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SILIQ（brodalumab injection）
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HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use SILIQ safely and effectively. See full prescribing information for SILIQ.
SILIQ™ (brodalumab) injection, for subcutaneous use
Initial U.S. Approval: 2017
WARNING: SUICIDAL IDEATION AND BEHAVIOR
See full prescribing information for complete boxed warning.
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Suicidal ideation and behavior, including completed suicides, have occurred in patients treated with SILIQ. (5.1, 6.1)
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Prior to prescribing, weigh potential risks and benefits in patients with a history of depression and/or suicidal ideation or behavior. (5.1)
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Patients with new or worsening suicidal thoughts and behavior should be referred to a mental health professional, as appropriate. (5.1)
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Advise patients and caregivers to seek medical attention for manifestations of suicidal ideation or behavior, new onset or worsening depression, anxiety, or other mood changes. (5.1)
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SILIQ is available only through a restricted program called the SILIQ REMS Program. (5.2)
INDICATIONS AND USAGE
SILIQ is a human interleukin-17 receptor A (IL-17RA) antagonist indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. (1)
DOSAGE AND ADMINISTRATION
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Administer 210 mg of SILIQ by subcutaneous injection at Weeks 0, 1, and 2 followed by 210 mg every 2 weeks. ( 2.1) DOSAGE FORMS AND STRENGTHS
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Injection: 210 mg/1.5 mL solution in a single-dose prefilled syringe. ( 3)
CONTRAINDICATIONS
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Crohn’s disease ( 4)
WARNINGS AND PRECAUTIONS
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Infections: Serious infections have occurred. Consider the risks and benefits prior to initiating SILIQ in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a serious infection develops, discontinue SILIQ until the infection resolves. ( 5.3)
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Tuberculosis (TB): eva luate patients for TB infection prior to initiating treatment with SILIQ. ( 5.4)
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Crohn’s Disease: Crohn’s disease occurred during clinical trials. Discontinue SILIQ if patient develops Crohn’s disease while taking SILIQ. ( 5.5)
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Immunizations: Avoid using live vaccines concurrently with SILIQ. ( 5.5)
ADVERSE REACTIONS
Most common adverse reactions (incidence ≥1%) were arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection site reactions, influenza, neutropenia, and tinea infections. (6)
To report SUSPECTED ADVERSE REACTIONS, contact Valeant Pharmaceuticals North America LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 2/2017
FULL PRESCRIBING INFORMATION: CONTENTS*
WARNING: SUICIDAL IDEATION AND BEHAVIOR
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Dosage
2.2 Tuberculosis Assessment Prior to Initiation of SILIQ
2.3 Important Administration Instructions
2.4 Preparation of SILIQ Prefilled Syringe
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Suicidal Ideation and Behavior
5.2 SILIQ REMS Program
5.3 Infections
5.4 Risk for Latent Tuberculosis Reactivation
5.5 Crohn’s Disease
5.6 Immunizations
6 ADVERSE REACTIONS
6.1 Clinical Trial Experience
6.2 Immunogenicity
7 DRUG INTERACTIONS 7.1 Live Vaccinations
7.2 CYP450 Substrates
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
16.2 Storage and Handling
17 PATIENT COUNSELING INFORMATION
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Sections or subsections omitted from the full prescribing information are not listed.
FULL PRESCRIBING INFORMATION
WARNING: SUICIDAL IDEATION AND BEHAVIOR
Suicidal ideation and behavior, including completed suicides, have occurred in patients treated with SILIQ. Prior to prescribing SILIQ, weigh the potential risks and benefits in patients with a history of depression and/or suicidal ideation or behavior. Patients with new or worsening suicidal ideation and behavior should be referred to a mental health professional, as appropriate. Advise patients and caregivers to seek medical attention for manifestations of suicidal ideation or behavior, new onset or worsening depression, anxiety, or other mood changes [see Warnings and Precautions (5.1)].
Because of the observed suicidal behavior in subjects treated with SILIQ, SILIQ is available only through a restricted program under a Risk eva luation and Mitigation Strategy (REMS) called the SILIQ REMS Program [see Warnings and Precautions (5.2)].
1 INDICATIONS AND USAGE
SILIQ™ is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies.
2 DOSAGE AND ADMINISTRATION
2.1 Dosage
The recommended SILIQ dose is 210 mg administered by subcutaneous injection at Weeks 0, 1, and 2 followed by 210 mg every 2 weeks.
If an adequate response has not been achieved after 12 to 16 weeks of treatment with SILIQ, consider discontinuing therapy. Continued treatment beyond 16 weeks in patients who have not achieved an adequate response is not likely to result in greater success.
2.2 Tuberculosis Assessment Prior to Initiation of SILIQ
eva luate patients for tuberculosis (TB) infection prior to initiating treatment with SILIQ [see Warnings and Precautions (5.4)].
2.3 Important Administration Instructions
Administer SILIQ subcutaneously. Each prefilled syringe is for single-dose only.
Instruct patients to review the Medication Guide before use (see Medication Guide). SILIQ is intended for use under the guidance and supervision of a healthcare professional. Patients may self-inject SILIQ when deemed appropriate by a healthcare professional and after proper training in subcutaneous injection technique using the prefilled syringe.
Advise patients who are self-administering to inject the full dose and to read the Instructions for Use before administration (see Instructions for Use).
Do not inject SILIQ into areas where the skin is tender, bruised, red, hard, thick, scaly, or affected by psoriasis.
2.4 Preparation of SILIQ Prefilled Syringe
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Allow SILIQ prefilled syringe to reach room temperature (approximately 30 minutes) before injecting. Do not warm in any other way. Do not remove the gray needle cap on the prefilled syringe while allowing it to reach room temperature.
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Visually inspect SILIQ for particles and discoloration prior to administration. SILIQ is a clear to slightly opalescent, colorless to slightly yellow solution. A few translucent to white, amorphous proteinaceous particles may be present. Do not use SILIQ if it is cloudy or discolored or if foreign matter is present.
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Instruct patients to use the prefilled syringe and to inject the full amount (1.5 mL), which provides 210 mg of SILIQ, according to the directions provided in the Instructions for Use [see Instructions for Use].
3 DOSAGE FORMS AND STRENGTHS
Injection: 210 mg/1.5 mL solution in a single-dose prefilled syringe. SILIQ is a clear to slightly opalescent, colorless to slightly yellow solution and may contain a few translucent to white, amorphous particles .
4 CONTRAINDICATIONS
SILIQ is contraindicated in patients with Crohn’s disease because SILIQ may cause worsening of disease [see Warnings and Precautions (5.5)].
5 WARNINGS AND PRECAUTIONS
5.1 Suicidal Ideation and Behavior
Suicidal ideation and behavior, including 4 completed suicides, occurred in subjects treated with SILIQ in the psoriasis clinical trials. There were no completed suicides in the 12-week placebo-controlled portion of the trials. SILIQ users with a history of suicidality or depression had an increased incidence of suicidal ideation and behavior as compared to users without such a history [see Adverse Reactions (6.1)]. A causal association between treatment with SILIQ and increased risk of suicidal ideation and behavior has not been established.
Prescribers should weigh the potential risks and benefits before using SILIQ in patients with a history of depression or suicidality. Patients with new or worsening symptoms of depression or suicidality should be referred to a mental health professional, as appropriate. Advise patients and caregivers to seek medical attention for manifestations of suicidal ideation and behavior, new onset or worsening depression, anxiety, or other mood changes. Prescribers should also re-eva luate the risks and benefits of continuing treatment with SILIQ if such events occur.
Because of the observed suicidal ideation and behavior in subjects treated with SILIQ, if an adequate response to SILIQ has not been achieved within 12 to 16 weeks, consider discontinuing therapy.
SILIQ is available only through a restricted program under a REMS [see Warnings and Precautions (5.2)].
5.2 SILIQ REMS Program
SILIQ is available only through a restricted program under a REMS called the SILIQ REMS Program because of the observed suicidal ideation and behavior in subjects treated with SILIQ [see Warnings and Precautions (5.1)].
Notable requirements of the SILIQ REMS Program include the following:
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Prescribers must be certified with the program.
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Patients must sign a Patient-Prescriber Agreement Form.
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Pharmacies must be certified with the program and must only dispense to patients who are authorized to receive SILIQ.
Further information, including a list of qualified pharmacies, is available at www.SILIQREMS.com or by calling the SILIQ REMS Program Call Center at 855-511-6135.
5.3 Infections
SILIQ may increase the risk of infections. In clinical trials, subjects treated with SILIQ had a higher rate of serious infections than subjects treated with placebo (0.5% versus 0.2%) and higher rates of fungal infections (2.4% versus 0.9%). One case of cryptococcal meningitis occurred in a subject treated with SILIQ during the 12-week randomized treatment period and led to discontinuation of therapy [see Adverse Reactions (6.1)].
During the course of clinical trials for plaque psoriasis, the exposure-adjusted rates for infections and serious infections were similar in the subjects treated with SILIQ and those treated with ustekinumab.
In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing SILIQ. Instruct patients to seek medical help if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy for the infection, monitor the patient closely and discontinue SILIQ therapy until the infection resolves.
5.4 Risk for Latent Tuberculosis Reactivation
eva luate patients for tuberculosis (TB) infection prior to initiating treatment with SILIQ. Do not administer SILIQ to patients with active TB infection. Initiate treatment for latent TB prior to administering SILIQ.
Consider anti-TB therapy prior to initiation of SILIQ in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Closely monitor patients receiving SILIQ for signs and symptoms of active TB during and after treatment.
5.5 Crohn’s Disease
In psoriasis trials, which excluded subjects with active Crohn’s disease, Crohn’s disease occurred in one subject during treatment with SILIQ and led to discontinuation of therapy. In other trials, exacerbation of Crohn’s disease was observed with SILIQ use.
SILIQ is contraindicated in patients with Crohn’s disease.
Discontinue SILIQ if the patient develops Crohn’s disease while taking SILIQ.
5.6 Immunizations
Avoid use of live vaccines in patients treated with SILIQ. No data are available on the ability of live or inactive vaccines to elicit an immune response in patients being treated with SILIQ.
6 ADVERSE REACTIONS
The following serious adverse reactions are discussed in greater detail in other sections of labeling:
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Suicidal Ideation and Behavior [see Warnings and Precautions (5.1)]
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Infections [see Warnings and Precautions (5.3)]
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Crohn’s Disease [see Contraindications (4), Warnings and Precautions (5.5)]
6.1 Clinical Trial Experience
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.
The overall safety population included 4558 subjects (3066 SILIQ, 613 ustekinumab, 879 placebo) in controlled clinical trials and open-label extension studies. The majority of subjects were male (69%), white (91%), and aged 40-64 years old (58%). One-third of subjects reported previous biologic use prior to enrollment. Across the clinical development program, 4464 subjects received at least one dose of SILIQ; 3755 subjects were exposed to SILIQ for at least 1 year.
Weeks 0 to 12:
Data from one multicenter, randomized, placebo-controlled trial (Trial 1), two multicenter, randomized, placebo- and active-controlled trials (Trials 2 and 3), and one dose-finding trial (Trial 4) in plaque psoriasis were pooled to eva luate the safety of SILIQ (210 mg weekly at Weeks 0, 1, and 2, followed by treatments every 2 weeks [Q2W]) compared to placebo for up to 12 weeks after treatment initiation.
During the 12-week, randomized treatment period, about 1% of the subjects in the treatment groups (SILIQ, ustekinumab and placebo) discontinued treatment because of adverse events. Adverse events leading to discontinuation of SILIQ included neutropenia, arthralgia, and urticaria. The proportion of subjects who developed serious adverse events was similar among the SILIQ, ustekinumab, and placebo groups.
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the SILIQ 210 mg Q2W group than in the placebo group during the 12-week randomized treatment period of the pooled trials.
Table 1: Adverse Reactions Occurring in ≥ 1% of Subjects in the SILIQ Group and More Frequently than in the Placebo Group in Plaque Psoriasis Trials through Week 12
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Adverse Reactions
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Placebo
(N=879)
n (%)
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SILIQ 210 mg
every 2 weeks*
(N=1496)
n (%)
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Ustekinumab
(N=613)†
n (%)
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Arthralgia
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29 (3.3)
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71 (4.7)
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15 (2.4)
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Headache
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31 (3.5)
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64 (4.3)
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23 (3.8)
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Fatigue
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10 (1.1)
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39 (2.6)
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16 (2.6)
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Diarrhea
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10 (1.1)
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33 (2.2)
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5 (0.8)
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Oropharyngeal pain
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10 (1.1)
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31 (2.1)
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8 (1.3)
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Nausea
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10 (1.1)
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28 (1.9)
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6 (1.0)
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Myalgia
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3 (0.3)
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26 (1.7)
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4 (0.7)
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Injection site reactions
(pain, erythema, bruising, hemorrhage, pruritus)
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11 (1.3)
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23 (1.5)
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12 (2.0)
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Influenza
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4 (0.5)
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19 (1.3)
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7 (1.1)
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Neutropenia
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4 (0.5)
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15 (1.0)
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5 (0.8)
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Tinea infections
(tinea pedis, versicolor, cruris)
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2 (0.2)
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15 (1.0)
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3 (0.5)
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Adverse reactions that occurred in less than 1% of subjects in the SILIQ group through Week 12 were conjunctivitis and candida infections (including oral [0.2%], genital [0.1%], and esophageal [0.1%] versus none in the placebo group).
Week 0 to End of Trial:
Through Week 52, exposure-adjusted rates of serious adverse events were similar between subjects treated with SILIQ and those treated with ustekinumab. Through the end of the trial, the exposure-adjusted rates of treatment-emergent serious adverse events were similar to those seen in the 52-week period in the subjects treated with SILIQ.
Specific Adverse Reactions:
Suicidal Ideation and Behavior
During the 12-week randomized treatment period in the pooled trials, one subject in the SILIQ group attempted suicide and none in the placebo or ustekinumab groups. From initiation through Week 52 of the trials, suicidal ideation or behavior occurred in 7 of 4019 subjects (0.2 per 100 subject-years) treated with SILIQ and in 2 of 613 subjects (0.4 per 100 subject-years) treated with ustekinumab.
During the course of the clinical trials for plaque psoriasis, suicidal ideation or behavior occurred in 34 of 4464 subjects treated with SILIQ (0.37 per 100 subject-years). Eight of the 10 subjects who attempted or completed suicide had a history of depression and/or suicidal ideation or behavior [see Warnings and Precautions (5.1, 5.2)].
Infections
During the 12-week randomized treatment period, infections occurred in 25.4% of the SILIQ group compared to 23.4% of the placebo group. The majority of infections consisted of nasopharyngitis, upper respiratory tract infec |
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