Cyramza (ramucirumab)

If toxicities occur, temporary or permanent discontinuance of ramucirumab may be required based on causality.

Ramucirumab should be permanently discontinued in patients who develop severe (grade 3 or 4) bleeding, arterial thromboembolic events, clinically important hypertension that is not controlled with antihypertensive therapy, hypertensive crisis, hypertensive encephalopathy, grade 3 or 4 infusion-related effects, GI perforation, nephrotic syndrome, proteinuria exceeding 3 g per 24 hours, or reversible posterior leukoencephalopathy syndrome (RPLS). (See Cautions: Warnings/Precautions.)

Ramucirumab therapy should be temporarily suspended prior to surgery or if wound healing complications develop during therapy. Therapy also should be temporarily interrupted in patients who develop severe hypertension or proteinuria. (See Hypertension and also Proteinuria under Dosage: Dosage Modification for Toxicity, in Dosage and Administration.)

Ramucirumab is administered by IV infusion over 1 hour. The drug should not be administered by rapid IV injection, such as IV ''push'' or ''bolus.''

Ramucirumab injection concentrate must be diluted prior to administration.

Diluted ramucirumab solution should be inspected visually for particulate matter and discoloration prior to administration; if particulate matter or discoloration is evident, the diluted solution should be discarded.

Diluted ramucirumab solution should be administered using an infusion pump. The manufacturer recommends administering the drug through a low-protein-binding 0.22-mcm inline filter. Diluted ramucirumab solution should not be administered in the same IV line with any other drug or electrolyte solution. The IV line should be flushed with 0.9% sodium chloride injection at the end of the infusion.

Unopened vials of ramucirumab injection concentrate should be protected from light, stored at 2-8degreesC, and should not be frozen or shaken.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Igg Antibodies And Derivatives/Efgartigimod-Alfa

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod-alfa may decrease concentrations of compounds that bind to the human FcRn.(3)

Igg Antibodies And Derivatives/Nipocalimab-Aahu

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Nipocalimab-aahu binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of nipocalimab-aahu states that nipocalimab-aahu should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, nipocalimab-aahu should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with nipocalimab-aahu have not been performed. Nipocalimab-aahu may decrease concentrations of compounds that bind to the human FcRn.(3)

Myelosuppressives; Immunomodulators/Sodium Iodide I 131

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1)

CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1)

DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Anti-Angiogenic Agents/Erlotinib

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism is unknown.

CLINICAL EFFECTS: Concurrent use of anti-angiogenic agents may increase the risk of gastrointestinal perforation in patients receiving erlotinib. Fatalities have been reported.(1)

PREDISPOSING FACTORS: Patients with a history of peptic ulceration or diverticular disease or who are receiving concomitant corticosteroids, NSAIDs, and/or taxane-based chemotherapy may be an increased risk of gastrointestinal perforation.(1)

PATIENT MANAGEMENT: Monitor patients receiving concurrent therapy for signs of gastrointestinal perforation. Discontinue erlotinib in patients who develop gastrointestinal perforation.(1)

DISCUSSION: In a phase II trial of concurrent bevacizumab plus erlotinib, 2 of 13 patients suffered fatal gastrointestinal perforations.(2) In another phase II trial of concurrent bevacizumab with erlotinib, 1 of 104 patients died of gastrointestinal perforation.(3)

Igg Antibodies And Derivatives/Rozanolixizumab-Noli

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3)

DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3)

The manufacturer states there are no known contraindications to the use of ramucirumab.

• Acute myocardial infarction
• Acute thromboembolic stroke
• Gastrointestinal hemorrhage
• Gastrointestinal perforation
• Hemorrhage
• Lactation
• Posterior reversible encephalopathy syndrome

• Acute arterial thromboembolism
• Child-pugh class A hepatic impairment
• Child-pugh class B hepatic impairment
• Child-pugh class C hepatic impairment
• Hepatic cirrhosis
• Hypertension
• Impaired wound healing
• Invasive surgical procedure
• Pregnancy
• Proteinuria
• Transient cerebral ischemia

• Hypothyroidism

Adverse effects reported in 5% or more of patients with advanced or metastatic gastric adenocarcinoma receiving ramucirumab as a single agent in the REGARD study and occurring at an incidence at least 2% higher than that reported with placebo include hypertension, diarrhea, bleeding or hemorrhage, headache, proteinuria, and hyponatremia. Clinically important adverse effects reported in less than 5% of patients receiving ramucirumab as a single agent in the REGARD study include neutropenia, epistaxis, rash, anemia, intestinal obstruction, arterial thromboembolic events, GI perforation, and infusion-related reactions.

Adverse effects reported in 5% or more of patients with advanced or metastatic gastric adenocarcinoma receiving ramucirumab in combination with paclitaxel in the RAINBOW study and occurring at an incidence at least 2% higher than that reported with placebo plus paclitaxel include fatigue or asthenia, neutropenia, diarrhea, epistaxis, peripheral edema, hypertension, stomatitis, proteinuria, thrombocytopenia, hypoalbuminemia, and GI hemorrhage. Clinically important adverse effects reported in less than 5% of patients receiving ramucirumab in combination with paclitaxel in the RAINBOW study include sepsis and GI perforation.

Adverse effects reported in 5% or more of patients with metastatic NSCLC receiving ramucirumab in combination with docetaxel in the REVEL study and occurring at an incidence at least 2% higher than that reported with placebo plus docetaxel include neutropenia, fatigue or asthenia, stomatitis or mucosal inflammation, epistaxis, febrile neutropenia, peripheral edema, thrombocytopenia, increased lacrimation, hypertension, diarrhea, decreased appetite, neuropathy, leukopenia, pyrexia, myalgia, arthralgia, back pain, dysgeusia, and insomnia. Clinically important adverse effects reported in less than 5% of patients receiving ramucirumab in combination with docetaxel in the REVEL study include hyponatremia and proteinuria.

Adverse effects reported in the RAISE study in 5% or more of patients with metastatic colorectal cancer receiving ramucirumab in combination with FOLFIRI and at an incidence at least 2% higher than that reported with placebo plus FOLFIRI include diarrhea, neutropenia, fatigue, hemorrhage, decreased appetite, epistaxis, stomatitis, vomiting, constipation, abdominal pain, thrombocytopenia, hypertension, peripheral edema, mucosal inflammation, proteinuria, pyrexia, headache, decreased weight, cough, liver injury or liver failure, palmar-plantar erythrodysesthesia (hand-foot syndrome), GI hemorrhage, venous thromboembolic event, hypoalbuminemia, and infusion-related reactions. Clinically important adverse effects reported in less than 5% of patients receiving ramucirumab in combination with FOLFIRI include GI perforation.

More Frequent

• Hypertension
• Neutropenic disorder
• Palmar-plantar erythrodysesthesia
• Proteinuria

Less Frequent

• Acute arterial thromboembolism
• Gastrointestinal obstruction
• Hypoalbuminemia
• Hyponatremia
• Hypothyroidism
• Thrombocytopenic disorder

Rare or Very Rare

• Arterial aneurysm
• Arterial dissection
• Bronchospastic pulmonary disease
• Gastrointestinal hemorrhage
• Gastrointestinal perforation
• Heart failure
• Hemangioma
• Hemorrhage
• Hypotension
• Impaired wound healing
• Nephrotic syndrome
• Posterior reversible encephalopathy syndrome
• Supraventricular tachycardia
• Thrombotic thrombocytopenic purpura

More Frequent

• Diarrhea
• Epistaxis
• Fatigue
• Headache disorder
• Stomatitis

Less Frequent

• Acute abdominal pain
• Anorexia
• Eye tearing
• Fever
• Nausea
• Peripheral edema
• Skin rash
• Vomiting

Rare or Very Rare

• Back pain
• Chest pain
• Chills
• Dyspnea
• Flushing
• Hypoxia
• Paresthesia
• Tremor
• Voice change
• Wheezing

No enhanced messaging available.

Safety and efficacy of ramucirumab have not been established in pediatric patients younger than 18 years of age.

In animals, exposure to ramucirumab at concentrations 0.2 times that of human clinical exposure resulted in toxicities in bone (i.e., thickening of epiphyseal growth plates, osteochondropathy).

Based on its mechanism of action, ramucirumab may cause fetal harm if administered to pregnant women. (See Fetal/Neonatal Morbidity and Mortality under Cautions: Warnings/Precautions.)

It is not known whether ramucirumab is distributed into human milk. Human immunoglobulin G (IgG) is distributed into milk; however, published data suggest that antibodies contained in breast milk do not enter the neonatal and infant circulation in substantial amounts. Nevertheless, because of the potential for serious adverse reactions to ramucirumab in nursing infants, the manufacturer states that nursing during ramucirumab therapy is not recommended. Data are lacking on the effects of the drug in nursing infants or on the production of milk.

In the REGARD and RAINBOW studies, 36% of patients with advanced or metastatic gastric adenocarcinoma receiving ramucirumab were 65 years of age or older, and 7% were 75 years of age or older. No overall differences in safety or efficacy were observed between geriatric and younger adults.

In the REVEL study, 36% of patients with metastatic NSCLC receiving ramucirumab in combination with docetaxel were 65 years of age or older, and 7% were 75 years of age or older. In an exploratory subgroup analysis, survival benefit was not observed in patients 65 years of age or older receiving ramucirumab in combination with docetaxel (hazard ratio 1.10).

In the RAISE study, 40% of patients with metastatic colorectal cancer receiving ramucirumab in combination with FOLFIRI were 65 years of age or older, and 10% were 75 years of age or older. No overall differences in safety or efficacy were observed between geriatric and younger adults in this study.