secukinumab (Rx)

>10%

Infections (28.7%)

Nasopharyngitis (11.4-12.3%)

1-10%

Diarrhea (2.6-4.1%)

URT infection (2.5-3.2%)

Rhinitis (1.4%)

Oral herpes (0.1-1.3%)

Pharyngitis (1-1.2%)

Urticaria (0.6-1.2%)

Rhinorrhea (0.3-1.2%)

Contraindications

Hypersensitivity

Cautions

May increase risk of infections; caution when considering use in patients with chronic infection or a history of recurrent infection

In the postmarketing setting, serious and some fatal infections reported; instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur; if a patient develops a serious infection, monitor the patient closely and discontinue therapy until infection resolves

Evaluate patients for tuberculosis (TB) infection before initiating; do not administer with active TB; for latent TB, initiate anti-TB therapy prior to initiation of secukinumab in patients with a history of latent or active TB in whom an adequate course of treatment cannot be confirmed; monitor patients closely for signs and symptoms of active TB during and after treatment

May exacerbate Crohn disease

Anaphylaxis and cases of urticaria reported; if this occurs, discontinue secukinumab immediately and initiate anaphylaxis treatment

Caution if latex allergic; the removable cap on the Sensoready pen and prefilled syringe contains natural rubber

Use caution when prescribing drug to patients with inflammatory bowel disease; exacerbations, in some cases serious, reported in clinical trials in plaque psoriasis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis

Drug interaction overview

• Immunizations

  • Prior to initiating therapy, consider completion of all age-appropriate immunizations according to current immunization guidelines
  • Patients treated with secukinumab should not receive live vaccines
  • Nonlive vaccines received during a course of secukinumab may not elicit an immune response sufficient to prevent disease
  • Therapy may alter a patient`s immune response to live vaccines; avoid use of live vaccines in patients receiving treatment

• CYP450 substrates

  • CYP450 enzymes are suppressed by increased levels of cytokines (eg, IL-1, IL-6, IL-10, TNF-alpha) during chronic inflammation
  • Results from a drug-drug interaction study in patients with moderate-to-severe psoriasis showed no clinically relevant interaction for drugs metabolized by CYP3A4.
  • Upon initiation or discontinuation of secukinumab in patients taking CYP450 substrates with narrow therapeutic indices, consider monitoring for therapeutic effect or drug concentration; adjust dose as needed

Pregnancy

Limited available human data regarding use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes

Animal data

• No adverse developmental effects were observed in infants born to pregnant monkeys after SC administration of secukinumab during organogenesis at doses up to 30 times the maximum recommended human dose (MRHD)

Lactation

Unknown if excreted in human milk or absorbed systemically after ingestion; data are unavailable regarding effects on breastfed children or milk production

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

Human IgG1 monoclonal antibody that selectively binds to and neutralizes the proinflammatory cytokine interleukin 17A (IL-17A)

IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses and plays a key role in the pathogenesis of plaque psoriasis

Absorption

Peak plasma time: 6 days (single dose); 31-34 days (weekly dosing during first month)

Peak plasma concentration (single dose, day 6): 13.7 mcg/mL (150 mg) and 27.3 mcg/mL (300 mg)

Steady-state: By 24 weeks with monthly dosing

Steady-state trough levels: 16.7 mcg/mL (150 mg) to 34.4 mcg/mL (300 mg)

At the 300-mg dose at week 4 and week 12, the mean trough concentrations resulting from the Sensoready pen were 23-30% higher than those from the lyophilized powder and 23-26% higher than those from the prefilled syringe based on cross-study comparisons

Distribution

Vd: Low; 7.1-8.6 L (IV administration)

Concentrations in interstitial fluid in lesional and nonlesional skin: 27-40% of those in serum at weeks 1 and 2

Metabolism

Expected to be metabolized in the same manner as any endogenous IgG via intracellular catabolism, following fluid phase or receptor-mediated endocytosis and degraded into small peptides and amino acids

Elimination

Half-life: 22-31 days

Systemic clearance: Slow; 0.14-0.22 L/day

Clearance and distribution increases with body weight

SC Preparation

Lyophilized powder for injection

• Prepared and reconstitute with sterile water for injection (SWI) by a trained healthcare provider using aseptic technique and without interruption
• The preparation time from piercing the stopper until end of reconstitution on average takes 20 minutes and should not exceed 90 minutes
• Prepare the required number of vials (1 vial for the 150-mg dose or 2 vials for the 300-mg dose)
• Remove vial and SWI from refrigerator for 15-30 minutes to reach room temperature
• Slowly inject 1 mL of SWI into the vial and direct the stream of SWI into the lyophilized powder
• Tilt the vial at an angle of approximately 45 degrees and gently rotate between the fingertips for approximately 1 minute
• Do not shake or invert the vial
• Allow the vial to stand for ~10 minutes at room temperature to allow for dissolution
• Note that foaming may occur
• Once again, tilt the vial at an angle of approximately 45 degrees and gently rotate between the fingertips for approximately 1 minute; do not shake or invert the vial
• Allow the vial to stand undisturbed at room temperature for ~5 minutes
• Reconstituted solution contains 150 mg/mL
• The reconstituted solution should be essentially free of visible particles, clear to opalescent, and colorless to slightly yellow
• Do not use if the lyophilized powder has not fully dissolved or if the liquid contains visible particles, is cloudy, or is discolored

Sensoready pen and prefilled syringe

• Before injection, remove Sensoready pen or prefilled syringe from the refrigerator and allow reach room temperature (15-30 minutes) without removing the needle cap
• The removable cap of the Sensoready pen and the prefilled syringe contains natural rubber latex and should not be handled by latex-sensitive individuals
• Inspect visually for particulate matter and discoloration prior to administration
• Solution should be clear to slightly opalescent, colorless to slightly yellow solution
• Do not use if the liquid contains visible particles, is discolored, or is cloudy
• Does not contain preservatives; therefore, administer the Sensoready pen or prefilled syringe within 1 hr after removal from the refrigerator
• Discard any unused product

SC Administration

Patient self-administration

• Patients may self-inject after proper training in SC injection technique using the Sensoready pen or prefilled syringe and when deemed appropriate
• Rotate administration site between the thighs or any quadrant of abdomen (or upper, outer arm if administered by a caregiver)
• Do not inject into areas where the skin is tender, bruised, erythematous, indurated, or affected by psoriasis

Administration by healthcare professional

• The lyophilized powder for reconstitution is for healthcare provider use only
• Administer each injection at a different anatomic location (eg, upper arms, thighs, or any quadrant of abdomen) from the previous injection, and not into areas where the skin is tender, bruised, erythematous, indurated, or affected by psoriasis

Storage

Store vials, Sensoready pens, and prefilled pens refrigerated at 2-8ºC (36-46ºF)

Keep in the original carton to protect from light until the time of use

Do not freeze

To avoid foaming, do not shake

Does not contain a preservative; discard any unused portion

Reconstituted vial

• After reconstitution, use the solution immediately or store in the refrigerator at 2-8ºC (36-46ºF) for up to 24 hr
• Do not freeze
• Allow to reach room temperature (15-30 minutes) before administration
• Does not contain preservatives; therefore, administer within 1 hr after removal from refrigerator