2023 Meeting Magazine - 29

For patients with ulcerative colitis or Crohn's disease taking strong CYP3A4
inhibitors, reduce the RINVOQ induction dosage to 30 mg once daily. The
recommended maintenance dosage is 15 mg once daily.
Strong CYP3A4 Inducers
Upadacitinib exposure is decreased when RINVOQ is co-administered with
strong CYP3A4 inducers (such as rifampin), which may lead to reduced
therapeutic effect of RINVOQ. Coadministration of RINVOQ with strong
CYP3A4 inducers is not recommended.
USE IN SPECIFIC POPULATIONS
Pregnancy
Risk Summary
Available data from the pharmacovigilance safety database and
postmarketing case reports on use of RINVOQ in pregnant women are
not sufficient to evaluate a drug-associated risk for major birth defects or
miscarriage. Based on animal studies, RINVOQ has the potential to adversely
affect a developing fetus. Advise patients of reproductive potential and
pregnant patients of the potential risk to the fetus.
In animal embryo-fetal development studies, oral upadacitinib
administration to pregnant rats and rabbits at exposures equal to or greater
than approximately 1.6 and 15 times the 15 mg dose, 0.8 and 7.6 times
the 30 mg dose, and 0.6 and 5.6 times the maximum recommended
human dose (MRHD) of 45 mg (on an AUC basis) resulted in dose-related
increases in skeletal malformations (rats only), an increased incidence of
cardiovascular malformations (rabbits only), increased post-implantation
loss (rabbits only), and decreased fetal body weights in both rats and
rabbits. No developmental toxicity was observed in pregnant rats and
rabbits treated with oral upadacitinib during organogenesis at exposures
approximately 0.29 and 2.2 times the 15 mg dose, 0.15 times and 1.1 times
the 30 mg dose, and at 0.11 and 0.82 times the MRHD (on an AUC basis).
In a pre- and post-natal development study in pregnant female rats, oral
upadacitinib administration at exposures approximately 3 times the 15 mg
dose, 1.4 times the 30 mg dose, and the same as the MRHD (on an AUC
basis) resulted in no maternal or developmental toxicity (see Data).
The background risks of major birth defects and miscarriage for the
indicated populations 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
miscarriages are 2-4% and 15-20%, respectively.
Report pregnancies to the AbbVie Inc.'s Adverse Event reporting line at
1-800-633-9110, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Clinical Considerations
Disease-Associated Maternal and/or Embryo/Fetal Risk
Published data suggest that increased disease activity is associated with the
risk of developing adverse pregnancy outcomes in women with rheumatoid
arthritis or inflammatory bowel disease. 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.
Data
Animal Data
In an oral embryo-fetal development study, pregnant rats received
upadacitinib at doses of 5, 25, and 75 mg/kg/day during the period of
organogenesis from gestation day 6 to 17. Upadacitinib was teratogenic
(skeletal malformations that consisted of misshapen humerus and bent
scapula) at exposures equal to or greater than approximately 1.7 times the
15 mg dose, 0.9 times the 30 mg dose, and 0.6 times the MRHD (on an
AUC basis at maternal oral doses of 5 mg/kg/day and higher). Additional
skeletal malformations (bent forelimbs/hindlimbs and rib/vertebral defects)
and decreased fetal body weights were observed in the absence of maternal
toxicity at an exposure approximately 84 times the 15 mg dose, 43 times
the 30 mg dose, and 31 times the MRHD (on an AUC basis at a maternal oral
dose of 75 mg/kg/day).
In a second oral embryo-fetal development study, pregnant rats received
upadacitinib at doses of 1.5 and 4 mg/kg/day during the period of
organogenesis from gestation day 6 to 17. Upadacitinib was teratogenic
(skeletal malformations that included bent humerus and scapula) at
exposures approximately 1.6 times the 15 mg dose, 0.8 times the 30 mg
dose, and 0.6 times the MRHD (on an AUC basis at maternal oral doses
of 4 mg/kg/day). No developmental toxicity was observed in rats at an
exposure approximately 0.29 times the 15 mg dose, 0.15 times the 30 mg
dose, and 0.11 times the MRHD (on an AUC basis at a maternal oral dose
of 1.5 mg/kg/day).
In an oral embryo-fetal developmental study, pregnant rabbits received
upadacitinib at doses of 2.5, 10, and 25 mg/kg/day during the period of
organogenesis from gestation day 7 to 19. Embryolethality, decreased fetal
body weights, and cardiovascular malformations were observed in the
presence of maternal toxicity at an exposure approximately 15 times the
15 mg dose, 7.6 times the 30 mg dose, and 5.6 times the MRHD (on an AUC
basis at a maternal oral dose of 25 mg/kg/day). Embryolethality consisted
of increased post-implantation loss that was due to elevated incidences of
both total and early resorptions. No developmental toxicity was observed in
rabbits at an exposure approximately 2.2 times the 15 mg dose, 1.1 times
the 30 mg dose, and 0.82 times the MRHD (on an AUC basis at a maternal
oral dose of 10 mg/kg/day).
In an oral pre- and post-natal development study, pregnant female rats
received upadacitinib at doses of 2.5, 5, and 10 mg/kg/day from gestation
day 6 through lactation day 20. No maternal or developmental toxicity
was observed in either mothers or offspring, respectively, at an exposure
approximately 3 times the 15 mg dose, 1.4 times the 30 mg dose, and
at approximately the same exposure as the MRHD (on an AUC basis at a
maternal oral dose of 10 mg/kg/day).
Lactation
Risk Summary
There are no data on the presence of upadacitinib in human milk, the
effects on the breastfed infant, or the effects on milk production. Available
pharmacodynamic/toxicological data in animals have shown excretion of
upadacitinib in milk (see Data). When a drug is present in animal milk, it is
likely that the drug will be present in human milk. Because of the potential
for serious adverse reactions in the breastfed infant, advise patients that
breastfeeding is not recommended during treatment with RINVOQ, and for 6
days (approximately 10 half-lives) after the last dose.
Data
A single oral dose of 10 mg/kg radiolabeled upadacitinib was administered
to lactating female Sprague-Dawley rats on post-partum days 7-8. Drug
exposure was approximately 30-fold greater in milk than in maternal plasma
based on AUC0-t values. Approximately 97% of drug-related material in milk
was parent drug.
Females and Males of Reproductive Potential
Pregnancy Testing
PATIENT COUNSELING INFORMATION
Verify the pregnancy status of females of reproductive potential prior to
starting treatment with RINVOQ [see Use in Specific Populations].
Contraception
Females
Based on animal studies, upadacitinib may cause embryo-fetal harm when
administered to pregnant women [see Use in Specific Populations]. Advise
female patients of reproductive potential to use effective contraception
during treatment with RINVOQ and for 4 weeks after the final dose.
Pediatric Use
Juvenile Idiopathic Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, and
Non-radiographic Axial Spondyloarthritis
The safety and effectiveness of RINVOQ in pediatric patients with juvenile
idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, or nonradiographic
axial spondyloarthritis have not been established.
Atopic Dermatitis
The safety and effectiveness of RINVOQ in pediatric patients 12 years of
age and older weighing at least 40 kg with atopic dermatitis have been
established. A total of 344 pediatric patients aged 12 to 17 years with
moderate to severe atopic dermatitis were randomized across three trials
(AD-1, AD-2 and AD-3) to receive either RINVOQ 15 mg (N=114) or 30 mg
(N=114) or matching placebo (N=116) in monotherapy or combination
with topical corticosteroids. Efficacy was consistent between the pediatric
patients and adults. The adverse reaction profile in the pediatric patients
was similar to the adults [see Adverse Reactions].
The safety and effectiveness of RINVOQ in pediatric patients less than 12
years of age with atopic dermatitis have not been established.
Ulcerative Colitis and Crohn's Disease
The safety and effectiveness of RINVOQ in pediatric patients with ulcerative
colitis and Crohn's disease have not been established.
Geriatric Use
Rheumatoid Arthritis and Psoriatic Arthritis
Of the 4381 patients treated in the five clinical trials, a total of 906
rheumatoid arthritis patients were 65 years of age or older, including 146
patients 75 years and older. Of the 1827 patients treated in the two psoriatic
arthritis Phase 3 clinical trials, a total of 274 patients were 65 years of
age or older, including 34 patients 75 years and older. No differences in
effectiveness were observed between these patients and younger patients;
however, there was a higher rate of overall adverse events, including
serious infections, in patients 65 years of age and older.
Atopic Dermatitis
Of the 2583 patients treated in the three Phase 3 clinical trials, a total of
120 patients with atopic dermatitis were 65 years of age or older, including
6 patients 75 years of age. No differences in effectiveness were observed
between these patients and younger patients; however, there was a higher
rate of serious infections and malignancies in those patients 65 years of age
or older in the 30 mg dosing group in the long-term trials.
Ulcerative Colitis
Of the 1097 patients treated in the controlled clinical trials, a total of 95
patients with ulcerative colitis were 65 years and older. Clinical studies of
RINVOQ did not include sufficient numbers of patients 65 years of age and
older with ulcerative colitis to determine whether they respond differently
from younger adult patients.
Crohn's Disease
Of the 1021 patients who were treated in the controlled induction clinical
trials, a total of 39 patients with Crohn's disease were 65 years of age or
older, and no patients were 75 years of age or older. Clinical studies of
RINVOQ did not include sufficient numbers of patients 65 years of age and
older with Crohn's disease to determine whether they respond differently
from younger adult patients.
Ankylosing Spondylitis
Of the 607 patients treated in the controlled clinical trials, a total of 32
patients with ankylosing spondylitis were 65 years and older. Clinical studies
of RINVOQ did not include sufficient numbers of patients 65 years of age
and older with ankylosing spondylitis to determine whether they respond
differently from younger adult patients.
Non-radiographic Axial Spondyloarthritis
Of the 313 patients treated in a phase 3 clinical trial, a total of 9 patients
with non-radiographic axial spondyloarthritis were 65 years and older.
Clinical studies of RINVOQ did not include sufficient numbers of patients
65 years of age and older with non-radiographic axial spondyloarthritis to
determine whether they respond differently from younger adult patients.
Renal Impairment
For patients with rheumatoid arthritis, psoriatic arthritis, ankylosing
spondylitis, or non-radiographic axial spondyloarthritis, no dosage adjustment
is needed in patients with mild (eGFR 60 to < 90 mL/min/1.73 m2), moderate
(eGFR 30 to < 60 mL/min/1.73 m2), or severe renal impairment (eGFR 15 to
< 30 mL/min/1.73 m2).
For patients with atopic dermatitis, the maximum recommended dosage
is 15 mg once daily for patients with severe renal impairment. No dosage
adjustment is needed in patients with mild or moderate renal impairment.
For patients with ulcerative colitis or Crohn's disease, the recommended
dosage for severe renal impairment is 30 mg once daily for induction and
15 mg once daily for maintenance. No dosage adjustment is needed in
patients with mild or moderate renal impairment.
RINVOQ has not been studied in patients with end stage renal disease
(eGFR <15 mL/min/1.73m2). Use in patients with atopic dermatitis,
ulcerative colitis, or Crohn's disease with end stage renal disease is not
recommended.
Hepatic Impairment
The use of RINVOQ has not been studied in patients with severe hepatic
impairment (Child Pugh C), and therefore not recommended for use in
patients with rheumatoid arthritis, psoriatic arthritis, atopic dermatitis,
ulcerative colitis, Crohn's disease, ankylosing spondylitis, and nonradiographic
axial spondyloarthritis.
For patients with rheumatoid arthritis, psoriatic arthritis, atopic dermatitis,
ankylosing spondylitis, and non-radiographic axial spondyloarthritis no
dosage adjustment is needed in patients with mild (Child Pugh A) or
moderate (Child Pugh B) hepatic impairment.
For patients with ulcerative colitis or Crohn's disease, the recommended
dosage for mild to moderate hepatic impairment is 30 mg once daily for
induction and 15 mg once daily for maintenance.
Advise the patient to read the FDA-approved patient labeling (Medication
Guide).
Serious Infections
Inform patients that they may be more likely to develop infections when
taking RINVOQ. Instruct patients to contact their healthcare provider
immediately during treatment if they develop any signs or symptoms of an
infection [see Warnings and Precautions].
Advise patients that the risk of herpes zoster is increased in patients taking
RINVOQ and in some cases can be serious [see Warnings and Precautions].
Malignancies
Inform patients that RINVOQ may increase their risk of certain cancers and
that periodic skin examinations should be performed while using RINVOQ.
Advise patients that exposure to sunlight and UV light should be limited
by wearing protective clothing and using a broad-spectrum sunscreen
[see Warnings and Precautions].
Major Adverse Cardiovascular Events
Inform patients that RINVOQ may increase their risk of major adverse
cardiovascular events (MACE) including myocardial infarction, stroke,
and cardiovascular death. Instruct all patients, especially current or past
smokers or patients with other cardiovascular risk factors, to be alert for the
development of signs and symptoms of cardiovascular events [see Warnings
and Precautions].
Thrombosis
Inform patients that events of deep venous thrombosis and pulmonary
embolism have been reported in clinical trials with RINVOQ. Instruct patients
to seek immediate medical attention if they develop any signs or symptoms
of a DVT or PE [see Warnings and Precautions].
Hypersensitivity Reactions
Advise patients to discontinue RINVOQ and seek immediate medical
attention if they develop any signs and symptoms of allergic reactions
[see Warnings and Precautions].
Gastrointestinal Perforations
Inform patients that gastrointestinal perforations have been reported in
clinical trials with RINVOQ and that risk factors include the use of NSAIDs,
corticosteroids, or history of diverticulitis. Instruct patients to seek medical
care immediately if they experience new onset of abdominal pain, fever,
chills, nausea, or vomiting [see Warnings and Precautions].
Retinal Detachment
Inform patients that retinal detachment has been reported in clinical trials
with RINVOQ. Advise patients to immediately inform their healthcare
provider if they develop any sudden changes in vision while receiving
RINVOQ [see Adverse Reactions].
Laboratory Abnormalities
Inform patients that RINVOQ may affect certain lab tests, and that blood
tests are required before and during RINVOQ treatment [see Warnings and
Precautions].
Vaccinations
Advise patients to avoid use of live vaccines with RINVOQ. Instruct patients
to inform their healthcare practitioner that they are taking RINVOQ prior to a
potential vaccination [see Warnings and Precautions].
Embryo-Fetal Toxicity
Advise pregnant women and females of reproductive potential that exposure
to RINVOQ during pregnancy may result in fetal harm. Advise females
to inform their healthcare provider of a known or suspected pregnancy
[see Warnings and Precautions and Use in Specific Populations].
Advise females of reproductive potential that effective contraception should
be used during treatment and for 4 weeks following the final dose of
upadacitinib [see Use in Specific Populations].
Advise females patients who are exposed to RINVOQ during pregnancy
to contact AbbVie Inc. at 1-800-633-9110 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
Lactation
Advise women not to breastfeed during treatment with RINVOQ and for 6
days after the last dose [see Use in Specific Populations].
Administration
Advise patients not to chew, crush, or split RINVOQ tablets.
Advise patients to avoid food or drink containing grapefruit during treatment
with RINVOQ [see Drug Interactions].
Medication Residue in Stool
Instruct patients to notify their healthcare provider if they repeatedly notice
medication residue (e.g., intact RINVOQ tablet or fragments) in stool or
ostomy output [see Warnings and Precautions].
Manufactured by: AbbVie Inc., North Chicago, IL 60064, USA
RINVOQ® is a registered trademark of AbbVie Biotechnology Ltd.
©2019-2023 AbbVie Inc.
Ref: 20079343 Revised: June 2023
LAB-9733 MASTER
US-RNQR-230547
https://www.rinvoqhcp.com/ http://www.fda.gov/medwatch http://www.fda.gov/medwatch
2023 Meeting Magazine

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