tecvayli

Important safety information

Hepatotoxicity : Can cause hepatotoxicity, including fatalities. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity ( 2.5 , 5.4 ) Infections : Can cause severe, life-threatening, or fatal infections. Monitor patients for signs and symptoms of infection and treat appropriately. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity. ( 2.5 , 5.5 ) Neutropenia : Monitor complete blood cell counts at baseline and periodically during treatment. Withhold TECVAYLI based on severity. ( 2.5 , 5.6 ) Hypersensitivity and Other Administration Reactions : Can cause systemic administration-related reactions and local injection site reactions. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity. ( 2.5 , 5.7 ) Embryo-Fetal Toxicity : May cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception. ( 5.8 , 8.1 , 8.3 ) 5.1 Cytokine Release Syndrome TECVAYLI can cause cytokine release syndrome (CRS), including life-threatening or fatal reactions [see Adverse Reactions (6.1) ] . In the clinical trials (monotherapy and combination therapy trials; N=448), CRS occurred in 64% of patients who received TECVAYLI at the recommended dosage, with Grade 1 CRS occurring in 46% of patients, Grade 2 in 18%, and Grade 3 in 0.2%. Recurrent CRS occurred in 27% of patients. Most patients experienced CRS during the initial step-up dosing schedule (step-up dose 1 (37%), step-up dose 2 (32%), or the initial treatment dose (20%)). CRS first occurred following subsequent doses of TECVAYLI in 2.5% of patients. The median time to onset of CRS was 2 (range: 1 to 9) days after the most recent dose and the median duration of CRS was 2 (range: 1 to 22) days. Clinical signs and symptoms of CRS included, but were not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation). Initiate therapy according to TECVAYLI step-up dosing schedule to reduce risk of CRS [see Dosage and Administration (2.1 , 2.5) ] . Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI accordingly [see Dosage and Administration (2.3 , 2.5) ] . At the first sign of CRS, immediately evaluate the patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold until CRS resolves or permanently discontinue TECVAYLI based on severity [see Dosage and Administration (2.5) ] . TECVAYLI is available only through a restricted program under a REMS [see Warnings and Precautions (5.3) ]. 5.2 Neurologic Toxicity including Immune Effector Cell-Associated Neurotoxicity Syndrome TECVAYLI can cause serious, life-threatening or fatal neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS) [see Adverse Reactions (6.1) ] . In the clinical trials (monotherapy and combination therapy trials; N=448), neurologic toxicity occurred in 60% of patients who received TECVAYLI at the recommended dosage, with Grade 3 or 4 neurologic toxicity in 6%. Neurologic toxicities reported in ≥5% of patients included headache (27%), sensory neuropathy (16%), motor dysfunction (15%), insomnia (12%), encephalopathy (11%), and dizziness (8%). Fatal neurologic toxicity occurred in 0.4% of patients, including Guillain-Barré syndrome and status epilepticus (one patient each). In MajesTEC-1, ICANS was reported in 6% of patients who received TECVAYLI as monotherapy at the recommended dosage [see Adverse Reactions (6.1) ] . Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the initial treatment dose (1.8%). Less than 3% of patients developed first occurrence of ICANS following subsequent TECVAYLI doses. The median time to onset of ICANS was 4 days (range: 2 to 8 days) after the most recent TECVAYLI dose with a median duration of 3 days (range: 1 to 20 days). The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia. In MajesTEC-3, ICANS was reported in 1.1% of patients who received the recommended TECVAYLI dosage in combination with daratumumab and hyaluronidase-fihj, including Grade 4 ICANS in 1 patient. All events of ICANS occurred during the step-up dosing schedule [see Adverse Reactions (6.1) ] . The median time to onset of ICANS was 2 days (range: 1 to 3 days) after the most recent dose and the median duration of ICANS was 2 days (range: 1 to 2 days). The clinical manifestations of ICANS reported were amnesia, encephalopathy and delirium. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS during TECVAYLI treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold until neurologic toxicity resolves or permanently discontinue TECVAYLI based on severity per recommendations and consider further management per current practice guidelines [see Dosage and Administration (2.5) ] . Due to the potential for neurologic toxicity, patients receiving TECVAYLI are at risk of depressed level of consciousness [see Adverse Reactions (6.1) ] . Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves [see Dosage and Administration (2.1) ] . TECVAYLI is available only through a restricted program under a REMS [see Warnings and Precautions (5.3) ]. 5.3 TECVAYLI and TALVEY REMS TECVAYLI is available only through a restricted program under a REMS called the "TECVAYLI and TALVEY REMS" because of the risks of CRS and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1 , 5.2) ]. Notable requirements of the TECVAYLI and TALVEY REMS include the following: Prescribers must be certified with the REMS by enrolling and completing training. Prescribers must counsel patients receiving TECVAYLI about the risk of CRS and neurologic toxicity, including ICANS, and provide patients with Patient Wallet Card. Pharmacies and healthcare settings that dispense TECVAYLI must be certified with this REMS and must verify prescribers are certified through this REMS. Wholesalers and distributers must only distribute TECVAYLI to certified pharmacies or healthcare settings. Further information about the "TECVAYLI and TALVEY REMS" is available at www.TEC-TALREMS.com or by telephone at 1-855-810-8064. 5.4 Hepatotoxicity TECVAYLI can cause hepatotoxicity, including fatalities. There was one fatal case of hepatic failure in MajesTEC-1. In patients who received TECVAYLI at the recommended dosage in the clinical trials (monotherapy and combination therapy trials; N=448), elevated aspartate aminotransferase (AST) occurred in 47% of patients, with Grade 3 or 4 elevations in 2.9%. Elevated alanine aminotransferase (ALT) occurred in 48% of patients, with Grade 3 or 4 elevations in 3.8%. Elevated total bilirubin occurred in 10% of patients with Grade 3 or 4 elevations in 0.7%. Liver enzyme elevation can occur with or without concurrent CRS. Monitor liver enzymes and bilirubin at baseline and during TECVAYLI treatment as clinically indicated. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity [see Dosage and Administration (2.5) ]. 5.5 Infections TECVAYLI can cause severe, life-threatening, or fatal infections. In MajesTEC-1 (N=165), in patients who received the…