t (2%), cognitive disorder (1%), speech disorder (< 1%)
Psychiatric disorders: confusion (7%), disorientation (3%)
Vascular disorders: capillary leak syndrome (< 1%).
Hypersensitivity reactions related to BLINCYTO treatment were hypersensitivity (1%) and bronchospasm (< 1%).
6.2 ImmunogenicityAs with all therapeutic proteins, there is potential for immunogenicity. The immunogenicity of BLINCYTO has been eva luated using either an electrochemiluminescence detection technology (ECL) or an enzyme-linked immunosorbent assay (ELISA) screening immunoassay for the detection of binding anti-blinatumomab antibodies. For patients whose sera tested positive in the screening immunoassay, an in vitro biological assay was performed to detect neutralizing antibodies.
In clinical studies, less than 1% of patients treated with BLINCYTO tested positive for binding anti-blinatumomab antibodies. All patients who tested positive for binding antibodies also tested positive for neutralizing anti-blinatumomab antibodies.
Anti-blinatumomab antibody formation may affect pharmacokinetics of BLINCYTO. No association was seen between antibody development and development of adverse events.
If formation of anti-blinatumomab antibodies with a clinically significant effect is suspected, contact Amgen at 1-800-77-AMGEN (1-800-772-6436) to discuss antibody testing.
The detection of anti-blinatumomab antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to blinatumomab with the incidence of antibodies to other products may be misleading.
7. DRUG INTERACTIONS
No formal drug interaction studies have been conducted with BLINCYTO. Initiation of BLINCYTO treatment causes transient release of cytokines that may suppress CYP450 enzymes. The highest drug- drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the second cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index. In these patients, monitor for toxicity (eg, warfarin) or drug concentrations (eg, cyclosporine). Adjust the dose of the concomitant drug as needed [see Clinical Pharmacology (12.2 and 12.3)].
8. USE IN SPECIFIC POPULATIONS
8.1 PregnancyPregnancy Category C
Risk Summary
There are no adequate and well-controlled studies of BLINCYTO in pregnant women. Based on its mechanism of action, BLINCYTO may cause fetal toxicity including B-cell lymphocytopenia when administered to a pregnant woman. BLINCYTO should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Animal Data
Animal reproduction studies have not been conducted with blinatumomab. In embryo-fetal developmental toxicity studies, a murine surrogate molecule was administered intravenously to pregnant mice during the period of organogenesis. The surrogate molecule crossed the placental barrier and did not cause embryo-fetal toxicity or teratogenicity. The expected depletions of B a |
