ramucirumab

High Alert

Advanced gastric cancer or gastroesophageal junction adenocarcinoma following unsuccessful combination treatment that included a fluoropyrimidine or platinum compound (as monotherapy or in combination with paclitaxel).
First-line treatment of metastatic non–small cell lung cancer (NSCLC) in patients whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations (in combination with erlotinib).
Metastatic NSCLC with disease progression on or after platinum-based chemotherapy (in combination with docetaxel).
Metastatic colorectal cancer with disease progression on or after treatment with bevacizumab, oxaliplatin, and a fluoropyrimidine (in combination with irinotecan, folinic acid, and 5–fluorouracil [FOLFIRI]).
Hepatocellular carcinoma in patients with an alpha fetoprotein of ≥400 ng/mL who have been previously treated with sorafenib.

Action ⬆ ⬇

A monoclonal antibody that binds to vascular endothelial growth factor receptor 2, antagonizing its effects, resulting in decreased angiogenesis.

Therapeutic effects:

Decreased growth and spread of gastric cancer, gastroesophageal junction adenocarcinoma, NSCLC, colorectal cancer, and hepatocellular carcinoma.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Unknown.

Half-Life: Unknown.

Time/Action Profile ⬆ ⬇

(improved survival)

ROUTE	ONSET	PEAK	DURATION
IV	within 1 mo	7–8 mo	24 mo

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Child-Pugh Class B or C cirrhosis (use only if benefits outweigh risk of further deterioration);
Surgery (discontinue prior to surgery, reinstate when healing is complete);
Serious or non-healing wounds;
Hypertension (must be controlled prior to treatment);
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, CARDIAC ARREST, MI

Derm: impaired wound healing

Endo: hypothyroidism

F and E: hyponatremia

GI: diarrhea, GI OBSTRUCTION/PERFORATION, worsened cirrhosis/hepatorenal syndrome

GU: ↓fertility (females), nephrotic syndrome, proteinuria

Hemat: bleeding, neutropenia

Neuro: encephalopathy, headache, POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES), STROKE

Misc: INFUSION-RELATED REACTIONS

Interactions ⬆ ⬇

Drug-drug:

↑risk of bleeding with anticoagulants, antiplatelet agents and NSAIDs.

Route/Dosage ⬆ ⬇

Gastric Cancer or Hepatocellular Carcinoma

IV (Adults ): 8 mg/kg every 2 wk until disease progression or unacceptable toxicity.

Non–Small Cell Lung Cancer

IV (Adults ): First-line treatment in tumors with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations: 10 mg/kg every 2 wk until disease progression or unacceptable toxicity; Disease progression on or after platinum-based therapy: 10 mg/kg on Day 1 of a 21-day cycle prior to docetaxel; continued until disease progression or unacceptable toxicity.

Colorectal Cancer

IV (Adults ): 8 mg/kg every 2 wk prior to FOLFIRI administration; continued until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

Solution for injection: 10 mg/mL

Assessment ⬆ ⬇

Monitor for infusion-related reactions (rigors/tremors, back pain/spasms, chest pain and/or tightness, chills, flushing, dyspnea, wheezing, hypoxia, paresthesia, bronchospasm, supraventricular tachycardia, hypotension) during infusion. Reduce infusion rate by 50% for Grade 1 or 2 reactions, and immediately and permanently discontinue ramucirumab if Grade 3 or 4 reactions occur.
Monitor BP prior to and at least every 2 wk during therapy. Hold therapy for severe hypertension until BP is under control. Permanently discontinue if unable to control hypertension.
Avoid administration for at least 28 days prior to and 28 days after surgery or until wound is healed.
If arterial thromboembolic events (MI, cardiac arrest, stroke, cerebral ischemia) occur, permanently discontinue.
Monitor for signs and symptoms of bleeding (bleeding, lightheadedness) during therapy. If Grade 3 or 4 bleeding occurs, permanently discontinue medication.
Monitor for signs and symptoms of GI perforation (severe diarrhea, vomiting, severe abdominal pain) during therapy. Discontinue medication permanently if perforation occurs.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.Monitor urinary protein periodically during therapy. Hold ramucirumab for urine protein ≥2 g/24 hr. Reinitiate therapy at reduced dose (reduce 8 mg dose to 6 mg/kg and 10 mg to 8 mg) every 2 wk once urinary protein levels <2 g/24 hr. If protein level returns to ≥2 g/24 hr hold therapy until urine protein <2 g per 24 hr and reduce dose (reduce 6 mg to 5 mg/kg and 8 mg to 6 mg) every 2 wk once urinary protein levels return to <2 g/24 hr. Discontinue therapy permanently if urine protein level >3 g/24 hr or if nephrotic syndrome occurs.

Implementation ⬆ ⬇

Hold ramucirumab therapy for at least 4 wk before elective surgery and for at least 2 wk after major surgery until adequate wound healing occurs.
Prior to each dose, premedicate all patients with IV histamine H₁ antagonist (diphenhydramine). Premedicate patients who have experienced a Grade 1 or 2 infusion reaction with dexamethasone and acetaminophen prior to each infusion.

IV Administration:

Intermittent Infusion: Withdraw required volume from vial. Diluent: Dilute with 0.9% NaCl for a final volume of 250 mL. Do not use dextrose-containing solutions. Gently invert to ensure adequate mixing. Solution is clear to slightly opalescent and colorless to slightly yellow; do not administer solutions that are discolored or contain particulate material. Solution is stable for 24 hr if refrigerated or 4 hr at room temperature. Discard unused solution.
Rate: Infuse over 60 min via infusion pump through a separate infusion line using a 0.22 micron filter; do not administer as IV push or bolus. Flush line with 0.9% NaCl at end of infusion. If 1st infusion is tolerated, administer all subsequent infusions over 30 min.
Y-Site Incompatibility: Do not dilute with other solutions or infuse with other electrolyte solutions or medications.

Patient/Family Teaching ⬆ ⬇

Explain purpose of ramucirumab to patient.
Advise patient to notify health care professional if bleeding or lightheadedness occur.
Instruct patient in self BP monitoring and advise patient to notify health care professional if signs and symptoms of hypertension (elevated BP, severe headache, lightheadedness, neurologic symptoms) or if severe diarrhea, vomiting, or severe abdominal pain occur.
Advise patient to notify health care professional of medication regimen prior to surgery; must be stopped for at least 4 wk before elective surgery and for at least 2 wk after major surgery until adequate wound healing occurs; may impair wound healing.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for at least 3 mo after last dose and avoid breastfeeding for 2 mo after last dose. Notify health care professional if pregnancy is suspected. Advise patient that ramucirumab may impair fertility in females.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇