Ramucirumab

Ramucirumab is an antineoplastic agent belonging to the pharmacological class of monoclonal antibodies, specifically Vascular Endothelial Growth Factor 2 (VEGF) inhibitors.

The FDA approved Ramucirumab for treating advanced gastric or gastroesophageal junction adenocarcinoma, colorectal cancer, non-small cell lung cancer, and hepatocellular carcinoma as a second-line or later therapy.

Exclusively administered via intravenous infusion, Ramucirumab's mean volume of distribution at steady state, determined through a population pharmacokinetic approach, is 5.4L (15%), with its metabolism following the general principle of catabolic clearance observed in antibodies.

The most common side effects of Ramucirumab include high blood pressure

Ramucirumab is available in injectable solutions.

The molecule is available in India, the United States, the United Kingdom, Australia, Germany, France, Canada, Japan, Brazil, China and Spain.

Ramucirumab is an antineoplastic agent belonging to the pharmacological class of monoclonal antibodies, specifically Vascular Endothelial Growth Factor 2(VEGF) inhibitors.

A human monoclonal antibody (IgG1) called ramucirumab works against the type II trans-membrane tyrosine kinase receptor known as vascular endothelial growth factor receptor 2 (VEGFR2), expressed on endothelial cells. By binding to VEGFR2, ramucirumab stops VEGF-A, VEGF-C, and VEGF-D from binding to the receptor. This prevents phosphorylation of the receptor in response to VEGF and downstream ligand-induced proliferation, permeability, and migration of human endothelial cells.

Ramucirumab takes approximately 84 days to reach a steady-state concentration.

The steady state of Ramucirumab is attained approximately after 12 weeks of administration.

Ramucirumab is available in injectable solutions.

Injectable solutions: To be administered parenterally as applicable.

As the physician recommends, take the medication orally once every two weeks; it can be taken with or without food as directed.

Non-small cell lung cancer

Stomach cancer or Gastric cancer

Colorectal cancer, or cancer of the colon and rectum

Hepatocellular Carcinoma

Parenterally: During the intravenous (IV) preparation of Ramucirumab, visually inspect vials for particulate matter or discolouration, discarding the vial if issues arise. Calculate and withdraw the required dose, then dilute in an IV infusion container with only 0.9% NaCl, achieving a final volume of 250 mL. Avoid dilution with other solutions, infusion with diverse electrolytes or medications, and freezing. Premedicate with an IV histamine-1 receptor antagonist, like diphenhydramine, before each injection. Actively inspect the diluted solution for particulate matter and discolouration during IV administration, discarding if issues are noted. Refrain from administering as an IV push or bolus. Initially, administer the IV infusion over 60 minutes; if well-tolerated, subsequent infusions may proceed over 30 minutes. In combination therapy, help Ramucirumab one hour before other treatments (e.g., paclitaxel, docetaxel). Conclude by actively flushing the line with sterile 0.9% NaCl at the infusion's end.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

Ramucirumab is available as an injectable solutions.

Combination therapy with docetaxel before starting ramucirumab, patients with genomic tumour aberrations of the epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) should have progressed in their disease.

IV ramucirumab 10 mg/kg on Day 1 in addition to

First-day intravenous docetaxel 75 mg/m2

Every 21 days, repeat the cycle.

Continue until the disease worsens or the toxicity becomes intolerable.

Combination therapy with erlotinib

10 mg/kg IV ramucirumab every two weeks, PLUS

Use erlotinib 150 mg PO qDay until the disease worsens or the toxicity becomes intolerable.

A single agent: Q2Wk IV ramucirumab 8 mg/kg

Combination with paclitaxel

Days 1 and 15: Intravenous Ramucirumab (8 mg/kg)

Days 1, 8, and 15: 80 mg/m2 of paclitaxel

Every 28 days, repeat the cycle.

Continue until the illness worsens or the toxicity becomes intolerable.

In combination with irinotecan, folinic acid, and fluorouracil, administer 8 mg/kg IV every two weeks.

Continue until the disease worsens or the toxicity becomes intolerable.

8 mg/kg IV every two weeks

Continue until the disease worsens or the toxicity becomes intolerable.

There aren't specific dietary restrictions; ensure regular meals. Eat lean meats, healthy fats, fruits, vegetables, and whole-grain foods to give you more energy.

Maintain hydration by drinking plenty of water, as dehydration is often seen in cancers. Avoid smoking and alcohol consumption.

The dietary restriction should be individualized as per patient requirements.

Eat balanced meals, stay hydrated, quit smoking, and limit alcohol intake.

The adverse reactions related to Ramucirumab can be categorized as:

Systemic circulation and lymph nodes: thrombotic microangiopathy

Benign, malignant, and unknown neoplasms: Hemangioma

Thoracic, mediastinal, and respiratory: dysphonia

Vascular: Arterial dissections, ruptures, and aneurysms, including aortic

Cardio: Heart failure

The clinically relevant drug interactions of Ramucirumab are briefly summarized here.

The common side effects of Ramucirumab include:

Elevated blood pressure

Diarrhea

Headache

Vomiting

Nose bleeds

Reduced blood sodium levels

Anaemia, or low red blood cell count

Nausea

Fatigue

Injection site reactions at the site of injection

Dry mouth

Sores on the mouth

Fever

Back pain

Pregnancy Category C (FDA): Use caution if the benefits outweigh the risks.

Pregnant women who take it may experience fetal harm due to its mechanism of action.

Pregnancy-related data on use are not currently available.

Advise a pregnant woman about the possible risk to her fetus by using animal models to connect angiogenesis, VEGF, and VEGFR2 to essential aspects of female reproduction, embryo-fetal development, and postnatal development.

Before starting treatment, make sure all females who are capable of bearing children are pregnant.

Women: Advise women who can bear children to use reliable contraception both during and for three months following the last dosage of their treatment.

Advise females who are potentially fertile that, according to data from animals, their fertility may be compromised.

The excretion of Ramucirumab in human milk is unknown. The effects of Ramucirumab on milk production or its presence in breast milk have not been studied. Although human milk contains excreted human IgG, evidence from published studies indicates that significant quantities of breast milk antibodies do not reach the circulation of newborns and infants. It is essential to consider the importance of the drug to the mother when deciding whether to stop nursing or stop taking it altogether because many drugs are excreted in human milk and because ramucirumab can cause severe adverse reactions in nursing infants.

As per the FDA, Ramucirumab's use in pediatric patients has not been established.

Mild to severe (CrCl 15–89 mL/min): Pharmacokinetics do not change to a clinically significant extent.

There is no need to change the dosage for mild-to-moderate cases (total bilirubin ≤3x ULN and any AST).

Severe (bilirubin total >3 times ULN plus any AST): Unknown pharmacokinetics

Patients with Child-Pugh B or C cirrhosis who were treated with single-agent ramucirumab experienced a reported decline in their clinical status.

Not available