fruzaqla

Important safety information

Hypertension: Control blood pressure prior to treatment and monitor during treatment. Manage with anti-hypertensive medications and adjustment of the dose of FRUZAQLA, if necessary. Withhold, dose reduce, or permanently discontinue based on severity of hypertension. ( 2.2 , 5.1 ) Hemorrhagic Events: Closely monitor patients who are at risk for bleeding. Withhold, reduce dose, or permanently discontinue FRUZAQLA based on severity and persistence of hemorrhage. ( 2.2 , 5.2 ) Infections: Monitor for infection during treatment and withhold FRUZAQLA during active infections. Do not start FRUZAQLA in patients with active infections. ( 5.3 ) Gastrointestinal (GI) Perforation: Periodically monitor for GI perforation. Permanently discontinue FRUZAQLA in patients who develop GI perforation or fistula. ( 5.4 ) Hepatotoxicity: Monitor liver laboratory tests prior to the start of FRUZAQLA and periodically during treatment. Withhold, reduce the dose, or permanently discontinue based on severity. ( 2.2 , 5.5 ) Proteinuria: Monitor urine protein. Discontinue FRUZAQLA for nephrotic syndrome ( 2.2 , 5.6 ) Palmar-Plantar Erythrodysesthesia: Withhold FRUZAQLA based on severity. ( 2.2 , 5.7 ) Posterior Reversible Encephalopathy Syndrome (PRES): Immediately discontinue FRUZAQLA if PRES is suspected and confirmed via Magnetic Resonance Imaging (MRI). ( 5.8 ) Impaired Wound Healing: Withhold FRUZAQLA for 2 weeks before major surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of FRUZAQLA after resolution of wound healing complications has not been established. ( 5.9 ) Arterial Thromboembolic Events: Initiation of FRUZAQLA in patients with a recent history of thromboembolic events should be carefully considered. Discontinue FRUZAQLA in patients who develop arterial thromboembolism. ( 5.10 ) Allergic Reactions to FD&C Yellow No. 5 (Tartrazine) and No. 6 (Sunset Yellow FCF): Contains FD&C Yellow No. 5 (tartrazine) and No. 6 (sunset yellow FCF) as color additives, which may cause allergic reactions (including bronchial asthma) in certain susceptible patients. ( 5.11 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of reproductive potential of the potential risk to the fetus and to use effective contraception. ( 5.12 , 8.1 , 8.3 ) 5.1. Hypertension FRUZAQLA can cause hypertension. Hypertension occurred in 450 of 911 (49%) patients with mCRC treated with FRUZAQLA, including Grade 3-4 events in 19%, and hypertensive crisis in three patients (0.3%). The median time to first onset of hypertension was 14 days from first dose of FRUZAQLA. Do not initiate FRUZAQLA unless blood pressure is adequately controlled. Monitor blood pressure weekly the first month, at least monthly thereafter and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue FRUZAQLA based on the severity of hypertension [see Dosage and Administration (2.2) ] . 5.2. Hemorrhagic Events FRUZAQLA can cause serious hemorrhagic events, which may be fatal. In 911 patients with mCRC treated with FRUZAQLA, 6% of patients experienced a gastrointestinal hemorrhage, including 13 patients (1%) with a Grade ≥3 event and 2 patients with fatal hemorrhages. Permanently discontinue FRUZAQLA in patients with severe or life-threatening hemorrhage. Monitor the International Normalized Ratio (INR) levels in patients receiving anticoagulants [see Dosage and Administration (2.2) ] . 5.3. Infections FRUZAQLA can cause an increased risk of infections, including fatal infections. In 781 patients treated with FRUZAQLA across three randomized, placebo-controlled trials, the overall incidence of infections was higher (18% vs. 12%) including for fatal infections (1% vs. 0.3%) as compared to the placebo arms (n=391). In 911 patients with mCRC treated with FRUZAQLA, the most common infections were urinary tract infections (6.8%), upper respiratory tract infections (3.2%) and pneumonia (2.5%); fatal infections included pneumonia (0.4%), sepsis (0.2%), bacterial infection (0.1%), lower respiratory tract infection (0.1%), and septic shock (0.1%). Withhold FRUZAQLA for Grade 3 or 4 infections, or worsening infection of any grade. Resume FRUZAQLA at the same dose when the infection has resolved. 5.4. Gastrointestinal Perforation FRUZAQLA can cause gastrointestinal perforation. In 911 patients with mCRC treated with FRUZAQLA, 12 patients (1.3%) experienced a Grade ≥3 gastrointestinal perforation, including one fatal event. Permanently discontinue FRUZAQLA in patients who develop gastrointestinal perforation or fistula. 5.5. Hepatotoxicity FRUZAQLA can cause liver injury. In 911 patients with mCRC treated with FRUZAQLA, 48% experienced increased ALT or AST, including Grade ≥3 events in 5%, and fatal events in 0.2%. Median time to first onset of elevated liver enzymes was 29 days from first dose of FRUZAQLA. Monitor liver function tests (ALT, AST, and bilirubin) before initiation and periodically throughout treatment with FRUZAQLA. Temporarily hold and then reduce or permanently discontinue FRUZAQLA depending on the severity and persistence of hepatotoxicity as manifested by elevated liver function tests [see Dosage and Administration (2.2) and Use in Specific Populations (8.6) ] . 5.6. Proteinuria FRUZAQLA can cause proteinuria. In 911 patients with mCRC treated with FRUZAQLA, 36% experienced proteinuria and 2.5% of patients experienced Grade ≥3 events. Median time to first onset of proteinuria was 22 days from first dose of FRUZAQLA. Monitor for proteinuria before initiation and periodically throughout treatment with FRUZAQLA. For proteinuria ≥2 g/24 hours, withhold FRUZAQLA until improvement to ≤Grade 1 proteinuria, resume FRUZAQLA at a reduced dose. Discontinue FRUZAQLA in patients who develop nephrotic syndrome [see Dosage and Administration (2.2) ]. 5.7. Palmar-Plantar Erythrodysesthesia (PPE) FRUZAQLA can cause PPE. In 911 patients with mCRC treated with FRUZAQLA, PPE occurred in 35%, including 8% with Grade 3 events. Median time to first onset of PPE was 19 days from first dose of FRUZAQLA. Based on severity, withhold FRUZAQLA and then resume at the same or reduced dose [see Dosage and Administration (2.2) ]. 5.8. Posterior Reversible Encephalopathy Syndrome (PRES) FRUZAQLA can cause PRES, a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI. PRES occurred in one of 911 patients with mCRC treated with FRUZAQLA. Perform an evaluation for PRES in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function. Discontinue FRUZAQLA in patients who develop PRES. 5.9. Impaired Wound Healing Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. In 911 patients with mCRC treated with FRUZAQLA, 1 patient experienced a Grade 2 event of wound dehiscence. Do not administer FRUZAQLA for at least 2 weeks prior to major surgery. Do not administer FRUZAQLA for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of FRUZAQLA after resolution of wound healing complications has not been established. 5.10. Arterial Thromboembolic Events FRUZAQLA may increase the risk of arterial thromboembolic events. In 911 patients with mCRC treated with FRUZAQLA, 7 patients (0.8%) experienced an arterial thromboembolic event; additionally, FRUZAQLA studies excluded patients with clinically significant cardiovascular disease, uncontrolled hypertension, or with thromboembolic events within the prior 6 months. Initiation of FRUZAQLA in patients with a recent history of thromboembolic events should be carefully considered. In patients who develop arterial thromboembolism discontinue FRUZAQLA. 5.11. Allergic Reactions to FD&C Yellow No. 5 (Tartrazine) and No. 6 (Sunset Yellow FCF) FRUZAQLA 1 mg capsules contain…