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