Guselkumab

Guselkumab
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: Sonya Gelfand

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Black Box Warning

Warning Title See full prescribing information for complete Boxed Warning. Condition Name: (Content)

Overview

Guselkumab 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

• (Dosage)

Condition 2

• Developed by: (Organisation)

• Class of Recommendation: (Class) (Link)

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

• Dosing Information/Recommendation

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Non–Guideline-Supported Use

Condition 1

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Condition 2

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Condition 3

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Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition 1

• Dosing Information

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Condition 2

• Dosing Information

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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)

• Dosing Information/Recommendation

• (Dosage)

Non–Guideline-Supported Use

Condition 1

• Dosing Information

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Condition 2

• Dosing Information

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Condition 3

• Dosing Information

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Contraindications

CONTRAINDICATIONS

Warnings

Warning Title See full prescribing information for complete Boxed Warning. Condition Name: (Content)

Conidition 1

(Description)

Conidition 2

(Description)

Conidition 3

(Description)

Adverse Reactions

Clinical Trials Experience

Central Nervous System

(list/description of adverse reactions)

Cardiovascular

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Respiratory

(list/description of adverse reactions)

Gastrointestinal

(list/description of adverse reactions)

Hypersensitive Reactions

(list/description of adverse reactions)

Miscellaneous

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Condition 2

Central Nervous System

(list/description of adverse reactions)

Cardiovascular

(list/description of adverse reactions)

Respiratory

(list/description of adverse reactions)

Gastrointestinal

(list/description of adverse reactions)

Hypersensitive Reactions

(list/description of adverse reactions)

Miscellaneous

(list/description of adverse reactions)

Postmarketing Experience

(Description)

Drug Interactions

• Drug 1
• Drug 2
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• Drug 5

Drug 1

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Drug 2

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Drug 3

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Drug 4

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Drug 5

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Use in Specific Populations

Pregnancy

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

Labor and Delivery

(Description)

Nursing Mothers

(Description)g

Pediatric Use

(Description)

Geriatic Use

(Description)

Gender

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Race

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Renal Impairment

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Hepatic Impairment

(Description)

Females of Reproductive Potential and Males

(Description)

Immunocompromised Patients

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Others

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Administration and Monitoring

Administration

(Oral/Intravenous/etc)

Monitoring

Condition 1

(Description regarding monitoring, from Warnings section)

Condition 2

(Description regarding monitoring, from Warnings section)

Condition 3

(Description regarding monitoring, from Warnings section)

IV Compatibility

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

Overdosage

Acute Overdose

Signs and Symptoms

(Description)

Management

(Description)

Chronic Overdose

Signs and Symptoms

(Description)

Management

(Description)

Pharmacology

Guselkumab
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Mechanism of Action

• Guselkumab is a human monoclonal IgG1λ antibody that selectively binds to the p19 subunit of interleukin 23 (IL-23) and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Guselkumab inhibits the release of proinflammatory cytokines and chemokines.

Structure

(Description with picture)

Pharmacodynamics

• Guselkumab reduced serum levels of IL-17A, IL-17F and IL-22 relative to pretreatment levels in evaluated subjects with psoriasis based on exploratory analysis of the pharmacodynamic markers. The relationship between these pharmacodynamic markers and the mechanism(s) by which guselkumab exerts its clinical effects is not fully understood.

Pharmacokinetics

• Guselkumab exhibited linear pharmacokinetics in healthy subjects and subjects with psoriasis following subcutaneous injections. In subjects with psoriasis, following subcutaneous administration of 100 mg of guselkumab at Weeks 0 and 4, and every 8 weeks thereafter, mean steady-state trough serum guselkumab concentration was approximately 1.2 mcg/mL.

Absorption

• Following a single 100 mg subcutaneous injection in healthy subjects, guselkumab reached a mean (± SD) maximum serum concentration of 8.09 ± 3.68 mcg/mL by approximately 5.5 days post dose. The absolute bioavailability of guselkumab following a single 100 mg subcutaneous injection was estimated to be approximately 49% in healthy subjects.

Distribution

• In subjects with plaque psoriasis, apparent volume of distribution was 13.5 L.

Elimination

• Apparent clearance in subjects with plaque psoriasis was 0.516 L/day. Mean half-life of guselkumab was approximately 15 to 18 days in subjects with plaque psoriasis across studies.

Metabolism

• The exact pathway through which guselkumab is metabolized has not been characterized. As a human IgG monoclonal antibody, guselkumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.

Specific Populations

• No apparent differences in clearance were observed in subjects ≥ 65 years of age compared to subjects < 65 years of age, suggesting no dose adjustment is needed for elderly patients. Clearance and volume of distribution of guselkumab increases as body weight increases, however, observed clinical trial data indicate that dose adjustment for body weight is not warranted. No specific studies have been conducted to determine the effect of renal or hepatic impairment on the pharmacokinetics of guselkumab.

Drug Interactions

• Population pharmacokinetic analyses indicated that concomitant use of ibuprofen, acetylsalicylic acid, or acetaminophen did not affect the clearance of guselkumab.

Cytochrome P450 Substrates

• The effects of guselkumab on the pharmacokinetics of midazolam (metabolized by CYP3A4), warfarin (metabolized by CYP2C9), omeprazole (metabolized by CYP2C19), dextromethorphan (metabolized by CYP2D6), and caffeine (metabolized by CYP1A2) were evaluated in an exploratory study with 6 to 12 evaluable subjects with moderate-to-severe plaque psoriasis. Changes in AUC_inf of midazolam, S-warfarin, omeprazole, and caffeine after a single dose of guselkumab were not clinically relevant. For dextromethorphan, changes in AUC_inf after guselkumab were not clinically relevant in 9 out of 10 subjects; however, a 2.9-fold change in AUC_inf was observed in one individual.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

• Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of guselkumab.
• No effects on fertility parameters were observed after male guinea pigs were subcutaneously administered guselkumab at a dose of 25 mg/kg twice weekly (15 times the MRHD based on a mg/kg comparison).
• No effects on fertility parameters were observed after female guinea pigs were subcutaneously administered guselkumab at doses up to 100 mg/kg twice-weekly (60 times the MRHD based on a mg/kg comparison).

Clinical Studies

• Three multicenter, randomized, double-blind trials (VOYAGE 1 [NCT02207231], VOYAGE 2 [NCT02207244], and NAVIGATE [NCT02203032]) enrolled subjects 18 years of age and older with moderate-to-severe plaque psoriasis who were eligible for systemic therapy or phototherapy. Subjects had an Investigator's Global Assessment (IGA) score of ≥3 ("moderate") on a 5-point scale of overall disease severity, a Psoriasis Area and Severity Index (PASI) score ≥12, and a minimum affected body surface area (BSA) of 10%. Subjects with guttate, erythrodermic, or pustular psoriasis were excluded.

VOYAGE 1 and VOYAGE 2

• In VOYAGE 1 and VOYAGE 2, 1443 subjects were randomized to either guselkumab (100 mg at Weeks 0 and 4 and every 8 weeks thereafter), placebo or U.S. licensed adalimumab (80 mg at Week 0 and 40 mg at Week 1, followed by 40 mg every other week thereafter).
• Both trials assessed the responses at Week 16 compared to placebo for the two co-primary endpoints:

• the proportion of subjects who achieved an IGA score of 0 ("cleared") or 1 ("minimal");
• the proportion of subjects who achieved at least a 90% reduction from baseline in the PASI composite score (PASI 90).

• Comparisons between guselkumab and U.S. licensed adalimumab were secondary endpoints at the following time points:

• at Week 16 (VOYAGE 1 and VOYAGE 2), the proportions of subjects who achieved an IGA score of 0 or 1, a PASI 90, and a PASI 75 response;
• at Week 24 (VOYAGE 1 and VOYAGE 2), and at Week 48 (VOYAGE 1), the proportions of subjects achieving an IGA score of 0, an IGA score of 0 or 1, and a PASI 90 response.

• Other evaluated outcomes included improvement in psoriasis symptoms assessed on the Psoriasis Symptoms and Signs Diary (PSSD) and improvements in psoriasis of the scalp at Week 16.
• In both trials, subjects were predominantly men and white, with a mean age of 44 years and a mean weight of 90 kg. At baseline, subjects had a median affected BSA of approximately 21%, a median PASI score of 19, and 18% had a history of psoriatic arthritis. Approximately 24% of subjects had an IGA score of severe. In both trials, 23% had received prior biologic systemic therapy.

Clinical Response

• Table 2 presents the efficacy results at Week 16 in VOYAGE 1 and VOYAGE 2.

This image is provided by the National Library of Medicine.

• Table 3 presents the results of an analysis of all the North America sites (i.e., U.S. and Canada), demonstrating superiority of guselkumab to U.S. licensed adalimumab.

This image is provided by the National Library of Medicine.

• An improvement was seen in psoriasis involving the scalp in subjects randomized to guselkumab compared to placebo at Week 16.
• Examination of age, gender, race, body weight, and previous treatment with systemic or biologic agents did not identify differences in response to guselkumab among these subgroups.

Maintenance and Durability of Response

• To evaluate maintenance and durability of response (VOYAGE 2), subjects randomized to guselkumab at Week 0 and who were PASI 90 responders at Week 28 were re-randomized to either continue treatment with guselkumab every 8 weeks or be withdrawn from therapy (i.e. receive placebo).
• At Week 48, 89% of subjects who continued on guselkumab maintained PASI 90 compared to 37% of subjects who were re-randomized to placebo and withdrawn from guselkumab. For responders at Week 28 who were re-randomized to placebo and withdrawn from guselkumab, the median time to loss of PASI 90 was approximately 15 weeks.

Patient Reported Outcomes

• Greater improvements in symptoms of psoriasis (itch, pain, stinging, burning and skin tightness) at Week 16 in guselkumab compared to placebo were observed in both trials based on the Psoriasis Symptoms and Signs Diary (PSSD). Greater proportions of subjects on guselkumab compared to U.S. licensed adalimumab achieved a PSSD symptom score of 0 (symptom-free) at Week 24 in both trials.

NAVIGATE

• NAVIGATE evaluated the efficacy of 24 weeks of treatment with guselkumab in subjects (N=268) who had not achieved an adequate response, defined as IGA ≥2 at Week 16 after initial treatment with U.S. licensed ustekinumab (dosed 45 mg or 90 mg according to the subject's baseline weight at Week 0 and Week 4). These subjects were randomized to either continue with U.S. licensed ustekinumab treatment every 12 weeks or switch to guselkumab 100 mg at Weeks 16, 20, and every 8 weeks thereafter. Baseline characteristics for randomized subjects were similar to those observed in VOYAGE 1 and VOYAGE 2.
• In subjects with an inadequate response (IGA ≥2 at Week 16 to U.S. licensed ustekinumab), greater proportions of subjects on guselkumab compared to U.S. licensed ustekinumab achieved an IGA score of 0 or 1 with a ≥2 grade improvement at Week 28 (31% vs 14%, respectively; 12 weeks after randomization).

How Supplied

• Guselkumab Injection is a clear and colorless to light yellow solution that may contain small translucent particles. Guselkumab is supplied as a single-dose 100 mg/mL prefilled syringe:

• NDC: 57894-640-01

Storage

• Guselkumab is sterile and preservative-free. Discard any unused portion.
• Store in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF).
• Store in original carton until time of use.
• Protect from light until use.
• Do not freeze.
• Do not shake.
• Keep out of reach of children.

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

• Advise the patient and/or caregiver to read the FDA-approved patient labeling before starting guselkumab therapy, and each time the prescription is renewed, as there may be new information they need to know.

Infections

• Instruct patients of the importance of communicating any history of infections to the healthcare provider and contacting their healthcare provider if they develop any symptoms of an infection

Instruction on Injection Technique

• Instruct the patient or caregivers to perform the first self-injection under the supervision and guidance of a qualified healthcare professional for proper training in subcutaneous injection technique. Instruct patients who are self-administering to inject the full dose of guselkumab.
• Instruct patients or caregivers in the technique of proper needle and syringe disposal. Needles and syringes should be disposed of in a puncture-resistant container. Advise patients and caregivers not to reuse needles or syringes.
• Remind patients if they forget to take their dose of guselkumab to inject their dose as soon as they remember. They should then take their next dose at the appropriate scheduled time.

This image is provided by the National Library of Medicine.

Precautions with Alcohol

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

Brand Names

• Tremfya

Look-Alike Drug Names

There is limited information regarding Guselkumab 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.