Approved Drug Label (PDF)
4
Contraindications
Additions
and/or revisions underlined:
IMULDOSA
is contraindicated in patients with clinically significant hypersensitivity to any
ustekinumab product or to any of the excipients in IMULDOSA [see Warnings and Precautions (5.5)].
5
Warnings and Precautions
5.1
Infections
Additions
and/or revisions underlined:
Ustekinumab
products may increase the risk of infections and reactivation of latent
infections. Serious bacterial, mycobacterial, fungal, and viral infections were
observed in patients receiving Ustekinumab products [see Adverse Reactions (6.1,
6.3)].
Serious
infections requiring hospitalization, or otherwise clinically significant
infections, reported in clinical trials included the following:
- Plaque Psoriasis: diverticulitis, cellulitis,
pneumonia, appendicitis, cholecystitis, sepsis, osteomyelitis, viral
infections, gastroenteritis and urinary tract infections.
- Psoriatic arthritis: cholecystitis.
- Crohn’s disease in adults: anal abscess, gastroenteritis,
ophthalmic herpes zoster, pneumonia, and listeria meningitis.
- Ulcerative colitis: gastroenteritis, ophthalmic
herpes zoster, pneumonia, and listeriosis.
. . .
6
Adverse Reactions
6.1
Clinical Trials Experience
Additions and/or
revisions underlined:
. . .
Adult Subjects with Plaque Psoriasis
. . .
Malignancies
In the controlled and non-controlled portions of
clinical trials in subjects with plaque psoriasis (median follow-up of 3.2
years, representing 8998 patient-years of exposure), 1.7% of
ustekinumab-treated subjects reported malignancies excluding non-melanoma skin
cancers (0.60 per hundred patient-years of follow-up). Non-melanoma skin cancer
was reported in 1.5% of ustekinumab-treated subjects (0.52 per hundred
patient-years of follow-up) [see Warnings and Precautions (5.4)]. The most
frequently observed malignancies other than non-melanoma skin cancer during the
clinical trials were: prostate, melanoma, colorectal and breast. Malignancies
other than non-melanoma skin cancer in ustekinumab-treated subjects during the
controlled and uncontrolled portions of trials were similar in type and number
to what would be expected in the general U.S. population according to the 1969-2004
SEER database (adjusted for age, gender and race).1
. . .
Adult Subjects with Crohn’s Disease
Revised subheading
The safety of ustekinumab was assessed in 1407
subjects with moderately to severely active Crohn’s disease (Crohn’s Disease
Activity Index [CDAI] greater than or equal to 220 and less than or equal to
450) in three randomized, double-blind, placebo-controlled, parallel-group,
multicenter trials. These 1407 subjects included 40 subjects who received a prior
investigational intravenous ustekinumab formulation but were not included in
the efficacy analyses. In trials CD-1 and CD-2 there were 470 subjects who
received ustekinumab 6 mg/kg as a weight-based single intravenous induction
dose and 466 who received placebo [see Dosage and Administration (2.3)]. Subjects
who were responders in either trial CD-1 or CD-2 were randomized to receive a
subcutaneous maintenance regimen of either 90 mg ustekinumab every 8 weeks, or
placebo for 44 weeks in trial CD-3. Subjects in these 3 trials may have
received other concomitant therapies including aminosalicylates, immunomodulatory
agents [azathioprine (AZA), 6-mercaptopurine (6-MP), methotrexate (MTX)], oral
corticosteroids (prednisone or budesonide), and/or antibiotics for their
Crohn’s disease [see Clinical Studies (14.4)].
.
. .
8
Use in Specific Populations
8.4 Pediatric Use
Additions and/or revisions underlined:
A pediatric assessment
for IMULDOSA demonstrates that IMULDOSA is safe and effective for pediatric
patients in an indication for which STELARA (ustekinumab) is approved. However,
IMULDOSA is not approved for such indication due to marketing exclusivity for
STELARA (ustekinumab).
. . .
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions and/or revisions underlined:
. . .
What is IMULDOSA?
. . .
It is not known if IMULDOSA is safe and effective
in children less than 18 years of age with ulcerative colitis or in
children less than 6 years of age with plaque psoriasis or psoriatic arthritis.
Who should not use IMULDOSA?
Do not use IMULDOSA if you are
allergic to any ustekinumab product or any of the ingredients in
IMULDOSA. See the end of this Medication Guide for a complete list of
ingredients in IMULDOSA.
. . .
Approved Drug Label (PDF)
5
Warnings and Precautions
Additions
and/or revisions underlined:
5.5 Serious Hypersensitivity
Reactions
Serious hypersensitivity reactions,
including anaphylaxis and angioedema, have been reported with ustekinumab
products in clinical trials and postmarketing. Some serious hypersensitivity
reactions have occurred during the first intravenous dose of ustekinumab
products [see Adverse Reactions (6.1, 6.3)]. If a severe or clinically significant hypersensitivity
reaction occurs, discontinue IMULDOSA immediately and initiate appropriate
medical treatment [see Contraindications
(4)].
6
Adverse Reactions
Additions
and/or revisions underlined:
The
following serious adverse reactions are discussed elsewhere in the label:
.
. .
- Serious Hypersensitivity Reactions [see Warnings and Precautions (5.5)]
.
. .
6.3
Postmarketing Experience
Additions
and/or revisions underlined:
.
. .
Immune system
disorders: Hypersensitivity
reactions (e.g., anaphylaxis, angioedema, dyspnea, rash, urticaria), including
a fatal case that presented with chest tightness and dyspnea during infusion of
the first dose.
.
. .
7
Drug Interactions
7.1
Concomitant Therapies
Additions
and/or revisions underlined:
In
trials in subjects with plaque psoriasis the safety of ustekinumab
products in combination with immunosuppressive agents or phototherapy has not
been evaluated. In trials in subjects with psoriatic arthritis,
concomitant MTX use did not appear to influence the safety or efficacy of
ustekinumab. In trials in subjects with Crohn's disease (CD-1 and
CD-2) and ulcerative colitis (UC-1), immunomodulators (6-MP, AZA,
MTX) were used concomitantly in approximately 30% of subjects and
corticosteroids were used concomitantly in approximately 40% and 50% of Crohn's
disease and ulcerative colitis subjects, respectively. Use of these concomitant
therapies did not appear to influence the overall safety or efficacy of
ustekinumab.
7.2 CYP450 Substrates
Additions and/or revisions
underlined:
The
formation of CYP450 enzymes can be suppressed by increased levels of certain
cytokines (e.g., IL-1, IL-6, TNF alpha, IFN) during chronic inflammation. Thus, use
of ustekinumab products, antagonists of IL-12 and IL-23, could normalize the
formation of CYP450 enzymes. Upon initiation or discontinuation of IMULDOSA
in patients who are receiving concomitant CYP450 substrates, particularly those
with a narrow therapeutic index, consider monitoring for therapeutic effect or
drug concentration and adjust the individual dosage of the CYP
substrate as needed. See the prescribing information of specific CYP
substrates.
A
CYP-mediated drug interaction
effect was not observed in subjects with Crohn’s disease [see Clinical Pharmacology (12.3)].
8
Use in Specific Populations
8.1
Pregnancy
Additions
and/or revisions underlined:
Risk
Summary
Available data from the Organization of
Teratology Information Specialists (OTIS)/MotherToBaby Pregnancy Registry,
published literature and pharmacovigilance in pregnant women have not
identified a ustekinumab- associated risk of major birth defects,
miscarriage or other adverse maternal or fetal outcomes (see Data). There are risks to the mother
and the fetus associated with inflammatory bowel disease (IBD) in
pregnancy. In animal reproductive and developmental toxicity studies, no
adverse developmental effects were observed in offspring after administration
of ustekinumab to pregnant monkeys at exposures greater than 100 times the
maximum recommended human dose (MRHD).
.
. .
Clinical
Considerations
Disease-associated
Maternal and Embryo/Fetal Risk
Published
data suggest that the risk of adverse pregnancy outcomes in women with IBD is
associated with increased disease activity. Adverse pregnancy outcomes include
preterm delivery (before 37 weeks of gestation), low birth weight (less than
2500 g) infants, and small for gestational age at birth.
Fetal/Neonatal
Adverse Reactions
Transport
of endogenous IgG antibodies across the placenta increases as pregnancy
progresses, and peaks during the third trimester. Therefore, ustekinumab products may be
present in infants exposed in utero.
The potential clinical impact of ustekinumab product exposure in
infants exposed in utero should be
considered.
Data
Human Data
An
observational pregnancy registry conducted by (OTIS)/MotherToBaby in the U.S.
and Canada (enrollment between 2013 and 2019) assessed the risk of major birth
defects, pattern of major and minor anomalies in live- born infants,
miscarriage, and adverse infant outcomes in women with ustekinumab exposure. In
the registry study, there were 101 participants and 107 pregnancies with
exposure to ustekinumab (88 prospective; 19 retrospective). Most participants
had a primary indication of CD (65.4%) or psoriasis (30.8%). The pregnancy
registry did not identify a ustekinumab-associated risk of major birth defects,
pattern of major or minor anomalies, increased risk of miscarriage or adverse
infant outcomes. Methodological limitations of the registry include small
sample size, lack of an internal comparison group, a mix of prospective and
retrospective reports, and unmeasured confounders. The conclusions from the
pregnancy registry were consistent with the published literature and
pharmacovigilance.
.
. .
8.4
Pediatric Use
Additions
and/or revisions underlined:
The
safety and effectiveness of IMULDOSA have been established for the treatment of
moderate to severe plaque psoriasis in pediatric patients 6 years of age and
older who are candidates for phototherapy or systemic therapy.
.
. .
Psoriatic
Arthritis
The
safety and effectiveness of IMULDOSA have been established for treatment of
psoriatic arthritis in pediatric patients 6 years of age and older.
Use
of IMULDOSA in these age groups is supported by evidence from adequate and well
controlled trials of ustekinumab in adult subjects with psoriasis and
PsA, pharmacokinetic data from adult subjects with psoriasis, adult subjects
with PsA and pediatric subjects with psoriasis, and safety data of ustekinumab
from two clinical trials in 44 pediatric subjects 6 to 11 years old with psoriasis
and 110 pediatric subjects 12 years of age and older with psoriasis. The
observed pre-dose (trough) concentrations are generally comparable between
adult subjects with psoriasis, adult subjects with PsA and pediatric subjects
with psoriasis, and the PK exposure is expected to be comparable between adult
and pediatric subjects with PsA [see
Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies
(14.1, 14.2, 14.3)].
.
. .
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION
GUIDE
Medication Guide has undergone
extensive changes; please refer to label for complete information.
PATIENT
COUNSELING INFORMATION
Additions
and/or revisions underlined:
Advise
the patient and/or caregiver to read the FDA-approved patient labeling
(Medication Guide and Instructions for Use).
.
. .
Serious
Hypersensitivity and Reactions
- Inform
patients that serious hypersensitivity reactions have been reported with
intravenous and subcutaneous administration of ustekinumab products. Instruct patients to discontinue IMULDOSA
and seek immediate medical attention if they experience any signs or symptoms
of hypersensitivity reactions [see
Warnings and Precautions (5.5)].
.
. .
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