Ustekinumab

Pronunciation: US-te-KIN-ue-mab
Class: Immunomodulator

Trade Names

Stelara
- Injection, solution 45 mg per 0.5 mL
- Injection, solution 90 mg/mL

Pharmacology

Human immunoglobulin G1 (IgG1) kappa monoclonal antibody that binds with high affinity and specificity to the p40 protein subunit used by both the interleukin (IL)–12 and IL-23 cytokines.

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Pharmacokinetics

Absorption

T max was 13.5 days and 7 days after a single subcutaneous administration of 45 and 90 mg, respectively. Steady state is reached by wk 28.

Distribution

The mean Vd during the terminal phase following a single IV administration ranged from 56.1 to 82.1 mL/kg. Following subcutaneous administration of 45 and 90 mg, it was 161 and 179 mL/kg, respectively.

Metabolism

Expected to be degraded via catabolic pathways in the same manner as endogenous IgG.

Elimination

The mean systemic Cl following a single IV administration ranged from 1.9 to 2.22 mL/day/kg. The mean half-life ranged from 14.9 to 45.6 days following IV and subcutaneous administration.

Special Populations

Renal Function Impairment

No pharmacokinetic data are available.

Hepatic Function Impairment

No pharmacokinetic data are available.

Elderly

There were no apparent changes in pharmacokinetic parameters (Cl and Vd) in subjects older than 65 y.

Weight

When given the same dose, subjects weighing more than 100 kg had lower median serum concentrations compared with those subjects weighing 100 kg or less.

Indications and Usage

For the treatment of adults (18 y and older) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.

Contraindications

None well documented.

Dosage and Administration

Adults 100 kg or less

Subcutaneously 45 mg initially and 4 wk later, followed by 45 mg every 12 wk.

More than 100 kg

Subcutaneously 90 mg initially and 4 wk later, followed by 90 mg every 12 wk. 45 mg was also shown to be efficacious; however, 90 mg resulted in greater efficacy in subjects more than 100 kg.

General Advice

  • Administer by subcutaneous injection. Do not shake.
  • The needle cover on the prefilled syringe contains dry natural rubber (a derivative of latex). The needle cover should not be handled by persons sensitive to latex.
  • Administer each injection at a different anatomic location (such as upper arms, gluteal regions, thighs, or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, erythematous, or indurated.
  • Visually inspect for particulate matter and discoloration; do not use if discolored or cloudy or if other particulate matter is present.
  • The safety and efficacy of ustekinumab have not been evaluated beyond 2 y.

Storage/Stability

Store refrigerated between 36° and 46°F. Do not freeze. Keep in original carton to protect from light until time of use.

Drug Interactions

CYP substrates (eg, cyclosporine, warfarin)

Upon initiating ustekinumab therapy in patients receiving CYP-450 substrates, particularly drugs with a narrow therapeutic index, monitor clinical effects (eg, warfarin) or drug concentrations (eg, cyclosporine) and adjust the dose of the drug as needed.

Vaccines

It is not known whether patients receiving ustekinumab will be vulnerable to dissemination of infection. Do not administer live vaccines to patients receiving ustekinumab. Do not administer Bacillus Calmette-Guérin (BCG) vaccines to patients receiving ustekinumab or for 1 y prior to initiation or 1 y following discontinuation of treatment. Use with caution in administering live vaccines to household contacts of patients receiving ustekinumab because of risk for viral shedding from the household contact and transmission to the patient. Non-live vaccination given during ustekinumab therapy may not elicit an immune response sufficient to prevent disease.

Adverse Reactions

CNS

Headache (5%); fatigue (3%); dizziness (2%); depression (1%).

Dermatologic

Pruritus (2%).

EENT

Nasopharyngitis (8%); pharyngolaryngeal pain (2%).

GI

Diarrhea (2%).

Hypersensitivity

Hypersensitivity reactions (including rash, urticaria), serious allergic reactions (including angioedema, dyspnea, hypotension), (postmarketing).

Local

Injection-site erythema (2%).

Musculoskeletal

Back pain (2%); myalgia (1%).

Respiratory

Upper respiratory tract infection (5%).

Miscellaneous

Infections (61%); malignancies.

Precautions

Monitor

Evaluate patients for tuberculosis (TB) infection prior to initiating treatment. Closely monitor for development of signs or symptoms of active TB infection during and after treatment.


Pregnancy

Category B .

Lactation

IgG is excreted in human milk, so it is expected that ustekinumab will be present in human milk.

Children

Safety and efficacy not established.

Hypersensitivity

Serious allergic reactions, including angioedema and possible anaphylaxis, have been reported postmarketing.

Allergy immunotherapy

Ustekinumab may decrease the protective effect of allergy immunotherapy and may increase the risk of an allergic reaction to a dose of allergen immunotherapy. Use with caution in patients receiving or who have received allergy immunotherapy, particularly for anaphylaxis.

Immunizations

Psoriatic patients should receive all age-appropriate immunizations prior to the start of treatment.

Immunogenicity

Antibodies to ustekinumab may develop. Presence of ustekinumab in the serum can interfere with the detection of these antibodies.

Infections

May increase the risk of infections and reactivation of latent infections. Serious bacterial, fungal, and viral infections were observed in patients receiving ustekinumab. Ustekinumab should not be given to patients with any clinically important active infection. Individuals genetically deficient in IL-12/IL-23 are particularly vulnerable to disseminated infections from mycobacteria (including nontuberculous, environmental mycobacteria), Salmonella (including nontyphi strains), and BCG vaccinations.

Malignancies

Because many immunosuppressants have the potential to increase the risk of malignancies, use with caution in patients at high risk of malignancy or with a history of malignancy.

Reversible posterior leukoencephalopathy syndrome

May occur during treatment. If suspected, discontinue ustekinumab and administer appropriate treatment.

Tuberculosis

Evaluate patients for TB infection prior to initiating treatment; do not administer to patients with active TB.

Overdosage

Symptoms

No data available.

Patient Information

  • Instruct patients to read the Medication Guide before starting therapy and each time the prescription is refilled.
  • Inform patients that the ability of their immune system to fight infection may be lowered. Instruct patients of the importance of communicating any history of infections and to notify their health care provider if they develop any symptoms of infection.
  • Counsel patients about the risk of malignancies while receiving ustekinumab.
  • Advise patients to seek immediate medical attention if they experience any symptoms of serious allergic reactions.

Copyright © 2009 Wolters Kluwer Health.

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