Drug information of secukinumab

Mechanism of effect

Secukinumab is a human monoclonal antibody that targets IL-17A cytokine to downregulate inflammation in psoriasis, an autoimmune dermatological disease. The pathophysiology of psoriasis has not been fully established, however it is known that dysregulation of innate and adaptive immune responses plays part in the chronic inflammation associated with the disease. IL-17 represents is a six-membered family (IL-17A to F) of pleiotropic pro-inflammatory cytokines, expression of which is found to be elevated in psoriatic skin. These cytokines act on many different cell types and provide defense against different extracellular pathogens causing fungal or bacterial infections. IL-17 cytokines are produced by many cells involved in immune system defense, such as Th17, mast cells, neutrophils, and dendritic cells - all implicated in promoting inflammation. There is evidence linking IL-17 to pathogenesis of multiple autoimmune diseases including rheumatoid arthritis, spondyloarthritis, psoriasis, Crohn's disease, multiple sclerosis, and even atherosclerosis.

Pharmacodynamic

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

Pharmacokinetics

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

Drug indications

Psoriasis , ankylosing spondylitis , plaque psoriasis , psoriatic arthritis

Dosage

Moderate-to-Severe Plaque or Scalp Psoriasis

Candidates for systemic therapy or phototherapy

Initial: 300 mg SC at weeks 0, 1, 2, 3, and 4

Monthly maintenance: Beginning at week 8, give 300 mg SC once monthly

For some patients, a dose of 150 mg may be acceptable

Active Psoriatic Arthritis

With coexistent moderate-to-severe plaque psoriasis, use the dosing and administration recommendations for plaque psoriasis

Recommended dosage

• For other patients with psoriatic arthritis, administer with or without a loading dosage by SC injection
• With loading dose: 150 mg SC at weeks 0, 1, 2, 3, and 4 and q4wk thereafter
• Without loading dose: 150 mg SC q4wk
• If a patient continues to have active psoriatic arthritis, consider a dosage of 300 mg
• May be administered with or without methotrexate

Ankylosing Spondylitis

Indicated for adults with active ankylosing spondylitis

Administer with or without a loading dosage by SC injection

With loading dose: 150 mg SC at weeks 0, 1, 2, 3, and 4 and q4wk thereafter

Without a loading dose: 150 mg SC q4wk

If a patient continues to have active ankylosing spondylitis, consider increasing dose to 300 mg q4wk

Non-radiographic Axial Spondyloarthritis

Indicated for active non-radiographic axial spondyloarthritis with objective signs of inflammation

Administer with or without loading dose

With loading dose: 150 mg SC at Weeks 0, 1, 2, 3, and 4, THEN q4Weeks thereafter

Without loading dose: 150 mg SC q4Weeks

Dosage Modifications

Renal or hepatic impairment

• Studies have not been conducted to assess effect on pharmacokinetics

Dosing Considerations

Evaluate patients for tuberculosis infection prior to initiating treatment (see Cautions)

Drug contraindications

Hypersensitivity to this drug , Receipt of live or attenuated live vaccine

Side effects

Infection , Diarrhea , Headache , weight decrease , Tachycardia , rash , vertigo , Dyspnea , urticaria , pruritus , Erythema , fever , myalgia , rectal hemorrhage , dysphagia , tiredness , swelling of the face, mouth, hands, or feet , swelling of the face , swelling of the tongue , stomach pain , Rhinorrhea , rhinitis

Interactions

Meningococcal conjugate vaccine , Rabies Vaccine , Benralizumab , RESLIZUMAB , Ethosuximide , Primidone , Tacrolimus , Tetanus immuneglobulin , Trastuzumab , Disopyramide , rotavirus vaccine , Japanese Encephalitis Virus Vaccine , DIPHTHERIA & TETANUS TOXOID (Td ) , Hepatitis B Vaccine , Anthrax vaccine , Polio vaccine, inactivated , Typhoid vaccine (live), oral , Yellow fever vaccine , Hib vaccine , Fosphenytoin , Hepatitis B Immune Globulin , Adenovirus types 4 and 7 live, oral , Ofatumumab , Zoster Vaccines , Rubella Vaccines , Mumps vaccine , Valproic acid , Varicella-Zoster Vaccines , Quinine , Mechlorethamine , Human papillomma virus vaccine , Carbamazepine , Clonidine , Influenza vaccine , Quinidine , Measles vaccine , Sirolimus , Cyclosporine , Phenobarbital , Phenytoin , Lomustine , Warfarin , alirocumab

Alerts

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

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

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

Points of recommendation

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

Pregnancy level

HAVE NOT BEEN ESTABLISHED

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)

Breast feeding warning

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

Related drugs

Sarilumab , RESLIZUMAB , Golimumab , Tocilizumab , Canakinumab , Basiliximab , Dupilumab , Ocrelizumab , Daclizumab , Benralizumab , sirukumab , mepolizumab , ixekizumab , Risankizumab , Tildrakizumab , Guselkumab , Brodalumab , Ustekinumab , caplacizumab

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