Brodalumab

Brodalumab
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yashasvi Aryaputra[2];

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Black Box 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 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. Because of the observed suicidal behavior in subjects treated with SILIQ, SILIQ is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the SILIQ REMS Program.

Overview

Brodalumab is a Acetylcholine release inhibitor, Adrenergic receptor agonist that is FDA approved for the (type of indication of drug) of a list of indications, separated by commas.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include a list of adverse reactions, separated by commas..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Condition 1

• Dosing Information

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Condition 2

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Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition 1

• Developed by: (Organisation)

• Class of Recommendation: (Class) (Link)

• Strength of Evidence: (Category A/B/C) (Link)

• Dosing Information/Recommendation

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Condition 2

• Developed by: (Organisation)

• Class of Recommendation: (Class) (Link)

• Strength of Evidence: (Category A/B/C) (Link)

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Non–Guideline-Supported Use

Condition 1

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Condition 3

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Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition 1

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Condition 2

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Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition 1

• Developed by: (Organisation)

• Class of Recommendation: (Class) (Link)

• Strength of Evidence: (Category A/B/C) (Link)

• Dosing Information/Recommendation

• (Dosage)

Condition 2

• Developed by: (Organisation)

• Class of Recommendation: (Class) (Link)

• Strength of Evidence: (Category A/B/C) (Link)

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Non–Guideline-Supported Use

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Condition 2

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Condition 3

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Contraindications

CONTRAINDICATIONS

Warnings

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 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. Because of the observed suicidal behavior in subjects treated with SILIQ, SILIQ is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the SILIQ REMS Program.

Conidition 1

(Description)

Conidition 2

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Conidition 3

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Adverse Reactions

Clinical Trials Experience

Central Nervous System

(list/description of adverse reactions)

Cardiovascular

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Respiratory

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Gastrointestinal

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Hypersensitive Reactions

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Miscellaneous

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Condition 2

Central Nervous System

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Cardiovascular

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Respiratory

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Gastrointestinal

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Hypersensitive Reactions

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Miscellaneous

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Postmarketing Experience

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Drug Interactions

• Drug 1
• Drug 2
• Drug 3
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• Drug 5

Drug 1

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Drug 2

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Drug 3

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Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

Risk Summary

• There are no human data on SILIQ use in pregnant women to inform a drug associated risk. Human IgG antibodies are known to cross the placental barrier; therefore, SILIQ 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).

• 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.

Data (Animal)

• 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).

Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Brodalumab in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Brodalumab during labor and delivery.

Nursing Mothers

Risk Summary

• 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 SILIQ and any potential adverse effects on the breastfed infant from SILIQ or from the underlying maternal condition.

Pediatric Use

• The safety and effectiveness of SILIQ have not been evaluated in pediatric patients.

Geriatic Use

• Of the 3066 plaque psoriasis subjects initially randomized to SILIQ 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.

Gender

There is no FDA guidance on the use of Brodalumab with respect to specific gender populations.

Race

There is no FDA guidance on the use of Brodalumab with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Brodalumab in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Brodalumab in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Brodalumab in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Brodalumab in patients who are immunocompromised.

Administration and Monitoring

Administration

Tuberculosis Assessment Prior to Initiation of SILIQ

• Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with SILIQ.

Important Administration Instructions

• Administer SILIQ subcutaneously. Each prefilled syringe is for single-dose only.

• Instruct patients to review the Medication Guide before use. 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.

Preparation of SILIQ Prefilled Syringe

• 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.

• 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.

• 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.

Monitoring

• Reductions in the fraction of body surface area affected, the nature and severity of psoriatic induration, erythema, and scaling are indicative of efficacy.

• TB; prior to and during therapy.

• Manifestations of suicidal ideation and behavior, new onset or worsening depression, anxiety, or other mood changes.

IV Compatibility

There is limited information regarding the compatibility of Brodalumab and IV administrations.

Overdosage

There is limited information regarding Brodalumab overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

Mechanism of Action

• Brodalumab is a human monoclonal IgG2 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.

Structure

There is limited information regarding Brodalumab Structure in the drug label.

Pharmacodynamics

• Elevated levels of IL-17A, IL-17C and IL-17F are found in psoriatic plaques. Serum IL-17A levels, measured at Weeks 12, 24, and 48 of SILIQ 210 mg every 2 weeks of treatment, were higher than the baseline levels in subjects with moderate to severe plaque psoriasis. The relationship between the pharmacodynamic activity and the mechanism(s) by which brodalumab exerts its clinical effects is unknown.

Pharmacokinetics

Absorption

• Following a single subcutaneous dose of 210 mg in subjects with plaque psoriasis, brodalumab reached peak mean (±SD) serum concentration (Cmax) of 13.4±7.3 mcg/mL by approximately 3 days post dose. The mean (±SD) area-under-the-concentration-time curve (AUC) of brodalumab was 111±64 mcg•day/mL.

• Following multiple subcutaneous doses of 210 mg every 2 weeks, steady-state was achieved by Week 4. The mean (±SD) Cmax was 20.6±14.6 mcg/mL and the mean (±SD) AUC over the two week dosing interval was 227±167 mcg•day/mL.

• Following subcutaneous administration, brodalumab bioavailability was approximately 55%.

Distribution

• Following a single subcutaneous administration of brodalumab 210 mg in subjects with plaque psoriasis, the mean (±SD) apparent volume of distribution (Vz/F) of brodalumab was 8.9±9.4 L.

Elimination

• The metabolic pathway of brodalumab has not been characterized. As a human monoclonal IgG2 antibody, brodalumab is expected to be degraded into small peptides and amino acids via catabolic pathways in a manner similar to endogenous IgG.

• Following a single subcutaneous administration of brodalumab 210 mg in subjects with plaque psoriasis, the mean (±SD) apparent total clearance (CL/F) was 3.0±3.5 L/day. The clearance of brodalumab increased with decreasing doses due to nonlinear elimination.

Dose Linearity

• Brodalumab exhibited non-linear pharmacokinetics with exposures that increased greater than dose-proportionally over a dose range from 140 mg (approximately 0.67 times the recommended dose) to 350 mg (approximately 1.67 times the recommended dose) following subcutaneous administrations in subjects with plaque psoriasis.

Weight

• Brodalumab trough concentrations were lower in subjects with higher body weight.

Specific Populations

Hepatic or Renal Impairment

• No trials were conducted to assess the effect of hepatic or renal impairment on the pharmacokinetics of brodalumab.

Age: Geriatric Population

• Population pharmacokinetic analysis indicated that age did not significantly influence the clearance of brodalumab in subjects with plaque psoriasis. Subjects who were 65 years or older had a similar brodalumab clearance as compared to subjects less than 65 years old.

Drug Interaction Studies

• In subjects with plaque psoriasis, one week following a single subcutaneous administration of 210 mg brodalumab, the exposure of midazolam (CYP3A4 substrate) was increased by 24%.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

• Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of SILIQ. The published literature is mixed on the potential effects on malignancy risk due to the inhibition of the IL-17RA, the pharmacological action of SILIQ. Some published literature suggests that IL-17A directly promotes cancer cell invasion, which suggests a potential beneficial effect of SILIQ. However, other reports indicate IL-17A promotes T-cell mediated tumor rejection, which suggests a potential adverse effect by SILIQ. However, inhibition of the IL-17RA with SILIQ has not been studied in these models. Therefore, the relevance of experimental findings in these models for malignancy risk in humans is unknown.

• In cynomolgus monkeys, there were no effects on fertility parameters such as changes in reproductive organs or sperm analysis following subcutaneous administration of brodalumab at dose levels up to 90 mg/kg/week for six months (26 times the MRHD on a mg/kg basis). The monkeys were not mated in this study to evaluate effects on fertility.

Clinical Studies

• Three multicenter, randomized, double-blind, controlled trials (Trials 1, 2, and 3) enrolled a total of 4373 subjects 18 years of age and older with at least a 6-month history of moderate to severe plaque psoriasis, defined as having a minimum affected body surface area (BSA) of 10%, a Psoriasis Area and Severity Index (PASI) score ≥ 12, a static Physician’s Global Assessment (sPGA) score ≥3 in the overall assessment (plaque thickness/induration, erythema, and scaling) of psoriasis on a severity scale of 0 to 5, and who were candidates for systemic therapy or phototherapy. In all three trials, subjects were randomized to subcutaneous treatment with placebo or SILIQ 210 mg at Weeks 0, 1, and 2, followed by treatments every 2 weeks [Q2W] through Week 12. In the two active comparator trials (Trials 2 and 3), subjects randomized to ustekinumab received a 45 mg dose if their weight was less than or equal to 100 kg and a 90 mg dose if their weight was greater than 100 kg at Weeks 0, 4, and 16, followed by the same dose every 12 weeks.

• All three trials assessed the change from baseline to Week 12 compared to placebo in the two co-primary endpoints: 1) PASI 75, the proportion of subjects who achieved at least a 75% reduction in the PASI composite score that takes into consideration both the percentage of body surface area affected and the nature and severity of psoriatic changes (induration, erythema, and scaling) within the affected region, and 2) the proportion of subjects with an sPGA of 0 (clear) or 1 (almost clear), and at least a 2-point improvement from baseline. In Trials 2 and 3, comparisons were also made to ustekinumab for the primary endpoint of the proportion of subjects who achieved a reduction in PASI score of 100% (PASI 100) from baseline at Week 12.

• Other evaluated outcomes included the proportion of subjects who achieved an sPGA of 0 (clear) at Week 12, and the proportion of subjects who achieved a Psoriasis Symptom Inventory (PSI) score of 0 (not at all) or 1 (mild) on every item (itch, redness, scaling, burning, stinging, cracking, flaking, and pain) at Week 12. Baseline demographics and disease characteristics were generally consistent across all treatment groups in all three trials. Subjects were predominantly men (69%) and white (91%), with a mean age of 45 years. The mean baseline body weight was 90.5 kg and 28% of subjects had body weight greater than 100 kg. The baseline PASI score ranged from 9.4 to 72 (median: 17.4) and the baseline affected BSA ranged from 10 to 97% (median: 21%). Baseline sPGA scores ranged from “3 (moderate)” (58%) to “5 (very severe)” (5%).

• Approximately 21% of subjects had a history of psoriatic arthritis. Approximately 30% of subjects had previously received a biologic therapy and 12% of subjects had failed previous biologic therapy.

Clinical Response at Week 12

• The results of Trials 1, 2, and 3 are presented in TABLE 2.

IMAGE GOES HERE

• Examination of age, gender, race, use of prior systemic or phototherapy, and use of prior biologics did not identify differences in response to SILIQ among these subgroups.

• At Week 12, compared to subjects in the placebo group, a greater proportion of subjects in SILIQ 210 mg Q2W group achieved a Psoriasis Symptom Inventory (PSI) score of 0 (not at all) or 1 (mild) on every item (itch, redness, scaling, burning, stinging, cracking, flaking, pain).

Maintenance of Effect

• In Trial 1, subjects randomized to receive SILIQ and who were responders at Week 12 (i.e., sPGA of 0 or 1) were re-randomized to receive either placebo or SILIQ. Among responders at Week 12, 83% (69/83) of subjects re-randomized to continued treatment with SILIQ 210 mg Q2W maintained this response (sPGA of 0 or 1) at Week 52 compared to none (0/84) who were re-randomized to placebo and withdrawn from SILIQ. In addition, 87% (72/83) of subjects re-randomized to continued treatment with SILIQ 210 mg Q2W achieved PASI 75 response at Week 52 compared to none (0/84) who were re-randomized to placebo and withdrawn from SILIQ.

• Trials 2 and 3 included a re-randomized phase during which subjects originally randomized to receive SILIQ during the first 12 weeks were re-randomized to one of four SILIQ regimens at the Week 12 visit and placebo subjects were crossed over to receive SILIQ 210 mg Q2W. Subjects receiving ustekinumab continued the same treatment until crossed over at Week 52 to SILIQ 210 mg Q2W. For sPGA 0 or 1 responders at Week 12, the percentage of subjects who maintained this response at Week 52 was 79% for subjects treated with SILIQ 210 mg Q2W. For PASI 100 responders at Week 12, 72% of the subjects who continued on SILIQ 210 mg Q2W maintained the response at Week 52.

How Supplied

• SILIQ (brodalumab) Injection is available in a single-dose prefilled syringe containing a sterile, preservative-free clear to slightly opalescent, colorless to slightly yellow solution that may contain a few translucent to white, amorphous particles.

• NDC 0187-0004-02: Carton of two 210 mg/1.5 mL single-dose prefilled syringes.

Storage

• Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light and physical damage during storage.

• When necessary, prefilled syringes can be stored at room temperature up to a maximum of 77°F (25°C) in the original carton for a maximum single period of 14 days with protection from light and sources of heat. Once the prefilled syringe has reached room temperature, do not place back into the refrigerator. Discard after 14 days at room temperature.

• Do not freeze.

• Do not shake.

Images

Drug Images

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Package and Label Display Panel

This image is provided by the National Library of Medicine.

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Patient Counseling Information

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.

• 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.

SILIQ REMS Program

• Because of the observed suicidal thoughts and behavior in subjects treated with SILIQ, SILIQ is available only through a restricted program called the SILIQ REMS Program. Inform the patient of the following:

• Patients must enroll in the program.

• 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 SILIQ Patient Wallet Card to other treating healthcare providers.

• SILIQ 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.

Infections

• Inform patients that SILIQ 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.

Crohn’s Disease

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

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.

• Instruct patients who are self-administering to inject the full dose of SILIQ.

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

Precautions with Alcohol

Alcohol-Brodalumab interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

• Siliq

Look-Alike Drug Names

There is limited information regarding Brodalumab Look-Alike Drug Names in the drug label.

Drug Shortage Status

Drug Shortage

Price

References

The contents of this FDA label are provided by the National Library of Medicine.