oms may resolve or improve within days, although some patients with RPLS can experience ongoing neurologic sequelae or death.
5.9 Proteinuria Including Nephrotic Syndrome
In Study 4, severe proteinuria occurred more frequently in patients treated with CYRAMZA plus FOLFIRI compared to patients receiving placebo plus FOLFIRI. Severe proteinuria was reported in 3% of patients treated with CYRAMZA plus FOLFIRI (including 3 cases [0.6%] of nephrotic syndrome) compared to 0.2% of patients treated with placebo plus FOLFIRI.
Monitor proteinuria by urine dipstick and/or urinary protein creatinine ratio for the development of worsening of proteinuria during CYRAMZA therapy.
Withhold CYRAMZA for urine protein levels that are 2 or more grams over 24 hours. Reinitiate CYRAMZA at a reduced dose once the urine protein level returns to less than 2 grams over 24 hours. Permanently discontinue CYRAMZA for urine protein levels greater than 3 grams over 24 hours or in the setting of nephrotic syndrome [see Dosage and Administration (2.3)].
5.10 Thyroid Dysfunction
Monitor thyroid function during treatment with CYRAMZA. In Study 4, the incidence of hypothyroidism reported as an adverse event was 2.6% in the CYRAMZA plus FOLFIRI treated patients and 0.9% in the placebo plus FOLFIRI treated patients.
5.11 Embryofetal Toxicity
Based on its mechanism of action, CYRAMZA can cause fetal harm when administered to pregnant women. Animal models link angiogenesis, VEGF and VEGF Receptor 2 (VEGFR2) to critical aspects of female reproduction, embryofetal development, and postnatal development. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with CYRAMZA and for at 3 least months after the last dose of CYRAMZA [see Use in Specific Populations (8.1, 8.3)].
6 ADVERSE REACTIONS
The following adverse drug reactions are discussed in greater detail in other sections of the label:
Hemorrhage [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)].
Arterial Thromboembolic Events [see Dosage and Administration (2.3) and Warnings and Precautions (5.2)].
Hypertension [see Dosage and Administration (2.3) and Warnings and Precautions (5.3)].
Infusion-Related Reactions [see Dosage and Administration (2.3) and Warnings and Precautions (5.4)].
Gastrointestinal Perforation [see Dosage and Administration (2.3) and Warnings and Precautions (5.5)].
Impaired Wound Healing [see Dosage and Administration (2.3) and Warnings and Precautions (5.6)].
Patients with Child-Pugh B or C Cirrhosis [see Warnings and Precautions (5.7)].
Reversible Posterior Leukoencephalopathy Syndrome [see Warnings and Precautions (5.8)].
Proteinuria Including Nephrotic Syndrome [see Warnings and Precautions (5.9)].
Thyroid Dysfunction [see Warnings and Precautions (5.10)].
6.1 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.
Gastric Cancer
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 wee |
