conducted with tildrakizumab in pregnant monkeys revealed no treatment-related effects to thedeveloping fetus when tildrakizumab was administered subcutaneously during organogenesis to near
parturition at doses up to 159 times the maximum recommended human dose (MRHD). When dosing wascontinued until parturition, a small increase in neonatal death was observed at 59 times the MRHD [seeData]. The clinical significance of this nonclinical finding is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. Thebackground risk of major birth defects and miscarriage for the indicated population is unknown. In theU.S. general population, the estimated background risk of major birth defects and miscarriage in clinicallyrecognized pregnancies is 2-4% and 15-20%, respectively.
8.2 Lactation
Risk Summary
There are no data on the presence of tildrakizumab in human milk, the effects on the breastfedinfant, or the effects on milk production. Human IgG is known to be present in human milk. Tildrakizumabwas detected in the milk of monkeys [see Data].
The developmental and health benefits of breastfeeding should be considered along with themother’s clinical need for ILUMYA and any potential adverse effects on the breastfed child from ILUMYAor from the underlying maternal condition.
Data
Animal Data
Very low levels of tildrakizumab were detected in breast milk of monkeys in the pre- and postnataldevelopmental study described in 8.1. The mean tildrakizumab concentrations in milk were approximately0.09 – 0.2% of that in serum on postpartum days 28 and 91.
8.4 Pediatric Use
Safety and effectiveness of ILUMYA in pediatric patients (<18 years of age) have not beenestablished.
8.5 Geriatric Use
A total of 1083 subjects were exposed to ILUMYA 100 mg during Phase 2 and 3 trials. A total of 92subjects were 65 years or older, and 17 subjects were 75 years or older. Although no differences in safetyor efficacy were observed between older and younger subjects, the number of subjects aged 65 and overis not sufficient to determine whether they respond differently from younger subjects [see ClinicalPharmacology (12.3)].
10 OVERDOSAGE
In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions andadminister appropriate symptomatic treatment immediately.
11 DESCRIPTION
Tildrakizumab-asmn is a humanized IgG1/k antibody that specifically binds to the p19 subunit ofinterleukin-23 (IL-23).
Tildrakizumab-asmn is produced in a recombinant Chinese hamster ovary (CHO) cell line and hasan approximate molecular mass of 147 kilodaltons.
ILUMYA (tildrakizumab-asmn) injection, for subcutaneous use, is a sterile, clear to slightlyopalescent, colorless to slightly yellow solution. ILUMYA is supplied in a single-dose prefilled syringe witha glass barrel and 29-gauge fixed, 1/2-inch needle.
The syringe is fitted with a passive needle guard and a needle cover.
Each 1 mL single-dose prefilled syringe contains 100 mg of tildrakizumab-asmn formulated in: Lhistidine(0.495 mg), L-histidine hydrochloride monohydrate (1.42 mg), polysorbate 80 (0.5 mg), sucrose(70.0 mg), and Water for Injection, USP with a pH of 5.7-6.3.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Tildrakizumab is a humanized IgG1/k monoclonal antibody that selectively binds to the p19 subunitof IL-23 and inhibits its interaction with the IL-23 receptor. IL-23 is a |
