warnings and cautions
5 WARNINGS AND PRECAUTIONS • Hypersensitivity: If clinically significant hypersensitivity or anaphylaxis occur, immediately discontinue MODEYSO and initiate appropriate medical treatment and supportive care. ( 5.1 ) • QTc Interval Prolongation: MODEYSO causes concentration dependent QTc interval prolongation. Interrupt or reduce the dose of MODEYSO in patients who develop QT prolongation, and permanently discontinue MODEYSO in patients with signs of life-threatening arrhythmias. ( 5.2 , 12.2 ) • Embryo-fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.3 , 8.1 , 8.3 ) 5.1 Hypersensitivity MODEYSO can cause severe hypersensitivity reactions. In the pooled safety population [see Adverse Reactions ( 6.1 )], Grade 3 hypersensitivity reactions occurred in 0.3% of patients receiving MODEYSO. Signs and symptoms of hypersensitivity may include rash, hives, fever, low blood pressure, wheezing, or swelling of the face or throat. Inform patients about the signs and symptoms of hypersensitivity reactions and instruct them to seek immediate medical attention if symptoms occur. If clinically significant hypersensitivity or anaphylaxis occur, immediately interrupt MODEYSO and initiate appropriate medical treatment and supportive care. Based on the severity of the adverse reaction, temporarily interrupt or permanently discontinue MODEYSO [see Dosage and Administration ( 2.4 )] . 5.2 QTc Interval Prolongation MODEYSO causes a concentration-dependent QTc interval prolongation [see Clinical Pharmacology ( 12.2 )] , which can increase the risk for ventricular tachyarrhythmias (e.g., torsades de pointes) or sudden death. In the pooled safety population [see Adverse Reactions ( 6.1 )] , of the 82 patients who underwent at least one post-baseline ECG assessment, 6% experienced an increase in QTc of >60 msec compared to baseline after receiving MODEYSO and 1.2% had an increase in QTc to >500 msec. Monitor ECGs and electrolytes prior to starting MODEYSO and then periodically during treatment as clinically indicated. Significant prolongation of the QT interval may occur when MODEYSO is taken concomitantly with other products that have a known potential to prolong the QT interval. Avoid concomitant use of MODEYSO with products known to prolong the QT interval. If concomitant use cannot be avoided, separate administration of MODEYSO and the QT-prolonging product [see Drug Interactions ( 7.2 ) and Clinical Pharmacology ( 12.2 )] . Increase the frequency of monitoring when administering MODEYSO to patients taking other products that have a known potential to prolong the QT interval and in patients with congenital long QT syndrome, existing QTc prolongation, a history of ventricular arrhythmias, electrolyte abnormalities, heart failure, or who are taking strong or moderate CYP3A4 inhibitors. Interrupt or reduce the dose of MODEYSO in patients who develop QT prolongation, and permanently discontinue MODEYSO in patients with signs of life-threatening arrhythmias [see Dosage and Administration ( 2.4 )] . 5.3 Embryo-fetal Toxicity Based on findings from animal studies and its mechanism of action, MODEYSO can cause fetal harm when administered to a pregnant woman. In embryo-fetal development studies, oral administration of dordaviprone to pregnant rats and rabbits during organogenesis caused embryo-fetal mortality, alterations to growth, and structural abnormalities at exposures below the human exposure at the highest recommended dose. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with MODEYSO and for 1 month after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with MODEYSO and for 1 month after the last dose [see Use in Specific Populations ( 8.1 , 8.3 )] .