
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.
COSENTYX (BLA-125504)
(SECUKINUMAB)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
10/04/2024 (SUPPL-80)
5 Warnings and Precautions
5.2 Hypersensitivity ReactionsAdditions and revisions underlined:
Serious hypersensitivity reactions including anaphylaxis, angioedema, and urticaria have been reported in COSENTYX treated subjects in clinical trials and in the post-marketing setting [see Adverse Reactions (6.1, 6.2)]. If an anaphylactic or other serious allergic reaction occurs, immediately discontinue administration of COSENTYX and initiate appropriate therapy [see Contraindications (4)].
6 Adverse Reactions
6.2 Postmarketing ExperienceAdditions and revisions underlined:
The following adverse reactions have been reported during post-approval use of COSENTYX. Because they 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.
Immune system disorders: anaphylaxis, angioedema
08/16/2024 (SUPPL-82)
5 Warnings and Precautions
5.1 Infections
Additions and/or revisions underlined:
COSENTYX may increase the risk of infections. In clinical trials, a higher rate of infections was observed in COSENTYX treated subjects compared to placebo-treated subjects. In placebo-controlled clinical trials in subjects with moderate to severe PsO, higher rates of common infections, such as nasopharyngitis (11.4% versus 8.6%), upper respiratory tract infection (2.5% versus 0.7%) and mucocutaneous infections with candida (1.2% versus 0.3%) were observed in subjects treated with COSENTYX compared to placebo-treated subjects. A similar increase in risk of infection in subjects treated with COSENTYX was seen in placebo-controlled trials in subjects with PsA, AS and nr- axSpA. The incidence of some types of infections, including fungal infections, appeared to be dose-dependent in clinical trials [see Adverse Reactions (6.1)].
In the postmarketing setting, serious bacterial, viral, and fungal opportunistic infections, and some fatal infections have been reported in patients receiving IL-17 inhibitors including COSENTYX. Cases of Hepatitis B virus reactivation have been reported [see Adverse Reactions (6.2)].
Exercise caution when considering the use of COSENTYX in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur. If a patient develops a serious infection, monitor the patient closely and discontinue COSENTYX until the infection resolves.
If signs of Hepatitis B virus reactivation occur, consult a hepatitis specialist. COSENTYX is not recommended for use in patients with active viral hepatitis.
5.3 Pre-Treatment Evaluation for Tuberculosis
Additions and/or
revisions underlined:
Evaluate patients
for active or latent TB infection prior
to initiating treatment with COSENTYX. Avoid
administration of COSENTYX to
patients with active TB infection. Initiate treatment of latent TB prior to
administering COSENTYX. Consider anti-TB therapy
prior to initiation of COSENTYX in patients with a past history of latent or active TB in whom an adequate course of treatment
cannot be confirmed. Monitor patients closely for signs and symptoms of active
TB during and after treatment.
In the postmarketing setting, cases were reported where patients with a history of latent tuberculosis (TB) who were treated with COSENTYX developed active TB.
6 Adverse Reactions
6.2 Postmarketing Experience
Additions and/or revisions underlined:
The following
adverse reactions have been reported
during post-approval use of COSENTYX.
Because they 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: Eczematous eruptions (atopic dermatitis-like eruptions, dyshidrotic eczema, and erythroderma) [see Warnings and Precautions (5.5)], and pyoderma gangrenosum.
Infections: bacterial, viral, and fungal opportunistic infections, including esophageal candidiasis, tracheobronchial candidiasis, cutaneous aspergillosis, cytomegalovirus gastroenteritis/colitis, herpes simplex encephalitis, herpes simplex keratitis, Pneumocystis jiroveci pneumonia, Hepatitis B virus reactivation, histoplasmosis, toxoplasmosis [see Warnings and Precautions (5.1)]
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATIONAdditions and/or
revisions underlined:
Advise the patient
to read the FDA-approved patient
labeling (Medication Guide
and Instructions for Use).
Infections
Inform patients that COSENTYX may lower the ability of their immune system to fight infections and that serious infections, including opportunistic infections, may occur with the use of COSENTYX. Instruct patients of the importance of communicating any history of infections to the doctor and contacting their doctor if they develop any symptoms of infection [see Warnings and Precautions (5.1)].
…
11/21/2023 (SUPPL-66)
6 Adverse Reactions
6.2 Postmarketing ExperienceAdditions and revisions underlined:
The following adverse reactions have been reported during postapproval use of COSENTYX. Because they 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: Eczematous eruptions (atopic dermatitis-like eruptions, dyshidrotic eczema, and erythroderma) [see Warnings and Precautions (5.5)], and pyoderma gangrenosum.
10/31/2023 (SUPPL-63)
5 Warnings and Precautions
5.1 Infections
Additions and/or revisions underlined:
COSENTYX may increase the risk of infections. In clinical trials, a higher rate of infections was observed in COSENTYX treated subjects compared to placebo-treated subjects. In placebo-controlled clinical trials in subjects with moderate to severe PsO, higher rates of common infections, such as nasopharyngitis (11.4% versus 8.6%), upper respiratory tract infection (2.5% versus 0.7%) and mucocutaneous infections with candida (1.2% versus 0.3%) were observed in subjects treated with COSENTYX compared to placebo-treated subjects. A similar increase in risk of infection in subjects treated with COSENTYX was seen in placebo-controlled trials in subjects with PsA, AS and nr- axSpA. The incidence of some types of infections, including fungal infections, appeared to be dose-dependent in clinical trials [see Adverse Reactions (6.1)].
…
5.3 Pre-Treatment Evaluation for Tuberculosis
Additions and/or revisions underlined:
Evaluate patients for active or latent TB infection prior to initiating treatment with COSENTYX. Avoid administration of COSENTYX to patients with active TB infection.
…
5.4 Inflammatory Bowel Disease
Additions and/or revisions underlined:
Inflammatory Bowel Disease (IBD) exacerbations, in some cases serious and/or leading to discontinuation of COSENTYX, occurred in COSENTYX treated subjects during clinical trials in PsO, PsA, AS, nr-axSpA, and HS. In adult subjects with HS, the incidence of IBD was higher in subjects who received COSENTYX 300 mg every 2 weeks (Ulcerative Colitis [UC] 1 case, EAIR 0.2/100 subject-years; Crohn`s Disease [CD] 1 case, EAIR 0.2/100 subject-years) compared to subjects who received COSENTYX 300 mg every 4 weeks (IBD 1 case, EAIR 0.2/100 subject-years). In addition, new onset IBD cases occurred in subjects treated with COSENTYX in clinical trials. In an exploratory trial in 59 subjects with active Crohn’s disease [COSENTYX is not approved for the treatment of Crohn`s disease], there were trends toward greater disease activity and increased adverse reactions in subjects treated with COSENTYX as compared to placebo-treated subjects.
Exercise caution when prescribing COSENTYX to patients with IBD. Patients treated with COSENTYX should be monitored for signs and symptoms of IBD [see Adverse Reactions (6.1)].
5.5 Risk of Hypersensitivity in Latex-Sensitive Individuals
Additions and/or revisions underlined:
The removable caps of the COSENTYX 150 mg/mL Sensoready pen and the COSENTYX 1 mL and 0.5 mL prefilled syringes contain natural rubber latex, which may cause a hypersensitivity reaction in latex-sensitive individuals.
…
6 Adverse Reactions
Addition of the following to the bulleted line listing:
- Eczematous Eruptions [see Warnings and Precautions (5.5)]
6.1 Clinical Trials Experience
Extensive changes; please refer to label for complete information
7 Drug Interactions
Additions and/or revisions underlined:
Certain CYP450 Substrates
Increased concentrations of cytokines (e.g., IL-17) during chronic inflammation associated with certain diseases including PsO, PsA, AS, nr-axSpA, ERA, and HS may suppress the formation of CYP enzymes.
Upon initiation or discontinuation of COSENTYX in patients who are receiving concomitant CYP450 substrates, particularly those where minimal decreases in the concentration may reduce CYP substrate effectiveness or minimal increases in the concentration may increase CYP substrate adverse reactions, consider monitoring for therapeutic effect or concentration of the CYP substrate and consider dosage adjustment of the CYP substrate as needed [see Clinical Pharmacology (12.3)].
8 Use in Specific Populations
8.4 Pediatric Use
Additions and/or revisions underlined:
Subcutaneous Administration Pediatric Plaque Psoriasis
The safety and effectiveness of COSENTYX have been established for the treatment of moderate to severe PsO in pediatric patients aged 6 years and older who are candidates for systemic therapy or phototherapy [see Adverse Reactions (6.1) and Clinical Studies (14.2)].
Safety and effectiveness of COSENTYX in pediatric patients with PsO below the age of 6 years have not been established.
Juvenile Psoriatic Arthritis
The safety and effectiveness of COSENTYX have been established for the treatment of active JPsA in pediatric patients aged 2 years and older who weigh 15 kg or more [see Adverse Reactions (6.1) and Clinical Studies (14.6)].
The safety and effectiveness of COSENTYX in pediatric patients less than 2 years of age with JPsA or with a body weight less than 15 kg has not been established.
Enthesitis-Related Arthritis
The safety and effectiveness of COSENTYX for the treatment of active ERA in pediatric patients aged 4 years and older who weigh 15 kg or more has been established [see Adverse Reactions (6.1) and Clinical Studies (14.6)].
The safety and effectiveness of COSENTYX in pediatric patients below the age of 4 years old or with body weight less than 15 kg have not been established.
Hidradenitis Suppurativa
The safety and effectiveness of COSENTYX in pediatric patients with HS have not been established.
8.5 Geriatric Use
Additions and/or revisions underlined:
Of the 3,430 PsO subjects exposed to subcutaneous COSENTYX in clinical trials, a total of 230 (7%) were 65 years of age or older, and 32 (1%) subjects were 75 years of age or older. Although no differences in safety or efficacy were
observed between subjects 65 years of age or older and younger adult subjects, the number of subjects 65 years of age and older was not sufficient to determine whether they respond differently from younger adult subjects.
Of the 1,060 subjects with HS exposed to COSENTYX in clinical trials, a total of 14 (1.3%) were 65 years of age and older. Clinical trials in HS did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions and/or revisions underlined:
What is COSENTYX?
COSENTYX is a prescription medicine used to treat:
…
• adults with moderate to severe hidradenitis suppurativa (HS)
It is not known if COSENTYX is safe and effective in children:
…
• with HS
…
How will I receive COSENTYX?
…
• If you inject more COSENTYX than prescribed, call your healthcare provider or Poison Help line at 1-800-222- 1222, or go to the nearest emergency room right away.
…
What are the possible side effects of COSENTYX?
…
The most common side effects of COSENTYX include:
• cold symptoms • diarrhea • upper respiratory tract infections
10/06/2023 (SUPPL-73)
4 Contraindications
(Additions and/or revisions underlined)
COSENTYX is contraindicated in patients with a previous serious hypersensitivity reaction to secukinumab or to any of the excipients in COSENTYX. Cases of anaphylaxis have been reported during treatment with COSENTYX [see Warnings and Precautions (5.2)].
6 Adverse Reactions
(Additions and/or revisions underlined)
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adverse Reactions in Clinical Trials of Subcutaneous COSENTYX
…
Adverse Reactions of Intravenous COSENTYX
The safety of intravenous COSENTYX is based on the pharmacokinetic exposure and extrapolation of the established safety of subcutaneous COSENTYX in PsA, AS and nr-axSpA patients [see Clinical Pharmacology (12.3)].
6.2 Immunogenicity
(Additions and/or revisions underlined)
As with all therapeutic proteins, there is the potential for immunogenicity. The immunogenicity of COSENTYX was evaluated using an electrochemiluminescence-based bridging immunoassay. Less than 1% of subjects treated with subcutaneous COSENTYX developed antibodies to secukinumab in up to 52 weeks of treatment…
8 Use in Specific Populations
8.4 Pediatric Use
(Additions and/or revisions underlined)
Subcutaneous Administration
The safety and effectiveness of COSENTYX have been established in pediatric patients aged 6 years and older with moderate to severe plaque psoriasis [see Adverse Reactions (6.1) and Clinical Studies (14.2)]. Safety and effectiveness of COSENTYX in pediatric patients with plaque psoriasis below the age of 6 years have not been established…
Intravenous Administration
The safety and effectiveness of intravenous COSENTYX in pediatric patients have not been established.
8.5 Geriatric Use
(Additions and/or revisions underlined)
Of the 3430 plaque psoriasis subjects exposed to subcutaneous COSENTYX in clinical trials, a total of 230 (7%) were 65 years or older, and 32 (1%) 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 years and older was not sufficient to determine whether they responded differently from younger subjects.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Additions and/or revisions underlined)
…
Instructions on Subcutaneous Injection Technique
If a patient or caregiver is to subcutaneously administer COSENTYX using the UnoReady pen, Sensoready pen, or the prefilled syringe, instruct him/her in injection techniques and assess their ability to inject subcutaneously to ensure the proper administration of COSENTYX [see Dosage and Administration (2.2, 2.9), Medication Guide, Instructions for Use].
…
Storage
Instruct patients to store COSENTYX in a refrigerator at 2°C to 8°C (36ºF to 46ºF) and to discard expired or unused COSENTYX.
Inform patients that if removed from refrigeration, COSENTYX 150 mg/mL Sensoready pens, 150 mg/mL and 75 mg/0.5 mL prefilled syringes may be stored for up to 4 days at room temperature not to exceed 86°F (30°C). Instruct patients to discard if kept outside of the refrigerator over 4 days [see How Supplied/Storage and Handling (16.2)].
07/24/2023 (SUPPL-54)
5 Warnings and Precautions
5.2 Hypersensitivity Reactions
(Newly added subsection)
Anaphylaxis and cases of urticaria occurred in COSENTYX treated subjects in clinical trials. If an anaphylactic or other serious allergic reaction occurs, administration of COSENTYX should be discontinued immediately and appropriate therapy initiated [see Contraindications (4), Adverse Reactions (6.1)].
5.5 Eczematous Eruptions
(Newly added subsection)
In postmarketing reports, cases of severe eczematous eruptions, including atopic dermatitis-like eruptions, dyshidrotic eczema, and erythroderma, were reported in patients receiving COSENTYX; some cases resulted in hospitalization. The onset of eczematous eruptions was variable, ranging from days to months after the first dose of COSENTYX.
Treatment may need to be discontinued to resolve the eczematous eruption. Some patients were successfully treated for eczematous eruptions while continuing COSENTYX.
5.6 Risk of Hypersensitivity in Latex-Sensitive Individuals
(Additions and/or revisions underlined)
The removable caps of the COSENTYX 150 mg/mL Sensoready pen and the COSENTYX 1 mL and 0.5 mL prefilled syringes contain natural rubber latex, which may cause an allergic reaction in latex-sensitive individuals. The safe use of COSENTYX 150 mg/mL Sensoready pen or 1 mL and 0.5 mL prefilled syringes in latex-sensitive individuals has not been studied.
6 Adverse Reactions
(Additions and/or revisions underlined)
The following adverse reactions are discussed in greater detail elsewhere in the labeling:
· Infections [see Warnings and Precautions (5.1)]
· Hypersensitivity Reactions [see Warnings and Precautions (5.2)]
· Inflammatory Bowel Disease [see Warnings and Precautions (5.4)]
6.1 Clinical Trials Experience
(Additions and/or revisions underlined)
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adult Plaque Psoriasis
A total of 3430 plaque psoriasis adult subjects were treated with COSENTYX in controlled and uncontrolled clinical trials. Of these, 1641 subjects were exposed for at least 1 year.
Four placebo-controlled Phase 3 trials in plaque psoriasis subjects were pooled to evaluate the safety of COSENTYX in comparison to placebo up to 12 weeks after treatment initiation, in Trials PsO1, PsO2, PsO3, and PsO4. In total, 2077 subjects were evaluated (691 to COSENTYX 300 mg group, 692 to COSENTYX 150 mg group, and 694 to placebo group). Subjects randomized to COSENTYX received 300 mg or 150 mg doses subcutaneously at Weeks 0, 1, 2, 3, and 4 followed by the same dose every 4 weeks [see Clinical Studies (14)].
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the COSENTYX groups than the placebo group during the 12-week placebo-controlled period of the placebo-controlled trials.
Adverse reactions that occurred at rates less than 1% in the placebo-controlled period of Trials PsO1, PsO2, PsO3, and PsO4 through Week 12 included: sinusitis, tinea pedis, conjunctivitis, tonsillitis, oral candidiasis, impetigo, otitis media, otitis externa, inflammatory bowel disease, increased liver transaminases, and neutropenia.
…
Inflammatory Bowel Disease
Cases of inflammatory bowel disease, in some cases serious, were observed in clinical trials with COSENTYX. In the plaque psoriasis program, with 3430 subjects exposed to COSENTYX over the entire treatment period for up to 52 weeks (2725 patient-years), there were 3 cases (0.11 per 100 patient-years) of exacerbation of Crohn’s disease, 2 cases (0.08 per 100 patient-years) of exacerbation of ulcerative colitis, and 2 cases (0.08 per 100 patient-years) of new onset ulcerative colitis. There were no cases in placebo subjects (N = 793; 176 patient-years) during the 12-week placebo-controlled period.
One case of exacerbation of Crohn’s disease was reported in open-label portions of clinical trials in plaque psoriasis.
Hypersensitivity Reactions
Anaphylaxis and cases of urticaria occurred in COSENTYX treated subjects in clinical trials [see Warnings and Precautions (5.2)].
Pediatric Plaque Psoriasis
The safety of COSENTYX was assessed in two Phase 3 trials in pediatric subjects with plaque psoriasis.
The first was a randomized, double-blind, placebo and active-controlled, 236-week trial (Trial PsO6) that enrolled 162 pediatric subjects 6 years of age and older, with severe plaque psoriasis (defined by PASI score greater than or equal to 20, an IGA modified 2011 score of 4, and involving greater than or equal to 10% of the body surface area [BSA]) who were candidates for systemic therapy. The 162 subjects were randomized to receive placebo, a biologic active control, or COSENTYX. In the COSENTYX groups, subjects with body weight less than 25 kg received 75 mg, subjects with body weight 25 to less than 50 kg received either 75 mg or 150 mg (2 times the recommended dose), and subjects with body weight of at least 50 kg received either 150 mg or 300 mg (2 times the recommended dose).
The second trial was a randomized, open-label, 208-week trial (Trial PsO7; NCT03668613) of 84 subjects 6 years of age and older with moderate to severe plaque psoriasis (defined by a PASI score greater than or equal to 12, IGA mod 2011 score of less than or equal to 3, and BSA involvement of greater than or equal to 10% at randomization) who were randomized into two COSENTYX arms [Arm 1: 75 mg for body weight (BW) < 50 kg or 150 mg for greater than or equal to 50 kg; and Arm 2: 75 mg for BW < 25 kg, 150 mg for BW greater than or equal to 25 kg and < 50 kg, or 300 mg for BW greater than or equal to 50 kg].
The safety profile reported in these trials was consistent with the safety profile reported in adult plaque psoriasis trials.
Infections
One case of methicillin-resistant Staphylococcus aureus (MRSA) toxic shock syndrome (TSS) was reported in a COSENTYX treated subject during the placebo-controlled period.
In the pediatric safety pool, which includes all subjects who took at least one dose of COSENTYX during the treatment periods [198 subjects (287 patient years)], 22 (11%) subjects reported greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 neutropenia (greater than or equal to 1,000 to < 1,500 cells/mm3) with 57% of subjects followed for one year or more and 30% of subjects followed for two years or more. During the placebo-controlled period which included a total of 80 subjects treated with secukinumab and 41 subjects treated with placebo up to 12 weeks, greater than or equal to CTCAE Grade 2 neutropenia was reported in 3 (4%) of the subjects treated with secukinumab compared with no subjects treated with placebo. No serious infections were associated with cases of neutropenia.
Adult Psoriatic Arthritis
COSENTYX was studied in two placebo-controlled PsA trials with 1003 adult patients (703 patients on COSENTYX and 300 patients on placebo). Of the 703 patients who received COSENTYX, 299 patients received a subcutaneous loading dose of COSENTYX (PsA1) and 404 patients received an intravenous loading dose of secukinumab (PsA2) followed by COSENTYX administered by subcutaneous injection every four weeks. During the 16-week placebo-controlled period of the trials in patients with PsA, the overall proportion of patients with adverse events was similar in the secukinumab and placebo-treatment groups (59% and 58%, respectively). The adverse events that occurred at a proportion of at least 2% and at a higher proportion in the COSENTYX groups than the placebo groups during the 16-week placebo-controlled period were nasopharyngitis, upper respiratory tract infection, headache, nausea, and hypercholesterolemia. The safety profile observed in patients with PsA treated with COSENTYX is consistent with the safety profile in psoriasis.
Similar to the clinical trials in patients with psoriasis, there was an increased proportion of patients with infections in the COSENTYX groups (29%) compared to placebo group (26%).
There were cases of Crohn’s disease and ulcerative colitis that include patients who experienced either exacerbations or the development of new disease. There were three cases of inflammatory bowel disease, of which two patients received secukinumab and one received placebo.
Adult Ankylosing Spondylitis
COSENTYX was studied in two placebo-controlled AS trials with 590 adult patients (394 patients on COSENTYX and 196 patients on placebo). Of the 394 patients who received COSENTYX, 145 patients received a subcutaneous load of COSENTYX (study AS1), and 249 received an intravenous loading dose of secukinumab (study AS2) followed by COSENTYX administered by subcutaneous injection every four weeks. During the 16-week placebo-controlled period of the trials in patients with AS, the overall proportion of patients with adverse events was higher in the secukinumab groups than the placebo-treatment groups (66% and 59%, respectively). The adverse events that occurred at a proportion of at least 2% and at a higher proportion in the COSENTYX groups than the placebo groups during the 16-week placebo- controlled period were nasopharyngitis, nausea, and upper respiratory tract infection. The safety profile observed in patients with ankylosing spondylitis treated with COSENTYX is consistent with the safety profile in psoriasis. In a third controlled study of AS (study AS3), the safety profile of the 300 mg dose of COSENTYX was consistent with the safety profile of the 150 mg dose of COSENTYX.
…
Adult Non-Radiographic Axial Spondyloarthritis
COSENTYX was studied in one randomized, double-blind, placebo-controlled nr-axSpA trial with 555 adult patients (185 patients on with load COSENTYX, 184 patients on without load COSENTYX and 186 patients on placebo). The safety profile for patients with nr-axSpA treated with COSENTYX was overall similar to the safety profile seen in patients with AS and other previous experience with COSENTYX. Patients in nr-axSpA1 study who received the loading dosing regimen compared to those without the loading regimen, had higher incidence of infections and infestations (92 per 100 patient-years vs 72 per 100 patient-years), including nasopharyngitis, upper respiratory tract infection and urinary tract infection, and gastrointestinal disorders (27 per 100 patient-years vs 22 per 100 patient-years), including gastritis, lower abdominal pain, colitis, diarrhea, and hematochezia.
Juvenile Psoriatic Arthritis and Enthesitis-Related Arthritis
COSENTYX was studied in one double-blind, placebo-controlled, event-driven, randomized trial in 86 pediatric patients aged 2 to less than 18 years old with Juvenile Psoriatic Arthritis (JPsA) and ERA. The safety profile reported in this study was consistent with the safety profile of secukinumab.
6.3 Postmarketing Experience
(Newly added subsection)
The following adverse reactions have been reported during postapproval use of COSENTYX. Because they 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: Eczematous eruptions (atopic dermatitis-like eruptions, dyshidrotic eczema, and erythroderma) [see Warnings and Precautions (5.5)].8 Use in Specific Populations
8.4 Pediatric Use
(Additions and/or revisions underlined)
Pediatric Plaque Psoriasis
The safety and effectiveness of COSENTYX have been established in pediatric patients aged 6 years and older with moderate to severe plaque psoriasis [see Adverse Reactions (6.1) and Clinical Studies (14.2)]. Safety and effectiveness of COSENTYX in pediatric patients with plaque psoriasis below the age of 6 years have not been established.
Juvenile Psoriatic Arthritis and Enthesitis-Related Arthritis
The safety and effectiveness of COSENTYX have been established in pediatric patients weighing 15 kg or more with JPsA (2 years and older) and ERA (4 years and older) [see Adverse Reactions (6.1) and Clinical Studies (14.6)].
The safety and effectiveness of COSENTYX in pediatric patients with JPsA below the age of 2 years and with body weight less than 15 kg have not been established.
The safety and effectiveness of COSENTYX in pediatric patients with ERA below the age of 4 years and with body weight less than 15 kg have not been established.
8.5 Geriatric Use
(Additions and/or revisions underlined)
Of the 3430 plaque psoriasis subjects exposed to COSENTYX in clinical trials, a total of 230 (7%) were 65 years or older, and 32 (1%) 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 years and older was not sufficient to determine whether they responded differently from younger subjects.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Additions and/or revisions underlined)
Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Infections
Inform patients that COSENTYX may lower the ability of their immune system to fight infections. Instruct patients of the importance of communicating any history of infections to the doctor and contacting their doctor if they develop any symptoms of infection [see Warnings and Precautions (5.1)].
Hypersensitivity
Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions
[see Warnings and Precautions (5.2)]. Eczematous Eruptions
Inform patients that skin reactions resembling eczema may occur with the use of COSENTYX. Instruct patients to seek medical advice if they develop signs or symptoms of eczema [see Warnings and Precautions (5.5)].
Risk of Hypersensitivity in Latex-Sensitive Individuals
Advise latex-sensitive patients that the removal caps of the COSENTYX 150 mg/mL Sensoready pen and the COSENTYX 1 mL and 0.5 mL prefilled syringes contain natural rubber latex, which may cause an allergic reaction in latex-sensitive individuals [see Warnings and Precautions (5.6)].
Immunization
Advise patients that vaccination with live vaccines is not recommended during COSENTYX treatment. Instruct patients to inform the healthcare practitioner that they are taking COSENTYX prior to a potential vaccination [see Warnings and Precautions (5.7)].
Instructions on Injection Technique
If a patient or caregiver is to administer COSENTYX using the UnoReady pen, Sensoready pen, or the prefilled syringe, instruct him/her in injection techniques and assess their ability to inject subcutaneously to ensure the proper administration of COSENTYX [see Dosage and Administration (2.7, 2.8, 2.9), Medication Guide, and Instructions for Use].
For pediatric patients, inform patients and caregivers that pediatric patients should not self-administer COSENTYX.
Instruct patients or caregivers in the technique of proper syringe and needle disposal and advise them not to reuse these items. Instruct patients to inject the full amount of COSENTYX according to the directions provided in the Medication Guide and Instructions for Use.
Storage
Instruct patients to store COSENTYX in a refrigerator at 2°C to 8°C (36ºF to 46ºF) and to discard expired or unused COSENTYX.
Inform patients that COSENTYX 150 mg/mL Sensoready pens, 150 mg/mL and 75 mg/0.5 mL prefilled syringes may be stored for up to 4 days at room temperature not to exceed 86°F (30°C). Instruct patients to discard if kept outside of the refrigerator over 4 days [see How Supplied/Storage and Handling (16.2)].
05/11/2023 (SUPPL-44)
5 Warnings and Precautions
5.5 Risk of Hypersensitivity in Latex-Sensitive IndividualsAdditions and/or revisions underlined:
The removable caps of the COSENTYX 150 mg/mL Sensoready pen and the COSENTYX 1 mL and 0.5 mL prefilled syringes contain natural rubber latex, which may cause an allergic reaction in latex-sensitive individuals. The safe use of COSENTYX 150 mg/mL Sensoready pen or 1 mL and 0.5 mL prefilled syringes in latex-sensitive individuals has not been studied.
8 Use in Specific Populations
8.4 Pediatric UseAdditions and/or revisions underlined
…
The safety and effectiveness of COSENTYX in pediatric patients with JPsA below the age of 2 years and with body weight less than 15 kg have not been established.
The safety and effectiveness of COSENTYX in pediatric patients with ERA below the age of 4 years and with body weight less than 15 kg have not been established.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
…
Risk of Hypersensitivity in Latex-Sensitive Individuals
Advise latex-sensitive patients that the removal caps of the COSENTYX 150 mg/mL Sensoready pen and the COSENTYX 1 mL and 0.5 mL prefilled syringes contain natural rubber latex, which may cause an allergic reaction in latex-sensitive individuals [see Warnings and Precautions (5.5)].
…
Instructions on Injection Technique
If a patient or caregiver is to administer COSENTYX using the UnoReady pen, Sensoready pen or the prefilled syringe, instruct him/her in injection techniques and assess their ability to inject subcutaneously to ensure the proper administration of COSENTYX [see Dosage and Administration (2.7, 2.8, 2.9), Medication Guide and Instructions for Use].
…
MEDICATION GUIDE
Additions and/or revisions underlined
…
How should I use COSENTYX?
Read the detailed “Instructions for Use” that comes with your COSENTYX for information on how to prepare and inject a dose of COSENTYX, and how to properly throw away (dispose of) used COSENTYX.
…
Do not handle the needle cap of the COSENTYX Sensoready pen or the 75 mg/0.5 mL or 150 mg/mL prefilled syringes if you are sensitive to latex.
…
12/22/2021 (SUPPL-50)
6 Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or revisions underlined:
Juvenile Psoriatic Arthritis and Enthesitis-Related Arthritis
COSENTYX was studied in one double-blind, placebo-controlled, event-driven, randomized trial in 86 pediatric patients aged 2 to < 18 years old with Juvenile Psoriatic Arthritis (JPsA) and ERA. The safety profile reported in this study was consistent with the safety profile of secukinumab.
8 Use in Specific Populations
8.4 Pediatric Use
Additions and/or revisions underlined:
The safety and effectiveness of COSENTYX have been established in pediatric subjects aged 6 years and older with moderate to severe plaque psoriasis [see Adverse Reactions (6.1), Clinical Studies (14.2)]. Safety and effectiveness of COSENTYX in pediatric patients with plaque psoriasis below the age of 6 years have not been established.
The safety and effectiveness of COSENTYX have been established in patients weighing 15 kg or more with JPsA (2 years and older) and ERA (4 years and older) [see Adverse Reactions (6.1), Clinical Studies (14.6)].
The safety and effectiveness of COSENTYX in pediatric patients below the age of 2 years and with body weight less than 15 kg have not been established.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Medication Guide
Additions and/or revisions underlined:
What is COSENTYX?
COSENTYX is a prescription medicine used to treat:
people 6 years of age and older with moderate to severe plaque psoriasis that involves large areas or many areas of the body, and who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet or UV light alone or with systemic therapy)
people 2 years of age and older with active psoriatic arthritis
adults with active ankylosing spondylitis
adults with active non-radiographic axial spondyloarthritis (nr-axSpA) and objective signs of inflammation
people 4 years of age and older with active enthesitis-related arthritis
COSENTYX may improve your psoriasis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis, and enthesitis-related arthritis, but it may also lower the ability of your immune system to fight infections.
It is not known if COSENTYX is safe and effective in children:
below 6 years of age with plaque psoriasis
- below 2 years of age and weighing less than 33 pounds
12/22/2021 (SUPPL-51)
6 Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or revisions underlined:
Juvenile Psoriatic Arthritis and Enthesitis-Related Arthritis
COSENTYX was studied in one double-blind, placebo-controlled, event-driven, randomized trial in 86 pediatric patients aged 2 to < 18 years old with Juvenile Psoriatic Arthritis (JPsA) and ERA. The safety profile reported in this study was consistent with the safety profile of secukinumab.
8 Use in Specific Populations
8.4 Pediatric Use
Additions and/or revisions underlined:
The safety and effectiveness of COSENTYX have been established in pediatric subjects aged 6 years and older with moderate to severe plaque psoriasis [see Adverse Reactions (6.1), Clinical Studies (14.2)]. Safety and effectiveness of COSENTYX in pediatric patients with plaque psoriasis below the age of 6 years have not been established.
The safety and effectiveness of COSENTYX have been established in patients weighing 15 kg or more with JPsA (2 years and older) and ERA (4 years and older) [see Adverse Reactions (6.1), Clinical Studies (14.6)].
The safety and effectiveness of COSENTYX in pediatric patients below the age of 2 years and with body weight less than 15 kg have not been established.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Medication Guide
Additions and/or revisions underlined:
What is COSENTYX?
COSENTYX is a prescription medicine used to treat:
people 6 years of age and older with moderate to severe plaque psoriasis that involves large areas or many areas of the body, and who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet or UV light alone or with systemic therapy)
people 2 years of age and older with active psoriatic arthritis
adults with active ankylosing spondylitis
adults with active non-radiographic axial spondyloarthritis (nr-axSpA) and objective signs of inflammation
people 4 years of age and older with active enthesitis-related arthritis
COSENTYX may improve your psoriasis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis, and enthesitis-related arthritis, but it may also lower the ability of your immune system to fight infections.
It is not known if COSENTYX is safe and effective in children:
below 6 years of age with plaque psoriasis
- below 2 years of age and weighing less than 33 pounds
05/28/2021 (SUPPL-43)
5 Warnings and Precautions
5.1 Infections
(Additions and/or revisions underlined)
COSENTYX may increase the risk of infections. In clinical trials, a higher rate of infections was observed in COSENTYX treated subjects compared to placebo-treated subjects. In placebo-controlled clinical trials in subjects with moderate to severe plaque psoriasis, higher rates of common infections, such as nasopharyngitis (11.4% versus 8.6%), upper respiratory tract infection (2.5% versus 0.7%) and mucocutaneous infections with candida (1.2% versus 0.3%) were observed with COSENTYX compared with placebo. A similar increase in risk of infection was seen in placebo-controlled trials in subjects with psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis. The incidence of some types of infections appeared to be dose-dependent in clinical studies [see Adverse Reactions (6.1)]. In the postmarketing setting, serious and some fatal infections have been reported in patients receiving COSENTYX.
Exercise caution when considering the use of COSENTYX in patients with a chronic infection or a history of recurrent infection.
Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur. If a patient develops a serious infection, monitor the patient closely and discontinue COSENTYX until the infection resolves.
5.2 Pre-Treatment Evaluation for Tuberculosis
(Additions and/or revisions underlined)
Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with COSENTYX. Avoid administration of COSENTYX to patients with active TB infection. Initiate treatment of latent TB prior to administering COSENTYX. Consider anti-TB therapy prior to initiation of COSENTYX in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Monitor patients closely for signs and symptoms of active TB during and after treatment.
5.6 Immunizations
(Additions and/or revisions underlined)
Prior to initiating therapy with COSENTYX, consider completion of all age appropriate immunizations according to current immunization guidelines. COSENTYX may alter a patient`s immune response to live vaccines. Avoid use of live vaccines in patients treated with COSENTYX.
6 Adverse Reactions
6.1 Clinical Trials Experience
(Extensive changes; please refer to labeling)
7 Drug Interactions
(Additions and/or revisions underlined)
CYP450 Substrates
The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNF?, IFN) during chronic inflammation.
Upon initiation or discontinuation of COSENTYX in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect or drug concentration and consider dosage adjustment of the CYP450 substrate as needed [see Clinical Pharmacology (12.3)].
8 Use in Specific Populations
8.4 Pediatric Use
(Additions and/or revisions underlined)
The safety and effectiveness of COSENTYX have been established in pediatric subjects aged 6 years and older with moderate to severe plaque psoriasis [see Adverse Reactions (6.1), Clinical Studies (14.2)]. Safety and effectiveness of COSENYX in pediatric patients with plaque psoriasis below the age of 6 years have not been established.
The safety and effectiveness of COSENTYX in pediatric patients in other indications have not been established.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Additions and/or revisions underlined)
Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).
Infections
Inform patients that COSENTYX may lower the ability of their immune system to fight infections. Instruct patients of the importance of communicating any history of infections to the doctor and contacting their doctor if they develop any symptoms of infection [see Warnings and Precautions (5.1)].
Hypersensitivity
Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions (5.4)].
Risk of Hypersensitivity in Latex-Sensitive Individuals
Advise latex-sensitive patients that the removal caps of the COSENTYX Sensoready pen and the COSENTYX 1 mL and 0.5 mL prefilled syringes contain natural rubber latex, which may cause an allergic reaction in latex-sensitive individuals [see Warnings and Precautions (5.5)].
Immunization
Advise patients that vaccination with live vaccines is not recommended during COSENTYX treatment. Instruct patients to inform the healthcare practitioner that they are taking COSENTYX prior to a potential vaccination [see Warnings and Precautions (5.6)].
Instructions on Injection Technique
If a patient or caregiver is to administer COSENTYX using the Sensoready pen or the prefilled syringe, instruct him/her in injection techniques and assess their ability to inject subcutaneously to ensure the proper administration of COSENTYX [see Dosage and Administration (2.6), Medication Guide and Instructions for Use].
For pediatric patients, inform patients and caregivers that pediatric patients should not self-administer COSENTYX using the pre-filled syringe or the Sensoready pen.
06/16/2020 (SUPPL-35)
5 Warnings and Precautions
Infections(Additions and/or revisions underlined)
COSENTYX may increase the risk of infections. In clinical trials, a higher rate of infections was observed in COSENTYX treated subjects compared to placebo-treated subjects. In placebo-controlled clinical trials in patients with moderate to severe plaque psoriasis, higher rates of common infections such as nasopharyngitis (11.4% versus 8.6%), upper respiratory tract infection (2.5% versus 0.7%) and mucocutaneous infections with candida (1.2% versus 0.3%) were observed with COSENTYX compared with placebo. A similar increase in risk of infection was seen in placebo-controlled trials in patients with psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis [see Adverse
Reactions (6.1)]. The incidence of some types of infections appeared to be dose-dependent in clinical studies [see Adverse Reactions (6.1)].
Inflammatory Bowel Disease
(Additions and/or revisions underlined)
Caution should be used when prescribing COSENTYX to patients with inflammatory bowel disease. Exacerbations, in some cases serious, occurred in COSENTYX treated patients during clinical trials in plaque psoriasis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis.
6 Adverse Reactions
Clinical Trials Experience(Newly added subsection)
Non-radiographic axial spondyloarthritis
COSENTYX was studied in one randomized, double-blind, placebo controlled non-radiographic axial spondyloarthritis trial with 555 patients (185 patients on with load COSENTYX, 184 patients on without load COSENTYX and 186 patients on placebo). The safety profile for patients with nr-axSpA treated with COSENTYX was overall similar to the safety profile seen in patients with AS and other previous experience with COSENTYX. Patients in nr-axSpA1 study who received the loading dosing regimen compared to those without the loading regimen, had higher incidence of infections and infestations (92 per 100 patient-years vs 72 per 100 patient years), including nasopharyngitis, upper respiratory tract infection and urinary tract infection, and gastrointestinal disorders (27 per 100 patient-years vs 22 per 100 patient-years), including gastritis, lower abdominal pain, colitis, diarrhea and hematochezia.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Medication Guide(Additions and/or revisions underlined)
COSENTYX is a prescription medicine used to treat adults:
-with active non-radiographic axial spondyloarthritis and objective signs of inflammation
COSENTYX may improve your psoriasis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial
spondyloarthritis but it may also lower the ability of your immune system to fight infections.
01/29/2020 (SUPPL-31)
6 Adverse Reactions
Clinical Trials Experience(Newly added information)
In a third controlled study of AS (study AS3), the safety profile of the 300 mg dose of COSENTYX was consistent with the safety profile of the 150 mg dose of COSENTYX.
01/23/2018 (SUPPL-13)
8 Use in Specific Populations
8.1 Pregnancy(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; additions and/or revisions are underlined)
Risk Summary
Limited available human data with COSENTYX use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. In an embryo-fetal development study, no adverse developmental effects were observed in infants born to pregnant monkeys after subcutaneous administration of secukinumab during organogenesis at doses up to 30 times the maximum recommended human dose (MRHD).
The background risk of major birth defects and miscarriage for the indicated population is unknown; however, the background risk in the U.S. general population of major birth defects is 2%-4% and of miscarriage is 15%-20% of clinically recognized pregnancies.
Data
Animal Data
An embryo-fetal development study was performed in cynomolgus monkeys with secukinumab…
(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; additions and/or revisions are underlined)
Risk Summary
It is not known whether secukinumab is excreted in human milk or absorbed systemically after ingestion. There are no data on the effects of COSENTYX on the breastfed child or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for COSENTYX and any potential adverse effects on the breastfed child from COSENTYX or from the underlying maternal condition.
09/15/2017 (SUPPL-16)
7 Drug Interactions
7.3 CYP450 SubstratesAdditions and/or revisions underlined:
The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNF?, IFN) during chronic inflammation.
Results from a drug-drug interaction study in subjects with moderate to severe psoriasis showed no clinically relevant interaction for drugs metabolized by CYP3A4.
Upon initiation or discontinuation of COSENTYX consider monitoring for therapeutic effect or drug concentration and consider dosage adjustment as needed.