TECLISTAMAB Drug Interactions: What You Need to Know

INTERACTIONS TECVAYLI causes release of cytokines [see Clinical Pharmacology (12.2) ] that may suppress activity of cytochrome P450 (CYP) enzymes, resulting in increased exposure of CYP substrates. The highest risk of drug-drug interaction is expected to occur from initiation of TECVAYLI step-up dosing schedule up to 7 days after the first treatment dose and during and after CRS [see Warnings and Precautions (5.1) ] . Monitor for toxicity or concentrations of drugs that are CYP substrates where minimal concentration changes may lead to serious adverse reactions. Adjust the dose of the concomitant CYP substrate drug as needed.

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AND PRECAUTIONS Hepatotoxicity : Can cause hepatotoxicity, including fatalities. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. ( 5.4 ) Infections : Can cause severe, life-threatening, or fatal infections. Monitor patients for signs and symptoms of infection and treat appropriately. Withhold in patients with active infection during the step-up dosing schedule. ( 2.4 , 5.5 ) Neutropenia : Monitor complete blood cell counts at baseline and periodically during treatment. ( 5.6) Hypersensitivity and Other Administration Reactions : Systemic administration-related reactions and local injection site reactions can occur. Withhold or consider permanent discontinuation based on severity. ( 2.4 , 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 <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . In the clinical trial, CRS occurred in 72% of patients who received TECVAYLI at the recommended dose, with Grade 1 CRS occurring in 50% of patients, Grade 2 in 21%, and Grade 3 in 0.6%. Recurrent CRS occurred in 33% of patients. Most patients experienced CRS following step-up dose 1 (42%), step-up dose 2 (35%), or the initial treatment dose (24%). Less than 3% of patients developed first occurrence of CRS following subsequent doses of TECVAYLI. The median time to onset of CRS was 2 (range: 1 to 6) days after the most recent dose with a median duration of 2 (range: 1 to 9) 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 <span class="opacity-50 text-xs">[see Dosage and Administration (2.1 , 2.4) ]</span> . Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI accordingly <span class="opacity-50 text-xs">[see Dosage and Administration (2.2 , 2.4) ]</span> . At the first sign of CRS, immediately evaluate patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold or permanently discontinue TECVAYLI based on severity <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) ]</span> . TECVAYLI is available only through a restricted program under a REMS <span class="opacity-50 text-xs">[see Warnings and Precautions (5.3) ]</span>.

5.2 Neurologic Toxicity including ICANS TECVAYLI can cause serious, life-threatening or fatal neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . In the clinical trial, neurologic toxicity occurred in 57% of patients who received TECVAYLI at the recommended dose, with Grade 3 or 4 neurologic toxicity occurring in 2.4% of patients. The most frequent neurologic toxicities were headache (25%), motor dysfunction (16%), sensory neuropathy (15%), and encephalopathy (13%). With longer follow-up, Grade 4 seizure and fatal Guillain-Barré syndrome (one patient each) occurred in patients who received TECVAYLI. In the clinical trial, ICANS was reported in 6% of patients who received TECVAYLI at the recommended dose <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . 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 doses of TECVAYLI. The median time to onset of ICANS was 4 (range: 2 to 8) days after the most recent dose with a median duration of 3 (range: 1 to 20) days. The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia. 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 during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or permanently discontinue TECVAYLI based on severity per recommendations and consider further management per current practice guidelines <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) ]</span> . Due to the potential for neurologic toxicity, patients receiving TECVAYLI are at risk of depressed level of consciousness <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . 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 <span class="opacity-50 text-xs">[see Dosage and Administration (2.1) ]</span> . TECVAYLI is available only through a restricted program under a REMS <span class="opacity-50 text-xs">[see Warnings and Precautions (5.3) ]</span>.

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 <span class="opacity-50 text-xs">[see Warnings and Precautions (5.1 , 5.2) ]</span>. 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 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 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 TECVAYLI to certified pharmacies or healthcare settings. 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 Hepatotoxicity TECVAYLI can cause hepatotoxicity, including fatalities. In patients who received TECVAYLI at the recommended dose in the clinical trial, there was one fatal case of hepatic failure. Elevated aspartate aminotransferase (AST) occurred in 34% of patients, with Grade 3 or 4 elevations in 1.2%. Elevated alanine aminotransferase (ALT) occurred in 28% of patients, with Grade 3 or 4 elevations in 1.8%. Elevated total bilirubin occurred in 6% of patients with Grade 3 or 4 elevations in 0.6%. Liver enzyme elevation can occur with or without concurrent CRS. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) ]</span>.

5.5 Infections TECVAYLI can cause severe, life-threatening, or fatal infections. In patients who received TECVAYLI at the recommended dose in the clinical trial, serious infections, including opportunistic infections, occurred in 30% of patients, with Grade 3 or 4 infections in 35%, and fatal infections in 4.2% <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . Monitor patients for signs and symptoms of infection prior to and during treatment with TECVAYLI and treat appropriately. Administer prophylactic antimicrobials according to guidelines <span class="opacity-50 text-xs">[see Dosage and Administration (2.2) ]</span> . Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) ]</span> . Monitor immunoglobulin levels during treatment with TECVAYLI and treat according to guidelines, including infection precautions and antibiotic or antiviral prophylaxis <span class="opacity-50 text-xs">[see Dosage and Administration (2.2) ]</span> .

5.6 Neutropenia TECVAYLI can cause neutropenia and febrile neutropenia. In patients who received TECVAYLI at the recommended dose in the clinical trial, decreased neutrophils occurred in 84% of patients, with Grade 3 or 4 decreased neutrophils in 56%. Febrile neutropenia occurred in 3% of patients <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span>. Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local institutional guidelines. Monitor patients with neutropenia for signs of infection. Withhold TECVAYLI based on severity <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) ]</span> .

5.7 Hypersensitivity and Other Administration Reactions TECVAYLI can cause both systemic administration-related reactions and local injection-site reactions.

Systemic

Reactions In patients who received TECVAYLI at the recommended dose in the clinical trial, 1.2% of patients experienced systemic-administration reactions, which included Grade 1 recurrent pyrexia and Grade 1 swollen tongue.

Local

Reactions In patients who received TECVAYLI at the recommended dose in the clinical trial, injection-site reactions occurred in 35% of patients with Grade 1 injection-site reactions in 30% and Grade 2 in 4.8%. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity [see Dosage and Administration (2.4) ] .

5.8 Embryo-Fetal Toxicity Based on its mechanism of action, TECVAYLI may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TECVAYLI and for 5 months after the last dose <span class="opacity-50 text-xs">[see Use in Specific Populations (8.1 , 8.3) ]</span> .