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Siliq

Generic Name: Brodalumab
Class: Skin and Mucous Membrane Agents, Miscellaneous

Warning

Warning: Suicidal Ideation and Behavior

See full prescribing information for complete boxed warning.

  • Suicidal ideation and behavior, including completed suicides, have occurred in patients treated with brodalumab.1

  • Prior to prescribing, weigh potential risks and benefits in patients with a history of depression and/or suicidal ideation or behavior.1

  • Patients with new or worsening suicidal thoughts and behavior should be referred to a mental health professional, as appropriate.1

  • 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.1

  • Brodalumab is available only through a restricted program called the Siliq REMS Program.1

REMS:

FDA approved a REMS for brodalumab to ensure that the benefits outweigh the risk. The REMS may apply to one or more preparations of brodalumab and consists of the following: elements to assure safe use and implementation system. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Brodalumab, a human immunoglobulin G2 kappa (IgG2 kappa) monoclonal antibody, is an antipsoriatic agent.1

Uses for Siliq

Brodalumab has the following uses:

Brodalumab 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

Siliq Dosage and Administration

General

Brodalumab is available in the following dosage form(s) and strength(s):

  • Injection: 210 mg/1.5 mL solution in a single-dose prefilled syringe.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

  • Administer 210 mg of brodalumab by subcutaneous injection at weeks 0, 1, and 2 followed by 210 mg every 2 weeks.1

Cautions for Siliq

Contraindications

  • Crohn’s disease.1

Warnings/Precautions

Suicidal Ideation and Behavior

Suicidal ideation and behavior, including 4 completed suicides, occurred in subjects treated with brodalumab in the psoriasis clinical trials. There were no completed suicides in the 12-week placebo-controlled portion of the trials. Brodalumab 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. A causal association between treatment with brodalumab and increased risk of suicidal ideation and behavior has not been established.1

Prescribers should weigh the potential risks and benefits before using brodalumab 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-evaluate the risks and benefits of continuing treatment with brodalumab if such events occur.1

Because of the observed suicidal ideation and behavior in subjects treated with brodalumab, if an adequate response to brodalumab has not been achieved within 12 to 16 weeks, consider discontinuing therapy.1

Brodalumab is available only through a restricted program under a REMS.1

REMS Program

Brodalumab 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 brodalumab.1

Notable requirements of the Siliq REMS Program include the following:1

  • Prescribers must be certified with the program.1

  • Patients must sign a Patient-Prescriber Agreement Form.1

  • Pharmacies must be certified with the program and must only dispense to patients who are authorized to receive brodalumab.1

Further information, including a list of qualified pharmacies, is available at or by calling the Siliq REMS Program Call Center at 855-511-6135.1

Infections

Brodalumab may increase the risk of infections. In clinical trials, subjects treated with brodalumab 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 brodalumab during the 12-week randomized treatment period and led to discontinuation of therapy.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 brodalumab and those treated with ustekinumab.1

In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing brodalumab. 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 brodalumab therapy until the infection resolves.1

Risk for Latent Tuberculosis Reactivation

Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with brodalumab. Do not administer brodalumab to patients with active TB infection. Initiate treatment for latent TB prior to administering brodalumab.1

Consider anti-TB therapy prior to initiation of brodalumab 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 brodalumab for signs and symptoms of active TB during and after treatment.1

Crohn’s Disease

In psoriasis trials, which excluded subjects with active Crohn’s disease, Crohn’s disease occurred in one subject during treatment with brodalumab and led to discontinuation of therapy. In other trials, exacerbation of Crohn’s disease was observed with brodalumab use.1

Brodalumab is contraindicated in patients with Crohn’s disease.1

Discontinue brodalumab if the patient develops Crohn’s disease while taking brodalumab.1

Immunizations

Avoid use of live vaccines in patients treated with brodalumab. No data are available on the ability of live or inactive vaccines to elicit an immune response in patients being treated with brodalumab.1

Specific Populations

Pregnancy

Risk Summary:There are no human data on brodalumab use in pregnant women to inform a drug associated risk. Human IgG antibodies are known to cross the placental barrier; therefore, brodalumab may be transmitted from the mother to the developing fetus. In a combined embryofetal development and pre- and post-natal development study, no adverse developmental effects were observed in infants born to pregnant monkeys after subcutaneous administration of brodalumab during organogenesis through parturition at doses up to 26 times the maximum recommended human dose (MRHD).1

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.1

Animal Data: A combined embryofetal development and pre- and post-natal development study was conducted in cynomolgus monkeys administered brodalumab. No brodalumab-related effects on embryofetal toxicity or malformations, or on morphological, functional or immunological development were observed in infants from pregnant monkeys administered weekly subcutaneous doses of brodalumab up to 26 times the MRHD from the beginning of organogenesis to parturition (on a mg/kg basis of 90 mg/kg/week).1

Lactation

There are no data on the presence of brodalumab in human milk, the effects on the breastfed infant, or the effects on milk production. Brodalumab was detected in the milk of lactating cynomolgus monkeys. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for brodalumab and any potential adverse effects on the breastfed infant from brodalumab or from the underlying maternal condition.1

Pediatric Use

The safety and effectiveness of brodalumab have not been evaluated in pediatric patients.1

Geriatric Use

Of the 3066 plaque psoriasis subjects initially randomized to brodalumab in clinical trials, 192 (6%) were ≥65 years old and no subjects were ≥75 years old. 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.1

Common Adverse Effects

Most common adverse reactions (incidence ≥1%) were arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection site reactions, influenza, neutropenia, and tinea infections.1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Brodalumab is a human monoclonal IgG2κ antibody that selectively binds to human IL-17RA and inhibits its interactions with cytokines IL-17A, IL-17F, IL-17C, IL-17A/F heterodimer, and IL-25. IL-17RA is a protein expressed on the cell surface and is a required component of receptor complexes utilized by multiple IL-17 family cytokines. Blocking IL-17RA inhibits IL-17 cytokine-induced responses including the release of pro-inflammatory cytokines and chemokines.1

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (medication guide and instructions for use) for brodalumab before the patient starts using the drug, and each time the prescription is renewed, as there may be new information they need to know.1

Suicidal Thoughts and Behavior

Instruct patients and their caregivers to monitor for the emergence of suicidal thoughts and behavior and promptly seek medical attention if the patient experiences suicidal thoughts, new or worsening depression, anxiety, or other mood changes,1

Instruct patients to carry the wallet card provided and to call the National Suicide Prevention Lifeline at 1-800-273-8255 if they experience suicidal thoughts.1

REMS Program

Because of the observed suicidal thoughts and behavior in subjects treated with brodalumab, the drug is available only through a restricted program called the Siliq REMS Program. Inform the patient of the following: patients must enroll in the program and patients will be given a Siliq patient wallet card that they should carry with them at all times. This card describes symptoms which, if experienced, should prompt the patient to immediately seek medical evaluation. Advise the patient to show the patient wallet card to other treating healthcare providers.1

Brodalumab is available only from certified pharmacies participating in the program. Therefore, provide patients with the telephone number and website for information on how to obtain the product.1

Infections

Inform patients that brodalumab may lower the ability of their immune system to fight infections. Instruct patients of the importance of communicating any history of infections to their healthcare providers and to contact their healthcare providers if they develop any signs or symptoms of infection.1

Crohn’s Disease

Instruct patients to seek medical advice if they develop signs and symptoms of Crohn’s disease.1

Instructions for Injection

Instruct the patient to perform the first self-injection under the guidance and supervision of a qualified healthcare professional for proper training in subcutaneous injection technique.1

Instruct patients who are self-administering to inject the full dose of brodalumab.1

Instruct patients or caregivers in the technique of proper syringe and needle disposal.1

Additional Information

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Brodalumab 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 brodalumab. Further information, including a list of qualified pharmacies, is available at or by calling the Siliq REMS Program Call Center at 855-511-6135.1

Brodalumab

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use

210 mg/1.5 mL

Siliq (available as single-use prefilled syringes)

Valeant

AHFS Drug Information. © Copyright 2017, Selected Revisions March 8, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Valeant Pharmaceuticals North America LLC. Siliq (brodalumab) injection for subcutaneous use prescribing information. 2017 Feb.

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