all over again [2:<2 g per 24 hours, resume therapy at a reduced dosage of 5 mg/kg every 2 weeks (for advanced or metastatic gastric adenocarcinoma or metastatic colorectal cancer) or 6 mg/kg every 3 weeks (for metastatic NSCLC). 1 (See Proteinuria under Cautions.) If nephrotic syndrome or proteinuria> 3 g per 24 hours occurs, permanently discontinue therapy. 1 Special Populations Hepatic Impairment Mild hepatic impairment (total bilirubin concentration within the ULN and AST concentration exceeding the ULN, or total bilirubin concentration >1 to 1.5 times the ULN and any AST concentration): No dosage adjustment required. 1 (See Hepatic Impairment under Cautions.) Renal Impairment No dosage adjustment required. 1 (See Renal Impairment under Cautions.) Geriatric Patients No specific dosage recommendations at this time. 1 (See Geriatric Use under Cautions.) Cautions for Ramucirumab Contraindications Manufacturer states none known. 1 Warnings/Precautions Warnings Hemorrhage Increased risk of hemorrhage and GI hemorrhage, including severe and sometimes fatal hemorrhage. 1 Severe bleeding reported; red blood cell transfusions required in some patients. 1 Risk of gastric hemorrhage associated with ramucirumab is unknown in patients with gastric cancer receiving NSAIAs. 1 Risk of pulmonary hemorrhage associated with ramucirumab is unknown in patients with NSCLC receiving therapeutic anticoagulation, long-term therapy with NSAIAs, or antiplatelet therapy other than once-daily aspirin. 1 Risk of pulmonary hemorrhage also unknown in patients with radiographic evidence of major airway or blood vessel invasion or intratumor cavitation. 1 Permanently discontinue therapy if severe (grade 3 or 4) hemorrhage occurs. 1 GI Perforation GI perforation, potentially fatal, reported. 1 2 Permanently discontinue ramucirumab if GI perforation occurs. 1 Impaired Wound Healing Data lacking on effect of ramucirumab on wound healing; 1 however, VEGFR inhibitors may impair wound healing. 1 3 Discontinue ramucirumab in patients with impaired wound healing. 1 Discontinue ramucirumab prior to scheduled surgery. 1 Base decision to resume therapy postoperatively on clinical assessment of adequacy of wound healing. 1 If wound healing complications develop during ramucirumab therapy, discontinue the drug until wound is fully healed. 1 Other Warnings and Precautions Arterial Thromboembolic Events Severe, sometimes fatal, arterial thromboembolic events (including MI, cardiac arrest, cerebrovascular accident, and cerebral ischemia) reported. 1 2 Permanently discontinue therapy if severe arterial thromboembolic event occurs. 1 Hypertension Grade 3 or 4 hypertension reported. 1 2 12 14 Control hypertension prior to initiating ramucirumab therapy. 1 Monitor BP every 2 weeks or more frequently as clinically indicated during therapy. 1 If severe hypertension occurs, interrupt therapy until hypertension is controlled. 1 Permanently discontinue ramucirumab in patients with clinically important hypertension that is not controlled with antihypertensive therapy or in patients who develop hypertensive crisis or hypertensive encephalopathy. 1 Infusion-related Effects Infusion-related reactions (e.g., bronchospasm, supraventricular tachycardia, hypotension, rigors/tremors, back pain/spasms, chest pain and/or tightness, chills, flushing, dyspnea, wheezing, hypoxia, paresthesia), sometimes severe, reported. 1 Generally occur more frequently during or following the first 2 infusions. 1 Premedication recommended prior to each infusion. 1 (See General under Dosage and Administration.) Monitor patients during infusions for manifestations of infusion-related reactions. 1 If infusion-related reactions occur, reduce infusion rate or discontinue therapy depending on severity of reaction. 1 (See Infusion-related Effects under Dosage and Administration.) Hepatic Effects New-onset or worsening encephalopathy, ascites, or hepatorenal syndrome reported in patients with preexisting Child-Pugh class B or C cirrhosis receiving single-agent ramucirumab. 1 (See Hepatic Impairment under Cautions.) Reversible Posterior Leukoencephalopathy Syndrome Reversible posterior leukoencephalopathy syndrome (RPLS) reported in <0.1% of patients receiving ramucirumab in clinical studies. 1 If manifestations of RPLS occur, confirm diagnosis by magnetic resonance imaging (MRI) and discontinue ramucirumab therapy. 1 Symptoms of RPLS may resolve or improve within days, but ongoing neurologic sequelae or death can occur in some patients. 1 Proteinuria Proteinuria reported. 1 Monitor urine dipstick proteinuria and/or urinary protein-to-creatinine ratio for development or worsening of proteinuria during therapy. 1 Interrupt ramucirumab therapy for proteinuria 2 g per 24 hours and resume therapy at a reduced dosage when proteinuria declines below this level. 1 If nephrotic syndrome or proteinuria> 3 g per 24 hours occurs, permanently discontinue ramucirumab. 1 (See Proteinuria under Dosage and Administration.) Thyroid Dysfunction Hypothyroidism and increases in TSH concentrations reported in patients receiving ramucirumab in combination with FOLFIRI. 1 Monitor thyroid function during therapy. 1 Fetal/Neonatal Morbidity and Mortality Can cause fetal harm. 1 Teratogenicity demonstrated in animals following disruption of VEGF signaling. 1 Women of childbearing potential should avoid pregnancy during ramucirumab therapy and for 3 months after drug discontinuance. 1 (See Advice to Patients.) Apprise patient of potential fetal hazard if ramucirumab used during pregnancy or if patient becomes pregnant while taking the drug. 1 Immunogenicity Antibodies to ramucirumab, including neutralizing antibodies to the drug, reported. 1 Impairment of Fertility Animal studies suggest that VEGFR inhibitors, such as ramucirumab, may impair female fertility or ability to maintain pregnancy. 1 Specific Populations Pregnancy Can cause fetal harm. 1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Lactation Not known whether distributed into milk. 1 The manufacturer recommends against nursing during ramucirumab therapy. 1 Pediatric Use Safety and efficacy not established in pediatric patients <18 years of age. 1 2 Thickening of epiphyseal growth plates and osteochondropathy observed in animals receiving ramucirumab at concentrations 0.2 times that of human clinical exposure. 1 Geriatric Use In the REGARD and RAINBOW studies in patients with gastric cancer, no overall differences in safety and efficacy relative to younger adults observed. 1 In an exploratory subgroup analysis of the REVEL study in patients with NSCLC, survival benefit not observed in patients 65 years of age receiving ramucirumab in combination with docetaxel. 1 In the RAISE study in patients with colorectal cancer, no overall differences in safety and efficacy relative to younger adults observed. 1 Hepatic Impairment Mild (total bilirubin concentration within the ULN and AST concentration exceeding the ULN, or total bilirubin concentration> 1 to 1.5 times the ULN and any AST concentration) or moderate (total bilirubin concentration >1.5 to 3 times ULN and any AST concentration) hepatic impairment did not substantially affect average steady-state concentrations of ramucirumab. 1 (See Hepatic Impairment under Dosage and Administration.) Not studied in patients with severe (total bilirubin concentration >3 times the ULN and any AST concentration) hepatic impairment. 1 New-onset or worsening encephalopathy, ascites, or hepatorenal syndrome reported in patients with preexisting Child-Pugh class B or C cirrhosis receiving ramucirumab as a single agent. 1 Use in patients with Child-Pugh class B or C cirrhosis only if potential benefit outweighs risk of clinical deterioration. 1 Renal Impairment Mild (Cl cr 60 89 mL/minute), moderate (Cl cr 30 59 mL/minute), or severe (Cl cr 15 29 mL/minute) renal impairment did not substantially affect average steady-state concentrations of ramucirumab. 1 Common Adverse Effects Monotherapy in patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (incidence 5% and 2% higher than with placebo): Hypertension, 1 2 diarrhea, 1 bleeding or hemorrhage, 2 headache, 1 8 proteinuria, 1 8 hyponatremia. 1 Combination therapy with paclitaxel in patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (incidence 5% and 2% higher than with placebo): Fatigue or asthenia, 1 11 neutropenia, 1 11 diarrhea, 1 11 epistaxis, 1 11 peripheral edema, 1 11 hypertension, 1 11 stomatitis, 1 11 proteinuria, 1 11 thrombocytopenia, 1 11 hypoalbuminemia, 1 11 GI hemorrhage. 1 Combination therapy with docetaxel in patients with metastatic NSCLC (incidence 5% and 2% higher than with placebo): Neutropenia, 1 12 fatigue or asthenia, 1 12 stomatitis or mucosal inflammation, 1 12 epistaxis, 1 12 febrile neutropenia, 1 12 peripheral edema, 1 12 thrombocytopenia, 1 12 increased lacrimation, 1 12 hypertension, 1 12 diarrhea, 12 decreased appetite, 12 neuropathy, 12 leukopenia, 12 pyrexia, 12 myalgia, 12 arthralgia, 12 back pain, 12 dysgeusia, 12 insomnia. 12 Combination therapy with fluorouracil, leucovorin (folinic acid), and irinotecan (FOLFIRI) (incidence 5% and 2% higher than with placebo): diarrhea, 1 14 neutropenia, 1 14 fatigue, 14 hemorrhage, 14 decreased appetite, 1 14 epistaxis, 1 14 stomatitis, 1 14 vomiting, 14 constipation, 14 abdominal pain, 14 thrombocytopenia, 1 14 hypertension, 1 14 peripheral edema, 1 14 mucosal inflammation, 14 proteinuria, 1 14 pyrexia, 14 headache, 14 decreased weight, 14 cough, 14 liver injury or liver failure, 14 palmar-plantar erythrodysesthesia (hand-foot syndrome), 1 14 GI hemorrhage, 1 14 venous thromboembolic event, 14 hypoalbuminemia, 1 infusion-related reactions. 14 Interactions for Ramucirumab Specific Drugs Drug Interaction Docetaxel No substantial effect on systemic exposure to either drug 1 13 Irinotecan No substantial effect on systemic exposure to either drug (including irinotecan active metabolite SN-38) 1 Paclitaxel No substantial effect on systemic exposure to either drug 1 13 Ramucirumab Pharmacokinetics Absorption Special Populations Hepatic impairment: No clinically meaningful differences in average steady-state ramucirumab concentrations observed between patients with mild (total bilirubin concentration >1 to 1.5 times the ULN and any AST concentration) or moderate (total bilirubin concentration >1.5 to 3 times the ULN and any AST concentration) hepatic impairment and those with normal hepatic function. 1 No formal pharmacokinetic studies in patients with severe (total bilirubin concentration >3 times the ULN and any AST concentration) hepatic impairment. 1 Renal impairment: No clinically meaningful differences in average steady-state ramucirumab concentrations observed between patients with mild (Cl cr 60 89 mL/minute), moderate (Cl cr 30 59 mL/minute), or severe (Cl cr 15 29 mL/minute) renal impairment and those with normal renal function. 1 Elimination Half-life 15 days in patients with advanced or metastatic gastric adenocarcinoma receiving 8 mg/kg every 2 weeks. 1 23 days in patients with metastatic NSCLC receiving 10 mg/kg every 3 weeks. 1 Special Populations Age, gender, and race do not substantially affect pharmacokinetics of ramucirumab. 1 9 Stability Storage Parenteral Injection 2 8 C in original carton to protect from light. 1 Do not freeze or shake. 1 Diluted solution: Room temperature ( <25 C) for up to 4 hours or 2 8 C for up to 24 hours after dilution. 1 Do not freeze or shake. 1 Compatibility For information on systemic interactions resulting from concomitant use, see Interactions. Parenteral Solution Compatibility Compatible Sodium chloride 0.9% Incompatible Dextrose 5% in water Actions Binds specifically to VEGFR-2 and blocks the interaction of VEGFR-2 with its ligands (VEGFR-A, VEGFR-C, and VEGFR-D), resulting in inhibition of VEGFR-stimulated activation of both VEGFR-2 and downstream signaling pathways. 1 8 9 The VEGFR signaling pathway plays an important role in tumor angiogenesis, tumor growth, and metastatic spread. 4 5 6 9 Binding of ramucirumab to VEGFR-2 blocks ligand-induced phosphorylation and activation of the receptor in vitro. 1 4 Inhibits VEGFR-mediated endothelial cell proliferation and migration in vitro. 4 Inhibits angiogenesis in vivo. 1 Advice to Patients Risk of severe bleeding. 1 Importance of informing clinician of any episodes or symptoms of bleeding (e.g., lightheadedness). 1 Risk of arterial thromboembolic events. 1 Risk of hypertension. 1 Importance of receiving routine monitoring of BP and informing clinician if BP is elevated or if manifestations of hypertension (e.g., severe headache, lightheadedness, neurologic symptoms) occur. 1 Importance of informing clinician if severe diarrhea, vomiting, or severe abdominal pain occurs. 1 Risk of wound healing complications. 1 Importance of informing clinician of any scheduled surgery. 1 Risk of fetal or neonatal toxicity and miscarriage. 1 Necessity of advising women receiving ramucirumab to use an effective method of contraception during and for 3 months after the last dose of ramucirumab. 1 Importance of immediately informing clinician if the patient becomes pregnant during therapy. 1 If pregnancy occurs, apprise patient of potential hazard to the fetus. 1 Importance of discontinuing nursing while receiving ramucirumab therapy. 1 Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements (e.g., NSAIAs), as well as any concomitant illnesses (e.g., hypertension, hepatic disease). 1 Importance of informing patients of other important precautionary information. 1 (See Cautions.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. Ramucirumab (Recombinant) Routes Dosage Forms Strengths Brand Names Manufacturer Parenteral Concentrate for injection, for IV infusion only 10 mg/mL (100 and 500 mg) Cyramza Eli Lilly AHFS DI Essentials. Copyright 2017, Selected Revisions August 7, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. Eli Lilly. Cyramza (ramucirumab) injection for intravenous infusion prescribing information. Indianapolis, IN; 2015 Apr. 2. Fuchs CS, Tomasek J, Yong CJ et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet . 2014; 383:31-9. [PubMed 24094768] 3. GlaxoSmithKline. Votrient (pazopanib hydrochloride) tablets prescribing information. Research Triangle Park, NC: 2014 Jun. 4. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 125477Orig1s000: Pharmacology review(s). From FDA website. 5. Escudier B, Gore M. Axitinib for the management of metastatic renal cell carcinoma. Drugs R D . 2011; 11:113-26. [PubMed 21679004] 6. Hu-Lowe DD, Zou HY, Grazzini ML et al. Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res . 2008; 14:7272-83. [PubMed 19010843] 7. US Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. Accessed 2014 Jun 23. 8. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 125477Orig1s000: Summary review. From FDA website. 9. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 125477Orig1s000: Medical review(s). From FDA website. 10. Eli Lilly. How to order Cyramza (ramucirumab). Indianapolis, IN. Accessed 2014 Jun 18. 11. Wilke H, Muro K, Van Cutsem E et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol . 2014; 15:1224-35. [PubMed 25240821] 12. Garon EB, Ciuleanu TE, Arrieta O et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet . 2014; 384:665-73. [PubMed 24933332] 13. Eli Lilly. Cyramza (ramucirumab) injection for intravenous infusion prescribing information. Indianapolis, IN; 2014 Dec. 14. Tabernero J, Yoshino T, Cohn AL et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol . 2015; 16:499-508. [PubMed 25877855] Next Interactions Print this page Add to My Med List More about ramucirumab Side Effects During Pregnancy Dosage Information Drug Interactions Support Group En Español 0 Reviews Add your own review/rating Drug class: VEGF/VEGFR inhibitors Consumer resources Ramucirumab Ramucirumab Intravenous (Advanced Reading) Professional resources Ramucirumab (Wolters Kluwer) Other brands: Cyramza Related treatment guides Gastric Cancer Colorectal Cancer Non-Small Cell Lung Cancer Stomach Cancer> ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only C Pregnancy Category Risk cannot be ruled out N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Drug Class VEGF / VEGFR inhibitors Related Drugs Gastric Cancer Herceptin , Keytruda , pembrolizumab , trastuzumab , Cyramza , More... Colorectal Cancer Avastin , fluorouracil , Xeloda , capecitabine , Opdivo , leucovorin , More... Stomach Cancer fluorouracil , Adriamycin , doxorubicin , mitomycin , Cyramza , Adrucil , More... Non-Small Cell Lung Cancer Avastin , methotrexate , Taxol , Opdivo , cisplatin , Taxotere , More... Ramucirumab Rating No Reviews - Be the first! No Reviews - Be the first! Not Rated - Be the first!} } latest
insurance Ramucirumab widespread
EmoticonEmoticon