Usage
Ramucirumab is prescribed for the treatment of several types of cancer, including:
- Gastric or gastroesophageal junction adenocarcinoma: Used in advanced stages, either alone or with paclitaxel, after prior chemotherapy containing fluoropyrimidine or platinum.
- Non-small cell lung cancer (NSCLC): Used after platinum-based chemotherapy, in combination with docetaxel, or as first-line treatment with erlotinib for patients with specific EGFR mutations.
- Hepatocellular carcinoma (HCC): For patients with alpha-fetoprotein (AFP) of 400 ng/mL or greater who have been previously treated with sorafenib.
- Colorectal cancer: Used in combination with FOLFIRI (folinic acid, fluorouracil, and irinotecan), for patients previously treated with bevacizumab, oxaliplatin-based, and fluoropyrimidine therapy.
Pharmacological Classification: Ramucirumab is a monoclonal antibody, specifically a vascular endothelial growth factor receptor 2 (VEGFR2) antagonist.
Mechanism of Action: Ramucirumab blocks the binding of VEGF to VEGFR2, thereby inhibiting angiogenesis (the formation of new blood vessels). This deprives tumors of the blood supply necessary for growth and metastasis.
Alternate Names
- International Nonproprietary Name (INN): ramucirumab
- Brand Name: Cyramza®
How It Works
Pharmacodynamics: Ramucirumab binds with high affinity to VEGFR2, blocking the binding of VEGF ligands. This inhibits ligand-induced activation of the receptor and downstream signaling pathways, ultimately preventing tumor angiogenesis.
Pharmacokinetics:
- Absorption: Administered intravenously, therefore 100% bioavailable.
- Metabolism: As a monoclonal antibody, metabolism is expected to be similar to endogenous IgG, primarily through degradation into small peptides and amino acids.
- Elimination: Primarily eliminated through protein catabolism, with a small amount possibly excreted in the urine and feces. The half-life is approximately 14 days.
Mode of Action: Ramucirumab specifically targets the extracellular domain of VEGFR2, preventing the binding of VEGF-A, VEGF-C, and VEGF-D. This inhibits receptor dimerization and activation of tyrosine kinases, leading to a reduction in downstream signaling, which subsequently inhibits endothelial cell proliferation, migration, and the formation of new blood vessels that supply the tumor.
Receptor Binding: Binds to VEGFR2.
Enzyme Inhibition: Indirectly inhibits downstream kinases involved in the VEGF signaling pathway.
Neurotransmitter Modulation: No direct effect on neurotransmitter modulation.
Elimination Pathways: Primarily through protein catabolism.
Dosage
Standard Dosage
Adults:
- Gastric Cancer/Gastroesophageal Junction Adenocarcinoma: 8 mg/kg IV infusion every 2 weeks, as a single agent or in combination with paclitaxel (80 mg/m² IV infusion on days 1, 8, and 15 of a 28-day cycle).
- NSCLC with docetaxel: 10 mg/kg IV infusion every 3 weeks (21-day cycle).
- NSCLC with erlotinib: 10 mg/kg IV infusion every 2 weeks.
- HCC: 8 mg/kg IV infusion every 2 weeks.
- Colorectal cancer: 8 mg/kg IV infusion every 2 weeks, in combination with FOLFIRI.
Children: No established dosage. Use with caution.
Special Cases:
- Elderly Patients: No specific dose adjustment, but closer monitoring is advised.
- Patients with Renal Impairment: No dose adjustment for mild to moderate impairment. No data available for severe renal impairment.
- Patients with Hepatic Dysfunction: No dose adjustment for mild to moderate impairment. Use with caution in severe hepatic impairment.
- Patients with Comorbid Conditions: Careful monitoring for patients with hypertension, bleeding disorders, or history of thromboembolic events.
Clinical Use Cases
Ramucirumab is not specifically indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose reductions may be necessary for severe hypertension, proteinuria, or other adverse effects.
Side Effects
Common Side Effects
Fatigue, hypertension, proteinuria, diarrhea, neutropenia, thrombocytopenia, stomatitis, epistaxis, headache.
Rare but Serious Side Effects
Hemorrhage (including gastrointestinal and cerebral hemorrhage), arterial thromboembolic events (including myocardial infarction and stroke), gastrointestinal perforation, impaired wound healing, infusion-related reactions, hypertension, posterior reversible encephalopathy syndrome (PRES).
Long-Term Effects
Chronic hypertension, proteinuria, risk of secondary malignancies with prolonged use.
Adverse Drug Reactions (ADR)
Severe bleeding, thromboembolic events, gastrointestinal perforation, PRES, severe infusion reactions.
Contraindications
Hypersensitivity to ramucirumab. Active bleeding. Severe uncontrolled hypertension. Pregnancy.
Drug Interactions
No formal drug interaction studies have been conducted. However, concomitant use with other antiangiogenic agents or drugs that affect wound healing should be done with caution. Bevacizumab increases the risk of severe bleeding and should not be co-administered. No clinically significant interactions with CYP450 enzymes have been observed.
Pregnancy and Breastfeeding
Pregnancy Safety Category: Contraindicated in pregnancy. May cause fetal harm due to inhibition of angiogenesis.
Breastfeeding: Not recommended. Potential for infant exposure through breast milk. Discontinue breastfeeding during treatment and for at least 3 months after the last dose.
Drug Profile Summary
- Mechanism of Action: VEGFR2 antagonist, inhibiting angiogenesis.
- Side Effects: Hemorrhage, hypertension, proteinuria, fatigue, neutropenia, thrombocytopenia.
- Contraindications: Hypersensitivity, active bleeding, uncontrolled hypertension, pregnancy.
- Drug Interactions: Caution with other antiangiogenic agents, bevacizumab is contraindicated.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy. Not recommended during breastfeeding.
- Dosage: 8-10 mg/kg IV every 2-3 weeks, depending on indication and combination therapy.
- Monitoring Parameters: Blood pressure, complete blood count, urinalysis (proteinuria), liver function tests, signs of bleeding, wound healing.
Popular Combinations
- Paclitaxel for gastric cancer.
- Docetaxel for NSCLC.
- Erlotinib for NSCLC with EGFR mutations.
- FOLFIRI for colorectal cancer.
Precautions
- General Precautions: Monitor blood pressure, complete blood count, urine protein, and liver function tests. Assess for signs of bleeding or impaired wound healing.
- Specific Populations: Contraindicated in pregnancy. Not recommended during breastfeeding. Use with caution in elderly patients and patients with renal or hepatic impairment.
- Lifestyle Considerations: Avoid activities with a high risk of bleeding or injury.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ramucirumab?
A: The dosage depends on the indication and whether it is used as monotherapy or in combination. Refer to the “Dosage” section above for detailed information.
Q2: What are the most serious side effects of Ramucirumab?
A: Hemorrhage, arterial thromboembolic events, gastrointestinal perforation, and severe infusion reactions are the most serious side effects.
Q3: Can Ramucirumab be used during pregnancy?
A: No, Ramucirumab is contraindicated during pregnancy due to the risk of fetal harm.
Q4: How is Ramucirumab administered?
A: Ramucirumab is administered intravenously as an infusion.
Q5: What should be monitored in patients receiving Ramucirumab?
A: Blood pressure, complete blood counts, liver function, renal function (proteinuria), and signs of bleeding should be closely monitored.
Q6: What are the common drug interactions with Ramucirumab?
A: Concomitant use with bevacizumab is contraindicated. Caution should be used with other antiangiogenic drugs. No clinically significant CYP450 interactions have been observed.
Q7: How does Ramucirumab work against cancer?
A: It is a VEGFR2 antagonist, which inhibits angiogenesis, therefore blocking tumor growth and spread.
Q8: What are the indications for using Ramucirumab?
A: Refer to the “Usage” section above for a list of approved indications.
Q9: Can Ramucirumab be used in patients with renal or hepatic impairment?
A: It can be used with caution in patients with mild to moderate impairment. No data are available for severe impairment.
A: Symptoms may include chills, fever, rash, itching, flushing, dyspnea, and hypotension. Premedication with antihistamines and corticosteroids can help reduce the risk.
