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Avastin® (bevacizumab)
INDICATIONS AND IMPORTANT SAFETY INFORMATION
Indications
Metastatic Renal Cell Carcinoma (mRCC)
Avastin is indicated for the treatment of metastatic renal cell carcinoma in combination with interferon alfa.
Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
Avastin is indicated for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non–squamous non–small cell lung cancer in combination with carboplatin and paclitaxel.
Metastatic Colorectal Cancer (mCRC)
Avastin is indicated for the first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5–fluorouracil–based chemotherapy.
Boxed WARNINGS
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Gastrointestinal (GI) perforation |
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Serious and sometimes fatal GI perforation occurs at a higher incidence in Avastin-treated patients compared to controls |
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The incidences of GI perforation ranged from 0.3% to 2.4% across clinical studies |
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Discontinue Avastin in patients with GI perforation |
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Surgery and wound healing complications |
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The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in Avastin-treated patients |
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Do not initiate Avastin for at least 28 days after surgery and until the surgical wound is fully healed. The appropriate interval between termination of Avastin and subsequent elective surgery required to reduce the risks of impaired wound healing/wound dehiscence has not been determined |
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Discontinue Avastin at least 28 days prior to elective surgery and in patients with wound healing complications requiring medical intervention |
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Hemorrhage |
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Severe or fatal hemorrhage, including hemoptysis, GI bleeding, hematemesis, central nervous system hemorrhage, epistaxis, and vaginal bleeding, occurred up to 5-fold more frequently in patients receiving Avastin. Across indications, the incidence of grade >3 hemorrhagic events among patients receiving Avastin ranged from 1.2% to 4.6%
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Do not administer Avastin to patients with serious hemorrhage or recent hemoptysis (>1/2 tsp of red blood)
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Discontinue Avastin in patients with serious hemorrhage (ie, requiring medical intervention) |
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Additional serious adverse events
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Additional serious and sometimes fatal adverse events with increased incidence in the Avastin-treated arm vs control included |
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Non-GI fistula formation (<0.3%) |
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Arterial thromboembolic events (grade >3, 2.4%) |
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Proteinuria including nephrotic syndrome (<1%) |
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Additional serious adverse events with increased incidence in the Avastin-treated arm vs control included |
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Hypertension (grade 3–4, 5%–18%) |
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Reversible posterior leukoencephalopathy syndrome (RPLS) (<0.1%) |
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Infusion reactions with the first dose of Avastin were uncommon (<3%), and severe reactions occurred in 0.2% of patients |
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Inform females of reproductive potential of the risk of ovarian failure prior to starting treatment with Avastin |
Most common adverse events
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Most common adverse reactions observed in Avastin patients at a rate >10% and at least twice the control arm rate were |
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— Epistaxis
— Headache
— Hypertension
— Rhinitis |
— Proteinuria
— Taste alteration
— Dry skin
— Rectal hemorrhage |
— Lacrimation disorder
— Back pain
— Exfoliative dermatitis |
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Across all studies, Avastin was discontinued in 8.4% to 21% of patients because of adverse reactions |
Pregnancy warning
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Avastin may impair fertility |
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Based on animal data, Avastin may cause fetal harm |
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Advise patients of the potential risk to the fetus during and following Avastin and the need to continue adequate contraception for at least 6 months following the last dose of Avastin |
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For nursing mothers, discontinue nursing or Avastin, taking into account the importance of Avastin to the mother
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In mRCC, the most common grade 3–5 adverse events in AVOREN, occurring at a >2% higher incidence in Avastin-treated patients vs controls, were fatigue (13% vs 8%), asthenia (10% vs 7%), proteinuria (7% vs 0%), hypertension (6% vs 1%), and hemorrhage (3% vs 0.3%)
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In NSCLC, grade 3–5 (nonhematologic) and grade 4–5 (hematologic) adverse events in Study E4599 occurring at a >2% higher incidence in Avastin-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 thrombus/embolism (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%)
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In first-line MCRC, the most common grade 3–4 events in Study 2107, which occurred at a >2% higher incidence in the Avastin 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%)
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In second-line MCRC, the most common grade 3–5 (nonhematologic) and 4–5 (hematologic) events in Study E3200, which occurred at a higher incidence (>2%) in the Avastin plus FOLFOX4 vs FOLFOX4 groups, were diarrhea (18% vs 13%), nausea (12% vs 5%), vomiting (11% vs 4%), dehydration (10% vs 5%), ileus (4% vs 1%), neuropathy–sensory (17% vs 9%), neurologic–other (5% vs 3%), fatigue (19% vs 13%), abdominal pain (8% vs 5%), headache (3% vs 0%), hypertension (9% vs 2%), and hemorrhage (5% vs 1%)
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Please see accompanying full prescribing information, including Boxed Warnings, for additional important safety information.
Herceptin® (trastuzumab)
INDICATIONS AND IMPORTANT SAFETY INFORMATION
Indications
Breast Cancer
Adjuvant indications
Herceptin is indicated for adjuvant treatment of HER2-overexpressing node-positive or node-negative (ER/PR-negative or with one high-risk feature*) breast cancer:
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As part of a treatment regimen containing doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel |
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With docetaxel and carboplatin |
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As a single agent following multi-modality anthracycline-based therapy |
*High-risk is defined as ER/PR positive with one of the following features: tumor size >2 cm, age <35 years, or tumor grade 2 or 3.
Metastatic indications
Herceptin is indicated:
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In combination with paclitaxel for the first line treatment of HER2-overexpressing metastatic breast cancer |
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As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease |
Gastric Cancer
Herceptin is indicated, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, who have not received prior treatment for metastatic disease.
Boxed WARNINGS and Additional Important Safety Information
Cardiomyopathy and Cardiac Monitoring
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Herceptin administration can result in sub-clinical and clinical cardiac failure. The incidence and severity was highest in patients receiving Herceptin with anthracycline-containing chemotherapy regimens. In a pivotal adjuvant breast cancer trial, one patient who developed CHF died of cardiomyopathy |
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Discontinue Herceptin treatment in patients receiving adjuvant breast cancer therapy and withhold Herceptin in patients with metastatic disease for clinically significant decrease in left ventricular function |
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Evaluate cardiac function prior to and during treatment. For adjuvant breast cancer therapy, also evaluate cardiac function after completion of Herceptin |
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Monitor frequently for decreased left ventricular function during and after Herceptin treatment. Monitor more frequently if Herceptin is withheld for significant left ventricular cardiac dysfunction
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Infusion Reactions and Pulmonary Toxicity
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Herceptin administration can result in serious and fatal infusion reactions and pulmonary toxicity |
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Symptoms usually occur during or within 24 hours of Herceptin administration |
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Interrupt Herceptin infusion for dyspnea or clinically significant hypotension |
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Monitor patients until symptoms completely resolve |
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Discontinue Herceptin for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome
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Embryo-Fetal Toxicity
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Exposure to Herceptin during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death |
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Advise women of the potential hazard to the fetus resulting from Herceptin exposure during pregnancy and provide contraception counseling to women of childbearing potential
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Exacerbation of Chemotherapy-Induced Neutropenia
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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 Herceptin in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone |
HER2 Testing
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Detection of HER2 protein overexpression is necessary for selection of patients appropriate for Herceptin therapy because these are the only patients studied and for whom benefit has been shown |
Most Common Adverse Reactions
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The most common adverse reactions associated with Herceptin in breast cancer were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia |
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The most common adverse reactions associated with Herceptin in metastatic gastric cancer were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia
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Please see the Herceptin full prescribing information including Boxed Warnings and additional important safety information.
Rituxan (rituximab)
INDICATIONS AND IMPORTANT SAFETY INFORMATION
RITUXAN® (Rituximab) is indicated for the treatment of patients with:
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Previously untreated follicular, CD20-positive, B-cell NHL in combination with first-line chemotherapy and, in patients achieving a complete or partial response to RITUXAN in combination with chemotherapy, as single-agent maintenance therapy |
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Relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL as a single agent
• Weekly x4 • Weekly x8 • Bulky disease • Retreatment |
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Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after first-line CVP chemotherapy |
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Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens |
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Previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC) |
RITUXAN is not recommended for use in patients with severe, active infections.
BOXED WARNINGS
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RITUXAN administration can result in serious, including fatal, adverse reactions. These include infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy (PML) |
Warnings and Precautions
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RITUXAN can also result in serious, including fatal, adverse reactions. These include hepatitis B reactivation with fulminant hepatitis and hepatic failure resulting in death; other infections, including bacterial, fungal, new or reactivated viral infections; cardiovascular events; severe, including fatal, renal toxicity; and abdominal pain, bowel obstruction and perforation, in some cases leading to death |
Additional Important Safety Information
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The most common adverse reactions of RITUXAN (incidence >25%) observed in clinical trials of patients with NHL were infusion reactions, fever, lymphopenia, chills, infection, and asthenia. The most frequent Grade 3 or 4 adverse reactions observed in NHL were cytopenias, including lymphopenia |
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The most common adverse reactions of RITUXAN (incidence >25%) observed in clinical trials of patients with CLL were infusion reactions and neutropenia. Most patients treated with R-FC experienced at least one Grade 3 or 4 adverse reaction. The most frequently reported Grade 3 or 4 adverse reaction was neutropenia |
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In clinical trials, CLL patients 70 years of age or older who received R-FC had more Grade 3 and 4 adverse reactions compared with younger CLL patients who received the same treatment
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For additional safety information, please see the full prescribing information, including BOXED WARNINGS and Medication Guide.
Attention Healthcare Provider: Provide Medication Guide to patient prior to RITUXAN infusion.
Tarceva® (erlotinib)
INDICATIONS AND IMPORTANT SAFETY INFORMATION
Indications
Non-small cell lung cancer (NSCLC)
Tarceva monotherapy is indicated for:
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the maintenance treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.
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the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen.
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Results from two, multicenter, placebo-controlled, randomized, phase III trials conducted in first-line patients with locally advanced or metastatic NSCLC showed no clinical benefit with the concurrent administration of Tarceva with platinum-based chemotherapy [carboplatin and paclitaxel or gemcitabine and cisplatin] and its use is not recommended in that setting.
Pancreatic cancer
Tarceva in combination with gemcitabine is indicated for the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer.
Important Safety Information
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There have been reports of serious interstitial lung disease (ILD)-like events, including fatalities, in patients receiving Tarceva for treatment of NSCLC, pancreatic cancer, or other advanced solid tumors. |
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Cases of hepatic failure, hepatorenal syndrome, acute renal failure (all including fatalities), and renal insufficiency have been reported during use of Tarceva. |
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Gastrointestinal perforation (including fatalities) has been reported in patients receiving Tarceva. |
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Bullous, blistering, and exfoliative skin conditions have been reported, including cases suggestive of Stevens-Johnson syndrome/toxic epidermal necrolysis, which in some cases were fatal. |
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In the pancreatic cancer trial, other serious adverse reactions associated with Tarceva plus gemcitabine and that may have included fatalities were myocardial infarction/ischemia, cerebrovascular accident, and microangiopathic hemolytic anemia with thrombocytopenia. |
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Corneal perforation and ulceration have been reported during use of Tarceva. |
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International Normalized Ratio (INR) elevations and infrequent reports of bleeding events, including gastrointestinal and non-gastrointestinal bleeding, have been reported in clinical studies. |
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Tarceva is pregnancy category D. When receiving Tarceva therapy, women should be advised to avoid pregnancy or breastfeeding. |
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The most common adverse reactions in patients with NSCLC receiving single-agent Tarceva 150 mg were rash and diarrhea. |
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The most common adverse reactions in patients with pancreatic cancer receiving Tarceva 100 mg plus gemcitabine were fatigue, rash, nausea, anorexia, and diarrhea. |
For additional Important Safety Information, please see accompanying full prescribing information.
XELODA® (capecitabine)
INDICATIONS AND IMPORTANT SAFETY INFORMATION
Indications
XELODA is indicated as a single agent for adjuvant treatment in patients with Dukes' C colon cancer who have undergone complete resection of the primary tumor when treatment with fluoropyrimidine therapy alone is preferred. XELODA was non-inferior to 5-fluorouracil and leucovorin (5-FU/LV) for disease-free survival (DFS). Physicians should consider results of combination chemotherapy trials, which have shown improvement in DFS and OS, when prescribing single-agent XELODA in the adjuvant treatment of Dukes' C colon cancer.
XELODA is indicated as first-line treatment of patients with metastatic colorectal carcinoma when treatment with fluoropyrimidine therapy alone is preferred. Combination chemotherapy has shown a survival benefit compared to 5-FU/LV alone. A survival benefit over 5-FU/LV has not been demonstrated with XELODA monotherapy. Use of XELODA instead of 5-FU/LV in combinations has not been adequately studied to assure safety or preservation of the survival advantage.
XELODA monotherapy is indicated for the treatment of patients with metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen or resistant to paclitaxel and for whom further anthracycline therapy is not indicated, eg, patients who have received cumulative doses of 400 mg/m2 of doxorubicin or doxorubicin equivalents. Resistance is defined as progressive disease while on treatment, with or without an initial response, or relapse within 6 months of completing treatment with an anthracycline-containing adjuvant regimen.
XELODA in combination with docetaxel is indicated for the treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing chemotherapy.
Boxed WARNING and Additional Important Safety Information
Boxed Warning
Warfarin Interaction - Coagulopathy
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Patients receiving concomitant capecitabine and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or prothrombin time) monitored frequently in order to adjust the anticoagulant dose accordingly. |
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A clinically important XELODA-Warfarin drug interaction was demonstrated in a clinical pharmacology trial. |
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Altered coagulation parameters and/or bleeding, including death, have been reported in patients taking XELODA concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon. |
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Postmarketing reports have shown clinically significant increases in prothrombin time (PT) and INR have been observed in patients who were stabilized on anticoagulants at the time XELODA was introduced. These events occurred within several days and up to several months after initiating XELODA therapy, and in a few cases within 1 month after stopping XELODA. These events occurred in patients with and without liver metastases. |
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Age greater than 60 and a diagnosis of cancer independently predispose patients to an increased risk of coagulopathy. |
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XELODA is contraindicated in patients with known dihydropyrimidine dehydrogenase (DPD) deficiency, or severe renal impairment. XELODA is also contraindicated in patients with known hypersensitivity to capecitabine or to any of its components or to
5-fluorouracil. |
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Additional serious adverse reactions include diarrhea, cardiotoxicity, hand-and-foot syndrome, and hyperbilirubinemia. XELODA can cause fetal harm. Advise women of the potential risk to the fetus. Do not treat patients with neutrophil counts <1.5 x 109/L or thrombocyte counts <100 x 109/L. |
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The most common adverse reactions (>30%) reported were diarrhea, hand-and-foot syndrome, nausea, vomiting, abdominal pain, fatigue/weakness, and hyperbilirubinemia. Other adverse reactions, including serious adverse reactions, have been reported. |
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In a phase 3 study of XELODA monotherapy in colon cancer in the adjuvant setting, serious adverse events (grade 3/4) occurring in >5% of patients receiving either XELODA or 5-FU/LV (%;%) were increase in bilirubin (20;7), hand-foot syndrome (17;<1), decrease in lymphocytes (13;13), diarrhea (12;14), decrease in neutrophils/granulocytes (3;27), decrease in neutrophils (3;27), stomatitis (2;14), and neutropenia (<1;5). The most common adverse events for all grades occurring in >30% of patients receiving either XELODA or 5 FU/LV were hand-foot syndrome (60;9), diarrhea (47;65), nausea (34;47), and stomatitis (22;60). A total of 18 deaths due to all causes occurred either on study or within 28 days of receiving study drug: 8 (0.8%) patients randomized to XELODA and 10 (1.0%) randomized to 5-FU/LV. |
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In two phase 3 trials of XELODA monotherapy in metastatic colorectal cancer, serious adverse events (grade 3/4) occurring in >5% of patients receiving either XELODA or 5 FU/LV (%;%) were hyperbilirubinemia (23;6), hand-foot syndrome (17;1), diarrhea (15;12), abdominal pain (<10;5), vomiting (<5;<5), ileus (5;3), stomatitis (<3;15), and neutropenia (3;21). The most common adverse events for all grades occurring in >30% of patients receiving either XELODA or 5 FU/LV were anemia (80;79), diarrhea (55;61), hand-foot syndrome (54;6), hyperbilirubinemia (48;17), nausea (43;51), fatigue/weakness (42;46), abdominal pain (35;31), vomiting (27;30), appetite decrease (26;31), stomatitis (25;62), and neutropenia (13;46). A total of 82 deaths due to all causes occurred either on study or within 28 days of receiving study drug: 50 (8.4%) patients randomized to XELODA and 32 (5.4%) randomized to 5-FU/LV. |
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In a single arm study of XELODA monotherapy in metastatic breast cancer, serious adverse events (grade 3/4) occurring in >5% of patients receiving XELODA (%) were lymphopenia (59), diarrhea (15), hand-foot syndrome (11), hyperbilirubinemia (11), fatigue (8), stomatitis (7), and dehydration (5). The most common adverse events for all grades occurring in >30% of patients receiving XELODA were lymphopenia (94), anemia (72), diarrhea (57), hand-foot syndrome (57), nausea (53), fatigue (41), dermatitis (37), and vomiting (37). |
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In a phase 3 study of XELODA combination therapy (XELODA plus docetaxel) in metastatic breast cancer, serious adverse events (grade 3/4) occurring at a >2% higher incidence in patients receiving XELODA plus docetaxel vs docetaxel alone (%;%) were lymphocytopenia (89;84), hand-foot syndrome (24;1), stomatitis (<18;5), diarrhea (<15;<6), anemia (10;<6), hyperbilirubinemia (9;4), nausea (7;2), vomiting (5;2), constipation (2;0), and nail disorder (2;0). The most common adverse events for all grades occurring at a >5% higher incidence in patients receiving XELODA plus docetaxel vs docetaxel alone were diarrhea (67;48), stomatitis (67;43), hand-foot syndrome (63;8), nausea (45;36), thrombocytopenia (41;23), vomiting (35;24), abdominal pain (30;24), hyperbilirubinemia (20;6), weakness (16;11), dyspepsia (14;8), lacrimation increase (12;7), and appetite decrease (10;5). |
Please see full prescribing infromation, including Boxed Warnings, for additional important safety information.
ZELBORAF® (vemurafenib) tablets
INDICATIONS AND IMPORTANT SAFETY INFORMATION
Indication and Usage
ZELBORAF® (vemurafenib) is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAFV600E mutation as detected by an FDA-approved test.
ZELBORAF is not recommended for use in patients with wild-type BRAF melanoma.
Important Safety Information
Cutaneous squamous cell carcinoma (cuSCC)
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Cases of cuSCC, including both SCCs of the skin and keratoacanthomas, have been reported in patients treated with ZELBORAF. The incidence of cuSCC in ZELBORAF-treated patients in the Phase III study was 24%. The median time to first appearance of cuSCC was 7 to 8 weeks. Potential risk factors included age >65 years, prior skin cancer, and chronic sun exposure. |
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All patients should receive a dermatologic evaluation prior to initiation of therapy, every 2 months while on therapy, and potentially for 6 months following discontinuation of ZELBORAF. Any suspicious skin lesions should be excised, evaluated, and treated as per standard of care. |
Hypersensitivity and Dermatologic Reactions
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Serious hypersensitivity reactions, including anaphylaxis, have been reported in association with ZELBORAF and upon re-initiation of treatment. Severe reactions may include generalized rash and erythema or hypotension. |
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Severe dermatologic reactions have been reported in patients receiving ZELBORAF, including 1 case of Stevens-Johnson syndrome and 1 case of toxic epidermal necrolysis in the Phase III study. |
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ZELBORAF treatment should be permanently discontinued in patients who experience a severe hypersensitivity or dermatologic reaction. |
QT prolongation
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Exposure-dependent QT prolongation has been observed in patients treated with ZELBORAF, which may lead to an increased risk for ventricular arrhythmias, including Torsade de Pointes. |
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Treatment is not recommended in patients with uncorrectable electrolyte abnormalities, with long QT syndrome, or who are taking medicines known to prolong the QT interval. ECG and electrolytes should be monitored before initiating treatment with ZELBORAF and after dose modification and routinely during treatment (15 days after treatment initiation then monthly for first 3 months of treatment and every 3 months thereafter or as clinically indicated). If the QTc exceeds 500 ms, ZELBORAF treatment should be temporarily interrupted, electrolyte abnormalities corrected, and cardiac risk factors for QT prolongation (e.g. congestive heart failure, bradyarrhythmias) controlled. Re-initiation of treatment should occur at a lower dose once the QTc decreases below 500 ms. Permanent discontinuation is recommended if, after correction of associated risk factors, the QTc increase meets both a value of >500 ms and >60 ms change from pre-treatment values. |
Liver laboratory abnormalities
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Liver laboratory abnormalities have occurred with ZELBORAF. |
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Liver enzymes (transaminases and alkaline phosphatase) and bilirubin should be monitored before initiation of treatment and monthly during treatment, or as clinically indicated. Lab abnormalities should be managed with dose reduction, treatment interruption, or treatment discontinuation. |
Photosensitivity
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Mild to severe photosensitivity was reported in patients treated with ZELBORAF in clinical trials. |
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While taking ZELBORAF, all patients should be advised to avoid sun exposure and, when outdoors, to wear protective clothing and use a broad spectrum UVA/UVB sunscreen and lip balm (SPF >30). For intolerable grade 2 or greater photosensitivity, dose modifications are recommended. |
Ophthalmologic Reactions
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In the Phase III study, 5 cases of uveitis were reported in patients treated with ZELBORAF. |
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Treatment with steroid and mydriatic ophthalmic drops may be required to manage uveitis. Patients should be routinely monitored for signs and symptoms of uveitis. |
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Additionally, 5 cases each of blurry vision and iritis and 6 cases of photophobia were reported in the Phase III study. One case of retinal vein occlusion was reported in the Phase II study. |
New Primary Malignant Melanoma
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Eight skin lesions in 7 patients were reported as new primary malignant melanoma in the Phase III study. |
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Cases were managed with excision and patients continued treatment without dose adjustment; monitoring for skin lesions should occur as outlined above [see cuSCC]. |
Use in Pregnancy: Pregnancy Category D
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ZELBORAF may cause fetal harm when administered to a pregnant woman based on its mechanism of action. There are no adequate and well-controlled studies in pregnant women. |
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If ZELBORAF is used during pregnancy or if the patient becomes pregnant while taking ZELBORAF, the patient should be apprised of the potential hazard to a fetus. |
BRAF Testing
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Confirmation of BRAFV600E mutation-positive melanoma as detected by an FDA-approved test is required for the selection of patients appropriate for ZELBORAF therapy. The efficacy and safety of ZELBORAF have not been studied in patients with wild-type BRAF melanoma. |
Most common adverse events
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The most common adverse reactions of any grade (>30%) reported were arthralgia, rash, alopecia, fatigue, photosensitivity reaction, nausea, pruritus, and skin papilloma. |
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The most common (>5%) grade 3 adverse reactions were cuSCC and rash. In clinical studies, cuSCC was predefined as a grade 3 event. |
Please see full prescribing information for important safety information.
Genentech BioOncology® Access Solutions®
Health Care Professional
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