade 3-4 VTE was 5% in patients receiving bevacizumab with chemotherapy compared to 2% in patients receiving chemotherapy alone. In this study, 22% of patients discontinued treatment in the bevacizumab with lomustine arm due to adverse reactions compared with 10% of patients in the lomustine arm. In patients receiving bevacizumab with lomustine, the adverse reaction profile was similar to that observed in other approved indications
• In NSCLC, Grade 3-5 (nonhematologic) and Grade 4-5 (hematologic) adverse reactions in Study E4599 occurring at a ≥2% higher incidence in bevacizumab-treated patients vs controls were neutropenia (27% vs 17%), fatigue (16% vs 13%), hypertension (8% vs 0.7%), infection without neutropenia (7% vs 3%), venous thromboembolism (5% vs 3%), febrile neutropenia (5% vs 2%), pneumonitis/pulmonary infiltrates (5% vs 3%), infection with Grade 3 or 4 neutropenia (4% vs 2%), hyponatremia (4% vs 1%), headache (3% vs 1%), and proteinuria (3% vs 0%)
• In first-line MCRC, the most common Grade 3-4 reactions in Study 2107, which occurred at a ≥2% higher incidence in the bevacizumab plus IFL vs IFL groups, were asthenia (10% vs 7%), abdominal pain (8% vs 5%), pain (8% vs 5%), hypertension (12% vs 2%), deep vein thrombosis (9% vs 5%), intra-abdominal thrombosis (3% vs 1%), syncope (3% vs 1%), diarrhea (34% vs 25%), constipation (4% vs 2%), leukopenia (37% vs 31%), and neutropenia (21% vs 14%)
• In second-line MCRC, the most common Grade 3-5 (nonhematologic) and 4-5 (hematologic) reactions in Study E3200, which occurred at a higher incidence (≥2%) in the bevacizumab plus FOLFOX4 vs FOLFOX4 groups, were fatigue (19% vs 13%), diarrhea (18% vs 13%), sensory neuropathy (17% vs 9%), nausea (12% vs 5%), vomiting (11% vs 4%), dehydration (10% vs 5%), hypertension (9% vs 2%), abdominal pain (8% vs 5%), hemorrhage (5% vs 1%), other neurological (5% vs 3%), ileus (4% vs 1%), and headache (3% vs 0%). These data are likely to underestimate the true adverse event rates due to the reporting mechanisms used in this study
• When continued beyond first progression in mCRC, no new safety signals were observed in the TML study (ML18147) when bevacizumab was administered in second-line mCRC patients who progressed on a bevacizumab containing regimen in first-line mCRC. The safety data was consistent with the known safety profile established in first- and second-line mCRC
• In Stage III or IV OC after primary surgery, 608 patients received CP+Avastin→Avastin, 607 patients received CP+Avastin→PBO, and 602 patients received CP+PBO→PBO. Grade 3-4 adverse reactions occurring at a higher incidence (≥2%) in either of the Avastin arms vs the chemotherapy only arm were fatigue (CP+Avastin→Avastin, 9%; CP+Avastin→PBO, 6%; CP+PBO→PBO, 6%), hypertension (CP+Avastin→Avastin, 10%; CP+Avastin→PBO, 6%; CP+PBO→PBO, 2%), platelet count decreased (CP+Avastin→Avastin, 21%; CP+Avastin→PBO, 20%; CP+PBO→PBO, 15%), and white blood cell count decreased (CP+Avastin→Avastin, 51%; CP+Avastin→PBO, 53%; CP+PBO→PBO, 50%)
• In platinum-sensitive recurrent OC, Grade 3 or 4 adverse reactions in the OCEANS study occurring at a higher incidence (≥2%) in 247 patients receiving Avastin plus carboplatin and gemcitabine (chemotherapy), compared to 233 patients receiving placebo plus chemotherapy, were thrombocytopenia (40% vs 34%), nausea (4% vs 1.3%), fatigue (6% vs 4%), headache (4% vs 0.9%), proteinuria (10% vs 0.4%), dyspnea (4% vs 1.7%), epistaxis (5% vs 0.4%), and hypertension (17% vs 0.9%)
• In platinum-sensitive recurrent OC, Grade 3 or 4 adverse reactions in the GOG-0213 study occurring at a higher incidence (≥2%) in 325 patients receiving Avastin plus carboplatin and paclitaxel (chemotherapy), compared to 332 patients receiving chemotherapy alone, were hypertension (11% vs 0.6%), fatigue (8% vs 3%), febrile neutropenia (6% vs 3%), proteinuria (8% vs 0%), abdominal pain (6% vs 0.9%), hyponatremia (4% vs 0.9%), headache (3% vs 0.9%), and pain in extremity (3.4% vs 0%)
• In platinum-resistant recurrent OC, Grade 3-4 adverse reactions in AURELIA occurring at a higher incidence (≥2%) in 179 patients receiving Avastin plus chemotherapy, compared to 181 patients receiving chemotherapy alone, were hypertension (6.7% vs 1.1%) and palmarplantar erythrodysaesthesia syndrome (4.5% vs 1.7%)

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Amgen at 1-800-772-6436.

Please see full Prescribing Information, for additional Important Safety Information.

Indications

MVASI^® is a vascular endothelial growth factor inhibitor indicated for the treatment of:

MVASI^®, in combination with intravenous fluorouracil-based chemotherapy, is indicated for the first- or second-line treatment of patients with metastatic colorectal cancer (mCRC).

MVASI^®, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy, is indicated for the second-line treatment of patients with mCRC who have progressed on a first-line bevacizumab product-containing regimen.

Limitations of Use: MVASI^® is not indicated for adjuvant treatment of colon cancer.

MVASI^®, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer (NSCLC).

MVASI^® is indicated for the treatment of recurrent glioblastoma (GBM) in adults.

MVASI^®, in combination with interferon-alfa, is indicated for the treatment of metastatic renal cell carcinoma (mRCC).

MVASI^®, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer (CC).

MVASI^®, in combination with carboplatin and paclitaxel, followed by MVASI as a single agent, is indicated for the treatment of patients with stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgical resection (OC).

MVASI^®, in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan, is indicated for the treatment of patients with platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who received no more than 2 prior chemotherapy regimens (OC).

MVASI^®, in combination with carboplatin and paclitaxel, or with carboplatin and gemcitabine, followed by MVASI as a single agent, is indicated for the treatment of patients with platinumsensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (OC).

Avastin^® (bevacizumab) is a registered trademark of Genentech USA, Inc.

BOXED WARNINGS: FATAL INFUSION-RELATED REACTIONS, SEVERE MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS REACTIVATION, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

• Infusion-Related Reactions: Rituximab product administration can result in serious, including fatal, infusion-related reactions. Deaths within 24 hours of rituximab infusion have occurred. Approximately 80% of fatal infusion-related reactions occurred in association with the first infusion. Monitor patients closely. Discontinue RIABNI^® infusion for severe reactions and provide medical treatment for Grade 3 or 4 infusion-related reactions.
• Severe Mucocutaneous Reactions: Severe, including fatal, mucocutaneous reactions can occur in patients receiving rituximab products. Discontinue RIABNI^® in patients who experience a severe mucocutaneous reaction. The safety of readministration of RIABNI^® to patients with severe mucocutaneous reactions has not been determined.
• Hepatitis B Virus (HBV) Reactivation: HBV reactivation can occur in patients treated with rituximab products, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection before treatment initiation, and monitor patients during and after treatment with RIABNI^®. Discontinue RIABNI^® and concomitant medications in the event of HBV reactivation.
• Progressive Multifocal Leukoencephalopathy (PML), including fatal PML, can occur in patients receiving rituximab products. Discontinue RIABNI^® and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML.

Warnings and Precautions

Infusion-Related Reactions (IRR)

• Rituximab products can cause severe, including fatal, infusion-related reactions. Severe reactions typically occurred during the first infusion with time to onset of 30-120 minutes.
• Rituximab-product-induced infusion-related reactions and sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, anaphylactoid events, or death.
• Premedicate patients with an antihistamine and acetaminophen prior to dosing. Institute medical management (e.g., glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusion-related reactions as needed. Depending on the severity of the infusion-related reaction and the required interventions, temporarily or permanently discontinue RIABNI^®. Resume infusion at a minimum 50% reduction in rate after symptoms have resolved.
• Closely monitor the following patients: those with preexisting cardiac or pulmonary conditions, those who experienced prior cardiopulmonary adverse reactions, and those with high numbers of circulating malignant cells (≥25,000/mm³).

Severe Mucocutaneous Reactions

• Mucocutaneous reactions, some with fatal outcome, can occur in patients treated with rituximab products. These reactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis.
• The onset of these reactions has been variable and includes reports with onset on the first day of rituximab exposure. Discontinue RIABNI^® in patients who experience a severe mucocutaneous reaction. The safety of readministration of rituximab products to patients with severe mucocutaneous reactions has not been determined.

Hepatitis B Virus Reactivation

• Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs classified as CD20-directed cytolytic antibodies, including rituximab products. Cases have been reported in patients who are hepatitis B surface antigen (HBsAg) positive and also in patients who are HBsAg negative but are hepatitis B core antibody (anti-HBc) positive. Reactivation also has occurred in patients who appear to have resolved hepatitis B infection (i.e., HBsAg negative, anti-HBc positive, and hepatitis B surface antibody [anti-HBs] positive).
• HBV reactivation is defined as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level or detection of HBsAg in a person who was previously HBsAg negative and anti-HBc positive. Reactivation of HBV replication is often followed by hepatitis, i.e., increase in transaminase levels. In severe cases, increase in bilirubin levels, liver failure, and death can occur.
• Screen all patients for HBV infection by measuring HBsAg and anti-HBc before initiating treatment with RIABNI^®. For patients who show evidence of prior hepatitis B infection (HBsAg positive [regardless of antibody status] or HBsAg negative but anti-HBc positive), consult with physicians with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy before and/or during RIABNI^® treatment.
• Monitor patients with evidence of current or prior HBV infection for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following RIABNI^® therapy. HBV reactivation has been reported up to 24 months following completion of rituximab therapy.
• In patients who develop reactivation of HBV while on RIABNI^®, immediately discontinue RIABNI^® and any concomitant chemotherapy, and institute appropriate treatment. Insufficient data exist regarding the safety of resuming rituximab product treatment in patients who develop HBV reactivation. Resumption of RIABNI^® treatment in patients whose HBV reactivation resolves should be discussed with physicians with expertise in managing HBV.

Progressive Multifocal Leukoencephalopathy (PML)

• JC virus infection resulting in multifocal leukoencephalopathy (PML) and death can occur in rituximab product-treated patients with hematologic malignancies or with autoimmune diseases. The majority of patients with hematologic malignancies diagnosed with PML received rituximab in combination with chemotherapy or as part of a hematopoietic stem cell transplant. The patients with autoimmune diseases had prior or concurrent immunosuppressive therapy. Most cases of PML were diagnosed within 12 months of their last infusion of rituximab.
• Consider the diagnosis of PML in any patient presenting with new-onset neurologic manifestations. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Discontinue RIABNI^® and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML.

Tumor Lysis Syndrome

• Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, some fatal, can occur within 12–24 hours after the first infusion of RIABNI^® in patients with non-Hodgkin's lymphoma (NHL). A high number of circulating malignant cells (≥25,000/mm³), or high tumor burden, confers a greater risk of TLS.
• Administer aggressive intravenous hydration and anti-hyperuricemic therapy in patients at high risk for TLS. Correct electrolyte bnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis as indicated.

Infections

• Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of rituximab product-based therapy. Infections have been reported in some patients with prolonged hypogammaglobulinemia (defined as hypogammaglobulinemia >11 months after rituximab exposure).
• New or reactivated viral infections included cytomegalovirus, herpes simplex virus, parvovirus B19, varicella zoster virus, West Nile virus, and hepatitis B and C. Discontinue RIABNI^® for serious infections and institute appropriate anti-infective therapy.
• RIABNI^® is not recommended for use in patients with severe, active infections.

Cardiovascular Adverse Reactions

• Cardiac adverse reactions, including ventricular fibrillation, myocardial infarction, and cardiogenic shock may occur in patients receiving rituximab products. Discontinue infusions for serious or life-threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of RIABNI^® for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina.

Renal Toxicity

• Severe, including fatal, renal toxicity can occur after rituximab product administration in patients with NHL. Renal toxicity has occurred in patients who experience TLS and in patients with NHL administered concomitant cisplatin therapy during clinical trials. The combination of cisplatin and RIABNI^® is not an approved treatment regimen. Monitor closely for signs of renal failure and discontinue RIABNI^® in patients with a rising serum creatinine or oliguria.

Bowel Obstruction and Perforation

• Abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving rituximab products in combination with chemotherapy. In postmarketing reports, the mean time to documented gastrointestinal perforation was 6 (range 1–77) days in patients with NHL. Evaluate if symptoms of obstruction such as abdominal pain or repeated vomiting occur.

Immunization

• The safety of immunization with live viral vaccines following rituximab product therapy has not been studied, and vaccination with live virus vaccines is not recommended before or during treatment.
• For patients treated with RIABNI^®, physicians should review the patient's vaccination status and patients should, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating RIABNI^®; administer non-live vaccines at least 4 weeks prior to a course of RIABNI^®.

Embryo-Fetal Toxicity

• Based on human data, rituximab products can cause fetal harm due to B-cell lymphocytopenia in infants exposed in utero. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception with RIABNI^® and for 12 months after the last dose.

Additional Important Safety Information

Adverse Reactions

• The most common Grade 3 or 4 adverse reactions in clinical trials of NHL and chronic lymphocytic leukemia (CLL) were infusion related reactions, neutropenia, leukopenia, anemia, thrombocytopenia, and infections. Additionally, lymphopenia and lung disorder were seen in NHL trials; and febrile neutropenia, pancytopenia, hypotension, and hepatitis B were seen in CLL trials.
• The most common adverse reactions (incidence ≥25%) in clinical trials of NHL and CLL were infusion-related reactions. Additionally, fever, lymphopenia, chills, infection, and asthenia were seen in NHL trials; and neutropenia was seen in CLL trials.

Pregnancy and Nursing Mothers

• Based on human data, rituximab products can cause adverse developmental outcomes including B-cell lymphocytopenia in infants exposed in utero. Advise pregnant women of the risk to a fetus. There are limited data on the presence of rituximab products in human milk and the effect on the breastfed child, and there are no data on the effect on milk production. Rituximab is detected in the milk of lactating cynomolgus monkeys, and maternal IgG is present in human breast milk. Rituximab has also been reported to be excreted at low concentrations in human breast milk. Given that the clinical significance of this finding for children is not known, advise women not to breastfeed during treatment with RIABNI^® and for 6 months after the last dose due to the potential of serious adverse events in breastfed children.

Attention Healthcare Provider: Provide Medication Guide to patient prior to RIABNI^® infusion and advise patients to read guide.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Amgen at 1-800-772-6436.

Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide, for additional Important Safety Information.

INDICATIONS

• Non-Hodgkin's Lymphoma (NHL)
RIABNI^® (rituximab-arrx) is indicated for the treatment of adult patients with:

• Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent.
• Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy.
• Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy.
• Previously untreated diffuse large B-cell, CD20-positive NHL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens.

• Chronic Lymphocytic Leukemia (CLL)
RIABNI, in combination with fludarabine and cyclophosphamide (FC), is indicated for the treatment of adult patients with previously untreated and previously treated CD20-positive CLL.