Ramucirumab – Uses, Dosage, Side Effects, Interaction Ramucirumab is an antineoplastic agent and direct VEGFR2 (vascular endothelial growth factor receptor 2) antagonist that blocks the binding of natural VEGF ligands, which are secreted by solid tumors to promote angiogenesis and enhance tumor blood supply. Ramucirumab is a human monoclonal antibody (IgG1) against vascular endothelial growth factor receptor 2 (VEGFR2), a type II trans-membrane tyrosine kinase receptor expressed on endothelial cells. By binding to VEGFR2, ramucirumab prevents the binding of its ligands (VEGF-A, VEGF-C, and VEGF-D), thereby preventing VEGF-stimulated receptor phosphorylation and downstream ligand-induced proliferation, permeability, and migration of human endothelial cells. VEGFR stimulation also mediates downstream signaling required for angiogenesis and is postulated to be heavily involved in cancer progression, making it a highly likely drug target. In contrast to other agents directed against VEGFR-2, ramucirumab binds a specific epitope on the extracellular domain of VEGFR-2, thereby blocking all VEGF ligands from binding to it. Ramucirumab is indicated for use in advanced gastric or gastro-esophageal junction adenocarcinoma as a single agent or in combination with paclitaxel after prior fluoropyrimidine- or platinum-containing chemotherapy. Ramucirumab is a human monoclonal antibody to the vascular endothelial growth factor (VEGF) receptor 2 and is an antiangiogenesis agent used in the therapy of advanced colorectal, gastric, and lung cancers. Ramucirumab has not been linked to serum enzyme elevations during therapy or to instances of idiosyncratic acute liver injury but has been reported to worsen liver failure in patients with decompensated cirrhosis (Child Class B or C). Mechanism of action Ramucirumab is a human monoclonal antibody (IgG1) against vascular endothelial growth factor receptor 2 (VEGFR2), a type II trans-membrane tyrosine kinase receptor expressed on endothelial cells. By binding to VEGFR2, ramucirumab prevents the binding of its ligands (VEGF-A, VEGF-C, and VEGF-D), thereby preventing VEGF-stimulated receptor phosphorylation and downstream ligand-induced proliferation, permeability, and migration of human endothelial cells. Ramucirumab is a direct VEGFR2 antagonist, that binds with high affinity to the extracellular domain of VEGFR2 and block the binding of natural VEGFR ligands (VEGF-A, VEGF-C and VEGF-D). These ligands are secreted by solid tumors to promote angiogenesis (formation of new blood vessels from pre-existing ones) and enhance tumor blood supply. The binding of ramucirumab to VEGFR2 leads to inhibition of VEGF-mediated tumor angiogenesis Indications Ramucirumab is indicated for the treatment of advanced or metastatic gastric or gastro-esophageal junction adenocarcinoma as a single agent or in combination with paclitaxel for patients who progress after prior fluoropyrimidine- or platinum-containing chemotherapy. It is indicated, in combination with erlotinib, for the first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor exon 19 deletions or exon 21 (L858R) point mutations. It is also indicated in combination with docetaxel for the treatment of metastatic non-small cell lung cancer in patients who have progressed following prior platinum-based chemotherapy. Patients who have EGFR or ALK genomic aberrations should also have disease progression following FDA-approved therapy for these aberrations. Ramucirumab, in combination with FOLFIRI (folinic acid, fluorouracil, and irinotecan), is indicated for the treatment of metastatic colorectal cancer in patients who have progressed following therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. Lastly, ramucirumab is indicated for the treatment of hepatocellular carcinoma in patients with an alpha-fetoprotein level ≥400 ng/mL and have previously been treated with sorafenib.[rx] Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma Hepatocellular Carcinoma Metastatic Colorectal Cancer (CRC) Metastatic Non-Small Cell Lung Cancer Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma As a single agent, or in combination with paclitaxel, for the treatment of advanced or metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy. In combination with FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil) for the treatment of metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine Use in Cancer Ramucirumab is approved to be used alone or with other drugs to treat: Colorectal cancer that has metastasized. It is used with FOLFIRI in patients whose disease has gotten worse during or after treatment with bevacizumab, oxaliplatin, and fluoropyrimidine. Hepatocellular carcinoma (a type of liver cancer). It is used alone in patients who have a high level of alpha-fetoprotein in the blood and have been treated with sorafenib tosylate. Non-small cell lung cancer that has metastasized. It is used: Erlotinib hydrochloride is the first-line therapy in patients whose disease has certain mutations in the EGFR gene. With docetaxel in patients whose disease has gotten worse during or after treatment with platinum chemotherapy. For patients whose disease has a mutation in the EGFR gene or ALK gene, ramucirumab is used if their disease has gotten worse after treatment with FDA-approved therapy for these mutations. Stomach adenocarcinoma or gastroesophageal junction adenocarcinoma (a rare type of esophageal cancer) that is advanced or has metastasized (spread to other parts of the body). It is used in patients whose disease has gotten worse after treatment with fluoropyrimidine or platinum chemotherapy. It is used alone or with paclitaxel. Ramucirumab is also being studied in the treatment of other types of cancer. Contraindications a condition with low thyroid hormone levels high blood pressure a heart attack a transient ischemic attack, a type of stroke that lasts only a few minutes an occurrence of a blood clot in an artery bleeding hardening of the liver bleeding of the stomach or intestines recent operation elevation of proteins in the urine impaired wound healing pregnancy a patient who is producing milk and breastfeeding a rupture in the wall of the stomach or intestine a type of brain disorder called posterior reversible encephalopathy syndrome acute thromboembolic stroke Child-Pugh class A liver impairment Child-Pugh class B liver impairment Child-Pugh class C liver impairment Dosage Strengths: 10 mg/mL Gastric Cancer AS A SINGLE AGENT OR IN COMBINATION WITH WEEKLY PACLITAXEL: 8 mg/kg IV over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. If the first infusion is tolerated, all subsequent infusions may be administered over 30 minutes. When given in combination, this drug should be administered prior to paclitaxel. Refer to the prescribing information for paclitaxel for dosage information. Premedicate patients with an IV a H1 antagonist (e.g., diphenhydramine). Patients who have developed a Grade 1 or 2 infusion reaction should be premedicated with histamine-1 receptor antagonist or dexamethasone (or equivalent) and acetaminophen prior to each infusion. Non-Small Cell Lung Cancer EGFR EXON 19 DELETIONS OR EXON 21 (L858R) SUBSTITUTION MUTATIONS IN COMBINATION WITH ERLOTINIB: 10 mg/kg IV over 60 minutes every 2 weeks until disease progression or unacceptable toxicity NOTE: If the first infusion is tolerated, all subsequent infusions may be administered over 30 minutes. DISEASE PROGRESSION ON OR AFTER PLATINUM-BASED CHEMOTHERAPY IN COMBINATION WITH DOCETAXEL: 10 mg/kg IV over 60 minutes on Day 1 of a 21-day cycle prior to docetaxel infusion until disease progression or unacceptable toxicity NOTE: If the first infusion is tolerated, all subsequent infusions may be administered over 30 minutes. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving this drug. Refer to the prescribing information for erlotinib or docetaxel for dosage information. Premedicate patients with an IV a H1 antagonist (e.g., diphenhydramine). Patients who have developed a Grade 1 or 2 infusion reaction should be premedicated with histamine-1 receptor antagonist or dexamethasone (or equivalent) and acetaminophen prior to each infusion. In combination with erlotinib for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations In combination with docetaxel, for the treatment metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy (patients with epidermal growth factor receptor [EGFR] or anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving this drug) Colorectal Cancer 8 mg/kg IV over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. If the first infusion is tolerated, all subsequent infusions may be administered over 30 minutes. Administer this drug prior to administration of FOLFIRI. Refer to the prescribing information for fluorouracil, leucovorin, and irinotecan for dosage information. Premedicate patients with an IV a H1 antagonist (e.g., diphenhydramine). Patients who have developed a Grade 1 or 2 infusion reaction should be premedicated with histamine-1 receptor antagonist or dexamethasone (or equivalent) and acetaminophen prior to each infusion. Hepatocellular Carcinoma 8 mg/kg IV over 60 minutes every 2 weeks until disease progression or unacceptable toxicity NOTE: If the first infusion is tolerated, all subsequent infusions may be administered over 30 minutes. Premedicate patients with an IV H1 antagonist (e.g., diphenhydramine). Patients who have developed a Grade 1 or 2 infusion reaction should be premedicated with histamine-1 receptor antagonist or dexamethasone (or equivalent) and acetaminophen prior to each infusion. As a single agent for the treatment of patients with hepatocellular carcinoma (HCC) who have an alpha-fetoprotein (AFP) of 400 ng/mL or greater and have been treated with sorafenib Liver Dose Adjustments Mild (total bilirubin within ULN and aspartate aminotransferase [AST] greater than ULN or total bilirubin greater than 1 to 1.5 times ULN and any AST) or moderate (total bilirubin greater than 1.5 to 3 x ULN and any AST) hepatic impairment: No adjustment recommended. Severe renal impairment: Data not available Clinical deterioration was reported in patients with Child-Pugh B or C cirrhosis who received this drug as a single agent. Dose Adjustments MANUFACTURER-RECOMMENDED DOSE MODIFICATIONS: HEMORRHAGE: Grade 3 or 4: Permanently discontinue therapy. GI PERFORATION: All Grades: Permanently discontinue therapy. WOUND HEALING COMPLICATIONS: All Grades: Withhold therapy for 28 days prior to elective surgery; resume therapy no sooner than 28 days after surgery and the wound is fully healed; discontinue therapy for wound healing complications that require medical intervention. ARTERIAL THROMBOEMBOLIC EVENTS: All Grades: Permanently discontinue therapy. HYPERTENSION: Severe hypertension: Withhold therapy until controlled. Severe hypertension not controlled with antihypertensives: Permanently discontinue therapy. INFUSION-RELATED REACTIONS (IRRs): Grade 1 or 2 IRRs: Reduce the infusion rate by 50%. Grade 3 or 4 IRRs: Permanently discontinue therapy. PROTEINURIA: The first occurrence of increased urine protein levels greater than or equal to 2 g per 24 hours: Withhold therapy until urine protein level is less than 2 g per 24 hours; resume therapy at a reduced dose: Reduce 8 mg dose to 6 mg; reduce 10 mg dose to 8 mg. Reoccurrence of urine protein level greater than 2 g per 24 hours following initial dose reduction: Withhold therapy until urine protein level is less than 2 g per 24 hours; resume therapy at a reduced dose: Reduce 6 mg dose to 5 mg; reduce 8 mg dose to 6 mg. Urine protein level greater than 3 g per 24 hours or in the setting of nephrotic syndrome: Permanently discontinue therapy. Administration advice: Therapy should be initiated and supervised by physicians experienced in oncology. Do not administer this drug as an IV push or bolus. Gently invert the container for adequate mixing. Do not dilute with other solutions or co-infuse with other electrolytes or drugs. Administer the drug via infusion pump over 60 minutes through a separate infusion line. Flush the line with sterile sodium chloride (0.9%) solution for injection at the end of the infusion. Therapy should be temporarily discontinued if severe hypertension develops. Continue use until disease progresses or unacceptable toxicity. Side Effects The Most Common diarrhea sores in the mouth or throat rash sudden weakness of an arm or leg drooping of one side of the face difficulty speaking or understanding crushing chest or shoulder pain slow or difficult speech chest pain shortness of breath headache dizziness or faintness seizures confusion change in vision or loss of vision extreme tiredness swelling of the face, eyes, stomach, hands, feet, ankles, or lower legs unexplained weight gain foamy urine sore throat, fever, chills, ongoing cough and congestion, or other signs of infection coughing up or vomiting blood or material that looks like coffee grounds, unusual bleeding or bruising, pink, red, or dark brown urine, red or tarry black bowel movements, or lightheadedness diarrhea, vomiting, abdominal pain, fever, or chills More common Back pain or spasms blurred vision burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings chest pain chills cloudy urine confusion cough coughing up blood decreased urine output dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position fainting fast, slow, pounding, or irregular heartbeat or pulse feeling of warmth feeling unusually cold fever headache increased thirst lower back or side pain muscle pain or cramps nausea nervousness nosebleeds painful or difficult urination pounding in the ears redness of the face, neck, arms, and occasionally, upper chest seizures shakiness in the legs, arms, hands, or feet shivering sweating swelling of the face, hands, ankles, feet, or lower legs trembling or shaking of the hands or feet trouble breathing unusual tiredness or weakness vomiting signs of stomach bleeding–severe stomach pain, bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds any wound that will not heal; headache, confusion, change in mental status, vision loss, seizure (convulsions); severe or ongoing nausea, vomiting, or diarrhea; rapid weight gain, especially in your face and midsection; low white blood cell counts–fever, mouth sores, skin sores, sore throat, cough, trouble breathing; kidney problems–puffy eyes, swelling in your ankles or feet, weight gain, urine that looks foamy; symptoms of a blood clot–sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance; or heart attack symptoms–chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating. sores or white patches in or around your mouth, red or swollen gums, trouble swallowing or talking, dry mouth, bad breath, altered sense of taste; Rare Bleeding gums difficulty swallowing dizziness inability to speak increased menstrual flow or vaginal bleeding loss of consciousness low blood pressure or pulse pain in the chest, groin, or legs, especially calves of the legs pain or discomfort in the arms, jaw, back, or neck pale skin paralysis prolonged bleeding from cuts red or black, tarry stools red or dark brown urine severe constipation severe headaches of sudden onset severe numbness, especially on one side of the face or body slurred speech sore throat stomach pain, cramping, or burning sudden loss of coordination sudden onset of slurred speech sudden vision changes sweating temporary blindness ulcers, sores, or white spots in the mouth unusual bleeding or bruising vomiting of material that looks like coffee grounds, severe and continuing Drug Interaction DRUG INTERACTION Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Ramucirumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Ramucirumab. Aducanumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Aducanumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Ramucirumab. Alirocumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Alirocumab. Amivantamab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Amivantamab. Anifrolumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Anifrolumab. Ansuvimab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Ansuvimab. A immune globulin The risk or severity of adverse effects can be increased when Ramucirumab is combined with Anthrax immune globulin human. A immunoglobulin The risk or severity of adverse effects can be increased when Ramucirumab is combined with Antilymphocyte immunoglobulin (horse). Antithymocyte The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Ramucirumab. Articaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Articaine. Asfotase alfa The risk or severity of adverse effects can be increased when Ramucirumab is combined with Asfotase alfa. Atezolizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Atezolizumab. Atoltivimab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Atoltivimab. Avelumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Avelumab. Bamlanivimab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Bamlanivimab. Basiliximab The risk or severity of adverse effects can be increased when Basiliximab is combined with Ramucirumab. Bebtelovimab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Bebtelovimab. Belantamab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Belantamab mafodotin. Belimumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Belimumab. Benralizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Benralizumab. Benzocaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Benzyl alcohol. Besilesomab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Besilesomab. Bevacizumab The risk or severity of adverse effects can be increased when Bevacizumab is combined with Ramucirumab. Bezlotoxumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Bezlotoxumab. Bimekizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Bimekizumab. Blinatumomab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Blinatumomab. Brentuximab vedotin The risk or severity of adverse effects can be increased when Ramucirumab is combined with Brentuximab vedotin. Brodalumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Brodalumab. Brolucizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Brolucizumab. Bupivacaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Bupivacaine. Burosumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Burosumab. Butacaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Butacaine. Butamben The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Butamben. Canakinumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Canakinumab. Caplacizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Caplacizumab. Capromab pendetide The risk or severity of adverse effects can be increased when Capromab pendetide is combined with Ramucirumab. Capsaicin The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Capsaicin. Casirivimab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Casirivimab. Catumaxomab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Catumaxomab. Cemiplimab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Cemiplimab. Certolizumab pegol The risk or severity of adverse effects can be increased when Ramucirumab is combined with Certolizumab pegol. Cetuximab The risk or severity of adverse effects can be increased when Cetuximab is combined with Ramucirumab. Chloroprocaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Chloroprocaine. Cilgavimab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Cilgavimab. Cinchocaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Cinchocaine. Cocaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Cocaine. C estrogens Conjugated estrogens may increase the thrombogenic activities of Ramucirumab. Daratumumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Daratumumab. Darbepoetin alfa The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Ramucirumab. Denosumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Denosumab. Dienestrol Dienestrol may increase the thrombogenic activities of Ramucirumab. Diethylstilbestrol Diethylstilbestrol may increase the thrombogenic activities of Ramucirumab. Digoxin Immune The risk or severity of adverse effects can be increased when Digoxin Immune Fab (Ovine) is combined with Ramucirumab. Dinutuximab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Dinutuximab. Diphenhydramine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Diphenhydramine. Dostarlimab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Dostarlimab. Dulaglutide The risk or severity of adverse effects can be increased when Ramucirumab is combined with Dulaglutide. Dupilumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Dupilumab. Durvalumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Durvalumab. Dyclonine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Dyclonine. Zaire vaccine The therapeutic efficacy of Ebola Zaire vaccine (live, attenuated) can be decreased when used in combination with Ramucirumab. Eculizumab The risk or severity of adverse effects can be increased when Eculizumab is combined with Ramucirumab. Efalizumab The risk or severity of adverse effects can be increased when Efalizumab is combined with Ramucirumab. Eflapegrastim The risk or severity of adverse effects can be increased when Ramucirumab is combined with Eflapegrastim. Eftrenonacog alfa The risk or severity of adverse effects can be increased when Ramucirumab is combined with Eftrenonacog alfa. Elotuzumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Elotuzumab. Emapalumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Emapalumab. Emicizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Emicizumab. Eptinezumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Eptinezumab. Erenumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Erenumab. Erythropoietin The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Ramucirumab. Esterified estrogens Esterified estrogens may increase the thrombogenic activities of Ramucirumab. Estetrol Estetrol may increase the thrombogenic activities of Ramucirumab. Estradiol Estradiol may increase the thrombogenic activities of Ramucirumab. Estradiol acetate Estradiol acetate may increase the thrombogenic activities of Ramucirumab. Estradiol benzoate Estradiol benzoate may increase the thrombogenic activities of Ramucirumab. Estradiol cypionate Estradiol cypionate may increase the thrombogenic activities of Ramucirumab. Estradiol valerate Estradiol valerate may increase the thrombogenic activities of Ramucirumab. Estriol Estriol may increase the thrombogenic activities of Ramucirumab. Estrone Estrone may increase the thrombogenic activities of Ramucirumab. Estrone sulfate Estrone sulfate may increase the thrombogenic activities of Ramucirumab. Ethinylestradiol Ethinylestradiol may increase the thrombogenic activities of Ramucirumab. Ethyl chloride The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Ethyl chloride. Etidocaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Etidocaine. Evolocumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Evolocumab. Fanolesomab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Fanolesomab. Fremanezumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Fremanezumab. Galcanezumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Galcanezumab. Gemtuzumab The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Ramucirumab. Golimumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Golimumab. Guselkumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Guselkumab. Hepatitis B immune The risk or severity of adverse effects can be increased when Hepatitis B immune globulin is combined with Ramucirumab. c, immune globulin The risk or severity of adverse effects can be increased when Ramucirumab is combined with Human cytomegalovirus immune globulin. Immunoglobulin G The risk or severity of adverse effects can be increased when Human immunoglobulin G is combined with Ramucirumab. Himmune globulin The risk or severity of adverse effects can be increased when Ramucirumab is combined with Human Rho(D) immune globulin. Human varicella- The risk or severity of adverse effects can be increased when Ramucirumab is combined with Human varicella-zoster immune globulin. Ibalizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Ibalizumab. Ibritumomab tiuxetan The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Ramucirumab. Idarucizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Idarucizumab. Imdevimab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Imdevimab. Imlifidase The therapeutic efficacy of Ramucirumab can be decreased when used in combination with Imlifidase. Inebilizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Inebilizumab. Infliximab The risk or severity of adverse effects can be increased when Infliximab is combined with Ramucirumab. Inotuzumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Inotuzumab ozogamicin. Ipilimumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Ipilimumab. Isatuximab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Isatuximab. Ixekizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Ixekizumab. Lanadelumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Lanadelumab. Levobupivacaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Levobupivacaine. Lidocaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Lidocaine. Loncastuximab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Loncastuximab tesirine. Maftivimab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Maftivimab. Margetuximab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Margetuximab. Meloxicam The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Meloxicam. Mepivacaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Mepivacaine. Mepolizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Mepolizumab. Mestranol Mestranol may increase the thrombogenic activities of Ramucirumab. Methoxy The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Ramucirumab. Mirvetuximab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Mirvetuximab Soravtansine. Mogamulizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Mogamulizumab. Mosunetuzumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Mosunetuzumab. Muromonab The risk or severity of adverse effects can be increased when Muromonab is combined with Ramucirumab. Natalizumab The risk or severity of adverse effects can be increased when Natalizumab is combined with Ramucirumab. Necitumumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Necitumumab. Nivolumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Nivolumab. Obiltoxaximab The risk or severity of adverse effects can be increased when Obiltoxaximab is combined with Ramucirumab. Obinutuzumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Obinutuzumab. Ocrelizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Ocrelizumab. Odesivimab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Odesivimab. Ofatumumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Ofatumumab. Olaratumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Olaratumab. Omalizumab The risk or severity of adverse effects can be increased when Omalizumab is combined with Ramucirumab. Oxetacaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Oxetacaine. Oxybuprocaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Oxybuprocaine. Palivizumab The risk or severity of adverse effects can be increased when Palivizumab is combined with Ramucirumab. Panitumumab The risk or severity of adverse effects can be increased when Panitumumab is combined with Ramucirumab. Peginesatide The risk or severity of Thrombosis can be increased when Peginesatide is combined with Ramucirumab. Pembrolizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Pembrolizumab. Pertuzumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Pertuzumab. Phenol The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Phenol. Polatuzumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Polatuzumab vedotin. Polyestradiol Polyestradiol phosphate may increase the thrombogenic activities of Ramucirumab. Pramocaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Pramocaine. Prilocaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Prilocaine. Procaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Procaine. Proparacaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Proparacaine. Propoxycaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Propoxycaine. Quinestrol Quinestrol may increase the thrombogenic activities of Ramucirumab. Ranibizumab The risk or severity of adverse effects can be increased when Ranibizumab is combined with Ramucirumab. Ravulizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Ravulizumab. Raxibacumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Raxibacumab. Reslizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Reslizumab. Risankizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Risankizumab. Rituximab The risk or severity of adverse effects can be increased when Rituximab is combined with Ramucirumab. Romosozumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Romosozumab. Ropivacaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Ropivacaine. Sacituzumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Sacituzumab govitecan. Sarilumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Sarilumab. Secukinumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Secukinumab. Siltuximab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Siltuximab. Sotrovimab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Sotrovimab. Spesolimab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Spesolimab. Sulesomab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Sulesomab. Sutimlimab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Sutimlimab. Estrogens, A Synthetic Conjugated Estrogens, A may increase the thrombogenic activities of Ramucirumab. Estrogens, B Synthetic Conjugated Estrogens, B may increase the thrombogenic activities of Ramucirumab. Tafasitamab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Tafasitamab. Teplizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Teplizumab. Tetanus immune The risk or severity of adverse effects can be increased when Ramucirumab is combined with Tetanus immune globulin, human. Tetracaine The risk or severity of methemoglobinemia can be increased when Ramucirumab is combined with Tetracaine. Tezepelumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Tezepelumab. Tibolone Tibolone may increase the thrombogenic activities of Ramucirumab. Tildrakizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Tildrakizumab. Tisotumab vedotin The risk or severity of adverse effects can be increased when Ramucirumab is combined with Tisotumab vedotin. Tixagevimab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Tixagevimab. Tocilizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Tocilizumab. Tositumomab The risk or severity of adverse effects can be increased when Tositumomab is combined with Ramucirumab. Tralokinumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Tralokinumab. Trastuzumab The risk or severity of adverse effects can be increased when Trastuzumab is combined with Ramucirumab. Trastuzumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Trastuzumab deruxtecan. Trastuzumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Trastuzumab emtansine. Tremelimumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Tremelimumab. Ustekinumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Ustekinumab. Vedolizumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Vedolizumab. Pregnancy and Lactation AU TGA pregnancy category: D US FDA pregnancy category: Not assigned. Pregnancy Based on its mechanism of action, this drug may cause fetal harm. If a patient becomes pregnant while taking this drug, she should be apprised of the potential hazard to a fetus. Female patients should be advised to avoid getting pregnant while receiving this drug and for at least 3 months after the last dose. Females of reproductive potential should be advised that this drug may impair fertility. Lactation No information is available on the clinical use of this drug during breastfeeding. Because it is a large protein molecule, the amount in milk is likely to be very low and absorption is unlikely because it is probably destroyed in the infant GI tract. How should this medicine be used? Ramucirumab injection comes as a liquid to be injected into a vein over 30 or 60 minutes by a doctor or nurse in a hospital or medical facility. For the treatment of stomach cancer, cancer of the colon or rectum, or HCC, it is usually given once every 2 weeks. For the treatment of NSCLC along with erlotinib, ramucirumab is usually given once every 2 weeks. For the treatment of NSCLC along with docetaxel, ramucirumab is usually given once every 3 weeks. The length of your treatment depends on how well your body responds to the medication and the side effects that you experience. Your doctor may need to interrupt or stop your treatment if you experience certain side effects. Your doctor will give you other medications to prevent or treat certain side effects before you receive each dose of ramucirumab injection. Tell your doctor or nurse if you experience any of the following while you receive ramucirumab: uncontrollable shaking of a part of the body; back pain or spasms; chest pain and tightness; chills; flushing; shortness of breath; wheezing; pain, burning, numbness, pricking, or tingling in the hands or feet or on the skin; breathing difficulties; or a fast heartbeat. What special precautions should I follow? Before receiving ramucirumab injection, tell your doctor and pharmacist if you are allergic to ramucirumab or any other medications or any of the ingredients in ramucirumab injection. Ask your pharmacist for a list of the ingredients. tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects. tell your doctor if you have or have ever had high blood pressure, or thyroid or liver disease. Also tell your doctor if you have a wound that has not healed yet, or if you develop a wound during treatment that is not healing properly. you should know that ramucirumab may cause infertility in women (difficulty becoming pregnant); however, you should not assume that you cannot get pregnant. Tell your doctor if you are pregnant or plan to become pregnant. You should have a pregnancy test before you start treatment. You should use birth control to prevent pregnancy during your treatment and for at least 3 months after your final treatment. Talk to your doctor about birth control methods that will work for you. If you become pregnant during your treatment with ramucirumab injection, call your doctor immediately. Ramucirumab may harm the fetus. tell your doctor if you are breastfeeding. You should not breastfeed during your treatment with ramucirumab and for 2 months after your final dose. if you are having surgery, including dental surgery, tell the doctor or dentist that you are receiving a ramucirumab injection. Your doctor may tell you not to receive a ramucirumab injection during the 28 days before your surgery. You may only be allowed to restart treatment with ramucirumab injection if it is at least 14 days after your surgery and the wound is healed. References https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125477s034lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125477s002lbl.pdf https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ramucirumab-hepatocellular-carcinoma https://www.cancer.gov/about-cancer/treatment/drugs/ramucirumab https://www.drugs.com/mtm/ramucirumab.html https://medlineplus.gov/druginfo/meds/a614026.html https://en.wikipedia.org/wiki/Ramucirumab https://go.drugbank.com/drugs/DB05578 https://pubchem.ncbi.nlm.nih.gov/#query=Ramucirumab https://www.ncbi.nlm.nih.gov/books/NBK547992/ https://www.webmd.com/drugs/2/drug-166215/ramucirumab-intravenous/details/list-contraindications Show More