veppanu

Select patients for treatment with VEPPANU based on the presence of ESR1 mutation. ( 2.1 ) Recommended Dosage: 200 mg orally once daily with food. ( 2.2 ) Interruption, dose reduction, or permanent discontinuation may be required due to adverse reactions. ( 2.3 ) 2.1 Patient Selection Select patients for treatment of ER-positive, HER2-negative advanced or metastatic breast cancer with VEPPANU based on the presence of ESR1 mutation(s) in plasma specimen using an FDA-authorized test [see Indications and Usage ( 1 ) and Clinical Studies ( 14 )] . Information on FDA-authorized tests for detection of ESR1 mutations in breast cancer is available at: http://www.fda.gov/CompanionDiagnostics. 2.2 Recommended Dosage and Administration The recommended dosage of VEPPANU is 200 mg taken orally once daily with food [see Clinical Pharmacology ( 12.3 )] until disease progression or unacceptable toxicity. Swallow VEPPANU tablet(s) whole. Do not chew, crush, dissolve, or split prior to swallowing. Do not take VEPPANU tablets that are broken, cracked, or look damaged. If a patient misses a dose or vomits after taking a dose, the patient should take the next dose at the regularly scheduled time. 2.3 Dosage Modifications for Adverse Reactions The recommended dose reduction for adverse reactions is 100 mg orally once daily. Permanently discontinue VEPPANU in patients who are unable to tolerate 100…

The following clinically significant adverse reaction is described elsewhere in the labeling: QTc Interval Prolongation [see Warnings and Precautions ( 5.1 )] Most common ( > 10%) adverse reactions with VEPPANU, including laboratory abnormalities, were decreased white blood cells, increased AST, musculoskeletal pain, fatigue, decreased hemoglobin, decreased neutrophils, increased ALT, increased alkaline phosphatase, nausea, decreased blood potassium, increased bilirubin, decreased appetite, electrocardiogram QT prolonged, decreased platelets, and constipation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Rigel Pharmaceuticals, Inc. at 1-800-983-1329 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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. The safety of VEPPANU was evaluated in patients with ER-positive, HER2-negative, advanced or metastatic breast cancer following endocrine therapy in VERITAC-2 [see Clinical Studies ( 14 )] . Patients received VEPPANU 200 mg orally once daily (N=312) or fulvestrant 500 mg intramuscularly on Days 1 and 15 of Cycle 1 and then on Day 1 of each subsequent 28-day cycle (N=307). Among…

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Strong CYP3A Inhibitors : Avoid concomitant use with strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce VEPPANU dosage. ( 2.4 , 7.1 ) Strong CYP3A Inducers : Avoid concomitant use with strong CYP3A inducers. If concomitant use cannot be avoided, increase VEPPANU dosage. ( 2.4 , 7.1 ) Certain P-gp Substrates : Avoid concomitant use with certain P-gp substrates where minimal increases in concentration may lead to serious adverse reactions. ( 7.2 ) Certain UGT1A9 Substrates : Refer to the Prescribing Information for UGT1A9 substrates where minimal increases in concentration may lead to serious adverse reactions. ( 7.2 ) 7.1 Effect of Other Drugs on VEPPANU Table 5 describes drug interactions where concomitant use of another drug affects VEPPANU. Table 5: Drug Interactions that Affect VEPPANU Strong CYP3A Inhibitors Prevention or Management Strong CYP3A Inhibitors: Avoid concomitant use of VEPPANU with strong CYP3A inhibitors in patients receiving VEPPANU 200 mg once daily. If concomitant use cannot be avoided, reduce VEPPANU dosage [see Dosage and Administration ( 2.4 )] . Avoid concomitant use with strong CYP3A inhibitors in patients receiving VEPPANU 100 mg once daily. Mechanism and Clinical Effect(s) Vepdegestrant is a CYP3A substrate. Concomitant use with a strong CYP3A inhibitor may increase vepdegestrant plasma concentration [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of VEPPANU-associated adverse reactions. Strong CYP3A Inducers Prevention or Management Avoid concomitant use with strong CYP3A inducers in patients receiving VEPPANU 200 mg once daily. If concomitant use cannot be avoided, increase VEPPANU dosage [see Dosage and Administration ( 2.4 )] . Avoid concomitant use with strong CYP3A inducers in patients receiving VEPPANU 100 mg once daily. Mechanism and Clinical Effect(s) Vepdegestrant is a CYP3A substrate. Concomitant use with a strong CYP3A inducer may decrease vepdegestrant plasma concentration [see Clinical Pharmacology ( 12.3 )] , which may reduce the effectiveness of VEPPANU. 7.2 Effect of VEPPANU on Other Drugs Table 6 describes drug interactions where concomitant use of VEPPANU affects another drug. Table 6: VEPPANU Drug Interactions that Affect Other Drugs Certain P-gp Substrates Prevention or Management Avoid concomitant use with certain P-gp substrates where minimal increases in concentration may lead to serious adverse reactions. Mechanism and Clinical Effect(s) Vepdegestrant is a P-gp inhibitor. Vepdegestrant increases exposure of P-gp substrates [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of adverse reactions related to these substrates. Certain UGT1A9 Substrates Prevention or Management Refer to the Prescribing Information for UGT1A9 substrates where minimal increases in the concentration may lead to serious adverse reactions. Mechanism and Clinical Effect(s) Vepdegestrant is a UGT1A9 inhibitor. Vepdegestrant increases exposure of UGT1A9 substrates [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of adverse reactions related to these substrates. 7.3 Drugs that Prolong QTc Interval Avoid concomitant use of VEPPANU with other drugs with a known potential to prolong the QTc interval. If concomitant use cannot be avoided: Obtain ECGs when initiating and during concomitant use, and as clinically indicated [see Warnings and Precautions ( 5.1 )] . Withhold VEPPANU if the QTc interval is >480 ms or the change from baseline is >60 ms [see Dosage and Administration ( 2.3 )] . Vepdegestrant causes QTc interval prolongation [see Clinical Pharmacology ( 12.2 )] . Concomitant use of VEPPANU with other drugs that prolong the QTc interval may result in a greater increase in the QTc interval and adverse reactions associated with QTc interval prolongation, including Torsade de Pointes, other serious arrhythmias, and sudden death [see Warnings and Precautions ( 5.1 )] .