Brentuximab Disease Interactions

Serious infections and opportunistic infections (e.g., pneumonia, bacteremia, sepsis/septic shock [including fatalities]) have been reported in patients treated with brentuximab vedotin. Patients should be monitored closely for the emergence of any infection during treatment with this agent. John Cunningham virus (JC virus) infection resulting in progressive multifocal leukoencephalopathy (PML) has been reported in patients treated with this agent. A diagnosis of PML should be considered in any patient presenting with new-onset signs/symptoms of CNS abnormalities. Therapy should be held for any suspected case of PML and discontinued if a diagnosis of PML is confirmed.

Tumor lysis syndrome (TLS), which may be life-threatening or fatal, has occurred in patients receiving certain monoclonal antibodies. Patients with high tumor burden and/or high circulating lymphocyte counts (greater than 25 x 10[9]/L) are at greater risk for developing TLS. Tumor lysis prophylaxis with anti-hyperuricemics and hydration prior to infusion may be recommended or should be considered. Electrolyte abnormalities should be corrected, and renal function and fluid balance should be monitored in patients who develop TLS. It is recommended to monitor for signs/symptoms of TLS, and temporary interruption or discontinuation of therapy might be required.

The use of brentuximab vedotin should be avoided in patients with moderate or severe liver dysfunction (Child-Pugh B or C). The frequency of grade 3 or higher adverse reactions and deaths was greater in patients with moderate and severe liver dysfunction compared to those with normal liver function. Fatal and serious cases of hepatotoxicity have occurred in patients receiving this agent. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Liver enzymes and bilirubin should be monitored. Patients experiencing new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of brentuximab vedotin.

Serious events of hyperglycemia (e.g., new-onset hyperglycemia, exacerbation of preexisting diabetes mellitus, ketoacidosis [including fatalities]) have been reported in brentuximab vedotin-treated patients. Hyperglycemia occurred more frequently in patients with high body mass index or diabetes. Serum glucose should be monitored and if hyperglycemia develops, antihyperglycemic agents should be administered as clinically indicated.

Peripheral neuropathy, predominantly sensory neuropathy, has occurred in patients treated with brentuximab vedotin. Patients should be monitored for symptoms of neuropathy, and those experiencing new or worsening peripheral neuropathy may require a delay, change in dosage, or discontinuation of brentuximab vedotin.

Fatal and serious events of noninfectious pulmonary toxicity including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, have been reported with the use of brentuximab vedotin. Care should be taken when using this agent in patients at risk of pulmonary events. Patients should be monitored for signs/symptoms of pulmonary toxicity (including cough and dyspnea). If new or worsening pulmonary symptoms develop, brentuximab vedotin dosing should be held during evaluation and until symptomatic improvement.

The use of brentuximab vedotin should be avoided in patients with severe renal dysfunction (CrCl less than 30 mL/min). The frequency of grade 3 or higher adverse reactions and deaths was greater in patients with severe renal dysfunction compared to those with normal renal function.

Fatal and serious events of acute pancreatitis have been reported with brentuximab vedotin. Other fatal and serious gastrointestinal (GI) complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with preexisting GI involvement may increase the risk of perforation. If new or worsening GI symptoms (including severe abdominal pain) develop, it is recommended to perform a prompt diagnostic evaluation and treat appropriately.