Get Email Alerts |
Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
RINVOQ (NDA-211675)
(UPADACITINIB)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
06/30/2026 (SUPPL-34)
5 Warnings and Precautions
5.8 Hypoglycemia in Patients with Diabetes
Newly added subsection:
Hypoglycemia, including severe hypoglycemia, has been reported following initiation of RINVOQ/RINVOQ LQ and other JAK inhibitors in patients with diabetes. During treatment with RINVOQ/RINVOQ LQ, consider increased monitoring of blood glucose as clinically indicated in patients with diabetes. Advise patients with diabetes to notify their healthcare provider if they develop signs or symptoms of hypoglycemia.
6 Adverse Reactions
Addition of the following to the bulleted line listing:
Hypoglycemia in Patients with Diabetes [see Warnings and Precautions (5.8)]
6.2 Postmarketing Experience
Newly added subsection:
The following adverse reactions have been identified during post-approval use of RINVOQ/RINVOQ LQ. 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 drug exposure:
Metabolism and nutrition disorders: Hypoglycemia
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEAdditions and/or revisions underlined:
…
8. Low blood sugar (hypoglycemia) in people with diabetes.
If you have diabetes, your healthcare provider may tell you to check your blood sugar (glucose) more often during treatment with RINVOQ/RINVOQ LQ. Call your healthcare provider if you have any problems with low blood sugar.
…
Before taking RINVOQ/RINVOQ LQ, tell your healthcare provider about all your medical conditions, including if you:
…
have diabetes
…
Additions and/or revisions underlined:
…
Hypoglycemia in Patients with Diabetes
Consider advising patients with diabetes to increase monitoring of blood glucose since hypoglycemia, including severe hypoglycemia, has been reported after starting RINVOQ/RINVOQ LQ. Advise patients with diabetes to notify their healthcare provider if they develop signs or symptoms of hypoglycemia [see Warnings and Precautions (5.8)].
…
10/10/2025 (SUPPL-28)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions and/o revisions underlined:
…
What is RINVOQ/RINVOQ LQ?
…
RINVOQ is used to treat adults with moderate to severe ulcerative colitis when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used and did not work well or could not be tolerated, or after taking a different injection or pill (systemic therapy) when your healthcare provider does not recommend TNF blockers.
- RINVOQ is used to treat adults with moderate to severe Crohn’s disease when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used and did not work well or could not be tolerated, or after taking a different injection or pill (systemic therapy) when your healthcare provider does not recommend TNF blockers.
…
04/28/2025 (SUPPL-25)
6 Adverse Reactions
6.1 Clinical Trials ExperienceAdditions and/or revisions underlined:
…
Adverse Reactions in Patients with Giant Cell Arteritis
In the Phase 3 study, 209 patients with giant cell arteritis received at least 1 dose of RINVOQ 15 mg, of whom 122 were exposed for at least one year during the 52-week placebo-controlled period. The safety profile observed in patients with giant cell arteritis was generally consistent with the known safety profile for RINVOQ.
Table 10: Adverse Reactions Reported in greater than or equal to 5% of Patients with Giant Cell Arteritis Treated with RINVOQ 15 mg in the Placebo-controlled Study
Please refer to label to view Table 10.
…
Specific Adverse Reactions
Opportunistic Infections (excluding tuberculosis and herpes zoster)
In the 52-week placebo-controlled period, opportunistic infections were reported in 1 patient (1.1 per 100 patient-years) treated with placebo and 4 patients (2.3 per 100 patient-years) treated with RINVOQ 15 mg.
ThrombosisIn the 52-week placebo-controlled period, venous thromboembolic events (pulmonary embolism or deep vein thrombosis) were observed in 4 patients (4.3 per 100 patient-years) treated with placebo and 7 patients (3.9 per 100 patient-years) treated with RINVOQ 15 mg. Events of arterial thrombosis were observed in 2 patients (1.1 per 100 patient-years) treated with RINVOQ 15 mg and 0 patients treated with placebo.
7 Drug Interactions
7.1 Strong CYP3A4 InhibitorsAdditions and/or revisions underlined:
Upadacitinib exposure is increased when it is co-administered with a strong CYP3A4 inhibitor (such as ketoconazole, clarithromycin, and grapefruit), which may increase the risk of adverse reactions [see Clinical Pharmacology (12.3)]. Monitor patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondylarthritis, pJIA, or giant cell arteritis closely for adverse reactions when co-administering RINVOQ/RINVOQ LQ with strong CYP3A4 inhibitors. Food or drink containing grapefruit should be avoided during treatment with RINVOQ/RINVOQ LQ.
…
8 Use in Specific Populations
8.6 Renal Impairment
Additions and/or revisions underlined:
For patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non- radiographic axial spondyloarthritis, pJIA, or giant cell arteritis 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).
8.7 Hepatic Impairment
Additions and/or revisions underlined:
…
For patients with rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, pJIA, or giant cell arteritis, no dosage adjustment is needed in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment.
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEAdditions and/or revisions underlined:
…
What is RINVOQ/RINVOQ LQ?
…
RINVOQ is used to treat adults with giant cell arteritis.
…
What are the possible side effects of RINVOQ/RINVOQ LQ?
…
The most common side effects of RINVOQ in people treated for giant cell arteritis include:
upper respiratory tract infections (common cold, sinus infections)
cough
low red blood cell count (anemia)
headache
rash
tiredness
shingles (herpes zoster)
swelling of the feet and hands (peripheral edema)
nausea
…
03/26/2025 (SUPPL-27)
6 Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or revisions of the following underlined text to Table 7:
Adverse Reaction: Upper respiratory tract infection*
RINVOQ 15mg Once Daily: 17
Adverse Reaction: Pyrexia
Placebo: 3
RINVOQ 15mg Once Daily: 3
RINVOOQ 30mg Once Daily: 6
Adverse Reaction: Herpes zoster
RINVOQ 15mg Once Daily: 5
RINVOQ 30MG Once Daily: 6
Additions and/or revisions underlined:
. . .
Specific Adverse Reactions Serious Infections
. . .
Placebo-controlled Maintenance Study: In UC-3, serious infections were reported in 8 patients (5.9 events per 100 patient-years) treated with placebo, 9 patients (5.0 events per 100 patient- years) treated with RINVOQ 15 mg, and 8 patients (3.7 events per 100 patient-years) treated with RINVOQ 30 mg through 52 weeks.
. . .
Laboratory Abnormalities
Hepatic Transaminase Elevations
. . .
In UC-3, elevations of ALT to greater than or equal
to 3 x ULN in at least one measurement were observed in 4.4% of patients
treated with RINVOQ 30 mg, 2% of patients treated with RINVOQ 15 mg, and 1.2%
of patients treated with placebo for 52 weeks. Elevations of AST to greater
than or equal to 3 x ULN in at least one measurement were observed in 2% of
patients treated with RINVOQ 30 mg, 1.6% of patients treated with RINVOQ 15 mg
and 0.4% of patients treated with placebo. Elevations of ALT to greater than or
equal to 5 x ULN were observed in 1.2% of patients treated with 30 mg,
0.4% of patients treated with 15 mg, and 0.4% of patients treated with placebo.
. . .
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Addition of the following to the bulleted line listing:
. . .
The most common side effects of RINVOQ in people treated for ulcerative colitis include:
. . .
fever
. . .
04/26/2024 (SUPPL-21)
6 Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or revisions underlined:
Adverse Reactions in Patients with Rheumatoid Arthritis
A total of 3833 adult patients with rheumatoid arthritis were treated with RINVOQ 15 mg or upadacitinib 30 mg tablets once daily in the Phase 3 clinical trials of whom 2806 were exposed for at least one year.
…
Adverse Reactions in Patients with Psoriatic Arthritis
A total of 1827 adult patients with psoriatic arthritis were treated with RINVOQ 15 mg or upadacitinib 30 mg tablets once daily in clinical trials, representing 1639.2 patient-years of exposure, of whom 722 were exposed to upadacitinib for at least one year.
…
Adverse Reactions in Patients with Polyarticular Juvenile Idiopathic Arthritis
A total of 83 pediatric patients with juvenile idiopathic arthritis (JIA) with active polyarthritis were treated with RINVOQ/RINVOQ LQ in the clinical trial, representing 123.7 patient-years of exposure, of whom 48 were exposed to RINVOQ/RINVOQ LQ for at least one year.
Overall, the safety profile observed in pediatric patients with JIA with active polyarthritis treated with RINVOQ/RINVOQ LQ was consistent with the known safety profile of RINVOQ.
8 Use in Specific Populations
8.4 Pediatric Use
Additions and/or revisions underlined:
Ankylosing Spondylitis, Non-radiographic Axial Spondyloarthritis,
Ulcerative Colitis, and Crohn’s Disease
The safety and effectiveness of RINVOQ/RINVOQ LQ in pediatric patients with ankylosing spondylitis, non-radiographic axial spondyloarthritis, ulcerative colitis, or Crohn’s disease have not been established.
Polyarticular Juvenile Idiopathic Arthritis and Psoriatic Arthritis
The safety and effectiveness of RINVOQ/RINVOQ LQ in pediatric patients 2 to less than 18 years of age with pJIA and psoriatic arthritis have been established.
The use of RINVOQ/RINVOQ LQ in these age groups is supported by evidence from well- controlled studies of RINVOQ in adults with rheumatoid arthritis and psoriatic arthritis, pharmacokinetic data from adult patients with rheumatoid arthritis and psoriatic arthritis and 51 pediatric patients with JIA with active polyarthritis, and safety data from 83 pediatric patients 2 to < 18 years of age with JIA with active polyarthritis. Upadacitinib plasma exposures in pediatric patients with pJIA and psoriatic arthritis at the recommended dosage are predicted to be comparable to those observed in adults with rheumatoid arthritis and psoriatic arthritis based on population pharmacokinetic modeling and simulation [see Dosage and Administration (2.4, 2.10), Adverse Reactions (6.1), Clinical Pharmacology (12.3) and Clinical Studies (14.8)].
The safety and effectiveness of RINVOQ/RINVOQ LQ in pediatric patients less than 2 years of age with pJIA or psoriatic arthritis have not been established.
…
The safety and effectiveness of RINVOQ LQ in pediatric patients with atopic dermatitis have not been established.
8.6 Renal Impairment
Additions and/or revisions underlined:
For patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non- radiographic axial spondyloarthritis, or pJIA 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).
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
Advise the patient and caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).
…
Administration
Advise patients that RINVOQ tablets are not substitutable with RINVOQ LQ [see Dosage and Administration (2.2)].
Advise patients not to chew, crush, or split RINVOQ tablets [see Dosage and Administration (2.2)].
For RINVOQ LQ, instruct patients and caregivers to read and follow the Instructions for Use for proper preparation, administration, storage, and disposal [See Dosage and Administration (2.1)].
Advise patients to avoid food or drink containing grapefruit during treatment with RINVOQ/RINVOQ LQ [see Drug Interactions (7.1)].
MEDICATION GUIDE
Extensive changes; please refer to label for complete information
04/26/2024 (SUPPL-22)
6 Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or revisions underlined:
Adverse Reactions in Patients with Rheumatoid Arthritis
A total of 3833 adult patients with rheumatoid arthritis were treated with RINVOQ 15 mg or upadacitinib 30 mg tablets once daily in the Phase 3 clinical trials of whom 2806 were exposed for at least one year.
…
Adverse Reactions in Patients with Psoriatic Arthritis
A total of 1827 adult patients with psoriatic arthritis were treated with RINVOQ 15 mg or upadacitinib 30 mg tablets once daily in clinical trials, representing 1639.2 patient-years of exposure, of whom 722 were exposed to upadacitinib for at least one year.
…
Adverse Reactions in Patients with Polyarticular Juvenile Idiopathic Arthritis
A total of 83 pediatric patients with juvenile idiopathic arthritis (JIA) with active polyarthritis were treated with RINVOQ/RINVOQ LQ in the clinical trial, representing 123.7 patient-years of exposure, of whom 48 were exposed to RINVOQ/RINVOQ LQ for at least one year.
Overall, the safety profile observed in pediatric patients with JIA with active polyarthritis treated with RINVOQ/RINVOQ LQ was consistent with the known safety profile of RINVOQ.
8 Use in Specific Populations
8.4 Pediatric Use
Additions and/or revisions underlined:
Ankylosing Spondylitis, Non-radiographic Axial Spondyloarthritis,
Ulcerative Colitis, and Crohn’s Disease
The safety and effectiveness of RINVOQ/RINVOQ LQ in pediatric patients with ankylosing spondylitis, non-radiographic axial spondyloarthritis, ulcerative colitis, or Crohn’s disease have not been established.
Polyarticular Juvenile Idiopathic Arthritis and Psoriatic Arthritis
The safety and effectiveness of RINVOQ/RINVOQ LQ in pediatric patients 2 to less than 18 years of age with pJIA and psoriatic arthritis have been established.
The use of RINVOQ/RINVOQ LQ in these age groups is supported by evidence from well- controlled studies of RINVOQ in adults with rheumatoid arthritis and psoriatic arthritis, pharmacokinetic data from adult patients with rheumatoid arthritis and psoriatic arthritis and 51 pediatric patients with JIA with active polyarthritis, and safety data from 83 pediatric patients 2 to < 18 years of age with JIA with active polyarthritis. Upadacitinib plasma exposures in pediatric patients with pJIA and psoriatic arthritis at the recommended dosage are predicted to be comparable to those observed in adults with rheumatoid arthritis and psoriatic arthritis based on population pharmacokinetic modeling and simulation [see Dosage and Administration (2.4, 2.10), Adverse Reactions (6.1), Clinical Pharmacology (12.3) and Clinical Studies (14.8)].
The safety and effectiveness of RINVOQ/RINVOQ LQ in pediatric patients less than 2 years of age with pJIA or psoriatic arthritis have not been established.
…
The safety and effectiveness of RINVOQ LQ in pediatric patients with atopic dermatitis have not been established.
8.6 Renal Impairment
Additions and/or revisions underlined:
For patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non- radiographic axial spondyloarthritis, or pJIA 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).
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
Advise the patient and caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).
…
Administration
Advise patients that RINVOQ tablets are not substitutable with RINVOQ LQ [see Dosage and Administration (2.2)].
Advise patients not to chew, crush, or split RINVOQ tablets [see Dosage and Administration (2.2)].
For RINVOQ LQ, instruct patients and caregivers to read and follow the Instructions for Use for proper preparation, administration, storage, and disposal [See Dosage and Administration (2.1)].
Advise patients to avoid food or drink containing grapefruit during treatment with RINVOQ/RINVOQ LQ [see Drug Interactions (7.1)].
MEDICATION GUIDE
Extensive changes; please refer to label for complete information
11/14/2023 (SUPPL-19)
5 Warnings and Precautions
5.1 Serious InfectionsAdditions and revisions underlined:
… A higher rate of serious infections was observed with RINVOQ 30 mg compared to RINVOQ 15 mg.
…
8 Use in Specific Populations
8.1 PregnancyAdditions and/or revisions underlined:
Pregnancy Surveillance Program
There is a pregnancy surveillance program for RINVOQ that monitors pregnancy outcomes in women exposed to RINVOQ. If RINVOQ exposure occurs during pregnancy, healthcare providers or patients should report the pregnancy by calling 1-800-633-9110.
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
…
Embryo-Fetal Toxicity
…
Advise women exposed to RINVOQ during pregnancy that there is a pregnancy surveillance program that monitors pregnancy outcomes [see Use in Specific Populations (8.1)].
…
MEDICATION GUIDE
Additions and/or revisions underlined:
…
Before taking RINVOQ, tell your healthcare provider about all of your medical conditions, including if you:
See “What is the most important information I should know about RINVOQ?”
…
Females who are able to become pregnant:
…
There is a pregnancy surveillance program for RINVOQ. The purpose of the program is to collect information about the health of you and your baby. If you become pregnant while taking RINVOQ, you are encouraged to report the pregnancy by calling 1-800-633-9110.
…
06/22/2023 (SUPPL-17)
5 Warnings and Precautions
5.7 Gastrointestinal Perforations
(Additions and/or revisions underlined)
Gastrointestinal perforations have been reported in clinical trials with RINVOQ [see Adverse Reactions (6.1)].
8 Use in Specific Populations
8.1 Pregnancy
Risk Summary
(Additions and/or revisions underlined)
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…
8.6 Renal Impairment
(Additions and/or revisions underlined)
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 [see Dosage and Administration (2.10)].
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 [see Clinical Pharmacology (12.3)].
8.7 Hepatic Impairment
(Additions and/or revisions underlined)
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 non- radiographic axial spondyloarthritis [see Dosage and Administration (2.10) and Clinical Pharmacology (12.3)].
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 [see Dosage and Administration (2.10)].
05/18/2023 (SUPPL-15)
5 Warnings and Precautions
5.11 Medication Residue in StoolNew subsection added:
Reports of medication residue in stool or ostomy output have occurred in patients taking RINVOQ. Most reports described anatomic (e.g., ileostomy, colostomy, intestinal resection) or functional gastrointestinal conditions with shortened gastrointestinal transit times. Instruct patients to contact their healthcare provider if medication residue is observed repeatedly.
Monitor patients clinically and consider alternative treatment if there is an inadequate therapeutic response.
Additions and/or revisions underlined:
Gastrointestinal perforations have been reported in clinical trials with RINVOQ.
Monitor RINVOQ-treated patients who may be at risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis and those taking concomitant medications including NSAIDs or corticosteroids). Evaluate promptly patients presenting with new onset abdominal pain for early identification of gastrointestinal perforation.
6 Adverse Reactions
6.1 Clinical Trials ExperienceAdditions and/or revisions underlined:
Adverse Reactions in Patients with Crohn’s Disease
RINVOQ was studied up to 12 weeks in patients with moderately to severely active CD in two randomized, double-blind, placebo-controlled induction studies (CD-1, CD-2). Long term safety
up to 52 weeks was evaluated in patients who responded to induction therapy in a randomized, double-blind, placebo-controlled maintenance study (CD-3), with additional data provided from a long-term extension (LTE) period [see Clinical Studies (14.5)].
In the two induction studies (CD-1, CD-2), 1021 patients were enrolled, of whom 674 patients received RINVOQ 45 mg once daily during the placebo-controlled period.
In the maintenance study (CD-3), 673 patients were enrolled, of whom 221 patients received RINVOQ 15 mg once daily and 229 patients received RINVOQ 30 mg once daily during the randomized, placebo-controlled period.
Overall, the safety profile observed in patients with Crohn’s disease treated with RINVOQ was consistent with the known safety profile for RINVOQ in other indications.
Adverse reactions reported in greater than or equal to 2% of patients treated with RINVOQ and at a higher rate than placebo in the induction and maintenance studies are shown in Tables 6 and 7, respectively.
Table 6: Adverse Reactions Reported in greater than or equal to 2% of Patients with Crohn’s Disease Treated with RINVOQ 45 mg in Placebo-Controlled Induction Studies (CD-1 and CD-2)
Please refer to label to view Table 6
Adverse reactions reported in less than 2% of patients in the RINVOQ 45 mg group and at a higher rate than in the placebo group through Week 12 included folliculitis, hypercholesterolemia, bronchitis, pneumonia, oral candidiasis, and hyperlipidemia.
Table 7: Adverse Reactions Reported in greater than or equal to 2% of Patients with Crohn’s Disease Treated with RINVOQ 15 mg or 30 mg in the Placebo-Controlled Maintenance Study (CD-3)1
Please refer to label to view Table 7
Adverse reactions reported in less than 2% of patients in the RINVOQ 15 mg or 30 mg group and at a higher rate than in the placebo group through Week 52 included hyperlipidemia, oral candidiasis, and hypercholesterolemia.
The safety profile of RINVOQ in the long-term extension study was similar to the safety profile observed in the placebo-controlled induction and maintenance periods.
Specific Adverse Reactions Serious
Infections
Induction Studies: In CD-1 and CD-2, serious infections were reported in 6 patients (8 per 100 patient-years) treated with placebo and 13 patients (9 per 100 patient-years) treated with RINVOQ 45 mg through 12 weeks of the placebo-controlled period.
Maintenance Study/LTE: In the long-term placebo-controlled period, serious infections were reported in 10 patients (7 per 100 patient-years) treated with placebo, 7 patients (4 per 100 patient-years) treated with RINVOQ 15 mg, and 13 patients (6 per 100 patient-years) treated with RINVOQ 30 mg.
Gastrointestinal Perforations
Induction Studies: During the induction studies in all patients treated with RINVOQ 45 mg (N=938), gastrointestinal perforation was reported in 4 patients (2 per 100 patient-years). In the placebo-controlled induction period, in CD-1 and CD-2, gastrointestinal perforation was reported in no patients treated with placebo (N=347) and 1 patient (1 per 100 patient-years) treated with RINVOQ 45 mg (N=674) through 12 weeks.
Maintenance Study/LTE: In the long-term placebo-controlled period, gastrointestinal perforation was reported in 1 patient (1 per 100 patient-years) treated with placebo, 1 patient (<1 per 100 patient-years) treated with RINVOQ 15 mg, and 1 patient (<1 per 100 patient-years) treated with RINVOQ 30 mg.
Patients who received placebo or RINVOQ 15 mg for maintenance therapy and lost response were treated with rescue RINVOQ 30 mg (N=336). Among these patients, gastrointestinal perforation was reported in 3 patients (1 per 100 patient-years) through long-term treatment.
…
7 Drug Interactions
7.1 Strong CYP3A4 InhibitorsAdditions and/or revisions underlined:
Upadacitinib exposure is increased when RINVOQ is co-administered with a strong CYP3A4 inhibitor (such as ketoconazole, clarithromycin, and grapefruit), which may increase the risk of RINVOQ adverse reactions [see Clinical Pharmacology (12.3)]. Monitor patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondylarthritis closely for adverse reactions when co-administering RINVOQ 15 mg once daily with strong CYP3A4 inhibitors. Food or drink containing grapefruit should be avoided during treatment with RINVOQ.
For patients with atopic dermatitis, coadministration of RINVOQ 30 mg once daily with strong CYP3A4 inhibitors is not recommended.
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 [see Dosage and Administration (2.11)].
8 Use in Specific Populations
8.4 Pediatric UseAdditions and/or revisions underlined:
…
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
Additions and/or revisions underlined:
…
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.
…
Additions and/or revisions underlined:
For patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and 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).
…
Additions and/or revisions underlined
…
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 [see Dosage and Administration (2.10)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
…
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 (5.7)].
…
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 (5.11)].
…
MEDICATION GUIDE
Additions and/or revisions underlined:
…
What is RINVOQ?
RINVOQ is a prescription medicine that is a Janus kinase (JAK) inhibitor. RINVOQ is used:
…
to treat adults with moderate to severe Crohn’s disease when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.
…
It is not known if RINVOQ is safe and effective in children with ulcerative colitis or with Crohn’s disease.
…
What are the possible side effects of RINVOQ?
RINVOQ may cause serious side effects, including:
…
The most common side effects of RINVOQ in people treated for Crohn’s disease include:
upper respiratory tract infections (common cold, sinus infections)
fever
shingles (herpes zoster)
Bronchitis
headache
pneumonia
increased blood levels of creatine phosphokinase
increased liver enzyme levels
low number of red blood cells (anemia)
herpes simplex virus infections, including cold sores
low number of white blood cells (neutropenia, leukopenia)
tiredness
cough
infection of the stomach and intestine
flu
acne
…
Some people taking RINVOQ may see medicine residue (a whole tablet or tablet pieces) in their stool. If this happens, call your healthcare provider.
…
04/10/2023 (SUPPL-12)
5 Warnings and Precautions
5.10 VaccinationsAdditions and revisions underlined:
Avoid use of live vaccines during or immediately prior to RINVOQ therapy initiation. Prior to initiating RINVOQ, it is recommended that patients be brought up to date with all immunizations, including varicella zoster or prophylactic herpes zoster vaccinations, in agreement with current immunization guidelines.
6 Adverse Reactions
6.1 Clinical Trials ExperienceAdditions and revisions underlined:
. . .
Other adverse reactions reported in less than 1% of patients in the RINVOQ 15 mg and/or 30 mg group and at a higher rate than in the placebo group through Week 16 included anemia, oral candidiasis, pneumonia, non-melanoma skin cancer, and the adverse event of retinal detachment.
. . .
The adverse reaction of non-melanoma skin cancer was reported in 1% of patients in the RINVOQ 30 mg group and none of the patients in the RINVOQ 15 mg or placebo group through Week 52.
. . .
7 Drug Interactions
7.1 Strong CYP3A4 InhibitorsAdditions and revisions underlined:
Upadacitinib exposure is increased when RINVOQ is co-administered with a strong CYP3A4 inhibitor (such as ketoconazole, clarithromycin, and grapefruit), which may increase the risk of RINVOQ adverse reactions [see Clinical Pharmacology (12.3)]. Monitor patients closely for adverse reactions when co-administering RINVOQ 15 mg once daily with strong CYP3A4 inhibitors. Food or drink containing grapefruit should be avoided during treatment with RINVOQ.
8 Use in Specific Populations
8.4 Pediatric UseAdditions and revisions underlined:
The safety and effectiveness of RINVOQ in pediatric patients with juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis have not been established.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Medication GuideNewly added information:
What should I avoid while taking RINVOQ?
Avoid food or drink containing grapefruit during treatment with RINVOQ. Eating grapefruit or drinking grapefruit juice may increase the risk of side effects
Newly added information:
Advise patients to avoid food or drink containing grapefruit during treatment with RINVOQ [see Drug Interactions (7.1)].
10/21/2022 (SUPPL-10)
6 Adverse Reactions
6.1 Clinical Trials ExperienceLaboratory Abnormalities
Hepatic Transaminase Elevations
Additions and/or revisions underlined:
Adverse Reactions in Patients with Ankylosing Spondylitis
A total of 596 patients with ankylosing spondylitis were treated with RINVOQ 15 mg in the two clinical trials representing 577.3 patient-years of exposure, of whom 220 were exposed to RINVOQ 15 mg for at least one year …
Adverse Reactions in Patients with Non-radiographic Axial Spondyloarthritis
A total of 187 patients with non-radiographic axial spondyloarthritis were treated with RINVOQ 15 mg in the clinical trial representing 116.6 patient-years of exposure, of whom 31 were exposed to RINVOQ 15 mg for at least one year.
Overall, the safety profile observed in patients with active non-radiographic axial spondyloarthritis treated with RINVOQ 15 mg was consistent with the safety profile observed in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.
8 Use in Specific Populations
8.4 Pediatric Use
Additions and/or revisions underlined:
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, and non-radiographic axial spondyloarthritis have not been established.
8.5 Geriatric Use
Newly added information:
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.
8.6 Renal Impairment
Additions and/or revisions underlined:
For patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and 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).
8.7 Hepatic Impairment
Additions and/or revisions underlined:
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, ankylosing spondylitis, and non-radiographic axial spondyloarthritis [see Dosage and Administration (2.9) and Clinical Pharmacology (12.3)].
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.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEWhat is RINVOQ?
RINVOQ is a prescription medicine that is a Janus kinase (JAK) inhibitor. RINVOQ is used:
Additions and/or revisions underlined:
to treat adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation when a tumor necrosis factor (TNF) blocker medicine has been used, and did not work well or could not be tolerated.
It is not known if RINVOQ is safe and effective in children with juvenile idiopathic arthritis, with psoriatic arthritis, with ankylosing spondylitis, or with non-radiographic axial spondyloarthritis.
What are the possible side effects of RINVOQ? RINVOQ may cause serious side effects, including:
See “What is the most important information I should know about RINVOQ?”
The most common side effects of RINVOQ in people treated for rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis include: …
04/29/2022 (SUPPL-3)
6 Adverse Reactions
6.1 Clinical Trials ExperienceAdditions underlined
…
Adverse Reactions in Patients with Ankylosing Spondylitis
A total of 596 patients with ankylosing spondylitis were treated with RINVOQ 15 mg in the two clinical trials representing 577.3 patient-years of exposure, of whom 228 were exposed to RINVOQ 15 mg for at least one year.
Overall, the safety profile observed in patients with active ankylosing spondylitis treated with RINVOQ 15 mg was consistent with the safety profile observed in patients with rheumatoid arthritis and psoriatic arthritis. During the 14-week placebo-controlled period in Trial AS-I, the frequency of headache was 5.4% with RINVOQ 15 mg and 2.1% with placebo. During the 14- week placebo-controlled period in Trial AS-II, the frequency of headache was 3.3% with RINVOQ 15 mg and 1.4% with placebo.
8 Use in Specific Populations
8.4 Pediatric UseAdditions underlined
Juvenile Idiopathic Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis
The safety and effectiveness of RINVOQ in pediatric patients with juvenile idiopathic arthritis, psoriatic arthritis, and ankylosing spondylitis have not been established.
…
Additions underlined
For patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, 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).
…
Additions underlined
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, or ankylosing spondylitis [see Dosage and Administration (2.8) and Clinical Pharmacology (12.3)].
For patients with rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, and ankylosing spondylitis, no dosage adjustment is needed in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment.
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEAdditions underlined
…
What is RINVOQ?
…
to treat adults with active ankylosing spondylitis when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.
RINVOQ is safe and effective in children 12 years of age and older weighing at least 88 pounds (40 kg) with atopic dermatitis.
It is not known if RINVOQ is safe and effective in children with juvenile idiopathic arthritis, with psoriatic arthritis, or with ankylosing spondylitis.
…
What are the possible side effects of RINVOQ? RINVOQ may cause serious side effects, including:
See “What is the most important information I should know about RINVOQ?”
The most common side effects of RINVOQ in people treated for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis include:
…
headache
…
03/16/2022 (SUPPL-7)
6 Adverse Reactions
6.1 Clinical Trials ExperienceExtensive changes; please refer to label
7 Drug Interactions
7.1 Strong CYP3A4 InhibitorsAdditions and/or revisions underlined:
Upadacitinib exposure is increased when RINVOQ is co-administered with a strong CYP3A4 inhibitor (such as ketoconazole and clarithromycin), which may increase the risk of RINVOQ adverse reactions [see Clinical Pharmacology (12.3)]. Monitor patients closely for adverse reactions when co-administering RINVOQ 15 mg once daily with strong CYP3A4 inhibitors.
For patients with atopic dermatitis, coadministration of RINVOQ 30 mg once daily with strong CYP3A4 inhibitors is not recommended.
For patients with ulcerative colitis taking strong CYP3A4 inhibitors, reduce the RINVOQ induction dosage to 30 mg once daily. The recommended maintenance dosage is 15 mg once daily [see Dosage and Administration (2.8)].
8 Use in Specific Populations
8.1 PregnancyAdditions and/or revisions underlined:
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 MHRD (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 1-888-633-9110, 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 ulcerative colitis. 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.
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).
Additions and/or revisions underlined:
…
Ulcerative Colitis
The safety and effectiveness of RINVOQ in pediatric patients with ulcerative colitis have not been established.
Additions and/or revisions underlined:
…
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.
Additions and/or revisions underlined:
For patients with rheumatoid arthritis and psoriatic arthritis, 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, 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 [see Dosage and Administration (2.7)].
RINVOQ has not been studied in patients with end stage renal disease (eGFR <15 mL/min/1.73m2). Use in patients with atopic dermatitis or ulcerative colitis with end stage renal disease is not recommended [see Clinical Pharmacology (12.3)].
Additions and/or revisions underlined:
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 or ulcerative colitis [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3)].
For patients with rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, no dosage adjustment is needed in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment.
For patients with ulcerative colitis, the recommended dosage for mild to moderate hepatic impairment is 30 mg once daily for induction and 15 mg once daily for maintenance [see Dosage and Administration (2.6)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEExtensive changes; please refer to label
01/14/2022 (SUPPL-4)
5 Warnings and Precautions
5.9 Embryo-Fetal Toxicity
… Administration of upadacitinib to rats and rabbits during organogenesis caused increases in fetal malformations. Verify the pregnancy status of patients of reproductive potential prior to starting treatment. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception …
5.10 Vaccinations
Avoid use of live vaccines during, or immediately prior to, RINVOQ therapy. Prior to initiating RINVOQ, it is recommended that patients be brought up to date with all immunizations, including varicella zoster or prophylactic herpes zoster vaccinations, in agreement with current immunization guidelines.
‘trials’ replaces ‘studies’ throughout section
5.1 Serious Infections
Additions and/or revisions underlined:
… Tuberculosis
Evaluate and test patients for latent and active tuberculosis (TB) infection prior to administration of RINVOQ. Patients with latent TB should be treated with standard antimycobacterial therapy before initiating RINVOQ. RINVOQ should not be given to patients with active TB. Consider anti-TB therapy prior to initiation of RINVOQ in patients with previously untreated latent TB or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but who have risk factors for TB infection …
… During RINVOQ use, monitor patients for the development of signs and symptoms of TB, including patients who tested negative for latent TB infection prior to initiating therapy.
5.3 Malignancy and Lymphoproliferative Disorders
Additions and/or revisions underlined:
Malignancies, including lymphomas, were observed in clinical trials of RINVOQ [see Adverse Reactions (6.1)].
Non-Melanoma Skin Cancer
Periodic skin examination is recommended for patients who are at increased risk for skin cancer.
Exposure to sunlight and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen.
Newly added subsection:
5.6 Hypersensitivity Reactions
Serious hypersensitivity reactions such as anaphylaxis and angioedema were reported in patients receiving RINVOQ in clinical trials. If a clinically significant hypersensitivity reaction occurs, discontinue RINVOQ and institute appropriate therapy [see Adverse Reactions (6.1)].
Additions and/or revisions underlined:
5.8 Laboratory Abnormalities
Neutropenia
Evaluate neutrophil counts at baseline and thereafter according to routine patient management. Avoid RINVOQ initiation and interrupt RINVOQ treatment in patients with a low neutrophil count (i.e., ANC less than 1000 cells/mm3) [see Dosage and Administration (2.1, 2.8)].
Lymphopenia
ALC less than 500 cells/mm3 were reported in RINVOQ-treated patients in clinical trials.
Evaluate lymphocyte counts at baseline and thereafter according to routine patient management. Avoid RINVOQ initiation or interrupt RINVOQ treatment in patients with a low lymphocyte count (i.e., less than 500 cells/mm3) [see Dosage and Administration (2.1, 2.8)].
Anemia
Decreases in hemoglobin levels to less than 8 g/dL were reported in RINVOQ-treated patients in clinical trials.
Evaluate hemoglobin at baseline and thereafter according to routine patient management. Avoid RINVOQ initiation or interrupt RINVOQ treatment in patients with a low hemoglobin level (i.e., less than 8 g/dL) [see Dosage and Administration (2.1, 2.8)].
Lipids
… Assess lipid parameters approximately 12 weeks after initiation of treatment, and thereafter according to the clinical guidelines for hyperlipidemia.
6 Adverse Reactions
Newly added to bulleted line listing:
Hypersensitivity Reactions [see Warnings and Precautions (5.6)]
6.1 Clinical Trials Experience
Additions and/or revisions underlined:
Adverse Reactions in Patients with Rheumatoid Arthritis …
Adverse Reactions in Patients with Psoriatic Arthritis …
Newly added information:
Adverse Reactions in Patients with Atopic Dermatitis
Three Phase 3 (AD-1, AD-2, and AD-3) and one Phase 2b (AD-4) randomized, double-blind, placebo-controlled, multicenter trials evaluated the safety of RINVOQ in patients with moderate- to-severe atopic dermatitis. The majority of patients were White (68%) and male (57%). The mean age was 34 years (ranged from 12 to 75 years) and 13% of the patients were 12 to less than 18 years. In these 4 trials, 2612 patients were treated with RINVOQ 15 mg or 30 mg orally once daily, with or without concomitant topical corticosteroids (TCS).In the Phase 3 clinical trials (AD-1, AD-2, and AD-3), a total of 1239 patients received RINVOQ 15 mg, of whom 791 were exposed for at least one year and 1246 patients received RINVOQ 30 mg, of whom 826 were exposed for at least one year.
Trials AD-1, AD-2, and AD-4 compared the safety of RINVOQ monotherapy to placebo through Week 16. Trial AD-3 compared the safety of RINVOQ + TCS to placebo + TCS through Week 16.
Weeks 0 to 16 (Trials AD-1 to AD-4)
In RINVOQ trials with and without TCS (Trials AD-1, 2, 3 and 4) through Week 16, the proportion of patients who discontinued treatment because of adverse reactions in the RINVOQ 15 mg, 30 mg and placebo groups were 2.3%, 2.9% and 3.8%, respectively. Table 3 summarizes the adverse reactions that occurred at a rate of at least 1% in the RINVOQ 15 mg or 30 mg groups during the first 16 weeks of treatment.
Table 3: Adverse Reactions Reported in greater than or equal to 1% of Patients with Atopic Dermatitis Treated with RINVOQ 15 mg or 30 mg (newly added table; please refer to label for complete information)
Other adverse reactions reported in less than 1% of patients in the RINVOQ 15 mg and/or 30 mg group and at a higher rate than in the placebo group through Week 16 included anemia, oral candidiasis, pneumonia, and the adverse event of retinal detachment.
The safety profile of RINVOQ through Week 52 was generally consistent with the safety profile observed at Week 16.
Overall, the safety profile observed in patients with AD treated with RINVOQ was similar to the safety profile in patients with RA. Other specific adverse reactions that were reported in patients with AD included eczema herpeticum/Kaposi’s varicelliform eruption.
Eczema Herpeticum/Kaposi’s Varicelliform Eruption
Placebo-controlled Period (16 weeks): Eczema herpeticum was reported in 4 patients (1.6 per 100 patient-years) treated with placebo, 6 patients (2.2 per 100 patient-years) treated with
RINVOQ 15 mg and 7 patients (2.6 per 100 patient-years) treated with RINVOQ 30 mg.
12-Month Exposure (Weeks 0 to 52): Eczema herpeticum was reported in 18 patients (1.6 per 100 patient-years) treated with RINVOQ 15 mg and 17 patients (1.5 per 100 patient-years) treated with RINVOQ 30 mg.
7 Drug Interactions
7.1 Strong CYP3A4 Inhibitors
Additions and/or revisions underlined:
Upadacitinib exposure is increased when RINVOQ is co-administered with a strong CYP3A4 inhibitor (such as ketoconazole), which may increase the risk of RINVOQ adverse reactions [see Clinical Pharmacology (12.3)]. Monitor patients closely for adverse reactions when co- administering RINVOQ 15 mg once daily with strong CYP3A4 inhibitors. Coadministration of RINVOQ 30 mg once daily with strong CYP3A4 inhibitors is not recommended.
7.2 Strong CYP3A4 Inducers
Additions and/or revisions underlined:
Upadacitinib exposure is decreased when RINVOQ is co-administered with strong CYP3A4 inducers (such as rifampin), which may lead …
8 Use in Specific Populations
8.4 Pediatric Use
Additions and/or revisions underlined:
Juvenile Idiopathic Arthritis and Psoriatic Arthritis
The safety and effectiveness of RINVOQ in pediatric patients with juvenile idiopathic arthritis and psoriatic arthritis have not been established.
Newly added information:
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 [see Clinical Studies (14.3)]. The adverse reaction profile in the pediatric patients was similar to the adults [see Adverse Reactions (6.1)].
The safety and effectiveness of RINVOQ in pediatric patients less than 12 years of age with atopic dermatitis have not been established.
8.5 Geriatric Use
Additions and/or revisions underlined:
Rheumatoid Arthritis and Psoriatic Arthritis
… 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.
Newly added information:
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.
8.6 Renal Impairment
Additions and/or revisions underlined:
For patients with rheumatoid arthritis and psoriatic arthritis, no dosage adjustment is needed in patients with mild, moderate or severe renal impairment.
For patients with atopic dermatitis, the maximum recommended dosage is 15 mg once daily for patients with severe renal impairment (CrCL < 30 mL/min). No dosage adjustment is needed in patients with mild or moderate renal impairment.
The use of RINVOQ has not been studied in patients with end stage renal disease, and therefore not recommended for use in this population [see Clinical Pharmacology (12.3)].
8.7 Hepatic Impairment
Additions and/or revisions underlined:
No dosage adjustment is needed in patients with mild (Child Pugh A) or moderate (Child Pugh B) 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 this population [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3)].
Additions and/or revisions underlined:
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 2 and 17 times the 15 mg dose and 0.9 and 8.5 times the maximum recommended human dose (MRHD) of 30 mg, respectively, resulted in dose-related increases in skeletal malformations …
… No developmental toxicity was observed in pregnant rats and rabbits treated with oral upadacitinib during organogenesis at approximately 0.3 and 2.5 times the 15 mg dose and 0.2 and 1.3 times the MRHD of 30 mg, respectively. In a pre- and post-natal development study in pregnant female rats, oral upadacitinib administration at exposures approximately 1.6 times the MRHD of 30 mg resulted in no maternal or developmental toxicity (see Data) …
… 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 1-888-633-9110, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Data
Animal Data
Additions and/or revisions underlined:
… Upadacitinib was teratogenic (skeletal malformations that consisted of misshapen humerus and bent scapula) at exposures equal to or greater than approximately 1.0 times the MRHD of 30 mg (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 48 times the MRHD of 30 mg (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 0.9 times the MRHD of 30 mg (on an AUC basis at maternal oral doses of 4 mg/kg/day). No developmental toxicity was observed in rats at an exposure approximately 0.2 times the MRHD of 30 mg (on an AUC basis at a maternal oral dose of 1.5 mg/kg/day) …
… Embryolethality, decreased fetal body weights, and cardiovascular malformations were observed in the presence of maternal toxicity at an exposure approximately 8.5 times the MRHD of 30 mg (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 1.3 times the MRHD of 30 mg (on an AUC basis at a maternal oral dose of 10 mg/kg/day) …
… No maternal or developmental toxicity was observed in either mothers or offspring, respectively, at an exposure approximately 1.6 times the MRHD of 30 mg (on an AUC basis at a maternal oral dose of 10 mg/kg/day).
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEExtensive changes; please refer to label for complete information.
Additions and/or
revisions underlined:
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 (5.3)].
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 (5.5)].
Newly added
information:
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 (5.6)].
Gastrointestinal Perforations
Inform patients that gastrointestinal perforations have been reported in clinical trials with RINVOQ and that risk factors include the use of NSAIDS 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 (5.7)].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 (6.1)].
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 (5.10)].
Additions and/or revisions underlined:
Embryo-Fetal Toxicity
Advise pregnant women and females of reproductive potential that exposure to RINVOQ during pregnancy may result in fetal harm … 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 (8.3)].
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 (8.2)].
12/14/2021 (SUPPL-2)
6 Adverse Reactions
6.1 Clinical Trials ExperienceAdditions underlined
…
Psoriatic Arthritis
A total of 1827 patients with psoriatic arthritis were treated with upadacitinib in clinical studies representing 1639.2 patient-years of exposure, of whom 722 were exposed to upadacitinib for at least one year. In the two Phase 3 studies, 907 patients received at least 1 dose of RINVOQ 15 mg, of whom 359 were exposed for at least one year.
Two placebo-controlled studies were integrated (640 patients on RINVOQ 15 mg once daily and 635 patients on placebo) to evaluate the safety of RINVOQ 15 mg in comparison to placebo for up to 24 weeks after treatment initiation.
Overall, the safety profile observed in patients with active psoriatic arthritis treated with RINVOQ 15 mg was consistent with the safety profile observed in patients with rheumatoid arthritis. During the 24-week placebo-controlled period, the frequencies of herpes zoster and herpes simplex were >1% (1.1% and 1.4%, respectively) with RINVOQ 15 mg and 0.8% and 1.3%, respectively with placebo. A higher incidence of acne and bronchitis was also observed in patients treated with RINVOQ 15 mg (1.3% and 3.9%, respectively) compared to placebo (0.3% and 2.7%, respectively).
8 Use in Specific Populations
8.5 Geriatric UseAdditions underlined
Of the 4381 patients treated in the five Phase 3 clinical studies, 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 studies, 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 the elderly.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEAdditions underlined
…
What is RINVOQ?
RINVOQ is a prescription medicine that is a Janus kinase (JAK) inhibitor used in adults to treat:
moderate to severe rheumatoid arthritis when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.
active psoriatic arthritis when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.
…
Before taking RINVOQ, tell your healthcare provider about all of your medical conditions, including if you:
…
have unexplained stomach (abdominal) pain, have a history of diverticulitis or ulcers in your stomach or intestines, or are taking NSAIDs.
…
12/14/2021 (SUPPL-5)
5 Warnings and Precautions
5.1Serious InfectionsAdditions underlined
…
Viral Reactivation
Viral reactivation, including cases of herpes
virus reactivation (e.g., herpes zoster) and hepatitis B virus reactivation,
were reported in clinical studies with RINVOQ [see Adverse Reactions (6.1)]. The risk of herpes zoster
appears to be higher in patients treated with RINVOQ in Japan. If a patient
develops herpes zoster, consider temporarily interrupting RINVOQ until the
episode resolves.
12/02/2021 (SUPPL-8)
Boxed Warning
Box Warning has been revised; see full information below:
WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE), AND THROMBOSIS
See full prescribing information for complete boxed warning.
Increased risk of serious bacterial, fungal, viral, and opportunistic infections leading to hospitalization or death, including tuberculosis (TB). Interrupt treatment with RINVOQ if serious infection occurs until the infection is controlled. Test for latent TB before and during therapy; treat latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative, latent TB test. (5.1)
Higher rate of all-cause mortality, including sudden cardiovascular death with another Janus kinase (JAK) inhibitor vs. tumor necrosis factor (TNF) blockers in rheumatoid arthritis (RA) patients. (5.2)
Malignancies have occurred in patients treated with RINVOQ. Higher rate of lymphomas and lung cancers with another JAK inhibitor vs. TNF blockers in RA patients. (5.3)
Higher rate of MACE (defined as cardiovascular death, myocardial infarction, and stroke) with another JAK inhibitor vs. TNF blockers in RA patients. (5.4)
Thrombosis has occurred in patients treated with RINVOQ. Increased incidence of pulmonary embolism, venous and arterial thrombosis with another JAK inhibitor vs. TNF blockers. (5.5)
5 Warnings and Precautions
5.2 MortalityNewly added subsection:
In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed in patients treated with the JAK inhibitor compared with TNF blockers.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with RINVOQ.
Subsection title revised; Additions and/or revisions underlined:
Malignancies were observed in clinical studies of RINVOQ [see Adverse Reactions (6.1)].
In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lymphomas was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lung cancers was observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers. In this study, current or past smokers had an additional increased risk of overall malignancies.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with RINVOQ, particularly in patients with a known malignancy (other than a successfully treated NMSC), patients who develop a malignancy when on treatment, and patients who are current or past smokers.
Non-Melanoma Skin Cancer
NMSCs have been reported in patients treated with RINVOQ. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.
Newly added subsection:
In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of major adverse cardiovascular events (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke was observed with the JAK inhibitor compared to those treated with TNF blockers. Patients who are current or past smokers are at additional increased risk.
Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with RINVOQ, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue RINVOQ in patients that have experienced a myocardial infarction or stroke.
Additions and/or revisions underlined:
Thrombosis, including deep venous thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis, have occurred in patients treated for inflammatory conditions with JAK inhibitors, including RINVOQ. Many of these adverse events were serious and some resulted in death.
In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of overall thrombosis, DVT, and PE were observed compared to those treated with TNF blockers.
If symptoms of thrombosis occur, patients should discontinue RINVOQ and be evaluated promptly and treated appropriately. Avoid RINVOQ in patients that may be at increased risk of thrombosis.
6 Adverse Reactions
Addition of the following to the bulleted line listing:
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEExtensive changes; please refer to label
Additions and/or revisions underlined:
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 (5.1)].
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 (5.1)].
Malignancies
Inform patients that RINVOQ may increase their risk of certain cancers. Instruct patients to inform their healthcare provider if they have ever had any type of cancer [see Warnings and Precautions (5.3)].
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 (5.4)].
Thrombosis
Advise patients that events of DVT and PE have been reported in clinical studies with RINVOQ. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of a DVT or PE [see Warnings and Precautions (5.5)].
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 (5.7)].
Pregnancy
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 (5.8) and Use in Specific Populations (8.1)]. 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 (8.3)].
Lactation
Advise women not to breastfeed during treatment with RINVOQ [see Use in Specific Populations (8.2)].
Administration
Advise patients not to chew, crush, or split RINVOQ tablets [see Dosage and Administration (2.2)].
07/10/2020 (SUPPL-1)
6 Adverse Reactions
6.1 Clinical Trials Experience(Addition/ revision underlined)
Neutropenia
… In clinical studies, treatment was interrupted in response to ANC less than 1000 cells/mm3.
8 Use in Specific Populations
8.4 Pediatric Use(Additions underlined)
The safety and efficacy of RINVOQ in children and adolescents aged 0 to less than 18 years have not yet been established. No data are available.