Progressive Multifocal Leukoencephalopathy: John Cunningham virus (JCV) reactivation resulting in progressive multifocal leukoencephalopathy (PML) and death can occur in Adcetris-treated patients. PML has been reported in patients who received this treatment after receiving multiple prior chemotherapy regimens. PML is a rare demyelinating disease of the central nervous system that results from reactivation of latent JCV and is often fatal.
Patients should be closely monitored for new or worsening neurological, cognitive, or behavioral signs or symptoms which may be suggestive of PML. Adcetris dosing should be held for any suspected case of PML. Suggested evaluation of PML includes neurology consultation, gadolinium-enhanced magnetic resonance imaging of the brain and cerebrospinal fluid analysis for JCV DNA by polymerase chain reaction (PCR) or a brain biopsy for evidence of JCV. A negative JCV PCR does not exclude PML. Additional follow-up and evaluation may be warranted if no alternative diagnosis can be established. Adcetris dosing should be permanently discontinued if a diagnosis of PML is confirmed.
The physician should be particularly alert to suggestive of PML that the patient may not notice (e.g., cognitive, neurological, or psychiatric symptoms).
Pulmonary Toxicity: Cases of pulmonary toxicity, including pneumonitis, interstitial lung disease and acute respiratory distress syndrome (ADRS), some fatal outcomes, have been reported in patients receiving Adcetris. Although a causal association with Adcetris has not been established, the risk of pulmonary toxicity cannot be ruled out. In the event of new or worsening pulmonary symptoms (e.g., cough, dyspnea), a prompt diagnostic evaluation should be performed and patients should be treated appropriately. Consider holding Adcetris dosing during evaluation and until symptomatic improvement.
Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with Adcetris. Fatal outcomes have been reported. If SJS or TEN occur, treatment with Adcetris should be discontinued and appropriate medical therapy should be administered.
Pancreatitis: Acute pancreatitis has been observed in patients treated with brentuximab vedotin. Fatal outcomes have been reported.
Patients should be closely monitored for new or worsening abdominal pain, which may be suggestive of acute pancreatitis. Patient evaluation may include physical examination, laboratory evaluation for serum amylase and serum lipase, and abdominal imaging, such as ultrasound and other appropriate diagnostic measures. Brentuximab vedotin should be held for any suspected case of acute pancreatitis. Brentuximab vedotin should be discontinued if a diagnosis of acute pancreatitis is confirmed.
Serious infections and opportunistic infections: Serious infections such as pneumonia, staphylococcal bacteraemia, sepsis/septic shock (including fatal outcomes) and herpes zoster, and opportunistic infections such as Pneumocystis jiroveci pneumonia and oral candidiasis have been reported in patients treated with Adcetris. Patients should be carefully monitored during treatment for the emergence of possible serious and opportunistic infections.
Infusion-Related Reactions: Immediate and delayed infusion-related reactions (IRR), as well as anaphylactic reactions, have been reported.
Patients should be carefully monitored during and after infusion. If an anaphylactic reaction occurs, administration of Adcetris should be immediately and permanently discontinued and appropriate medical therapy should be administered.
If an infusion-related reaction occurs, the infusion should be interrupted and appropriate medical management instituted. The infusion may be restarted at a slower rate after symptom resolution.
Patients who have experienced a prior infusion-related reaction should be premedicated for subsequent infusions. Premedication may include paracetamol, an antihistamine and a corticosteroid.
Infusion-related reactions are more frequent and more severe in patients with antibodies to Adcetris (see ADVERSE REACTIONS).
Peripheral Neuropathy: ADCETRIS may cause peripheral neuropathy, both sensory and motor. ADCETRIS-induced peripheral neuropathy is typically an effect of cumulative exposure to this medicinal product and is reversible in most cases. In clinical trials, the majority of patients had resolution or improvement of their symptoms (see ADVERSE REACTIONS). Patients should be monitored for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paraesthesia, discomfort, a burning sensation, neuropathic pain or weakness. Patients experiencing new or worsening peripheral neuropathy may require a delay and a dose reduction of ADCETRIS or discontinuation of treatment (see DOSAGE & ADMINISTRATION).
Haematological toxicities: Grade 3 or Grade 4 anaemia, thrombocytopenia, and prolonged (≥1 week) Grade 3 or Grade 4 neutropenia can occur with Adcetris. Fatal and serious cases of febrile neutropenia have been reported with Adcetris. Complete blood counts should be monitored prior to administration of each dose of Adcetris. Patients should be monitored closely for fever. If Grade 3 or Grade 4 neutropenia develops, manage by dose modifications or discontinuations (refer to Dosage & Administration). In frontline treatment of patients with advanced HL, or in patients with previously untreated sALCL or other CD30-expressing PTCL, receiving combination therapy, primary prophylaxis with G-CSF is recommended for all patients beginning with the first dose.
Tumor Lysis Syndrome: Tumor lysis syndrome (TLS) has been reported with Adcetris. Patients with rapidly proliferating tumor and high tumor burden are at risk of tumor lysis syndrome. These patients should be monitored closely and managed according to best medical practice. Management of TLS may include aggressive hydration, monitoring of renal function, correction of electrolyte abnormalities, anti-hyperuricaemic therapy and supportive care.
Gastrointestinal Complications: Gastrointestinal (GI) complications including intestinal obstruction, ileus, enterocolitis, neutropenic colitis, erosion, ulcer, perforation and haemorrhage, some with fatal outcomes, have been reported in patients treated with Adcetris. Some cases of GI perforations were reported in patients with GI involvement of underlying lymphoma. In the event of new or worsening GI symptoms, perform a prompt diagnostic evaluation and treat appropriately.
Hepatotoxicity: Hepatotoxicity in the form of elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) has been reported with Adcetris. Serious cases of hepatotoxicity, including fatal outcomes, have also occurred. Pre-existing liver disease, comorbidities, and concomitant medications may also increase the risk. Liver function should be routinely monitored in patients receiving Adcetris. Patients experiencing hepatotoxicity may require a delay, change in dose or discontinuation of Adcetris (see ADVERSE REACTIONS).
Hyperglycaemia: Hyperglycaemia has been reported during clinical trials in patients with an elevated Body Mass Index (BMI) with or without a history of diabetes mellitus. However, any patient who experiences an event of hyperglycaemia should have their serum glucose closely monitored. Anti-diabetic treatment should be administered as appropriate.
Sodium content in excipients: This medicinal product contains a maximum of 2.1 mmol (or 47 mg) of sodium per dose. To be taken into consideration for patients on a controlled sodium diet.
Use in Pregnancy: Adcetris may cause fetal harm when administered to pregnant women.