Ustekinumab

L04A - Immunosuppressants ATC L04AC05 Antibody approved 2009 Parenteral First-in-class

JFDA label: Stelara 45 mg/0.5 ml PFS Solution for injection

Mechanism of Action

Inhibitor of Interleukin-12 — Interleukin-12 inhibitor; Inhibitor of Interleukin-23 — Interleukin-23 inhibitor

Target	Action	Gene / class
Interleukin-12 efficacy	INHIBITOR
Interleukin-23 efficacy	INHIBITOR

Indications

Approved

Crohn disease
Plaque psoriasis
Psoriatic arthritis

Contraindications

Source: Lexicomp

Additional contraindications (not in the US labeling): Severe infections such as sepsis, tuberculosis, and opportunistic infections Absolute
Clinically significant hypersensitivity to ustekinumab or any component of the formulation Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (4)

Common depression · dizziness · fatigue · Headache

Renal and urinary disorders (4)

Common urinary tract infection · Vaginal mycosis · vulvovaginal candidiasis

Not Known Perirectal abscess

Blood and lymphatic system disorders (1)

Common Skin carcinoma

Immune system disorders (1)

Very Common Antibody development

Gastrointestinal disorders (6)

Common dental disease · nausea · Vomiting

Not Known Appendicitis · cholecystitis · gastroenteritis

Skin and subcutaneous tissue disorders (2)

Common acne vulgaris · Pruritus

Musculoskeletal and connective tissue disorders (4)

Common Arthralgia · back pain · weakness

Not Known Osteomyelitis

Infections and infestations (3)

Very Common Infection

Not Known Sepsis · viral infection

General disorders and administration site conditions (1)

Common Erythema at injection site

Respiratory, thoracic and mediastinal disorders (5)

Very Common Nasopharyngitis

Common Bronchitis · pharyngolaryngeal pain · sinusitis

Not Known Pneumonia

Dosing

Source: Lexicomp

Crohn disease: Induction: IV: ≤55 kg: 260 mg as single dose >55 kg to 85 kg: 390 mg as single dose >85 kg: 520 mg as single dose Maintenance: SubQ: 90 mg every 8 weeks; begin maintenance dosing 8 weeks after the IV induction dose. Plaque psoriasis: SubQ: Initial and maintenance: ≤100 kg: 45 mg at 0 and 4 weeks, and then every 12 weeks thereafter >100 kg: 90 mg at 0 and 4 weeks, and then every 12 weeks thereafter. Note: Doses of 45 mg given to patients >100 kg were also efficacious; however, 90 mg is the recommended dose in these patients due to greater efficacy. Psoriatic arthritis: SubQ: Note: When used for psoriatic arthritis, may be administered alone or in combination with methotrexate. Initial and maintenance: 45 mg at 0 and 4 weeks, and then every 12 weeks thereafter. Coexistent psoriatic arthritis and moderate to severe plaque psoriasis in patients >100 kg: Initial and maintenance: 90 mg at 0 and 4 weeks, and then every 12 weeks thereafter.

Plaque psoriasis: Children ≥12 years of age and Adolescents: SubQ: mg/kg at 0 and 4 weeks, and then every 12 weeks thereafter ≥60 kg to ≤100 kg: 45 mg at 0 and 4 weeks, and then every 12 weeks thereafter >100 kg: 90 mg at 0 and 4 weeks, and then every 12 weeks thereafter

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Warnings & Precautions

Source: Lexicomp

Antibody formation

Antibody formation to ustekinumab has been observed with therapy.

Hypersensitivity reactions

Hypersensitivity, including anaphylaxis and angioedema, has been reported. Discontinue immediately with signs/symptoms of hypersensitivity reaction and treat appropriately as indicated.

Infections

May increase the risk for infections or reactivation of latent infections. Serious bacterial, fungal, and viral infections have been observed with use. Avoid use in patients with clinically important active infection until the infection resolves or is successfully treated. Exercise caution when considering use in patients with a history of new/recurrent infections, with conditions that predispose them to infections (eg, diabetes or residence/travel from areas of endemic mycoses), with chronic, latent, or localized infections, or who are genetically deficient in IL-12/IL-23 (IL-12/IL-23 genetic deficiency may predispose patients to disseminated infection). Patients who develop a new infection while undergoing treatment should consult their health care provider and be monitored closely. If a patient develops a serious infection, therapy should be discontinued or withheld until successful resolution of infection.

Malignancy

May increase the risk for malignancy although the impact on the development and course of malignancies is not fully defined. Rapidly appearing cutaneous squamous cell carcinomas (multiple) have been reported in patients receiving ustekinumab who were at risk for developing nonmelanoma skin cancer. Monitor all patients closely for the development of nonmelanoma skin cancer; closely follow patients >60 years of age, with a history of prolonged immunosuppression, and in patients with a history of PUVA treatment. Use with caution in patients with prior malignancy (use not studied in this population).

Neurotoxicity

Reversible posterior leukoencephalopathy syndrome (RPLS) has been observed (rare). RPLS symptoms include headache, seizures, confusion, and visual disturbances; may be fatal. Monitor; discontinue ustekinumab if symptoms occur and administer appropriate therapy.

Tuberculosis

Do not use in patients with active tuberculosis (TB). Patients should be evaluated for latent tuberculosis infection with a tuberculin skin test prior to starting therapy. Treatment of latent TB should be initiated before ustekinumab therapy is used. Consider antituberculosis treatment in patients with a history of latent or active tuberculosis if an adequate prior treatment course cannot be confirmed. During and following treatment, monitor for signs/symptoms of active TB. Concurrent drug therapy issues:

Allergen immunotherapy

Use caution in patients receiving or who have received allergen immunotherapy, particularly for anaphylaxis; ustekinumab may decrease the protective effect of allergen immunotherapy, which may increase the risk of an allergic reaction to allergen immunotherapy.

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Immunosuppressive therapy

Use in combination with other immunosuppressive drugs during psoriasis studies has not been evaluated; use caution. Use in combination with methotrexate during psoriatic arthritis studies did not appear to affect safety or efficacy. Special populations:

Patients >100 kg

May require higher dose to achieve adequate serum levels. Dosage form specific issues:

Latex

Packaging may contain natural latex rubber.

Polysorbate 80

Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling. Other warnings/precautions:

Immunizations

Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently; inactivated or nonlive vaccines may be given concurrently, but may not elicit a proper immune response. BCG vaccines should not be given 1 year prior to, during, or 1 year following treatment.

Phototherapy

Use in combination with phototherapy has not been studied; use caution.

Pregnancy & Lactation

Pregnancy

Adverse events have not been observed in animal reproduction studies; there are limited data related to the use of ustekinumab in human pregnancy. In general, other agents are preferred for the treatment of plaque psoriasis in pregnant women (Hsu 2012). Data collection to monitor pregnancy and infant outcomes following exposure to ustekinumab is ongoing. Patients may enroll themselves by calling 1-877-311-8972.

Lactation

It is not known if ustekinumab is present in breast milk. Ustekinumab is a recombinant IgG monoclonal antibody and maternal IgG molecules are known to be present in breast milk; however, systemic exposure to a breastfed infant is expected to be low secondary to the large size of the molecule and the degradation of ustekinumab within in the GI tract. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant ex

Monitoring

Clinical pearl	Tuberculosis screening (prior to initiating and periodically during therapy); CBC; ustekinumab-antibody formation; monitor for signs/symptoms of infection, reversible posterior leukoencephalopathy syndrome (RPLS), and squamous cell skin carcinoma

Biology & Pharmacokinetics

Pharmacokinetics

Half-life	10 to 126 days; Psoriasis: 14.9 ± 4.6 to 45.6 ± 80.2 days; Crohn disease: ~19 days

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Adalimumab	major
Bacillus calmette-guerin substrain tice live antigen	major
Baricitinib	major
Certolizumab pegol	major
Cladribine	major
Etanercept	major
Fingolimod	major
Golimumab	major
Infliximab	major
Leflunomide	major
Measles virus vaccine live attenuated	major
Mumps virus strain B level jeryl lynn live antigen	major
Natalizumab	major
Ozanimod	major
Rotavirus vaccine	major
Rubella virus vaccine	major
Sarilumab	major
Satralizumab	major
Siponimod	major
Smallpox (Vaccinia) Vaccine, Live	major
Talimogene laherparepvec	major
Teriflunomide	major
Tocilizumab	major
Tofacitinib	major
Typhoid vaccine (live)	major
Upadacitinib	major
Varicella Zoster Vaccine (Recombinant)	major
Yellow Fever Vaccine	major
Abatacept	moderate
Abemaciclib	moderate
Acalabrutinib	moderate
Acetohydroxamic acid	moderate
Aflibercept	moderate
Albendazole	moderate
Aldesleukin	moderate
Alefacept	moderate
Alemtuzumab	moderate
Alprazolam	moderate
Altretamine	moderate
Aminophylline	moderate

Showing 40 of 100+.

Registered Products (13)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
IMULDOSA Â® 45mg solution for injection in pre-filled syringe	Injection Ustekinumab 45 mg/0.5 ml	0.5 ml	Sabbagh Drug Store	—
IMULDOSA Â® 90mg solution for injection in pre-filled syringe	Injection Ustekinumab 90 mg/1 ml	1 ml	Sabbagh Drug Store	—
SitovabÂ® 130mg concentrate for solution for infusion in vial	Infusion Ustekinumab 130 mg	(1 (5) MG/ML)	MS PHARMA/JORDAN / MS PHARMA/JORDAN / General	—
SitovabÂ® 45 mg solution for injection in pre-filled syringe	Powder for Injection 45 mg	(1 (0.5) ML)	MS Pharma Jordan	—
SitovabÂ® 90 mg solution for injection in pre-filled syringe	Powder for Injection 90 mg	(1 (1) ML)	MS PHARMA/JORDAN / MS PHARMA/JORDAN / General	—
Stelara 130 mg Vial Concentrate Solution for Infusion	Infusion 130 mg	1 vial	Shawi & Rushedat Drug Store	—
Stelara 45 mg/0.5 ml PFS Solution for injection	Powder for Injection 45 mg/0.5 ml	one PFS	Shawi & Rushedat Drug Store	—
Stelara 45mg Pre-Filled Pen	Pre-filled Pen Ustekinumab 45 mg	(1 PFP)	Shawi & Rushedat Drug Store	—
Stelara 90 mg Pre-Filled Pen	Pre-filled Pen Ustekinumab 90 mg	(1 PFP)	Shawi & Rushedat Drug Store	—
Stelara 90mg/1ml PFS Solution for injection	Injection 90 mg/1 ml	1 PFS	Shawi & Rushedat Drug Store	—
Steqeyma	Tablet Ustekinumab 90 mg mg/1.0 ml SYR	(1 SYR)	Hikma Pharmaceuticals	—
Steqeyma	Vial Ustekinumab 130 mg/26 ml VIL	1 vial	Hikma Pharmaceuticals	—
Steqeyma	Tablet Ustekinumab 45 mg mg/0.5 ml SYR	(1 SYR)	Hikma Pharmaceuticals	—