Label Changes for:
Changes have been made to the WARNINGS and PRECAUTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
WARNINGS AND PRECAUTIONS
- Limited data are available on the response to vaccinations with inactivated (killed) antigens in patients receiving ILARIS replaces No data are available statement.
USE IN SPECIFIC POPULATIONS
- The limited human data from postmarketing reports on use of ILARIS in pregnant women are not sufficient to inform a drug associated risk. Monoclonal antibodies, such as canakinumab, are transported across the placenta in a linear fashion as pregnancy progresses; therefore, potential fetal exposure is likely to be greater during the second and third trimesters of pregnancy. In animal embryo-fetal development studies with marmoset monkeys, there was no evidence of embryotoxicity or fetal malformations with subcutaneous administration of canakinumab during the period of organogenesis and later in gestation at doses that produced exposures approximately 11 times the exposure at the maximum recommended human dose (MRHD) and greater. Delays in fetal skeletal development were observed in marmoset monkeys following prenatal exposure to ILARIS at concentrations approximately 11 times the MRHD and greater. Similar delays in fetal skeletal development were observed in mice administered a murine analog of ILARIS during the period of organogenesis. Delays in skeletal ossification are changes from the expected ossification state in an otherwise normal structure/bone: these findings are generally reversible or transitory and not detrimental to postnatal survival.
- The estimated background risk of major birth defects and miscarriage for the indicated population(s) are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
- In embryo-fetal development studies, pregnant marmoset monkeys received canakinumab from gestation days 25 to 140 at doses that produced exposures approximately 11 times that achieved with MRHD and greater (on a plasma AUC basis with maternal subcutaneous doses of 15, 50, or 150 mg/kg twice weekly). ILARIS did not elicit any evidence of embryotoxicity or fetal malformations. There were increases in the incidence of incomplete ossification of the terminal caudal vertebra and misaligned and/or bipartite vertebra in fetuses at all dose levels when compared to concurrent controls suggestive of delay in skeletal development in the marmoset. Since ILARIS does not cross-react with mouse or rat IL-1ß, pregnant mice were subcutaneously administered a murine analog of ILARIS at doses of 15, 50, or 150 mg/kg during the period of organogenesis on gestation days 6, 11, and 17. The incidence of incomplete ossification of the parietal and frontal skull bones of fetuses was increased in a dose-dependent manner at all dose levels tested.
- There is no information regarding the presence of canakinumab in human milk, the effects on the breastfed infant, or the effects on milk production. Human IgG is known to be present in human milk. The effects of canakinumab in breast milk and possible systemic exposure in the breastfed infant are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ILARIS and any potential adverse effects on the breastfed infant from canakinumab or from the underlying maternal condition.
PATIENT COUNSELING INFORMATION
- Advise female patients of the potential risk to a fetus.
5 WARNINGS AND PRECAUTIONS
5.1 Serious Infections
- ...Infections, predominantly of the upper respiratory tract, in some instances serious, have been reported with ILARIS. Generally, the observed infections responded to standard therapy. Isolated cases of unusual or opportunistic infections (e.g., aspergillosis, atypical mycobacterial infections, cytomegalovirus, herpes zoster) were reported during ILARIS treatment. A causal relationship of ILARIS to these events cannot be excluded. In clinical trials, ILARIS has not been administered concomitantly with tumor necrosis factor (TNF) inhibitors. An increased incidence of serious infections has been associated with administration of another IL-1 blocker in combination with TNF inhibitors. Coadministration of ILARIS with TNF inhibitors is not recommended because this may increase the risk of serious infections [see Drug Interactions (7.1)].
What are the possible side effects of Ilaris?
- Decrease in white blood cells (neutropenia) which help your body fight infections