fotivda

Important safety information

Hypertension and Hypertensive Crisis: Control blood pressure prior to initiating FOTIVDA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the FOTIVDA dose. ( 5.1 ) Cardiac Failure: Monitor for signs or symptoms of cardiac failure throughout treatment with FOTIVDA. ( 5.2 ) Cardiac Ischemia and Arterial Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe arterial thromboembolic events, such as myocardial infarction and stroke. ( 5.3 ) Venous Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe venous thromboembolic events. ( 5.4 ) Hemorrhagic Events: Closely monitor patients who are at risk for or who have a history of bleeding. ( 5.5 ) Proteinuria: Monitor throughout treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment with FOTIVDA. ( 5.6 ) Perforations and Fistulas: Monitor for symptoms. Discontinue FOTIVDA for severe or life-threatening gastrointestinal perforation. ( 5.7 ) Thyroid Dysfunction: Monitor before initiation and throughout treatment with FOTIVDA. ( 5.8 ) Risk of Impaired Wound Healing: Withhold FOTIVDA for at least 24 days before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established. ( 5.9 ) Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue FOTIVDA if signs or symptoms of RPLS occur. ( 5.10 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.11 , 8.1 , 8.3 ) Allergic Reactions to Tartrazine: The 0.89 mg capsule of FOTIVDA contains FD&C Yellow No.5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients. ( 5.12 ) 5.1 Hypertension and Hypertensive Crisis FOTIVDA can cause severe hypertension and hypertensive crisis. Hypertension occurred in 45% of patients treated with FOTIVDA, with 22% of the events ≥ Grade 3. Median time to onset of hypertension was 2 weeks (range: 0 – 192 weeks). Hypertensive crisis occurred in 0.8% of patients . One patient (0.1%) died due to hypertensive emergency after FOTIVDA overdose [see OVERDOSAGE (10) ] . FOTIVDA has not been studied in patients with systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg. Control blood pressure prior to treatment with FOTIVDA. Monitor blood pressure after 2 weeks and at least monthly thereafter during treatment with FOTIVDA. Treat patients with anti- hypertensive therapy when hypertension occurs during treatment with FOTIVDA. Withhold FOTIVDA for severe hypertension despite optimal anti-hypertensive therapy. For persistent hypertension despite use of anti-hypertensive medications, reduce the FOTIVDA dose [see DOSAGE AND ADMINISTRATION (2.2) ] . Discontinue FOTIVDA if hypertension is severe and persistent despite anti-hypertensive therapy and dose reduction of FOTIVDA, or in patients who experience hypertensive crisis. If FOTIVDA is interrupted, monitor patients receiving anti-hypertensive medications for hypotension. 5.2 Cardiac Failure FOTIVDA can cause serious, sometimes fatal, cardiac failure. Cardiac failure in FOTIVDA- treated patients occurred in 1.6%, with 1% of events ≥ Grade 3, and 0.6% events were fatal. FOTIVDA has not been studied in patients with symptomatic cardiac failure within the preceding 6 months before FOTIVDA treatment initiation. Periodically monitor patients for symptoms of cardiac failure throughout treatment with FOTIVDA. Management of cardiac failure events may require interruption, dose reduction, or permanent discontinuation of FOTIVDA therapy [see DOSAGE AND ADMINISTRATION (2.2) ] . 5.3 Cardiac Ischemia and Arterial Thromboembolic Events FOTIVDA can cause serious, sometimes fatal, cardiac ischemia and arterial thromboembolic events. Cardiac ischemia in FOTIVDA-treated patients occurred in 3.2%, with 1.5% of events ≥ Grade 3, and 0.4% events were fatal. Arterial thromboembolic events were reported in 2% of FOTIVDA-treated patients, including death due to ischemic stroke (0.1%). FOTIVDA has not been studied in patients who had an arterial thrombotic event, myocardial infarction, or unstable angina within the preceding 6 months before FOTIVDA treatment initiation. Closely monitor patients who are at risk for, or who have a history of these events (such as myocardial infarction and stroke), during treatment with FOTIVDA. Discontinue FOTIVDA in patients who develop any severe or life-threatening arterial thromboembolic event [see DOSAGE AND ADMINISTRATION (2.2) ] . 5.4 Venous Thromboembolic Events FOTIVDA can cause serious, sometimes fatal, venous thromboembolic events. Venous thromboembolic events occurred in 2.4% of patients treated with FOTIVDA, including death (0.3%). Closely monitor patients who are at risk for, or who have a history of these events during treatment with FOTIVDA. Discontinue FOTIVDA in patients who develop any severe or life-threatening venous thromboembolic event [see DOSAGE AND ADMINISTRATION (2.2) ] . 5.5 Hemorrhagic Events FOTIVDA can cause serious, sometimes fatal, hemorrhagic events. Hemorrhagic events occurred in 11% of patients treated with FOTIVDA, including death (0.2%). FOTIVDA has not been studied in patients with significant bleeding within the preceding 6 months before FOTIVDA treatment initiation. Closely monitor patients who are at risk for or who have a history of bleeding during treatment with FOTIVDA. Discontinue FOTIVDA in patients who develop severe or life-threatening hemorrhagic events [see DOSAGE AND ADMINISTRATION (2.2) ] . 5.6 Proteinuria FOTIVDA can cause proteinuria. Proteinuria occurred in 8% of FOTIVDA-treated patients with 2% of events Grade 3. Of the patients who developed proteinuria, 3/81 (3.7%) had acute kidney injury either concurrently or later during treatment. Monitor patients for proteinuria before initiation of, and periodically throughout, treatment with FOTIVDA. For patients who develop moderate to severe proteinuria, reduce the dose or interrupt FOTIVDA treatment. Discontinue FOTIVDA in patients who develop nephrotic syndrome [see DOSAGE AND ADMINISTRATION (2.2) ] . 5.7 Gastrointestinal Perforation and Fistula Formation Gastrointestinal perforation including fatal cases, has been reported in patients receiving FOTIVDA. Monitor for symptoms of gastrointestinal perforation or fistula periodically throughout treatment with FOTIVDA. Permanently discontinue FOTIVDA in patients who develop severe or life-threatening gastrointestinal perforation. 5.8 Thyroid Dysfunction FOTIVDA can cause thyroid dysfunction. Thyroid dysfunction events in FOTIVDA-treated patients occurred in 11%, with 0.3% Grade 3 or 4 events. Hypothyroidism was reported in 8% of patients and hyperthyroidism was reported in 1% of patients. Monitor thyroid function before initiation of, and periodically throughout, treatment with FOTIVDA. Treat hypothyroidism and hyperthyroidism to maintain euthyroid state before and during treatment with FOTIVDA. 5.9 Risk of Impaired Wound Healing Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway, such as FOTIVDA. Therefore, FOTIVDA has the potential to adversely affect wound healing. Withhold FOTIVDA for at least 24 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established. 5.10 Reversible Posterior Leukoencephalopathy Syndrome Reversible posterior leukoencephalopathy syndrome (RPLS), a…