Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Infections
Additions and/or
revisions underlined:
. . .
Serious infections requiring hospitalization, or
otherwise clinically significant infections, reported in clinical trials
included the following:
. . .
- Crohn's disease in adults: anal abscess, gastroenteritis, ophthalmic herpes zoster, pneumonia, and
listeria meningitis.
. . .
5.5 Serious
Hypersensitivity Reactions
Subsection title revised:
Additions and/or
revisions underlined:
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 WEZLANA immediately
and initiate appropriate medical treatment [see
Contraindications (4)].
6
Adverse Reactions
6.1 Clinical
Trials Experience
Additions and/or
revisions underlined:
. . .
Adult Subjects with Crohn's Disease
. . .
6.3 Postmarketing
Experience
Additions and/or
revisions underlined:
The following adverse reactions have been reported
during post-approval use of ustekinumab products. Because these reactions are
reported voluntarily from a population of uncertain size, it is not always
possible to reliably estimate their frequency or establish a causal
relationship to ustekinumab product exposure.
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 the first dose.
. . .
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions and/or
revisions underlined:
.
. .
Serious
Hypersensitivity Reactions
- Inform patients that serious hypersensitivity
reactions have been reported with intravenous and subcutaneous administration
of ustekinumab products. Instruct patients to discontinue WEZLANA and seek immediate
medical attention if they experience any signs or symptoms of hypersensitivity
reactions [see Warnings and Precautions
(5.5)].
.
. .
MEDICATION GUIDE
Additions and/or
revisions underlined:
.
. .
It
is not known if WEZLANA 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.
.
. .
.
. .
Approved Drug Label (PDF)
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).
All
pregnancies have a background risk of birth defect, loss, or other adverse
outcomes. In the U.S. general population, the estimated background risk of
major birth defects and miscarriage of clinically recognized pregnancies is 2%
to 4% and 15% to 20%, respectively.
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.
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions
and/or revisions underlined:
…
What is WEZLANA?
…
It
is not known if WEZLANA is safe and effective in children with Crohn’s disease
or ulcerative colitis or in children less than 6 years of age with plaque
psoriasis or psoriatic arthritis.
…
How should I use
WEZLANA?
Use
WEZLANA exactly as the healthcare provider tells you to. The healthcare
provider will determine the right dose of WEZLANA, the amount for each
injection, and how often it should be given. Be sure to keep all scheduled
follow-up appointments.
…
Injecting WEZLANA
under the skin
…
If
you inject too much WEZLANA, call the healthcare provider or Poison
Help line at 1-800-222-1222, or go to the nearest emergency room right
away.
…
What are the
possible side effects of WEZLANA?…
After
a prefilled syringe, 45 mg vial or prefilled ConfiPen autoinjector has been
stored at room temperature, do not return it to the refrigerator.
Throw away (discard) the prefilled syringe, the 45 mg
vial or prefilled ConfiPen autoinjector if it is not used within 30 days at
room temperature storage.
…
Approved Drug Label (PDF)
6
Adverse Reactions
Addition of the
following to the bulleted line listing:
- Noninfectious
Pneumonia [see Warnings and Precautions
(5.8)]
6.1
Clinical Trials Experience
Title
revision to table 5; please refer to label for complete information.
7
Drug Interactions
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?, 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
WEZLANA 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
Limited
data from observational studies, published case reports, and postmarketing
surveillance on the use of ustekinumab products during pregnancy are
insufficient to inform a drug associated risk of major birth defects,
miscarriage, and other adverse maternal or fetal outcomes. Transport of human
IgG antibody across the placenta increases as pregnancy progresses and peaks
during the third trimester; therefore, ustekinumab products may be transferred
to the developing fetus [see Clinical
Considerations]. 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).
The
background risk of major birth defects and miscarriage for the indicated
population(s) are unknown. All pregnancies have a background risk of birth
defect, loss, or other adverse outcomes. In the U.S. general population, the
estimated background risk of major birth defects and miscarriage of clinically
recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical
Considerations
Fetal/Neonatal
Adverse Reactions
Because
ustekinumab products may theoretically interfere with immune response to
infections, consider risks and benefits prior to administering live vaccines to
infants exposed to WEZLANA in utero.
There are insufficient data regarding exposed infant serum levels of
ustekinumab products at birth and the duration of persistence of ustekinumab
products in infant serum after birth. Although a specific timeframe to delay
administration of live attenuated vaccines in infants exposed in utero is unknown, consider the risks
and benefits of delaying a minimum of 6 months after birth because of the
clearance of the product.
Data
…
In
a combined embryo-fetal development and pre- and post-natal development
toxicity study, pregnant cynomolgus monkeys were administered subcutaneous
doses of ustekinumab twice weekly at exposures greater than 100 times the MRHD
from the beginning of organogenesis to Day 33 after delivery.
…
8.2 Lactation
Additions
and/or revisions underlined:
Limited
data from published literature suggests that ustekinumab is present in human
breast milk.
There are no available data on the effects of ustekinumab products on
milk production. The effects of local gastrointestinal exposure and limited systemic
exposure in the breastfed infant to ustekinumab products are unknown. No
adverse effects on the breastfed infant causally related to ustekinumab
products have been identified in the published literature or postmarketing
experience.
…
8.4 Pediatric Use
Additions and/or revisions underlined:
Plaque
Psoriasis
The safety and effectiveness of WEZLANA have been
established for the treatment of moderate to severe plaque psoriasis in
pediatric patients 6 to 17 years of age who are candidates for phototherapy
or systemic therapy.
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions
and/or revisions underlined:
Before you receive
WEZLANA, tell your doctor about all of your medical conditions, including if
you:
…
- received WEZLANA while you were pregnant. It is
important that you tell your baby’s healthcare provider before any vaccinations
are given to your baby.
…
How should I use
WEZLANA?
- The needle cover
on the WEZLANA prefilled syringe and prefilled ConfiPen™ autoinjector
does not contain latex.
…
Read the detailed
Instructions for Use for instructions about how to prepare and inject a dose of
WEZLANA, and how to properly throw away (dispose of) used needles and syringes.
The WEZLANA syringe, needle, vial and ConfiPen autoinjector must
never be re-used.
…
How should I store
WEZLANA?
Store WEZLANA vials, prefilled syringes and prefilled
ConfiPen autoinjector in a refrigerator between 36°F to 46°F (2°C to 8°C).
Store WEZLANA in the original carton to protect it
from light until time to use it.
Do not freeze WEZLANA.
If needed, individual prefilled syringe, 45 mg vial and
prefilled ConfiPen autoinjector may also be stored at room temperature up
to 30°C (86°F) for a maximum single period of up to 30 days in the original
carton to protect from light. Record the date when the prefilled syringe, the
45 mg vial or prefilled ConfiPen autoinjector is first removed from the
refrigerator on the carton in the space provided. Once the prefilled syringe,
the 45 mg vial or prefilled ConfiPen autoinjector has been stored at
room temperature, it should not be returned to the refrigerator.
Discard the prefilled syringe, the 45 mg vial or
prefilled ConfiPen autoinjector if not used within 30 days at room
temperature storage. Do not use WEZLANA after the expiration date on the carton
or on the prefilled syringe, on the 45 mg vial or on the prefilled ConfiPen
autoinjector.
…
Inactive
ingredients: Single-dose prefilled syringe for subcutaneous use contains histidine, histidine hydrochloride monohydrate, Polysorbate 80,
and sucrose. Single-dose vial for subcutaneous use contains histidine,
histidine hydrochloride monohydrate, Polysorbate 80 and sucrose. Single-dose
prefilled ConfiPen autoinjector for subcutaneous use contains
histidine, histidine hydrochloride monohydrate, Polysorbate 80, and sucrose.
Single-dose vial for intravenous infusion contains edetate disodium,
histidine, histidine hydrochloride monohydrate, methionine, Polysorbate 80, and
sucrose.
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