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Cyramza

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Cyramza

Cyramza Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Cyramza (ramucirumab) is a recombinant human IgG1 monoclonal antibody used a single-agent is for the treatment of patients with advanced or metastatic, gastric or gastro-esophageal junction adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy. Common side effects include high blood pressure, diarrhea, headache, and low levels of sodium in the blood.

The recommended dose of Cyramza Is 8 mg/kg every 2 weeks administered as an intravenous infusion over 60 minutes. Cyramza may interact with other drugs. Tell your doctor all medications and supplements you use. During pregnancy, Cyramza should be used only if prescribed. It is unknown if this drug passes into breast milk. Consult your doctor before breastfeeding.

Our Cyramza (ramucirumab) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Cyramza FDA Prescribing Information: Side Effects
(Adverse Reactions)

SIDE EFFECTS

The following adverse drug reactions are discussed in greater detail in other sections of the label:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Safety data are presented from two randomized, placebo controlled clinical trials in which patients received CYRAMZA: Study 1, a randomized (2:1), double-blind, clinical trial in which 351 patients received either CYRAMZA 8 mg/kg intravenously every two weeks or placebo every two weeks and Study 2, a double-blind, randomized (1:1) clinical trial in which 656 patients received paclitaxel 80 mg/m² on days 1, 8, and 15 of each 28-day cycle plus either CYRAMZA 8 mg/kg intravenously every two weeks or placebo every two weeks. Both trials excluded patients with ECOG performance status of 2 or greater, uncontrolled hypertension, major surgery within 28 days, or patients receiving chronic anti-platelet therapy other than once daily aspirin. Study 1 excluded patients with bilirubin ≥ 1.5 mg/dL and Study 2 excluded patients with bilirubin > 1.5 times the upper limit of normal.

CYRAMZA Administered as a Single Agent

Among 236 patients who received CYRAMZA (safety population) in Study 1, median age was 60 years, 28% were women, 76% were W hite, and 16% were Asian. Patients in Study 1 received a median of 4 doses of CYRAMZA; the median duration of exposure was 8 weeks, and 32 (14% of 236) patients received CYRAMZA for at least six months.

In Study 1, the most common adverse reactions (all grades) observed in CYRAMZA-treated patients at a rate of ≥ 10% and ≥ 2% higher than placebo were hypertension and diarrhea. The most common serious adverse events with CYRAMZA were anemia (3.8%) and intestinal obstruction (2.1%). Red blood cell transfusions were given to 11% of CYRAMZA-treated patients versus 8.7% of patients who received placebo.

Table 1 provides the frequency and severity of adverse reactions in Study 1.

Table 1: Adverse Reactions Occurring at Incidence Rate ≥ 5% and a ≥ 2% Difference Between Arms in Patients Receiving CYRAMZA in Study 1

Adverse Reactions (MedDRA)a System Organ Class CYRAMZA (8 mg/kg)
N=236
Placebo
N=115
All Grades (Frequency %) Grade 3-4 (Frequency %) All Grades (Frequency %) Grade 3-4 (Frequency %)
Gastrointestinal Disorders
  Diarrhea 14 1 9 2
Metabolism and Nutrition Disorders
  Hyponatremia 6 3 2 1
Nervous System Disorders
  Headache 9 0 3 0
Vascular Disorders
  Hypertension 16 8 8 3
aMedDRA Version 15.0.

Clinically relevant adverse reactions reported in ≥ 1% and < 5% of CYRAMZA-treated patients in Study 1 were: neutropenia (4.7% CYRAMZA versus 0.9% placebo), epistaxis (4.7% CYRAMZA versus 0.9% placebo), rash (4.2% CYRAMZA versus 1.7% placebo), intestinal obstruction (2.1% CYRAMZA versus 0% placebo), and arterial thromboembolic events (1.7% CYRAMZA versus 0% placebo) [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].

Across clinical trials of CYRAMZA administered as a single agent, clinically relevant adverse reactions (including Grade ≥ 3) reported in CYRAMZA-treated patients included proteinuria, gastrointestinal perforation, and infusion-related reactions.

In Study 1, according to laboratory assessment, 8% of CYRAMZA-treated patients developed proteinuria versus 3% of placebo-treated patients. Two patients discontinued CYRAMZA due to proteinuria. The rate of gastrointestinal perforation in Study 1 was 0.8% and the rate of infusion-related reactions was 0.4% [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].

CYRAMZA Administered in Combination with Paclitaxel

Among 327 patients who received CYRAMZA (safety population) in Study 2, median age was 60 years, 31% were women, 63% were W hite, and 33% were Asian. Patients in Study 2 received a median of 9 doses of CYRAMZA; the median duration of exposure was 18 weeks, and 93 (28% of 327) patients received CYRAMZA for at least six months.

In Study 2, the most common adverse reactions (all grades) observed in patients treated with CYRAMZA plus paclitaxel at a rate of ≥ 30% and ≥ 2% higher than placebo plus paclitaxel were fatigue, neutropenia, diarrhea, and epistaxis. The most common serious adverse events with CYRAMZA plus paclitaxel were neutropenia (3.7%) and febrile neutropenia (2.4%); 19% of patients treated with CYRAMZA plus paclitaxel received granulocyte colony-stimulating factors. Adverse reactions resulting in discontinuation of any component of the CYRAMZA plus paclitaxel combination in 2% or more patients in Study 2 were neutropenia (4%) and thrombocytopenia (3%).

Table 2 provides the frequency and severity of adverse reactions in Study 2.

Table 2: Adverse Reactions Occurring at Incidence Rate ≥ 5% and a ≥ 2% Difference Between Arms in Patients Receiving CYRAMZA plus Paclitaxel in Study 2

Adverse Reactions (MedDRA) System Organ Class CYRAMZA plus Paclitaxel
(N=327)
Placebo plus Paclitaxel
(N=329)
All Grades (Frequency %) Grade ≥ 3 (Frequency %) All Grades (Frequency %) Grade ≥ 3 (Frequency %)
Blood and Lymphatic System Disorders
  Neutropenia 54 41 31 19
  Thrombocytopenia 13 2 6 2
Gastrointestinal Disorders
  Diarrhea 32 4 23 2
  Gastrointestinal hemorrhage events 10 4 6 2
  Stomatitis 20 1 7 1
General Disorders and Administration Site Disorders
  Fatigue/Asthenia 57 12 44 6
  Peripheral edema 25 2 14 1
Metabolism and Nutrition Disorders
  Hypoalbuminemia 11 1 5 1
Renal and Urinary Disorders
  Proteinuria 17 1 6 0
Respiratory, Thoracic, and Mediastinal Disorders
  Epistaxis 31 0 7 0
Vascular Disorder
  Hypertension 25 15 6 3

Clinically relevant adverse reactions reported in ≥ 1% and < 5% of the CYRAMZA plus paclitaxel treated patients in Study 2 were sepsis (3.1% CYRAMZA plus paclitaxel versus 1.8% placebo plus paclitaxel) and gastrointestinal perforations (1.2% CYRAMZA plus paclitaxel versus 0.3% for placebo plus paclitaxel).

Immunogenicity

As with all therapeutic proteins, there is the potential for immunogenicity. In clinical trials, 53/884 (6%) of CYRAMZA-treated patients with post baseline serum samples tested positive for treatment-emergent anti-ramucirumab antibodies by an enzyme-linked immunosorbent assay (ELISA). However, this assay has limitations in detecting anti-ramucirumab antibodies in the presence of ramucirumab; therefore, the incidence of antibody development may not have been reliably determined. Neutralizing antibodies were detected in 9 of the 53 patients who tested positive for treatment-emergent anti-ramucirumab antibodies.

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to CYRAMZA with the incidences of antibodies to other products may be misleading.

Read the entire FDA prescribing information for Cyramza (Ramucirumab Solution for Intravenous Infusion) »

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You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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