talvey

Important safety information

Oral Toxicity and Weight Loss : Monitor for oral toxicity and weight loss. Withhold or permanently discontinue based on severity. ( 5.4 ) Infections : Can cause serious, life-threatening, or fatal infections. Monitor for signs and symptoms of infection; treat appropriately. Withhold or consider permanent discontinuation based on severity. ( 5.5 ) Cytopenias : Monitor complete blood counts. ( 5.6 ) Skin Toxicity : Monitor for skin toxicity, including rash progression, for early intervention and treat appropriately. Withhold as recommended based on severity. ( 5.7 ) Hepatotoxicity: Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold or consider permanent discontinuation based on severity. ( 5.8 ) Embryo-Fetal Toxicity : May cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception. ( 5.9 , 8.1 , 8.3 ) 5.1 Cytokine Release Syndrome (CRS) TALVEY can cause cytokine release syndrome, including life-threatening or fatal reactions [see Adverse Reactions (6.1) ] . In the clinical trial, CRS occurred in 76% of patients who received TALVEY at the recommended dosages, with Grade 1 CRS occurring in 57% of patients, Grade 2 in 17%, and Grade 3 in 1.5%. Recurrent CRS occurred in 30% of patients. Most events occurred following step-up dose 1 (29%) or step-up dose 2 (44%) at the recommended dosages. CRS occurred in 33% of patients with step-up dose 3 in the biweekly dosing schedule (N=153). CRS occurred in 30% of patients with the first 0.4 mg/kg treatment dose and in 12% of patients treated with the first 0.8 mg/kg treatment dose. The CRS rate for both dosing schedules combined was less than 3% for each of the remaining doses in Cycle 1 and less than 3% cumulatively from Cycle 2 onward. The median time to onset of CRS was 27 (range: 0.1 to 167) hours from the last dose, and the median duration was 17 (range: 0 to 622) hours. Clinical signs and symptoms of CRS include but are not limited to pyrexia, hypotension, chills, hypoxia, headache, and tachycardia. Potentially life-threatening complications of CRS may include cardiac dysfunction, acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC). Initiate TALVEY therapy with step-up dosing and administer pre-treatment medications (corticosteroids, antihistamine, and antipyretics) prior to each dose of TALVEY in the step-up dosing schedule to reduce the risk of CRS. Monitor patients following administration accordingly. In patients who experience CRS, pre-treatment medications should be administered prior to the next TALVEY dose [see Dosage and Administration (2.2 , 2.3) ]. Counsel patients to seek medical attention should signs or symptoms of CRS occur. At the first sign of CRS, immediately evaluate patient for hospitalization and institute treatment with supportive care based on severity and consider further management per current practice guidelines. Withhold TALVEY until CRS resolves or permanently discontinue based on severity [see Dosage and Administration (2.5) ] . TALVEY is available only through a restricted program under a REMS [see Warnings and Precautions (5.3) ] . 5.2 Neurologic Toxicity including ICANS TALVEY can cause serious, life-threatening, or fatal neurologic toxicity, including ICANS [see Adverse Reactions (6.1) ] . In the clinical trial, neurologic toxicity, including ICANS, occurred in 55% of patients who received TALVEY at the recommended dosages, with Grade 3 or 4 neurologic toxicity occurring in 6% of patients. The most frequent neurologic toxicities were headache (20%), encephalopathy (15%), sensory neuropathy (14%), and motor dysfunction, including ataxia/cerebellar ataxia (10%). ICANS was reported in 9% of 265 patients where ICANS was collected and who received TALVEY at the recommended dosages [see Adverse Reactions (6.1) ] . Recurrent ICANS occurred in 3% of patients. Most patients experienced ICANS following step-up dose 1 (3%), step-up dose 2 (3%), step-up dose 3 of the biweekly dosing schedule (1.8%), or the initial treatment dose of the weekly dosing schedule (2.6%) (N=156) or the biweekly dosing schedule (3.7%) (N=109). The median time to onset of ICANS was 2.5 (range: 1 to 16) days after the most recent dose with a median duration of 2 (range: 1 to 22) days. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical signs and symptoms of ICANS may include but are not limited to confusional state, depressed level of consciousness, disorientation, somnolence, lethargy, and bradyphrenia. Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate the patient and provide supportive care based on severity; withhold or permanently discontinue TALVEY based on severity and consider further management per current practice guidelines [see Dosage and Administration (2.5) ]. Due to the potential for neurologic toxicity, patients receiving TALVEY are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during the step-up dosing schedule and for 48 hours after completion of the step-up dosing schedule [see Dosage and Administration (2.2) ] and in the event of new onset of any neurological symptoms, until symptoms resolve. TALVEY is available only through a restricted program under a REMS [see Warnings and Precautions (5.3) ] . 5.3 TECVAYLI and TALVEY REMS TALVEY 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 program by enrolling and completing training. Prescribers must counsel patients receiving TALVEY about the risk of CRS and neurologic toxicity, including ICANS and provide patients with Patient Wallet Card. Pharmacies and healthcare settings that dispense TALVEY must be certified with the TECVAYLI and TALVEY REMS program and must verify prescribers are certified through the TECVAYLI and TALVEY REMS program. Wholesalers and distributers must only distribute TALVEY to certified pharmacies. Further information about the TECVAYLI and TALVEY REMS program is available at www.TEC-TALREMS.com or by telephone at 1-855-810-8064. 5.4 Oral Toxicity and Weight Loss TALVEY can cause oral toxicities, including dysgeusia, dry mouth, dysphagia, and stomatitis [see Adverse Reactions (6.1) ] . In the clinical trial, 80% of patients had oral toxicity, with Grade 3 occurring in 2.1% of patients who received TALVEY at the recommended dosages. The most frequent oral toxicities were dysgeusia (49%), dry mouth (34%), dysphagia (23%), and ageusia (18%). The median time to onset of oral toxicity was 15 (range: 1 to 634) days, and the median time to resolution to baseline was 43 (1 to 530) days. Oral toxicity did not resolve to baseline in 65% of patients. TALVEY can cause weight loss [see Adverse Reactions (6.1) ] . In the clinical trial, 62% of patients experienced weight loss, regardless of having an oral toxicity, including 29% of patients with Grade 2 (10% or greater) weight loss and 2.7% of patients with Grade 3 (20% or greater) weight loss. The median time to onset of Grade 2 or higher weight loss was 67 (range: 6 to 407) days, and the median time to resolution was 50 (range: 1 to 403) days. Weight loss did not resolve in 57% of patients who reported weight loss. Monitor patients for signs and symptoms of oral toxicity. Counsel patients to seek medical attention should signs or symptoms of oral toxicity occur and provide supportive care as per current clinical practice including consultation with a…