ZYNLONTA (Page 3 of 6)
- 1
- Pneumonia includes pneumonia and lung infection
- 2
- Sepsis includes sepsis, escherichia sepsis, and septic shock
Selected Other Adverse Reactions
- Inflammatory-related conditions were reported in 3% of patients in LOTIS-2, including pericarditis, pneumonitis, pleuritis, and dermatitis.
Table 2 summarizes the laboratory abnormalities in LOTIS-2.
Laboratory Abnormality | ZYNLONTA * | |
---|---|---|
All Grades (%) | Grade 3 or 4 (%) | |
Hematologic | ||
Platelets decreased | 58 | 17 |
Neutrophils decreased | 52 | 30 |
Hemoglobin decreased | 51 | 10† |
Chemistry | ||
GGT increased | 57 | 21 |
Glucose increased | 48 | 8 |
AST increased | 41 | <1† |
Albumin decreased | 37 | <1† |
ALT increased | 34 | 3 |
6.2 Postmarketing Experience
The following adverse reactions have been identified during post approval use of ZYNLONTA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Skin and Subcutaneous Tissue Disorders: telangiectasia, blister, rash vesicular
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Based on its mechanism of action, ZYNLONTA can cause embryo-fetal harm when administered to a pregnant woman, because it contains a genotoxic compound (SG3199) and affects actively dividing cells [see Clinical Pharmacology (12.1) and Nonclinical Toxicology (13.1)]. There are no available data on the use of ZYNLONTA in pregnant women to evaluate for drug-associated risk. No animal reproduction studies were conducted with ZYNLONTA. Advise pregnant women of the potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Data
Animal Data
Animal reproductive or developmental toxicity studies were not conducted with loncastuximab tesirine-lpyl. The cytotoxic component of ZYNLONTA, SG3199, crosslinks DNA, is genotoxic, and is toxic to rapidly dividing cells, suggesting it has the potential to cause embryotoxicity and teratogenicity.
8.2 Lactation
Risk Summary
There is no data on the presence of loncastuximab tesirine-lpyl or SG3199 in human milk, the effects on the breastfed child, or milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with ZYNLONTA and for 3 months after the last dose.
8.3 Females and Males of Reproductive Potential
ZYNLONTA can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)].
Pregnancy Testing
Pregnancy testing is recommended for females of reproductive potential prior to initiating ZYNLONTA.
Contraception
Females
Advise women of reproductive potential to use effective contraception during treatment and for 10 months after the last dose.
Males
Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during the treatment with ZYNLONTA and for 7 months after the last dose [see Nonclinical Toxicology (13.1)].
Infertility
Males
Based on the results from animal studies, ZYNLONTA may impair fertility in males. The effects were not reversible in male cynomolgus monkeys during the 12-week drug-free period [see Nonclinical Toxicology (13.1)].
8.4 Pediatric Use
Safety and effectiveness of ZYNLONTA in pediatric patients have not been established.
8.5 Geriatric Use
Of the 145 patients with large B-cell lymphoma who received ZYNLONTA in clinical trials, 55% were 65 years of age and older, while 14% were 75 years of age and older [see Clinical Studies (14.1)]. No overall differences in safety or effectiveness were observed between these patients and younger patients.
8.6 Hepatic Impairment
No dose adjustment is recommended for patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal [ULN] and aspartate aminotransferase (AST) > ULN or total bilirubin > 1 to 1.5 × ULN and any AST). Monitor patients with mild hepatic impairment for potential increased incidence of adverse reactions and modify the ZYNLONTA dosage in the event of adverse reactions [see Dosage and Administration (2.3)].
ZYNLONTA has not been studied in patients with moderate or severe hepatic impairment (total bilirubin > 1.5 × ULN and any AST) [see Clinical Pharmacology (12.3)].
11 DESCRIPTION
Loncastuximab tesirine-lpyl is a CD19-directed antibody and alkylating agent conjugate, consisting of a humanized IgG1 kappa monoclonal antibody conjugated to SG3199, a pyrrolobenzodiazepine (PBD) dimer cytotoxic alkylating agent, through a protease-cleavable valine-alanine linker. SG3199 attached to the linker is designated as SG3249, also known as tesirine.
Loncastuximab tesirine-lpyl has an approximate molecular weight of 151 kDa. An average of 2.3 molecules of SG3249 are attached to each antibody molecule. Loncastuximab tesirine-lpyl is produced by chemical conjugation of the antibody and small molecule components. The antibody is produced by mammalian (Chinese hamster ovary) cells, and the small molecule components are produced by chemical synthesis.
ZYNLONTA (loncastuximab tesirine-lpyl) for injection is supplied as a sterile, white to off-white, preservative-free, lyophilized powder, which has a cake-like appearance, for intravenous infusion after reconstitution and dilution. Each single-dose vial delivers 10 mg of loncastuximab tesirine-lpyl, L-histidine (2.8 mg), L-histidine monohydrochloride (4.6 mg), polysorbate 20 (0.4 mg), and sucrose (119.8 mg). After reconstitution with 2.2 mL Sterile Water for Injection, USP, the final concentration is 5 mg/mL with a pH of approximately 6.0.
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