Cytokine Release Syndrome

• Cytokine release syndrome (CRS), including potentially life-threatening reaction has been observed following administration of TECELRA. CRS occurred in 75% of patients, 2% of whom had Grade ≥ 3 CRS. The median time to onset was 2 days (range: 1 to 5 days) and the median time to resolution was 3 days (range: 1 to 14 days). The most common symptoms were fever (97%), tachycardia (52%), hypotension (30%), nausea/vomiting (21%) and headache (15%) [see Adverse Reactions (6)]. Management for CRS (including Grade 1) was tocilizumab (55%). Thirteen patients received one dose and five patients received more than one dose. Of the five patients who received more than one dose of tocilizumab, two patients received dexamethasone in addition to tocilizumab.
• Ensure that healthcare providers administering TECELRA have immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions. 
• During and following TECELRA administration, closely monitor patients for signs and symptoms of CRS. Following treatment with TECELRA, monitor patients for at least 7 days at the healthcare facility for CRS. Continue to monitor patients for CRS for at least 4 weeks following treatment with TECELRA. 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.