Ustekinumab
Pronunciation
(yoo stek in YOO mab)
Index TermsCNTO 1275Dosage Forms
Excipient information
presented when available (limited, particularly for generics); consult specific
product labeling.
Solution, Intravenous:
Stelara: 130 mg/26 mL (26 mL)
[contains edetate disodium dihydrate, polysorbate 80]
Solution, Subcutaneous
[preservative free]:
Stelara: 45 mg/0.5 mL (0.5 mL)
[contains polysorbate 80]
Solution Prefilled Syringe,
Subcutaneous [preservative free]:
Stelara: 45 mg/0.5 mL (0.5
mL); 90 mg/mL (1 mL) [contains polysorbate 80]
Brand Names: U.S.StelaraPharmacologic CategoryAntipsoriatic AgentInterleukin-12 InhibitorInterleukin-23 InhibitorMonoclonal AntibodyPharmacology
Ustekinumab is a human
monoclonal antibody that binds to and interferes with the proinflammatory
cytokines, interleukin (IL)-12 and IL-23. Biological effects of IL-12 and IL-23
include natural killer (NK) cell activation, CD4+ T-cell differentiation and
activation. Ustekinumab also interferes with the expression of monocyte
chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interferon-inducible
protein-10 (IP-10), and interleukin-8 (IL-8). Significant clinical improvement
in psoriasis and psoriatic arthritis patients is seen in association with
reduction of these proinflammatory signalers.
Distribution
Vd (central
compartment): 2.74 L; Vdss: Crohn disease: 4.62 L
Time to Peak
Plasma: 45 mg: 13.5 days; 90
mg: 7 days
Half-Life
Elimination
10 to 126 days; Psoriasis:
14.9 ± 4.6 to 45.6 ± 80.2 days; Crohn disease: ~19 days
Special Populations Note
Body weight: When given the
same dose, subjects weighing >100 kg had lower median serum concentrations
compared with those subjects weighing ≤100 kg. The median trough serum
concentrations of ustekinumab in subjects >100 kg in the 90 mg group were
comparable with those in subjects ≤100 kg in the 45 mg group.
Use: Labeled Indications
Crohn disease: Treatment of moderately to severely active Crohn disease
in adults who have failed or were intolerant to immunomodulatory or
corticosteroid therapy, but never failed tumor necrosis factor (TNF) blocker
therapy or who have failed or were intolerant to treatment with one or more TNF
blockers.
Plaque psoriasis: Treatment of moderate to severe plaque psoriasis in
patients ≥12 years of age who are candidates for phototherapy or systemic
therapy
Psoriatic arthritis: Treatment of active psoriatic arthritis (as monotherapy or
in combination with methotrexate) in adults
Contraindications
Clinically significant
hypersensitivity to ustekinumab or any component of the formulation
Canadian labeling: Additional contraindications (not in the US labeling):
Severe infections such as sepsis, tuberculosis, and opportunistic infections
Dosing: Adult
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.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Plaque psoriasis: Children ≥12 years of age and Adolescents: SubQ:
<60 kg: 0.75 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
Dosing: Renal Impairment
There are no dosage
adjustments provided in the manufacturer's labeling (has not been studied).
Dosing: Hepatic Impairment
There are no dosage
adjustments provided in the manufacturer's labeling (has not been studied).
Reconstitution
IV: After calculating the
appropriate dosage and volume of ustekinumab (using 130 mg per 26 mL vials), withdraw
an equal volume of fluid from 250 mL bag of NS and discard. Add ustekinumab to
the NS bag; final volume of bag should be 250 mL. Gently mix bag.
Administration
IV: Infuse over at least 1
hour; use of IV set with an in-line, low-protein binding filter (0.2
micrometer) required. Do not infuse concomitantly in the same IV line with
other agents.
Subcutaneous: Administer by
subcutaneous injection into the top of the thigh, abdomen, upper arms, or
buttocks. Rotate sites. Do not inject into tender, bruised, erythematous, or
indurated skin. Avoid areas of skin where psoriasis is present. Discard any
unused portion. Intended for use under supervision of physician; self-injection
may occur after proper training.
Storage
Refrigerate vials and
prefilled syringes at 2°C to 8°C (36°F to 46°F); do not freeze. Store vials
upright. Keep the product in the original carton to protect from light until
the time of use. Do not shake. Discard any unused portion. Once diluted,
solution for IV infusion may be stored up to 4 hours at room temperature (up to
25°C [77°F]).
Drug Interactions
BCG (Intravesical):
Immunosuppressants may diminish the therapeutic effect of BCG
(Intravesical). Avoid combination
Belimumab: Monoclonal
Antibodies may enhance the adverse/toxic effect of Belimumab. Avoid
combination
Coccidioides immitis Skin
Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides
immitis Skin Test. Monitor therapy
Denosumab: May enhance the
adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious
infections may be increased. Monitor therapy
Echinacea: May diminish the
therapeutic effect of Immunosuppressants. Consider therapy modification
Fingolimod: Immunosuppressants
may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the
concomitant use of fingolimod and other immunosuppressants when possible. If
combined, monitor patients closely for additive immunosuppressant effects (eg,
infections). Consider therapy modification
InFLIXimab: Ustekinumab may
enhance the immunosuppressive effect of InFLIXimab. Avoid combination
Leflunomide:
Immunosuppressants may enhance the adverse/toxic effect of Leflunomide.
Specifically, the risk for hematologic toxicity such as pancytopenia,
agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider
not using a leflunomide loading dose in patients receiving other
immunosuppressants. Patients receiving both leflunomide and another
immunosuppressant should be monitored for bone marrow suppression at least
monthly. Consider therapy modification
Natalizumab:
Immunosuppressants may enhance the adverse/toxic effect of Natalizumab.
Specifically, the risk of concurrent infection may be increased. Avoid
combination
Nivolumab: Immunosuppressants
may diminish the therapeutic effect of Nivolumab. Consider therapy
modification
Ocrelizumab: May enhance the
immunosuppressive effect of Immunosuppressants. Monitor therapy
Pidotimod: Immunosuppressants
may diminish the therapeutic effect of Pidotimod. Monitor therapy
Pimecrolimus: May enhance the
adverse/toxic effect of Immunosuppressants. Avoid combination
Roflumilast: May enhance the
immunosuppressive effect of Immunosuppressants. Consider therapy
modification
Sipuleucel-T:
Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor
therapy
Tacrolimus (Topical): May
enhance the adverse/toxic effect of Immunosuppressants. Avoid
combination
Tertomotide:
Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor
therapy
Tofacitinib:
Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib.
Management: Concurrent use with antirheumatic doses of methotrexate or
nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and
this warning seems particularly focused on more potent immunosuppressants. Consider
therapy modification
Trastuzumab: May enhance the
neutropenic effect of Immunosuppressants. Monitor therapy
Vaccines (Inactivated):
Immunosuppressants may diminish the therapeutic effect of Vaccines
(Inactivated). Management: Vaccine efficacy may be reduced. Complete all
age-appropriate vaccinations at least 2 weeks prior to starting an
immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate
at least 3 months after immunosuppressant discontinuation.Consider therapy
modification
Vaccines (Live):
Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live).
Immunosuppressants may diminish the therapeutic effect of Vaccines (Live).
Management: Avoid use of live organism vaccines with immunosuppressants;
live-attenuated vaccines should not be given for at least 3 months after
immunosuppressants. Avoid combination
Adverse Reactions
>10%:
Infection: Infection
(psoriasis: 27% to 72%; severe infection: ≤3%)
Respiratory: Nasopharyngitis
(Crohn disease: 11%)
1% to 10%:
Central nervous system:
Headache (psoriasis: 5%), fatigue (psoriasis: 3%), dizziness (psoriasis: 2%),
depression (psoriasis: 1%)
Dermatologic: Pruritus (2% to
4%), acne vulgaris (Crohn disease: 1%)
Gastrointestinal: Vomiting
(Crohn disease: 4%), nausea (psoriatic arthritis: 3%), dental disease
(infection; 1%)
Genitourinary: Vaginal mycosis
(Crohn disease: ≤5%), vulvovaginal candidiasis (Crohn disease: ≤5%), urinary
tract infection (Crohn disease: 4%)
Hematologic & oncologic:
Skin carcinoma (nonmelanoma including squamous cell carcinoma; psoriasis: 2%)
Immunologic: Antibody
development (≤6%; associated with reduced efficacy in psoriasis patients)
Local: Erythema at injection
site (1% to 5%)
Neuromuscular & skeletal:
Arthralgia (psoriatic arthritis: 3%), back pain (psoriasis: 2%), weakness
(Crohn disease: 1%)
Respiratory: Bronchitis (Crohn
disease: 5%), sinusitis (Crohn disease: 3%), pharyngolaryngeal pain (psoriasis:
2%)
Frequency not defined:
Gastrointestinal:
Appendicitis, cholecystitis, gastroenteritis
Genitourinary: Perirectal
abscess
Infection: Sepsis, viral
infection
Neuromuscular & skeletal:
Osteomyelitis
Respiratory: Pneumonia
<1%, postmarketing, and/or
case reports: Anaphylaxis, angioedema, bacterial infection, bleeding at injection
site, bruising at injection site, cellulitis, diverticulitis, erythrodermic
psoriasis, fungal infection, herpes zoster, hypersensitivity reaction,
induration at injection site, irritation at injection site, itching at
injection site, malignant neoplasm, meningitis due to listeria monocytogenes,
ocular herpes simplex, pain at injection site, pustular psoriasis, reversible
posterior leukoencephalopathy syndrome, skin rash, swelling at injection site,
urticaria
Warnings/Precautions
Concerns related to adverse
effects:
• 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.
Monitoring Parameters
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
Pregnancy Considerations
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.
Patient Education
• Discuss specific use of drug
and side effects with patient as it relates to treatment. (HCAHPS: During this
hospital stay, were you given any medicine that you had not taken before?
Before giving you any new medicine, how often did hospital staff tell you what
the medicine was for? How often did hospital staff describe possible side
effects in a way you could understand?)
• Patient may experience
rhinitis, headache, vomiting, common cold symptoms, injection site irritation,
or pharyngitis. Have patient report immediately to prescriber signs of
infection, signs of posterior reversible encephalopathy syndrome (confusion,
not alert, vision changes, seizures, or severe headache), shortness of breath,
flushing, angina, severe dizziness, passing out, severe loss of strength and
energy, vaginitis, mole changes, or skin growths (HCAHPS).
• Educate patient about signs
of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad
cough; blue skin color; seizures; or swelling of face, lips, tongue, or
throat). Note: This is not a comprehensive list of all side
effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer:
Should not be printed and given to patients. This information is intended to
serve as a concise initial reference for health care professionals to use when
discussing medications with a patient. You must ultimately rely on your own
discretion, experience, and judgment in diagnosing, treating, and advising
patients.
