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Guselkumab

Class: Skin and Mucous Membrane Agents, Miscellaneous
Chemical Name: Immunoglobulin G1, anti-(human interleukin 23) (human CNTO 1959 heavy chain), disulfide with human CNTO 1959λ-chain, dimer
Molecular Formula: C6402H9864N1676O1994S42
CAS Number: 1350289-85-8
Brands: Tremfya ([Web])

Medically reviewed by Drugs.com on Apr 27, 2022. Written by ASHP.

Introduction

Inhibitor of interleukin-23 (IL-23), a proinflammatory cytokine; a recombinant human IgG1λ monoclonal antibody directed against the p19 subunit of IL-23.

Uses for Guselkumab

Plaque Psoriasis

Management of moderate to severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy.

Guidelines generally support use of IL-23 inhibitors as monotherapy for moderate to severe 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).

Psoriatic Arthritis

Management of active psoriatic arthritis in adults; may be used alone or in combination with a conventional disease-modifying antirheumatic drug (DMARD; e.g., methotrexate).

Disease-modifying treatments for psoriatic arthritis include oral small molecules (e.g., methotrexate, sulfasalazine, cyclosporine, leflunomide, apremilast), biologic DMARDs (e.g., TNF blocking agents, secukinumab, ixekizumab, ustekinumab, brodalumab, abatacept), and/or targeted synthetic DMARDs (e.g., tofacitinib).

Guidelines from the American College of Rheumatology and the National Psoriasis Foundation for management of psoriatic arthritis were last updated in 2018. Guselkumab is not included in these guidelines; however, current evidence suggests that the drug may provide an additional therapeutic option.

Recommendations for use and selection of disease-modifying therapies in psoriatic arthritis vary based on the presence of certain disease characteristics (e.g., psoriatic spondylitis/axial disease, enthesitis) and comorbidities (e.g., inflammatory bowel disease, diabetes).

Guselkumab Dosage and Administration

General

Pretreatment Screening

  • Evaluate for tuberculosis infection prior to initiation of guselkumab; start antimycobacterial therapy if indicated.

  • Administer all age-appropriate vaccines prior to starting guselkumab therapy.

Patient Monitoring

  • Monitor closely for signs or symptoms of infection or active tuberculosis during and after treatment with guselkumab.

Other General Considerations

  • Guselkumab may be used alone or in combination with conventional DMARDs for the treatment of psoriatic arthritis.

Administration

Administer by sub-Q injection; IV or IM use not recommended.

Sub-Q Administration

Available as single-dose prefilled syringes and single-dose prefilled autoinjectors.

Administer by sub-Q injection into the thigh, lower abdomen, or upper arm; do not administer abdominal injections within 2 inches of the umbilicus. Use thigh (the preferred site) or abdomen for self-administration; upper arm may be used if administered by a caregiver or clinician. Avoid injections into areas where the skin is tender, bruised, red, hard, thick, or scaly. Do not inject into psoriatic lesions.

Allow prefilled syringe or autoinjector to sit at room temperature inside the carton for at least 30 minutes prior to injection without removing the needle cap; do not warm the drug in any other way (e.g., microwave, hot water). Do not shake prefilled syringe or autoinjector.

Intended for use under the supervision of a clinician, but may be self-administered if clinician determines the patient and/or caregiver is competent to safely administer the drug after appropriate training.

Dosage

Adults

Plaque Psoriasis
Sub-Q

100 mg at weeks 0 and 4, followed by 100 mg every 8 weeks.

Psoriatic Arthritis
Sub-Q

100 mg at weeks 0 and 4, followed by 100 mg every 8 weeks.

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations.

Renal Impairment

Manufacturer makes no specific dosage recommendations.

Geriatric Patients

Dosage adjustment based on age not necessary.

Increased Body Weight

Dosage adjustment for body weight is not necessary.

Cautions for Guselkumab

Contraindications

  • Known hypersensitivity to guselkumab or any ingredient in the formulation.

Warnings/Precautions

Hypersensitivity Reactions

Anaphylaxis reported. If an anaphylactic or other serious allergic reaction occurs, discontinue guselkumab immediately and initiate appropriate supportive treatment.

Infectious Complications.

Possible increased risk of infections. Bacterial, fungal, and viral infections, including gastroenteritis, upper respiratory tract infections, tinea infections, and herpes simplex infections, reported.

Do not use in patients with clinically important active infections. Consider risks and benefits before initiating therapy in patients with chronic infection or history of recurrent infection.

If a serious infection occurs or does not respond to standard therapy, discontinue guselkumab and closely monitor patient until infection resolves.

Evaluate all patients for active or latent tuberculosis prior to initiation of guselkumab therapy. Do not use in patients with active tuberculosis infection; when indicated, initiate appropriate antimycobacterial regimen for treatment of latent tuberculosis infection prior to guselkumab therapy. Also consider antimycobacterial therapy prior to initiation of guselkumab in patients with a history of latent or active tuberculosis in whom an adequate course of antimycobacterial treatment for these indications cannot be confirmed. Closely monitor for signs and symptoms of active tuberculosis during and after treatment.

Immunization

Consider administering all age-appropriate vaccines recommended by current immunization guidelines before initiating guselkumab.

Avoid live vaccines during therapy.

Immunogenicity

Formation of anti-guselkumab antibodies, including neutralizing antibodies, reported; such antibodies were associated with lower trough concentrations of the drug, but generally not associated with loss of efficacy or injection site reactions.

Specific Populations

Pregnancy

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

Pregnancy registry at 1-877-311-8972.

Lactation

Not known whether guselkumab distributes into human milk, affects human milk production, or affects breast-fed infants.

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 and efficacy relative to younger adults; 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 upper respiratory tract infection, headache, injection site reactions, arthralgia, bronchitis, diarrhea, gastroenteritis, tinea infections, herpes simplex infections.

Interactions for Guselkumab

Drugs Metabolized by Hepatic Microsomal Enzymes

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

Interactions unlikely with substrates of CYP1A2, 2C9, 2C19, or 3A4.

Interaction potential of CYP2D6 substrates cannot be ruled out by available data.

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

Vaccines

Avoid live vaccines. No data available regarding response to live or inactivated vaccines in patients receiving guselkumab.

Specific Drugs

Drug

Interaction

Comments

Caffeine

Possible effect on caffeine metabolism; because increased levels of cytokines during chronic inflammation may alter formation of CYP isoenzymes, guselkumab could normalize enzyme formation

Limited data suggest no substantial effect on caffeine AUC

Conventional DMARDs (e.g., methotrexate)

No effect on guselkumab clearance

Dextromethorphan

Possible effect on dextromethorphan metabolism; because increased levels of cytokines during chronic inflammation may alter formation of CYP isoenzymes, guselkumab could normalize enzyme formation

Limited data cannot rule out interaction potential

Midazolam

Possible effect on midazolam metabolism; because increased levels of cytokines during chronic inflammation may alter formation of CYP isoenzymes, guselkumab could normalize enzyme formation

Limited data suggest no substantial effect on midazolam AUC

NSAIAs (aspirin, ibuprofen)

Aspirin, ibuprofen: No effect on guselkumab clearance

Omeprazole

Possible effect on omeprazole metabolism; because increased levels of cytokines during chronic inflammation may alter formation of CYP isoenzymes, guselkumab could normalize enzyme formation

Limited data suggest no substantial effect on omeprazole AUC

Oral corticosteroids

No effect on guselkumab clearance

Warfarin

Possible effect on warfarin metabolism; because increased levels of cytokines during chronic inflammation may alter formation of CYP isoenzymes, guselkumab could normalize enzyme formation

Limited data suggest no substantial effect on warfarin AUC

Consider monitoring therapeutic effect of warfarin and consider warfarin dosage adjustment as needed upon initiation of guselkumab

Guselkumab Pharmacokinetics

Absorption

Bioavailability

Bioavailability is approximately 49% following sub-Q administration.

Peak serum concentrations achieved by approximately 5.5 days following a single 100-mg sub-Q dose.

Pharmacokinetics are dose proportional over a sub-Q dose range of 10–300 mg.

Distribution

Extent

Not known whether distributed into human milk.

Special Populations

Volume of distribution increases with increasing body weight.

Elimination

Metabolism

Metabolic pathway not characterized.

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

Half-life

15–18 days.

Special Populations

Pharmacokinetics not formally studied in renal or hepatic impairment.

Clearance increases with increasing body weight.

Age ≥65 years does not substantially alter clearance.

Stability

Storage

Parenteral

Injection

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

Actions

  • Binds with specificity to the p19 subunit of IL-23, a naturally occurring cytokine that stimulates production of proinflammatory cytokines, including interleukin-17 (IL-17) and interleukin-22 (IL-22). IL-17 and IL-22 contribute to chronic inflammation in patients with psoriasis.

  • Disrupts IL-23-mediated signaling and inhibits the release of proinflammatory cytokines and chemokines.

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. Instruct patients to read the medication guide prior to initiation of therapy and each time the prescription is refilled.

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

  • Advise patients to discontinue guselkumab and seek immediate medical attention if they experience symptoms of a serious allergic reaction (e.g., feeling of faintness; swelling of eyelids, face, lips, mouth, tongue, or throat; dyspnea or throat tightness; chest tightness; rash).

  • Possible increased susceptibility to infections. Instruct patients to promptly inform a clinician if any signs or symptoms of infection (e.g., fever, sweats, or chills; muscle aches; cough, shortness of breath, or blood in the phlegm; weight loss; warm, red, or painful sores on the body; diarrhea or stomach pain; burning upon urination or increased urination) occur.

  • Inform patients of the importance of reviewing vaccination status with clinician and receiving all appropriate vaccinations prior to initiation of guselkumab.

  • Inform clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., active infection) or any history of tuberculosis or other infections.

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

  • Advise 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.

Guselkumab

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use

100 mg/mL

Tremfya (available as single-dose prefilled syringes and single-dose patient-controlled autoinjectors)

Janssen Biotech

AHFS DI Essentials™. © Copyright 2022, Selected Revisions April 27, 2022. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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