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Brodalumab

Brand name: Siliq
Drug class: Skin and Mucous Membrane Agents, Miscellaneous
Chemical name: Disulfide with human monoclonal light chain, anti-(human interleukin 17 receptor A) (human monoclonal heavy chain), immunoglobulin G dimer
Molecular formula: C6372H9840N1712O1988S52
CAS number: 1174395-19-7

Medically reviewed by Drugs.com on Mar 31, 2022. Written by ASHP.

Warning

    Suicidal Ideation and Behavior
  • Suicidal ideation and behavior, including completed suicides, reported.

  • Weigh potential risks and benefits before initiating brodalumab therapy in patients with a history of depression and/or suicidal ideation or behavior.

  • Refer patients with new or worsening suicidal ideation and behavior 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 of depression or anxiety, or other mood changes.

  • Available only through a restricted distribution program under a REMS.

Risk Evaluation and Mitigation Strategy (REMS):

FDA approved a REMS for brodalumab to ensure that the benefits outweigh the risks. 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 https://www.accessdata.fda.gov/scripts/cder/rems/.

Introduction

Interleukin-17 receptor A (IL-17RA) antagonist; human IgG2 kappa monoclonal antibody.

Uses for Brodalumab

Plaque Psoriasis

Management of moderate to severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy and who have failed to respond to or have lost response to other systemic therapies.

Guidelines generally support the use of IL-17 inhibitors as monotherapy in adults with moderate-to-severe plaque psoriasis.

Recommendations for use and selection of psoriasis therapies vary based on patient age, disease characteristics (e.g., severity, location, presence of psoriatic arthritis), and comorbidities (e.g., inflammatory bowel disease).

Brodalumab Dosage and Administration

General

Pretreatment Screening

  • Evaluate patients for tuberculosis prior to initiation of brodalumab therapy.

Patient Monitoring

  • Monitor for signs and symptoms of active tuberculosis or other infection.

  • Monitor for new or worsening symptoms of depression or suicidal ideation.

  • Monitor for signs and symptoms of Crohn disease.

REMS

  • Due to risk of suicidal ideation and behavior, including completed suicides, brodalumab is available only under a restricted distribution program (Siliq REMS program).

  • Prescribers and pharmacies must be certified with the REMS program before they can prescribe or dispense the drug.

  • Patients must sign a Patient-Prescriber Agreement Form.

  • Pharmacies must only dispense to patients who are authorized to receive brodalumab.

  • Call 855-511-6135 or visit [Web] for additional information and to enroll in the program.

Administration

Sub-Q Administration

Administer by sub-Q injection into the upper arms, thighs, or any quadrant of the abdomen; avoid injections within 2 inches of the navel. Administration into upper outer arm should be performed by a caregiver or clinician.

Rotate injection sites.

Do not inject into areas where the skin is tender, bruised, erythematous, indurated, or affected by psoriasis or into scars or stretch marks.

Intended for use under the guidance and supervision of a clinician, but may be self-administered after appropriate training.

Use of Prefilled Syringe

Remove syringe from refrigerator and allow to sit at room temperature for approximately 30 minutes prior to injection. Do not warm solution in any other way. Do not remove needle cap while syringe is warming to room temperature.

Do not shake the solution.

Inject entire contents of prefilled syringe (1.5 mL providing 210 mg).

Dosage

Adults

Plaque Psoriasis
Sub-Q

210 mg at weeks 0, 1, and 2, followed by 210 mg every 2 weeks.

If adequate response not obtained after 12–16 weeks, consider discontinuing the drug. Continued therapy beyond 16 weeks not likely to result in greater success.

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations.

Renal Impairment

Manufacturer makes no specific dosage recommendations.

Geriatric Patients

Manufacturer makes no specific dosage recommendations.

Cautions for Brodalumab

Contraindications

  • Crohn disease.

Warnings/Precautions

Warnings

Suicidal Ideation and Behavior

Suicidal ideation and behavior, including completed suicides, reported.

Because of risk of suicidality, available only through a restricted distribution program under a REMS.

Weigh potential risks and benefits before initiating brodalumab therapy in patients with a history of depression and/or suicidal ideation or behavior.

Refer patients with new or worsening symptoms of depression or suicidal ideation and behavior to a mental health professional, as appropriate, and advise patients and caregivers to seek medical attention for manifestations of suicidal ideation or behavior, new onset or worsening of depression or anxiety, or other mood changes.

Reassess risks and benefits of continuing brodalumab therapy if such adverse effects occur; consider discontinuance if an adequate response is not attained within 12–16 weeks.

Other Warnings and Precautions

Infectious Complications

Increased risk of infections. Higher rates of serious infections and fungal infections observed in patients receiving brodalumab compared with those receiving placebo. Most infections did not warrant drug discontinuance, and most fungal infections were not serious.

Brodalumab-associated neutropenia (generally transient) reported; no serious neutropenia-associated infections reported.

Consider risks and benefits prior to initiating brodalumab in patients with chronic infection or history of recurrent infection. Closely monitor patients who develop a serious infection or an infection that does not respond to standard therapy, and discontinue brodalumab until infection resolves.

Evaluate patients for tuberculosis before initiating brodalumab. Do not administer to patients with active tuberculosis infection. When indicated, initiate appropriate antimycobacterial regimen for treatment of latent tuberculosis infection before initiating brodalumab. Also consider antimycobacterial therapy for patients with a history of latent or active tuberculosis in whom an adequate course of antimycobacterial treatment cannot be confirmed. Closely monitor patients for active tuberculosis during and after brodalumab treatment.

Exacerbation of Crohn Disease

Clinical studies in psoriasis patients excluded individuals with Crohn disease; one patient receiving brodalumab in these studies developed Crohn disease and discontinued the drug. In other studies, brodalumab exacerbated Crohn disease.

Discontinue brodalumab if patient develops Crohn disease.

Immunization

Avoid live vaccines. (See Vaccines under Interactions.)

Immunogenicity

Formation of antibrodalumab antibodies reported; neutralizing antibodies not detected.

Specific Populations

Pregnancy

Data regarding use and associated risks in pregnant women not available. Potential for fetal exposure since human IgG crosses the placenta.

No evidence of adverse embryofetal toxicity or malformations and no adverse effects on morphologic, functional, or immunologic development in animal studies.

Lactation

Not known whether brodalumab distributes into human milk, affects milk production, or affects breast-fed infant. Brodalumab distributes into milk in cynomolgus monkeys.

Consider benefits of breast-feeding and importance of the drug to the woman; also consider any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.

Geriatric Use

No apparent differences in safety or efficacy between geriatric patients and younger adults with psoriasis; however, insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults.

Hepatic Impairment

No formal studies to date.

Renal Impairment

No formal studies to date.

Common Adverse Effects

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

Interactions for Brodalumab

Drugs Metabolized by Hepatic Microsomal Enzymes

Because elevated levels of certain cytokines during chronic inflammation may alter formation of CYP isoenzymes, brodalumab-induced changes in cytokine levels may affect formation of CYP enzymes.

CYP substrates: Upon initiation or discontinuance of brodalumab, consider monitoring therapeutic effect or drug concentration and consider dosage adjustment of the CYP substrate, especially if substrate has a narrow therapeutic index.

Vaccines

Avoid live vaccines.

No available data to date regarding response to live or inactivated vaccines.

Specific Drugs

Drug

Interaction

Comments

Cyclosporine

Possible effect on cyclosporine metabolism; brodalumab-induced changes in cytokine concentrations may affect CYP enzyme formation

Consider monitoring cyclosporine concentrations and consider cyclosporine dosage adjustment upon initiation or discontinuance of brodalumab

Midazolam

Increased midazolam exposure

Warfarin

Possible effect on warfarin metabolism; brodalumab-induced changes in cytokine concentrations may affect CYP enzyme formation

Consider monitoring therapeutic effect of warfarin and consider warfarin dosage adjustment upon initiation or discontinuance of brodalumab

Brodalumab Pharmacokinetics

Absorption

Bioavailability

Bioavailability is approximately 55% following sub-Q administration.

Peak serum concentrations achieved by approximately 3 days following a single 210-mg sub-Q dose.

Steady-state concentrations achieved by week 4 following sub-Q administration of brodalumab 210 mg every 2 weeks.

Exhibits nonlinear pharmacokinetics; exposure increases in more than dose-proportional manner over a sub-Q dose range of 140–350 mg.

Special Populations

Patients with higher body weight have lower trough concentrations.

Distribution

Extent

Not known whether distributed into human milk.

Elimination

Metabolism

Metabolic pathway not characterized.

Expected to be degraded into small peptides and amino acids via catabolic pathways in a similar manner as endogenous IgG.

Elimination is nonlinear; clearance increases with decreasing doses.

Special Populations

Pharmacokinetics not formally studied in renal or hepatic impairment.

Population analysis suggests age does not substantially affect clearance in adults with plaque psoriasis. Clearance appears to be similar in patients ≥65 years of age and younger adults.

Stability

Storage

Parenteral

Injection

2–8°C. Keep in original carton and protect from light. Do not freeze.

May store in original carton at 20–25°C for a maximum single period of 14 days, with protection from light and heat. Following storage at room temperature, do not return to refrigerator; discard if not used within 14 days.

Actions

  • Binds to IL-17RA and inhibits interaction with IL-17A, IL-17C, IL-17F, IL-17A/F heterodimer, and IL-25 (also known as IL-17E), thus blocking IL-17 cytokine-induced responses, including release of proinflammatory cytokines and chemokines.

  • Elevated levels of IL-17A, IL-17C, and IL-17F found in psoriatic lesions.

Advice to Patients

  • Provide all patients with a copy of the manufacturer's patient information (medication guide and instructions for use) with each prescription of the drug. Advise patient to read the medication guide prior to initiation of therapy and each time the prescription is refilled.

  • Advise patients and their caregivers that suicidal behavior and ideation (including completed suicides) have been reported in patients receiving brodalumab. Advise patients and their caregivers to monitor for the emergence of suicidality and to immediately seek medical attention if the patient experiences suicidal thoughts, new or worsening depression or anxiety, or other changes in mood or behavior.

  • Advise patients that brodalumab is available only through a restricted distribution program; instruct patients on the program requirements and how to obtain the drug. Advise patients to carry the wallet card that describes symptoms requiring immediate medical evaluation, to show this card to other treating clinicians, and to call the National Suicide Prevention Lifeline at 800-273-8255 if they experience suicidal thoughts.

  • Instruct patient and/or caregiver regarding proper storage, dosage, and administration of brodalumab, including the use of aseptic technique, and proper disposal of prefilled syringes if it is determined that the patient and/or caregiver is competent to safely administer the drug.

  • Inform patients that brodalumab may lower the ability of their immune system to fight infection. Advise patients to promptly inform clinician if any signs or symptoms of infection (e.g., fever, sweats, or chills; muscle aches; cough or shortness of breath; warm, red, or painful sores on the body; diarrhea or stomach pain; burning upon urination or increased urination) occur.

  • Advise patients to inform a clinician if they experience signs and symptoms of Crohn disease (e.g., abdominal pain, diarrhea, weight loss).

  • Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses (e.g., active infection, Crohn disease) or any history of tuberculosis, other infections, mood disorders, or suicidality.

  • Advise women to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Inform patients of other important precautionary information. (See Cautions.)

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.

Distribution of brodalumab is restricted. Contact manufacturer or consult the brodalumab website [Web] for specific availability information.

Brodalumab

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use

210 mg/1.5mL

Siliq (available as single-use prefilled syringes)

Bausch Health

AHFS DI Essentials™. © Copyright 2022, Selected Revisions March 31, 2022. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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