Tildrakizumab-asmn (Monograph)

Brand name: Ilumya
Drug class: Immunomodulatory Agents
Molecular formula: C₆₄₂₆H₉₉₁₈N₁₆₉₈O₂₀₀₀S₄₆
CAS number: 1326244-10-3

Medically reviewed by Drugs.com on Mar 10, 2024. Written by ASHP.

Introduction

Inhibitor of interleukin-23 (IL-23); a recombinant humanized IgG₁ kappa monoclonal antibody that binds specifically to the p19 subunit of IL-23.

Uses for Tildrakizumab-asmn

Plaque Psoriasis

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

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).

Tildrakizumab-asmn Dosage and Administration

General

Pretreatment Screening

Evaluate patients for tuberculosis prior to initiation of tildrakizumab therapy.

Administration

Sub-Q Administration

Manufacturer states tildrakizumab-asmn should only be administered by a clinician.

Available as single-use, prefilled syringes.

If previously refrigerated, allow prefilled syringe to sit at room temperature inside the closed carton for 30 minutes prior to injection. Do not remove the needle cap while the drug is warming to room temperature.

Do not shake the injection.

No need to remove air bubbles if present in syringe.

Administer by sub-Q injection into an accessible area with clear skin (e.g., upper arm, anterior thigh, lower abdomen); do not make abdominal injections within 2 inches of the navel. Do not make injections into areas where the skin is tender, bruised, red, or indurated. Do not inject into psoriatic lesions, scars, stretch marks, or blood vessels.

Dosage

Adults

Plaque Psoriasis

Sub-Q

100 mg at 0 and 4 weeks, then every 12 weeks.

If a dose is missed, administer the missed dose as soon as possible and resume dosing at the regularly scheduled interval.

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 Tildrakizumab-asmn

Contraindications

Serious hypersensitivity reaction to tildrakizumab or any ingredient in the formulation.

Warnings/Precautions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., angioedema, urticaria) reported. If a serious hypersensitivity reaction occurs, discontinue tildrakizumab immediately and initiate appropriate supportive treatment.

Infectious Complications

May increase risk of infection. In clinical trials in patients with plaque psoriasis, upper respiratory infections reported more frequently with tildrakizumab-asmn 100 mg than with placebo (14 versus 12%).

Do not initiate tildrakizumab in patients with any clinically important active infection until the infection resolves or is adequately treated. Consider risks and benefits before initiating therapy in patients with chronic infection or history of recurring infections.

If a clinically important or serious infection develops or does not respond to standard therapy, monitor the patient closely and consider discontinuing tildrakizumab until the infection resolves.

Evaluate patients for tuberculosis prior to initiation of tildrakizumab. Do not administer to patients with active tuberculosis. When indicated, initiate appropriate antimycobacterial regimen for treatment of latent tuberculosis prior to tildrakizumab therapy. Also consider antimycobacterial therapy prior to tildrakizumab therapy in individuals 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 tildrakizumab treatment.

Immunization

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

Avoid live vaccines during therapy.

Immunogenicity

Antibodies to tildrakizumab-asmn, including neutralizing antibodies, reported. Neutralizing antibodies associated with decreased drug concentrations and reduced efficacy.

Specific Populations

Pregnancy

Data regarding use in pregnant women are inadequate to establish risk of adverse developmental outcomes. Potential for fetal exposure since human IgG crosses the placenta.

No evidence of adverse embryofetal developmental effects in monkeys; when tildrakizumab administration continued until parturition, small increase in neonatal deaths observed; clinical relevance unknown.

Lactation

Not known whether tildrakizumab distributes into human milk, affects milk production, or affects breast-fed infants. Human IgG is present in breast milk; very low concentrations of the drug detected in breast milk in monkeys.

Because tildrakizumab is a large protein, absorption by a breast-fed infant is thought to be unlikely after the first few weeks postpartum since the drug will probably be destroyed in the infant's GI tract.

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 overall 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

Pharmacokinetic data in patients with hepatic impairment not available.

Renal Impairment

Pharmacokinetic data in patients with renal impairment not available.

Common Adverse Effects

Patients with psoriasis (≥1%): Upper respiratory infection, injection site reaction, diarrhea.

Drug Interactions

Vaccines

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

Specific Drugs

Drug	Interaction
Caffeine	No clinically important effect on AUC of caffeine (CYP1A2 substrate)
Dextromethorphan	AUC of dextromethorphan (CYP2D6 substrate) increased by 20%
Midazolam	No clinically important effect on AUC of midazolam (CYP3A4 substrate)
Omeprazole	No clinically important effect on AUC of omeprazole (CYP2C19 substrate)
Warfarin	No clinically important effect on AUC of warfarin (CYP2C9 substrate)

Tildrakizumab-asmn Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is 73–80% following sub-Q administration.

Peak concentration achieved by approximately day 6 following a single 200-mg sub-Q dose; steady-state concentrations attained by week 16 when administered at weeks 0 and 4 and every 12 weeks thereafter.

Pharmacokinetics are dose proportional over a sub-Q dose range of 50–200 mg.

Special Populations

Plasma concentrations are lower in patients with a higher body weight.

Distribution

Extent

Not known whether distributed into human milk. Distributed into milk in lactating monkeys.

Crossed the placenta in monkeys.

Elimination

Metabolism

Metabolic pathway not characterized. Expected to be degraded into small peptides and amino acids via catabolic pathways in similar manner as endogenous IgG.

Half-life

Approximately 23 days.

Special Populations

Age does not substantially alter pharmacokinetics.

Pharmacokinetics not formally studied in renal or hepatic impairment.

Stability

Storage

Parenteral

Injection

2–8°C; do not freeze. May store at 25°C for up to 30 days; do not store at temperature >25°C; do not return to refrigerator after storage at room temperature. Store in original carton to protect from light until use.

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 release of proinflammatory cytokines and chemokines.

Advice to Patients

Provide all patients with a copy of the manufacturer's patient information (medication guide) with each prescription of the drug.
Importance of advising patients of the potential benefits and risks of tildrakizumab.
Possible increased susceptibility to infections. Importance of promptly informing 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.
Importance of advising patients to seek immediate medical attention if they experience any symptoms of serious allergic reactions.
Importance of reviewing vaccination status with clinician and receiving all appropriate vaccinations prior to initiation of tildrakizumab.
Importance of informing 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.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing 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.