spesolimab (Rx)

1-10%

Asthenia and fatigue (9%)

Nausea and vomiting (9%)

Headache (9%)

Pruritus and prurigo (6%)

Infusion-site hematoma and bruising (6%)

Urinary tract infection (6%)

Bacteremia (3%)

Bacteriuria (3%)

Cellulitis (3%)

Herpes dermatitis and oral herpes (3%)

Upper respiratory tract infection (3%)

Dyspnea (3%)

Eye edema (3%)

Urticaria (3%)

Frequency Not Defined

Drug reaction with eosinophilia and systemic symptoms (DRESS)

Injection site erythema, swelling, pain, induration, and warmth

Contraindications

Hypersensitivity to spesolimab or excipients

Cautions

Infections

• May increase risk of infections
• Consider potential risk in patients with chronic infection or history of recurrent infection
• Not recommended in patients with any clinically important active infection until the infection resolves or is adequately treated
• Instruct patients to seek medical advice if signs or symptoms of infection occurs after spesolimab treatment

Risk of tuberculosis (TB)

• Evaluate patients for TB infection before initiating
• Do not administer with active TB infection
• Consider initiating anti-TB therapy before starting spesolimab in patients with latent TB or history of TB in whom an adequate course of treatment cannot be confirmed
• Monitor for signs and symptoms of active TB during and after treatment

Hypersensitivity and infusion-related reactions

• Hypersensitivity reactions may include immediate reactions (eg, anaphylaxis) and delayed reactions (eg, drug reaction with eosinophilia and systemic symptoms [DRESS])
• DRESS reported during clinical trials
• Discontinue immediately if anaphylaxis or other serious hypersensitivity occurs; immediately initiate appropriate treatment
• If mode or moderate infusion-related reaction occurs, stop infusion and consider appropriate medical therapy (eg, systemic antihistamines and/or corticosteroids)
• Upon resolution, may restart infusion at slower rate and gradually increase to complete infusion

Drug interaction overview

• Live vaccines

  • Avoid use of live vaccines in patients treated with spesolimab, owing to potentially increased risk of infections
  • Studies have not been conducted in spesolimab-treated patients who have recently received live viral or live bacterial vaccines

Pregnancy

Data regarding use pregnant females are insufficient to inform a drug-associated risk of adverse pregnancy-related outcomes

Human IgG crosses the placental barrier; therefore, spesolimab may be transmitted from mother to developing fetus

Animal studies

• IV administration of a surrogate antibody against IL36R in mice during organogenesis did not elicit any reproductive toxicity

Lactation

Data are not available on presence in human milk, effects on breastfed infants, or effects on milk production

Monoclonal antibodies are expected to be present in human milk

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Anti-interleukin-36 (IL-36) monoclonal antibody; binding to the IL-36 receptor decreases release of proinflammatory and profibrotic pathways in patients with inflammatory dermatoses

Absorption

Peak plasma concentration: 238 mcg/mL

AUC: 4,750 mcg⋅day/mL

Distribution

Vd (steady-state): 6.4 L

Metabolism

Metabolic pathway not characterized

As a humanized IgG1 monoclonal antibody, it is expected to degrade into small peptides and amino acids via catabolic pathways (like endogenous IgG)

Elimination

Half-life: 25.5 days

IV Incompatibilities

Do not mix with other medicinal products

Do not infuse other drugs concomitantly while using the same IV access line

IV Compatibilities

0.9% NaCl

Infusion sets

• Polyvinylchloride (PVC)
• Polyethylene (PE)
• Polypropylene (PP)
• Polybutadiene and polyurethane (PUR)

In-line filters

• Polyethersulfone (PES, neutral and positively charged)
• Positively charged polyamide (PA)

IV Preparation

Inspect vials visually for particulate matter and discoloration before administration

Solution should appear colorless to slightly brownish-yellow, clear to slightly opalescent; discard vial if solution is cloudy, discolored, or contains large or colored particulates

Draw and discard 15 mL from a 100-mL container of 0.9% NaCl

Slowly replace with 15 mL of spesolimab (complete contents from 2 vials of 450 mg/7.5 mL)

Mix gently before use

Use diluted solution immediately

IV Administration

Administer as continuous IV infusion over 90 minutes through an IV line containing a sterile, non-pyrogenic, low protein binding in-line filter (pore size of 0.2 micron)

If infusion is slowed or temporarily stopped, the total infusion time (including stop time) should not exceed 180 minutes

Pre-existing IV line may be used; must flush with 0.9% NaCl before and at end of infusion

Monitor for hypersensitivity or infusion-related reactions

Storage

Unopened vials

• Refrigerate at 2-8ºC (36-46ºF) in original carton to protect from light
• Do not freeze
• Before use, may store unopened vials at 20-25ºC (68-77ºF), for up to 24 hr in original carton to protect from light

Diluted solution

• If not used immediately, may refrigerate at 2-8ºC (36-46ºF) for up to 4 hr
• Protect from light