ustekinumab (Rx)

>10%

Upper respiratory infection

1-10%

Nasopharyngitis

Back pain

Cellulitis

Depression

Diarrhea

Fatigue

Headache

Injection site erythema

Myalgia

Fatigue

Nasal congestion

Urticaria

Rash

Pruritus

Antibody formation

<1% (selected)

Severe infection

Malignancy

Reversible posterior leukoencephalopathy syndrome

Postmarketing Reports

Immune system disorders: Serious hypersensitivity reactions (including anaphylaxis and angioedema), other hypersensitivity reactions (including rash and urticaria)

Skin reactions: Pustular psoriasis, erythrodermic psoriasis

Respiratory, thoracic and mediastinal disorders: Lower respiratory tract infection; interstitial pneumonia, eosinophilic pneumonia and cryptogenic organizing pneumonia

Contraindications

Hypersensitivity

Active serious infection

Concomitant live vaccines

Cautions

Use caution in patients genetically deficient in IL-12/IL-23

Reversible posterior leukoencephalopathy syndrome (RPLS) reported (1 case); if RPLS is suspected, administer appropriate therapy and discontinue treatment

Provide age-appropriate immunization prior to initiating therapy

Hypersensitivity reactions reported, including anaphylaxis and angioedema

Infections

• Do not administer treatment to patients with active tuberculosis infection; initiate treatment of latent tuberculosis (TB) prior to administering ustekinumab; closely monitor for signs and symptoms of active tuberculosis during and after treatment
• May increase risk of infections and reactivation of latent infections; serious bacterial, fungal, mycobacterial, and viral infections observed with treatment; evaluate for TB infection before initiating drug
• Cases of interstitial pneumonia, eosinophilic pneumonia and cryptogenic organizing pneumonia have been reported; if diagnosis is confirmed, discontinue therapy and institute appropriate treatment
• Other serious infections requiring hospitalization reported include diverticulitis, cellulitis, pneumonia, appendicitis, cholecystitis, sepsis, osteomyelitis, viral infections, and UTIs
• Do not initiate in patients with any clinically important active infection until infection resolves or is adequately treated; consider risks and benefits of treatment before initiating therapy in patients with a chronic infection or a history of recurrent infection
• Instruct patients to seek medical advice if signs or symptoms suggestive of infection occur and consider discontinuing therapy for serious or clinically significant infections until infection resolves or is adequately treated

• Infections observed by disease treated

  • Serious infections requiring hospitalization, or otherwise clinically significant infections, reported in clinical studies included the following
  • Psoriasis: Diverticulitis, cellulitis, pneumonia, appendicitis, cholecystitis, sepsis, osteomyelitis, viral infections, gastroenteritis, and urinary tract infections
  • Psoriatic arthritis: Cholecystitis
  • Crohn disease: Anal abscess, gastroenteritis, ophthalmic herpes zoster, pneumonia, and listeria meningitis
  • Ulcerative colitis: Gastroenteritis, ophthalmic herpes zoster, pneumonia, and listeriosis

Malignancies

• Increased risk of malignancy
• Reports of the rapid appearance of multiple cutaneous squamous cell carcinomas in patients with pre-existing risk factors for developing nonmelanoma skin cancer; monitor all patients for nonmelanoma skin cancer

Drug interactions overview

• Formation of CYP450 enzymes can be altered by increased levels of certain cytokines (eg, IL-1, IL-6, IL-10, TNFα, IFN) during chronic inflammation; ustekinumab (IL-12 and IL-23 antagonist) may normalize the formation of CYP450 enzyme; monitor therapeutic effects (eg, warfarin) or concentration (eg, cyclosporine) with concomitant CYP450 substrates use (especially narrow therapeutic index drugs)
• Psoriasis studies the safety of ustekinumab in combination with immunosuppressive agents or phototherapy has not been evaluated; in psoriatic arthritis studies, concomitant methotrexate use did not appear to influence the safety or efficacy
• May decrease the protective effect of allergen immunotherapy
• Avoid use of live vaccines with ustekinumab
• BCG vaccines should not be given during treatment or for one year prior to initiating treatment or one year following discontinuation of treatment; use caution when administering live vaccines to household contacts of patients receiving treatment due to the potential risk for shedding from the household contact and transmission to patient

Pregnancy

Pregnancy registry (1-877-311-8972) available that monitors pregnancy outcomes in women exposed to ustekinumab during pregnancy

Limited data on ustekinumab use in pregnant women to inform a drug associated risk

In animal reproductive and developmental toxicity studies, no adverse developmental effects were observed after administration of ustekinumab to pregnant monkeys at exposures greater than 100 times the human exposure at the maximum recommended human subcutaneous dose (MRHD)

Lactation

Data are not available on the presence of ustekinumab in human milk, effects on the breastfed infant, or effects on milk production

Developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ustekinumab and any potential adverse effects on the breastfed child from ustekinumab or from the underlying maternal condition

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 IgG1κ monoclonal antibody binds to the p40 protein subunit used by IL-12 and IL-23 cytokines; IL-12 and IL-23 are involved in inflammatory and immune responses (eg, natural killer cell activation, CD4+ T-cell differentiation, and activation)

Absorption

Bioavailability: 57% (SC)

Peak plasma time: 13.5 days (45 mg-dose); 7 days (90 mg-dose)

Distribution

Vd (steady-state): 4.62 L

Metabolism

Ustekinumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG

Excretion

Half-life: 14.9-45.6 days (SC, psoriasis); 19 days (Crohn disease)

Clearance: 0.19 L/day

SC Preparation

Visually inspect for particulate matter and discoloration; solution is clear, colorless to light yellow and may contain a few small translucent or white particles

Do not use if solution discolored or cloudy, or if other particulate matter present

Does not contain preservatives; therefore, discard any unused product remaining in the vial and/or syringe

SC Administration

See full prescribing information for how to use prefilled syringe injector

For children and adolescents, injection should be administered by a healthcare provider; if determine appropriate, a patient may self-inject or a caregiver may inject dose after proper training in SC injection technique

Administer at a different anatomic location (eg, upper arms, gluteal regions, thighs, or any quadrant of abdomen) than the previous injection

Do not inject into areas where the skin is tender, bruised, erythematous, or indurated

When using the single-dose vial, a 27-gauge, 0.5-inch needle is recommended

IV Preparation

Must be diluted, prepared and infused by a healthcare professional using aseptic technique

Calculate dose and the number of ustekinumab vials needed based on patient weight (see Adult Dosing)

Each 26 mL vial contains 130 mg of ustekinumab

Withdraw and discard volume from the 250-mL infusion bag of 0.45% and 0.9% NaCl equal to the calculated drug volume (discard 26 mL NaCl for each vial of needed, for 2 vials- discard 52 mL, for 3 vials- discard 78 mL, 4 vials- discard 104 mL)

Withdraw 26 mL from each vial needed and add it to the 250 mL infusion bag; final volume in the infusion bag should be 250 mL; gently mix

Visually inspect diluted solution before infusion; do not use if visibly opaque particles, discoloration or foreign particles are observed

IV Administration

Infuse over at least 1 hr

Use only an infusion set with an in-line, sterile, nonpyrogenic, low protein-binding filter (pore size 0.2 micrometer)

Do not infuse concomitantly in the same IV line with other agents

Does not contain preservatives

Each vial is for single use only

Discard any remaining solution

Storage

Unopened vials

• Refrigerate at 2-8ºC (36-46ºF); do not freeze
• Protect from light

Prefilled syringes

• Refrigerate at 2-8ºC (36-46ºF); do not freeze
• Once removed from refrigerator, may store at room temperature (up to 30ºC [86ºF]) for up to 30 days
• Store vials upright; protect from light until the time of use
• Do not shake

Diluted IV solution

• If necessary, diluted solution may be stored for up to 7 hr at room temperature up to 25ºC (77ºF); do not freeze
• Complete infusion within 8 hr after dilution (cumulative time after preparation including the storage and the infusion period)
• Discard any unused portion of the infusion solution