
Drug Safety-related Labeling Changes (SrLC) Database
ANDA | Abbreviated New Drug Application |
BLA | Biologics License Application |
CDER | Center for Drug Evaluation and Research |
MG | Medication Guide |
NDA | New Drug Application |
PCI | Patient Counseling Information |
PI | Patient Information |
PLR | Physician Labeling Rule |
PLLR | Pregnancy and Lactation Labeling Rule |
Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
BW | Box Warning |
WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
TALTZ (BLA-125521)
(IXEKIZUMAB)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
08/20/2024 (SUPPL-32)
5 Warnings and Precautions
5.1 InfectionsNewly added information:
In the postmarketing setting, serious bacterial, viral, and fungal opportunistic infections have been reported in patients receiving IL-17 inhibitors including TALTZ.
6 Adverse Reactions
Newly added information:
Eczematous Eruptions [see Warnings and Precautions (5.4)]
Newly added subsection:
In the postmarketing setting, cases of severe eczematous eruptions, including atopic dermatitis-like eruptions, dyshidrotic eczema, and erythroderma were reported in patients receiving TALTZ; some cases resulted in hospitalization. The onset of eczematous eruptions was variable, ranging from days to months after the first dose of TALTZ. Treatment may need to be discontinued to resolve the eczematous eruption. Some patients with limited psoriasis treatment options were successfully treated for eczema while continuing TALTZ.
Additions and revisions underlined:
Laboratory Assessment of Cytopenia
Neutropenia
Over the entire treatment period (Weeks 0 to 60), neutropenia occurred in 11% of subjects treated with TALTZ (0.24 per subject-year of follow-up) compared to 3% of subjects treated with placebo (0.14 per subject-year of follow-up). In subjects treated with TALTZ, the incidence rate of neutropenia during Weeks 13 to 60 was lower than the incidence rate during Weeks 0 to 12.
In the 12-week, placebo-controlled period, neutropenia > or = Grade 2 (<1,000 cells/mm3) occurred in 0.2% of the TALTZ group (0.007 per subject-year of follow-up) compared to 0.1% of the placebo group (0.006 per subject-year of follow-up). The majority of cases of neutropenia were either Grade 2 (2% for TALTZ 80 mg Q2W versus 0.3% for placebo; 21,000 to <1,500 cells/mm3) or Grade 1 (7% for TALTZ 80 mg Q2W versus 3% for placebo; 21,500 cells/mm3 to 2,000 cells/mm3). Neutropenia in the TALTZ group was not associated with an increased rate of infection compared to the placebo group.
Newly added information:
Infections: bacterial, viral, and fungal opportunistic infections, including cryptococcal meningoencephalitis, esophageal and disseminated mucocutaneous candidiasis, pulmonary tuberculosis, toxoplasmosis, varicella zoster virus reactivation, cytomegalovirus colitis, pulmonary aspergillosis.
Skin and subcutaneous tissue disorders: Eczematous eruptions (erythroderma, atopic dermatitis-like eruptions, and dyshidrotic eczema).
8 Use in Specific Populations
8.1 PregnancyAdditions and revisions underlined:
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to TALTZ during pregnancy. Pregnant women exposed to TALTZ are encouraged to enroll in the TALTZ Pregnancy Registry by calling 1-800-284-1695. Contact information for the registry is also available on http://www.pregnancyregistry.lilly.com.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Medication GuideAdditions and revisions underlined:
Some people have had serious infections while taking TALTZ, including tuberculosis (TB), and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have been hospitalized from these infections.
If you become pregnant while taking TALTZ, you are encouraged to enroll in the pregnancy registry by calling
1-800-284-1695 or by visiting online at www.pregnancyregistry.lilly.com.
• Use TALTZ exactly as prescribed by your or your child’s healthcare provider.
• For children 6 to 17 years of age:
Your child’s healthcare provider will decide which dose of TALTZ is right for your child and if you can give TALTZ
to your child at home.
If your child’s healthcare provider decides that you may give TALTZ injections at home, you should receive
training on the right way to prepare and inject TALTZ. Do not try to give TALTZ to your child until you have been
shown how to inject TALTZ.
Children should not inject themselves with TALTZ. You or an adult caregiver should prepare and give TALTZ
injections to your child.
Children will be given a TALTZ injection every 4 weeks.
Additions and revisions underlined:
Infection: Inform patients that TALTZ may lower the ability of their immune system to fight infections, and that serious infections, including opportunistic infections, may occur with the use of TALTZ. Instruct patients of the importance of communicating any history of infections to the healthcare provider, and contacting their healthcare provider if they develop any symptoms of infection [see Warnings and Precautions (5.1)].
Allergic Reactions: Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions (5.3)].
Eczematous Eruptions: Inform patients that skin reactions resembling eczema may occur with the use of TALTZ. Instruct patients to seek medical advice if they develop signs or symptoms of eczema [see Warnings and Precautions (5.4)].
07/27/2022 (SUPPL-24)
8 Use in Specific Populations
8.1 PregnancyAdditions and/or revisions underlined
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to TALTZ during pregnancy. Pregnant women exposed to TALTZ are encouraged to enroll in the TALTZ Pregnancy Registry by calling 1-800-284-1695. Contact information for the registry is also available on https://www.taltz.com.
Risk Summary
Available data from the published literature and the pharmacovigilance database with TALTZ use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.
Human IgG is known to cross the placental barrier; therefore, TALTZ may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys during organogenesis at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus.
When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD [see Data]. The clinical significance of these nonclinical findings is unknown.
The 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 to 4% and 15 to 20%, respectively.
Data
Animal Data
…
These neonatal deaths were attributed to early delivery, trauma, or congenital defect. The clinical significance of these findings is unknown. No ixekizumab-related effects on functional or immunological development were observed in the surviving infants from birth through 6 months of age.
8.2 Lactation
Risk Summary
There are no available data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TALTZ and any potential adverse effects on the breastfed infant from TALTZ or from the underlying maternal condition.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined
…
Pregnancy: Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to TALTZ during pregnancy. Advise patients to contact the registry at 1-800-284-1695 to enroll [see Use in Specific Populations (8.1)].
MEDICATION GUIDE
…
Before using TALTZ, tell your healthcare provider about all of your medical conditions, including if you:
have any of the conditions or symptoms listed in the section “What is the most important information I should know about TALTZ?”
…
are pregnant or plan to become pregnant. It is not known if TALTZ can harm your unborn baby.
Pregnancy Exposure Registry: There is a pregnancy registry to collect information about women who are exposed to TALTZ during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. If you become pregnant while taking TALTZ, you are encouraged to enroll in the pregnancy registry by calling 1-800-284-1695 or by visiting online at https://www.taltz.com.
…
05/29/2020 (SUPPL-19)
5 Warnings and Precautions
5.1 InfectionsAdditions and/or revisions underlined:
TALTZ may increase the risk of infection. In clinical trials in adult patients with plaque psoriasis, the TALTZ group had a higher rate of infections than the placebo group (27% vs. 23%). Upper respiratory tract infections, oral candidiasis, conjunctivitis and tinea infections occurred more frequently in the TALTZ group than in the placebo group. A similar increase in risk of infection was seen in placebo-controlled trials in patients with pediatric psoriasis, psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis [see Adverse Reactions (6.1)].
6 Adverse Reactions
6.1 Clinical Trials Experience
Newly added information following Ankylosing Spondylitis:
Non-radiographic Axial Spondyloarthritis
TALTZ was studied in a placebo-controlled trial in patients with non-radiographic axial spondyloarthritis. A total of 303 patients were studied (198 patients on TALTZ and 105 on placebo). A total of 96 patients in this trial received TALTZ 80 or 160 mg at Week 0, followed by 80 mg every 4 weeks (Q4W). Overall, the safety profile observed in patients with non-radiographic axial spondyloarthritis treated with TALTZ 80 mg Q4W up to Week 16 is consistent with the previous experience of TALTZ in other indications.
6.2 Immunogenicity
Newly added information following Ankylosing Spondylitis Population:
Non-radiographic Axial Spondyloarthritis Population
Of patients treated with TALTZ 80 mg every 4 weeks for up to 52 weeks (nr-axSpA1), 8.9% developed anti-drug antibodies, all of which were low titer. No patient had neutralizing antibodies.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEWhat is TALTZ?
Newly added information:
adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation.
03/26/2020 (SUPPL-20)
5 Warnings and Precautions
5.1 Infections(additions underlined)
TALTZ may increase the risk of infection. In clinical trials in adult patients with plaque psoriasis, the TALTZ group had a higher rate of infections than the placebo group (27% vs. 23%). Upper respiratory tract infections, oral candidiasis, conjunctivitis and tinea infections occurred more frequently in the TALTZ group than in the placebo group. A similar increase in risk of infection was seen in placebo-controlled trials in patients with pediatric psoriasis, psoriatic arthritis and ankylosing spondylitis.
…
(subsection revised, additions underlined)
Patients treated with TALTZ may be at increased risk of inflammatory bowel disease. In clinical trials, Crohn’s disease and ulcerative colitis, including exacerbations, occurred at a greater frequency in the TALTZ group than the placebo control group. During TALTZ treatment, monitor for onset or exacerbation of inflammatory bowel disease and if IBD occurs, discontinue TALTZ and initiate appropriate medical management.
6 Adverse Reactions
6.1 Clinical Trials Experience(additions underlined)
…
Inflammatory Bowel Disease
In adult subjects with plaque psoriasis, Crohn’s disease and ulcerative colitis, including exacerbations, occurred at a greater frequency in the TALTZ 80 mg Q2W group (Crohn’s disease 0.1%, ulcerative colitis 0.2%) than the placebo group (0%) during the 12-week, placebo-controlled period in clinical trials.
…
Pediatric Plaque Psoriasis
TALTZ was evaluated in a placebo-controlled trial in pediatric subjects with moderate-to-severe psoriasis 6 to less than 18 years of age. A total of 171 subjects were studied (115 subjects on TALTZ and 56 subjects on placebo). Overall, the safety profile observed in pediatric subjects with plaque psoriasis treated with TALTZ every 4 weeks is consistent with the safety profile in adult subjects with plaque psoriasis with the exception of the frequencies of conjunctivitis (2.6%), influenza (1.7%), and urticaria (1.7%).
In this clinical trial, Crohn’s disease occurred at a greater frequency in the TALTZ group (0.9%) than the placebo group (0%) during the 12-week, placebo-controlled period. Crohn’s disease occurred in a total of 4 TALTZ treated subjects (2.0%) in the clinical trial.
…
In adult patients with ankylosing spondylitis, Crohn’s disease and ulcerative colitis, including exacerbations, occurred in 2 patients (1.0%) and 1 patient (0.5%), respectively, in the TALTZ 80 mg Q4W group and 1 patient (0.5%) and 0%, respectively, in the placebo group during the 16-week, placebo-controlled period in clinical trials. Of these patients, serious events occurred in 1 patient in the TALTZ 80 mg Q4W group and 1 patient in the placebo group.
(additions underlined)
…
Plaque Psoriasis Population
By Week 12, approximately 9% of adult subjects treated with TALTZ every 2 weeks developed antibodies to ixekizumab. Approximately 22% of subjects treated with TALTZ at the recommended dosing regimen developed antibodies to ixekizumab during the 60-week treatment period. The clinical effects of antibodies to ixekizumab are dependent on the antibody titer; higher antibody titers were associated with decreasing drug concentration and clinical response.
Of the adult subjects who developed antibodies to ixekizumab during the 60-week treatment period, approximately 10%, which equates to 2% of subjects treated with TALTZ at the recommended dosing regimen, had antibodies that were classified as neutralizing. Neutralizing antibodies were associated with reduced drug concentrations and loss of efficacy.
In pediatric psoriasis subjects treated with ixekizumab at the recommended dosing regimen up to 12 weeks, 21 subjects (18%) developed anti-drug antibodies, 5 subjects (4%) had confirmed neutralizing antibodies associated with low drug concentrations. No conclusive evidence could be obtained on the potential association of neutralizing antibodies and clinical response and/or adverse events due to small number of pediatric subjects in the study.
…
8 Use in Specific Populations
8.4 Pediatric Use(additions underlined)
The safety and effectiveness of TALTZ have been established in pediatric subjects aged 6 years to less than 18 years with moderate-to-severe plaque psoriasis. The safety and effectiveness of TALTZ in other pediatric indications and for pediatric subjects less than 6 years of age have not been established.
(addition underlined)
Of the 4204 adult psoriasis subjects exposed to TALTZ, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE(additions underlined)
…
What is TALTZ?
TALTZ is a prescription medicine used to treat:
people 6 years of age and older with moderate-to-severe plaque psoriasis who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet or UV light).
adults with active psoriatic arthritis. TALTZ can be used alone or with the medicine methotrexate.
adults with active ankylosing spondylitis.
It is not known if TALTZ is safe and effective in children for conditions other than plaque psoriasis or in children under 6 years of age.
…
How should I use TALTZ?
…
For children weighing 110 pounds (50 kg) or less, TALTZ must be given by a healthcare provider. TALTZ will be given every 4 weeks.
For children weighing more than 110 pounds (50 kg), if your healthcare provider decides that your caregiver may give your injections of TALTZ at home, your caregiver should ask and receive training from the healthcare provider on the right way to prepare and inject TALTZ. TALTZ will be given every 4 weeks.
For adults, if your healthcare provider decides that you or a caregiver may give your injections of TALTZ at home, you should receive training on the right way to prepare and inject TALTZ. Do not try to inject TALTZ yourself, until you or your caregiver have been shown how to inject TALTZ.
…
What are the possible side effects of TALTZ?
…
The most common side effects of TALTZ in adults and children include:
injection site reactions
nausea
upper respiratory infections
fungal infections
08/23/2019 (SUPPL-16)
5 Warnings and Precautions
Additions and/or revisions underlined:
5.1 Infections
A similar increase in risk of infection was seen in placebo-controlled trials in patients with psoriatic arthritis and ankylosing spondylitis.
5.4 Inflammatory Bowel Disease
… Crohn’s disease and ulcerative colitis, including exacerbations, occurred at a greater frequency in the TALTZ 80 mg Q2W group (Crohn’s disease 0.1%, ulcerative colitis 0.2%) than the placebo group (0%) during the 12-week, placebo-controlled period in clinical trials in patients with plaque psoriasis. In patients with ankylosing spondylitis, Crohn’s disease and ulcerative colitis, including exacerbations, occurred in 2 patients (1.0%) and 1 patient (0.5%), respectively, in the TALTZ 80 mg Q4W group and 1 patient (0.5%) and 0%, respectively, in the placebo group during the 16-week, placebo-controlled period in clinical trials. Of these patients, serious events occurred in 1 patient in the TALTZ 80 mg Q4W group and 1 patient in the placebo group.
6 Adverse Reactions
6.1 Clinical Trials ExperienceNewly added information following Psoriatic Arthritis:
Ankylosing Spondylitis
TALTZ was studied in two placebo-controlled trials in patients with ankylosing spondylitis. A total of 566 patients were studied (376 patients on TALTZ and 190 on placebo). A total of 195 patients in these trials received TALTZ 80 or 160 mg at Week 0, followed by 80 mg every 4 weeks (Q4W). Overall, the safety profile observed in patients with ankylosing spondylitis treated with TALTZ Q4W is consistent with the safety profile in patients with plaque psoriasis.
6.2 Immunogenicity
Newly added information following Psoriatic Arthritis:
Ankylosing Spondylitis Population
For patients treated with TALTZ 80 mg every 4 weeks for up to 16 weeks (AS1, AS2), 5.2% developed anti-drug antibodies, and 1.5% had neutralizing antibodies.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDENewly added section; please refer to label for complete information.
12/01/2017 (SUPPL-4)
5 Warnings and Precautions
5.1 Infections(Additions and/or revisions are underlined)
TALTZ may increase the risk of infection. In clinical trials in patients with plaque psoriasis, the TALTZ group had a higher rate of infections than the placebo group (27% vs. 23%). Upper respiratory tract infections, oral candidiasis, conjunctivitis and tinea infections occurred more frequently in the TALTZ group than in the placebo group. A similar increase in risk of infection was seen in placebo-controlled trials in patients with psoriatic arthritis.
(Additions and/or revisions are underlined)
During TALTZ treatment, monitor for onset or exacerbation of inflammatory bowel disease. Crohn’s disease and ulcerative colitis, including exacerbations, occurred at a greater frequency in the TALTZ group (Crohn’s disease 0.1%, ulcerative colitis 0.2%) than the placebo group (0%) during the 12-week, placebo-controlled period in clinical trials in patients with plaque psoriasis.
6 Adverse Reactions
6.1 Clinical Trials Experience(Additions and/or revisions are underlined)
…
Plaque Psoriasis
Weeks 0 to 12:
Three placebo-controlled trials in subjects with plaque psoriasis were integrated to evaluate the safety of TALTZ compared to placebo for up to 12 weeks…
Psoriatic Arthritis
TALTZ was studied in two placebo-controlled trials in patients with psoriatic arthritis. A total of 678 patients were studied (454 patients on TALTZ and 224 on placebo). A total of 229 patients in these trials received TALTZ 160 mg at Week 0, followed by 80 mg every 4 weeks (Q4W). Overall, the safety profile observed in patients with psoriatic arthritis treated with TALTZ Q4W is consistent with the safety profile in patients with plaque psoriasis with the exception of the frequencies of influenza (1.3%) and conjunctivitis (1.3%).
(Additions and/or revisions are underlined)
As with all therapeutic proteins there is the potential for immunogenicity with TALTZ. The assay to test for neutralizing antibodies has limitations detecting neutralizing antibodies in the presence of ixekizumab; therefore, the incidence of neutralizing antibodies development could be underestimated.
Plaque Psoriasis Population
By Week 12, approximately 9% of subjects treated with TALTZ every 2 weeks developed antibodies to ixekizumab…
Psoriatic Arthritis Population
For subjects treated with TALTZ 80 mg every 4 weeks for up to 52 weeks (PsA1), 11% developed anti-drug antibodies, the majority of which were low titer, and 8% had confirmed neutralizing antibodies.
…For these reasons, comparison of incidence of antibodies to TALTZ across indications or with the incidences of antibodies to other products may be misleading.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Medication Guide(Additions and/or revisions are underlined)
What is TALTZ?
TALTZ is a prescription medicine used to treat adults:
with moderate to severe plaque psoriasis, and who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet or UV light)
with active psoriatic arthritis. TALTZ can be used alone or with the medicine methotrexate.
07/05/2017 (SUPPL-3)
5 Warnings and Precautions
5.3 Hypersensitivity(Additions and/or revisions are underlined)
Serious hypersensitivity reactions, including angioedema and urticaria (each ?0.1%), occurred in the TALTZ group in clinical trials. Anaphylaxis, including cases leading to hospitalization, has been reported in post marketing use with TALTZ. If a serious hypersensitivity reaction occurs, discontinue TALTZ immediately and initiate appropriate therapy.
6 Adverse Reactions
6.3 Postmarketing Experience(Newly added subsection)
The following adverse reactions have been identified during post-approval use of TALTZ. Because the 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 TALTZ exposure.
Immune system disorders: anaphylaxis